We have recently welcomed new undergraduate student Kirsten Quay into the Menden-Deuer Lab
Kirsten is a double major in Cell and Molecular Biology and Math at the University of Rhode Island
She has joined us to help out with basic lab functions and our culture library
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URI is an equal opportunity employer committed to the principles of affirmative action
Craig Menden joins O’Melveny & Myers after more than six years with Willkie Farr & Gallagher
O’Melveny & Myers has added Willkie Farr & Gallagher partner Craig Menden to its M&A and emerging technologies industry groups in Silicon Valley and Newport Beach
Menden will continue advising his public and private sector clients in the technology and life sciences sectors on mergers and acquisitions
He is experienced in negotiating varied deal structures including venture-backed private buyouts
National Law Journal
The Recorder
New York Law Journal
The Legal Intelligencer
Brugh Lower of Gibbons has entered an appearance for industrial equipment supplier Devco Corporation in a pending trademark infringement lawsuit
accusing the defendant of selling knock-off Graco products
18 in New Jersey District Court by Rivkin Radler on behalf of Graco Inc
Read More
Yalowitz of Arnold & Porter Kaye Scholer have entered their appearances for Hanaco Venture Capital and its executives
24 in New York Southern District Court by Zell
accuses the defendants of negligently and fraudulently managing the plaintiff's $1 million investment
Read More
Attorneys from A&O Shearman has stepped in as defense counsel for Toronto-Dominion Bank and other defendants in a pending securities class action
11 in New York Southern District Court by Bleichmar Fonti & Auld
accuses the defendants of concealing the bank's 'pervasive' deficiencies in regards to its compliance with the Bank Secrecy Act and the quality of its anti-money laundering controls
Read More
a Pennsylvania company providing shared communications infrastructure
Wolf of Gordon Rees Scully Mansukhani to fend off a pending breach-of-contract lawsuit
25 in Michigan Eastern District Court by Hooper Hathaway PC on behalf of The Town Residences LLC
accuses Crown Castle of failing to transfer approximately $30,000 in utility payments from T-Mobile in breach of a roof-top lease and assignment agreement
Read More
Schwartz of McCarter & English have stepped in as defense counsel to Electrolux Home Products Inc
26 in New York Eastern District Court by Poulos Lopiccolo PC and Nagel Rice LLP on behalf of David Stern
alleges that the defendant's refrigerators’ drawers and shelving repeatedly break and fall apart within months after purchase
Read More
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The most famous picture of Edin Terzic is also the saddest
It shows him with tears in his eyes at the foot of the Westfalenstadion’s southern terrace
It was May 27, 2023, the final day of last season. Borussia Dortmund had waited 11 years to be champions again and with only a win over a mid-table opponent needed
80,000 fans had packed the stadium ready to celebrate
They went two goals down before drawing 2-2 against Mainz and handed the title to Bayern Munich
the local boyhood Dortmund fan now head coach
He looked utterly broken by the experience
Terzic is still badly bruised. He came very close to the sack twice this campaign. But the story of his season — and his coaching career — could yet be defined by Saturday, when the 41-year-old leads Dortmund to Wembley for the Champions League final
a boy from a small town near Dortmund who played in the fourth tier of German football
clawed his way up through the professional game as a coach and could now earn his personal redemption
The buildings in its old town are painted in sombre
His Bosnian father and Croatian mother settled in the region after arriving as guestworkers in Germany’s industrial heartland
were educated at the town’s Holy Spirit High School
is a two-mile walk up a road that rises gently out of the town
through a residential suburb and up into a hill which sits within the trees
experienced the tensions between their old lives and their new
Edin and Alen remember having to vacate their bedrooms for relatives who had fled the civil war in Yugoslavia
“We would listen hours on end to radio transmissions
that was the only way to find out news then,” he told The Athletic in 2023
“I partially experienced what war did to those people
We also stopped going to my parents’ home countries on holidays.”
Terzic is not just a Borussia Dortmund fan: he is a product of the region
met his wife Kora there and then married her at Nordkirchen Castle
one of the grandest places in North Rhine-Westphalia
He met Kora while he was a student at Ruhr University Bochum (RUB)
where he studied under professor Peter Lange
Lange is retired now but has spent a lifetime in football
Many of his former students occupy prominent positions in the game today
Lange also coached Terzic as a player. Together, they were two-time winners of the Germany University Championship. Terzic played up front and his partner in attack was Hannes Wolf, who would later coach Stuttgart, Bayer Leverkusen and Hamburg
Lange remembers Terzic as a good footballer
“Edin completed his studies very conscientiously,” Lange says
“He studied all scientific areas intensively
and football was — and still is — his absolute focus
“He took everything that university and sports science could offer in preparation for his career
Edin is actually much more qualified than many top German coaches who went before him — like Ottmar Hitzfeld
He played in the fourth tier of German football
The highlight of his playing days was winning the Westfalen Cup with Westfalia Herne in 2006
Terzic scored twice in the final against Delbrucker
It remains the highest point in Herne’s history
has remained in touch with Terzic in the years since and sees little difference in the person he is now to who he was then
“Edin used to be exactly the same as he is today,” Schulz told Reviersport in 2023
“He doesn’t change and knows where he comes from
he always writes back with ‘Hello Coach’.”
believes the modest nature of Terzic’s playing career seems to have shaped him as a coach
engendering a work ethic that has defined his approach
“It fits into the context of Edin as someone who hasn’t been a professional player himself
“He’s the passionate boy from the neighbourhood
his old strike partner from their RUB days
It could not have been better timed. Jurgen Klopp had been there for two years and by 2013 Dortmund had won back-to-back Bundesliga titles
had thrashed Bayern Munich 5-2 to win the DFB-Pokal Final in 2012
That Terzic is the coach leading them back there on Saturday owes much to a piece of opposition analysis — but not for Dortmund
GO DEEPER
Why Dortmund winning Champions League final would be a victory for football
By 2012, Terzic had come to know Slaven Bilic, then the head coach of the Croatian national team. Bilic was preparing for Euro 2012. Croatia would face the Republic of Ireland in the group stage
Bilic wondered whether Terzic could help him construct a game plan to beat an Irish side who had conceded only eight goals in 12 qualifying games
Terzic said: “I put down a few observations and ideas for playing. Things like Luka Modric’s position
The Irish always closed down the No 10 space really effectively
so in order to get Modric on the ball as often possible
Bilic and his players would exploit a lack of height in the Irish defence and their vulnerability at full-back
Bilic would become a catalyst for Terzic’s growth
“Edin is like a younger brother to Slaven,” says Kenneth Asquez
When the Croatian was appointed head coach of Besiktas in 2013
“Slaven contacted Michael Zorc at Dortmund
but he’d seen Slav’s great work with Croatia and thought Dortmund could benefit,” Asquez adds
“They agreed on a ‘loan’ for a couple of years — it ended up being five
“The best attribute I find he has as a manager is his human attributes
He’ll be like a father figure to a player who’s down and then
he’ll be the school teacher with a naughty schoolboy who hasn’t pulled up his socks
Successful Dortmund head coaches in the modern era have possessed those human qualities. But when Bilic left West Ham and Terzic returned to the Westfalenstadion
Peter Bosz was dismissed just six months after arriving and there was a feeling that Dortmund’s native culture was on the wane
and Zorc believed that one way to address this was with some homespun DNA
Terzic was appointed as an assistant to Lucien Favre
It was a direct link back to the Klopp era
It also provided the board with a connection to the playing squad
it put Terzic in the right place at the right time
He became interim head coach when Favre was sacked in December 2020
He won the DFB-Pokal at the end of that season
acquiring the credibility needed to take the job permanently when Marco Rose
It has not been an easy ride for Terzic — not least because of the end of last season
After the draw against Mainz that saw Dortmund miss out on the Bundesliga
Alongside the pressures of the year and the disappointment at its end
After a long illness, his father had passed away in October 2022, just before a Champions League game against Sevilla
Terzic finds it difficult to detach from football
He rarely talks to his players at full-time because he says he gets too emotional
there are certain rooms from which the game has had to be banned
he and his wife took their daughters on holiday
but then it was quickly back into the rhythm of professional football
he has been maintaining a dossier full of ideas
His hard work might be how Dortmund have recovered for this run in Europe
The performances have kept him in this job
he was a bit under pressure in his job and the Champions League helped keep him there,” says Asquez
GO DEEPER
Champions League final offers Borussia Dortmund a route to glorious Wembley redemption
but also reconfigured his coaching staff by bringing former players Nuri Sahin and Sven Bender back to the club to work with the attack and defence respectively
And while locals know that he is a local and grew up a fan
“You don’t hear (the chant) ‘Terzic is one of us’ very often,” says Stephen Uersfeld
Terzic has faced plenty of opposition since taking charge full time
Fans have unified around this Champions League run — and
the final — but this is not necessarily the most harmonious relationship
I believe he’s been great for BVB,” says Uersfeld
after a bad run of form culminating in a dreadful home defeat to Hoffenheim
Dortmund themselves remain very keen to stress Terzic’s homespun credentials and the blue-collar qualities of his story
He loves the club and shows it in how he identifies with the club and the loyalty he shows in every minute he works for this club
“His emotion and the intensity he represents: that is Dortmund
our dreams… that is something he was able to transfer to the team week by week
He is really someone who is able to convince and attract people with his belief in their abilities.”
with whom Terzic had worked with at West Ham
But Terzic’s emotional side can also be divisive
While Koers describes him as a “gentle” person and as someone who knows everybody’s name at the club and how to make people feel that they matter
his manner of speaking and his tendency to appeal to fans’ emotions can be grating
“His speeches are sometimes overloaded with pathos
that can make him quite a meme-able coach when things don’t go well.”
especially as a coach,” says Arthur Kaldynski
a Dortmund season ticket holder since the 1990s
While Dortmund have often been poor in the Bundesliga
individual players have raised their games for these European occasions
There are really two Dortmunds: one is the fifth-best team in the Bundesliga; the other is a battle-hardened warrior side
who come alive under the lights and who have forced their way to Wembley by force of will
but one who can live out a boyhood dream and make up for last season on Saturday night
and Terzic (middle of front row) as part of RUM’s football team on tour in Rome
alongside her trusty TA and graduate student Rickie Ewton
taught another successful Biological Oceanography class this semester
Bio Oce teaches students the fundamentals of biology in the ocean through field work
Pictured here are Susanne and Rickie with all the students in their class
Jersey Number 1 Jess MendenClass: JuniorHeight: 5-8High School: ShakopeeHometown: Shakopee
MNPrev School: TCUBioStatsMediaBioBioStatsMedia2010 JUNIOR SEASON:Appeared in 77 sets on the season averaged 0.22 aps and 1.23 dps had one assist and five receptions in the first match of the season at the Golden Gopher Invite on Aug
27 against Denver tallied seven receptions and four digs against Stony Brook on Aug
played in one set against Baylor at the Diet Coke Classic Tournament and accounted for one dig had three assists and two digs against NC Central on Sept
10 tallied seven digs and two assists in the championship game against Duke on Sept
11 had one dig and one assist against UC Santa Barbara on Sept
17 tallied four digs against San Diego State the next day played in two sets against No
22 Michigan and tallied three digs played in the match against Purdue on Oct
1 but did not post any numbers had one attack against Indiana on Oct
3 added seven digs to the defense in the three-set match against Iowa on Oct
6 had 11 digs for the defense in the four-set loss to No
15 tallied three assists and four digs against Ohio State on Oct
16 had one ace and four digs against No
22 tallied two assists and eight digs against Wisconsin on Oct
24 had six digs and two perfect service receptions in three sets against Iowa on Oct
29 accounted for one assist and three digs against Indiana on Nov
5 had one dig against Purdue the next day tallied two assists and five digs against No
12 made her first appearance at libero when Jessica Granquist went down momentarily with an injury in the first set against Michigan State Nov
13 had seven digs and 13 receptions on the match saw action in one set against Wisconsin on Nov
19 where she collected four digs tallied two digs and one assist in the match against No
20 played one set against Ohio State on Nov
26 but did not post any statistics played three sets of five in the match against No
2009 SOPHOMORE SEASON: Played in 11 sets in 10 matches averaged 0.36 assists per set and 0.55 digs per set in her Minnesota debut on Aug
she had two service receptions and one dig had season-high of two assists in one set against Navy on Sept
1 tallied one dig against USF on Sept
12 assisted for one kill in a three-set victory over Big Ten opponent Iowa on Sept
26 played two sets and gathered one assist
and a season best of four digs against powerhouse Penn State on Oct
2008 FRESHMAN SEASON (AT TCU): Played in nine matches
0.79 dps and 0.37 kps had five assists in first collegiate match against Louisiana Tech on Aug
29 hit 1.000 (5-0-5) with five kills
25 assists and six digs against UMKC on Aug
30 had 23 assists against Texas Southern on Sept
HIGH SCHOOL: Played for Head Coach Matt Busch
Earned all-state honors as a junior and senior
Was a four-time all-conference performer
Named second-team all-metro as a junior and first-team as a senior
Helped lead her team to a state championship as a senior
Was a five-time academic all-state performer
Honored as a Prep Volleyball All-American
1989 Parents are Ken and Barb Has an older brother
Lindsey Majoring in Business and Marketing Education
and Pierre Marrec set sail for another successful research cruise at the beginning of September
the Menden-Deuer team collected lots of valuable data on another great cruise aboard the R/V Endeavor
Susanne travelled to Woods Hole to attend the defense of Arianna Krinos
successfully defended her dissertation and will surely move on to more great things in life
Susanne, president of the Association for the Sciences of Limnology and Oceanography (ASLO), poses for a picture with the ASLO Board of Director members, Ajit Subramaniam (to her right) and Amina Pollard (to her left), on a rooftop terrace in Madison, Wisconsin while celebrating the 2024 Aquatic Sciences Meeting
Rickie, Frankie, and Alex have returned from yet another successful research cruise along the NES LTER transect
Although our lab has attended many summer and winter cruises
this was only the second spring cruise we attended
The cruise took place during an unusual bloom of phytoplankton
for which the whole science party was giddy to sample and understand the underlying drivers that led to its formation
This was also Rickie’s 10th research cruise as part of our lab
and she was excited to celebrate double digits during the calmest cruise she has experienced
This research investigates planktonic predator-prey interactions by combining studies of microscopic cell-cell interactions and responses with measurement of population growth and consumption rates
We can then embed these empirical observations in a theoretically-motivated model that identifies the linkages between organismal behaviors and their population-level ramifications
The motivation for this study is that although heterotrophic protists are important consumers of phytoplankton biomass and productivity
we still have an incomplete understanding of the processes that drive ecologically relevant rates of plankton growth and mortality
The large number of biological and abiotic variables in the dynamic surface ocean makes it impossible to quantify phytoplankton predation rates by heterotrophic protists empirically
We combine video analysis of the interactions and population distributions of free-swimming microscopic predators and prey with traditional methods of measuring prey disappearance and predator growth through enumeration at the population level
these three independent measures aim to identify key factors necessary to characterize predator foraging behaviors and success
Menden-Deuer 2006; Menden-Deuer & Grünbaum 2006; Menden-Deuer 2010; Harvey & Menden-Deuer 2011; Harvey & Menden-Deuer 2012
Mary successfully defended her Master’s thesis in April 2015 and returned to complete her Ph.D
Mary’s dissertation addressed the movements and spatial distributions of Antarctic krill in situ – even in winter – to decipher the role of krill in the Southern Ocean food web
Mary then became postdoctoral scholar at the Plymouth Marine Laboratory being co-advised by Dr
Mary is the recipient of a Marie Curie Post-doctoral fellowship
Anne Ward joined the lab as part of the 2018 GSO/URI SURFO (summer REU) program
Anna examined turbulence effects on protistan herbivory grazing and growth rates
She also participated in the LTER cruise EN617
Anna is an undergraduate at the University of California San Diego
Her work was selected for presentation at the 2019 ASLO meeting in San Juan
Megan completed several projects including growth rates of Ceratium lineatum under varying nutrient conditions
She was awarded a Stan Cobb Endowment for Independent Research
Andria joined the Menden-Deuer lab as a summer NSF SURFO (REU) student
by sampling water bodies near her home in Mississippi
Andria holds an undergraduate degree in biology from Jackson and has a love for studying the natural world
This project investigates the feeding and behavior of krill along the Antarctic Peninsula using a combination of acoustic
paired with shipboard experiments and molecular analyses and is done with collaborators Durbin
Rynearson and Zhou at the University of Massachusetts
During 2 cruises to the Antarctic Peninsula
the scientists combined their scientific questions and methodological approaches to investigate how krill feeding changes over the seasons to determine the species varying roles in the Antarctic food web
particularly since that region is now a sentinel for climate change
URI to deploy an in situ imaging system to concurrently obtain the vertical distribution and movements of Antarctic krill
Antarctic krill are a pivotal species in the Antarctic food web and subject to significant changes in seasonal ice cycles and temperature
Our project records krill in situ in their ambient habitat in large numbers (1000s of krill)
Our direct observations contribute to understanding the activity and distribution of krill as a function of season as well as co-occurring biological (e.g
Metrics details
The effectiveness of most cancer targeted therapies is short-lived
Tumors often develop resistance that might be overcome with drug combinations
the number of possible combinations is vast
necessitating data-driven approaches to find optimal patient-specific treatments
Here we report AstraZeneca’s large drug combination dataset
consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines
and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers
160 teams participated to provide a comprehensive methodological development and benchmarking
Winning methods incorporate prior knowledge of drug-target interactions
Synergy is predicted with an accuracy matching biological replicates for >60% of combinations
20% of drug combinations are poorly predicted by all methods
Genomic rationale for synergy predictions are identified
including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells
particularly considering the diversity of biological mechanisms that may influence drug response
A further limit to the translatability of many computational approaches is their reliance on data features that may not be present during the course of patient care
such as on-treatment tumor molecular profiles
This Challenge was designed to explore fundamental traits that underlie effective combination treatments and synergistic drug behavior
We shared with the scientific community 11,576 experimentally tested drug combinations on 85 cancer cell lines
Molecular data was provided for the untreated (baseline) cell lines
alongside chemical information for the respective drugs
Participants used the described data to train and test models
and were encouraged to extend computational techniques to leverage a priori knowledge of cellular signaling networks
we report on the results of this Challenge where we have identified novel and performant methods using a rigorous evaluation framework on previously unpublished data
We describe the details of these approaches
as well as general trends arising from the meta-analysis of all submissions
are freely provided to the research community
and available to benchmark future algorithms in the field
we describe putative mechanistic models derived from the observed predictive features underlying synergistic responses
particularly between receptor tyrosine kinase and PI3K/AKT pathway inhibitors
Drug combinations and cell lines profiled
a Molecular characterization of the cell lines included genetics
b Participants were encouraged to mine external data and pathway resources
c Participants were provided the putative targets for all and chemical structures for ~\({\raise0.5ex\hbox{$\scriptstyle 1$}\kern-0.1em/\kern-0.15em \lower0.25ex\hbox{$\scriptstyle 3$}}\) of drugs (with this manuscript structures are now provided for all drugs)
d The cell line panel contained 85 cell lines from six different cancer types
combination synergy scores capped within a range of −100 to 100
e The drug portfolio comprised approximately half oncogenic signaling targeting agents
and half cytotoxic drugs of which 14 were untargeted chemotherapies
f Drugs split by the putative targeted pathway
ESR1 inhibitors were predominantly combined with other drugs in estrogen receptor-positive breast cancer cell lines since these agents are standard of care within this cancer subtype
although too few combinations were shared between the datasets to conclude with statistical confidence
The Challenge was divided into two primary sub-challenges
In sub-challenge 1 (SC1) participants were asked to predict continuous synergy scores for drug combinations for which training data on those same combinations were available
participants were asked to predict binary synergy status on drug combinations for which no training data was provided
thereby requiring participants to infer synergy using transferable data/knowledge patterns identified from previously seen independent drug pairs
SC1 was further subdivided into two parts: SC1A allowed the use of all available data for model prediction
while SC1B limited data use to just mutation and copy-number variation (mimicking current clinical assay feasibility)
A total of 969 participants of diverse geography and expertize registered for the Challenge (Supplementary Fig. 6a, b)
One-hundred sixty teams submitted across any portion of the Challenge and 78 teams submitted for final assessment
SC1A received final submissions from 76 teams
Performance of teams in the AstraZeneca-DREAM challenge
a Participant performance in SC1A and SC1B— the distribution of performance of random predictions was used to estimate a lower limit
and the distribution of synergy correlations between biological replicates were used to estimate the upper limit
b Participant performance ranked in SC2 based on the primary metric
Distribution of bootstrap prediction performances for each team are shown by each boxplot with the dot showing their actual performance
c Participant performance plotted with upper and lower limits for SC2 based on the tie-break metric
d Ensemble models compared to the performance of individual models ranked from best to poorest performing in SC2
SML is an ensemble of the best performing models based on estimation of their BAC
Random Aggregation is an ensemble combining a random combination of models
Standard error of mean represented by error bars are estimated from ten random splits of the data
Drug target annotation is key in top-performing algorithms
as is the meta information about variants including their functional impact and tumor driver gene status
a Cross validation-based distributions of NAD primary metric of SC1B when replacing or adding drug/cell line label with respective features
NAD baseline model (red) used cell line labels and drug labels only as feature inputs
In the other models different drug specific (drug targets
drug target-associated Gene Ontology terms or direct interactions between drug targets in a signaling network) or cell line specific (mutations or CNVs of selected
cancer related genes) features (green and blue
respectively) were added either in place of or in addition to the baseline model features
Ensemble model (cyan) is the averaged prediction of the different models
Single asterisks refers to t-test P < 0.05
and triple asterisks for P < 0.001 compared to baseline model
b Heatmap of decrease in performance (average weighted Pearson correlation) of SC1B for DMIS support vector regression method when a particular feature type is removed (diagonal) or two feature types are removed at once (off diagonal)
Features of poorly and well predicted combinations
a Heatmap of Pearson correlation between observed and predicted synergy scores for 118 combinations across 73 teams participating in SC1A/B
Algorithms used by each team is marked in the matrix below
Size of node is proportional to number of drugs targeting a specific pathway in the entire dataset and width of edges is proportional to the number of drug combinations within the poorly or well predicted combination subset
Red edges highlight target pathway combinations unique to either the well predicted or poorly predicted combinations
c Types of interactions between the nearest neighboring gene and the two drug targets of poorly and well predicted combinations
Boxplots show the difference in the proportion of interactions of each type for poorly and well predicted combinations (t-test)
d Proportion of poorly and well predicted combinations for different network distances (minimum number of interactions in the OmniPath shortest path) between the two targets of a drug combination
difference significance estimated with chi-squared test
e Difference in average synergy for combinations categorized by the network distance between targets are tested with t-test
Combinations where targets were found to not be connected in a protein network had significantly lower average synergy (t-test P = 0.031) and lower max synergy (t-test P = 0.0021)
Drug synergy and monotherapy resistance biomarker relationship. a Cell lines and b PDX models show increased frequency of synergistic drug combinations if they contain biomarkers with stronger association to monotherapy resistance (Methods; Supplementary Methods)
The fraction of combination experiments is selected by order of most significant linked monotherapy resistance biomarker associations
The solid and dashed line are the LOcal regrESSion (LOESS) curve fit and its standard error
The effect size is the mean difference in synergy scores of mutant vs
e Comparison of ADAM17 combined with PIK3CB/D against ADAM17 in combination with pan-PIK3C inhibitor
f Network cartoon of PI3K signaling and role of ADAM17
NAD baseline (using only cell line and drug identities as features) and full NAD model for no targeted agents (None
and combinations of two targeted agents (Both drugs)(mean +/− 95% CI)
ANOVA P-values: *P = 1.322e-31 for different performance between baseline and full model; #: P = 5.584e-5 for association between model performance and number of targeted drugs in the combinations
we showed that some trends represented in these data can be reproduced in vivo
and that clinically efficacious combination pairs can be identified
Our double-blinded benchmark of 78 methods provides an unbiased comprehensive evaluation of the state-of-art of drug synergy prediction
Collectively this Challenge manuscript equips the scientific community with data and a methodological baseline for algorithm development
alongside a suite of computational methods to direct new experiments towards likely synergistic drug combinations
The results of the AstraZeneca-Sanger Drug Combination Prediction DREAM Challenge have shed important light on the best practices and limitations in predicting drug synergy
By evaluating predictions from a large number of teams
we were able to discern important strategies for predicting drug synergy from molecular and chemical traits
we observed that the machine learning method itself has little impact on overall performance
Aggressive pre-filtering that incorporates clean sparse network data to consider feature relevance to drug targets and cancer was successfully used by top performers to limit model complexity and improve model generalizability
many teams reached the upper-bound of performance levels based on variability in experimental replicates
This was further confirmed when top-performing models were applied to an independent dataset
demonstrating robustness to assay variability
these observations advocate for a more biologically rationalized approach to biomarker discovery
accounting for directionality and exclusivity of signaling and functional relationships between biomarkers and targets
suggested only modest improvement to prediction from inclusion of all data in SC1A compared to only genetics in SC1B
attenuating respectively targeting drug activity
and may also relieve the inhibitory effects of substrate competition or dimerization between PIK3CA and PIK3CB/D
These approaches can be complemented by adaptive and sequential strategies reactive to monitoring of the patient tumor and physiology
Success in these areas will be dependent on the availability and access to large-scale data needed for model development and validation
Public-private partnerships—as exemplified by this Challenge and AstraZeneca’s generous sharing of data with the research community—will be critical to future efforts
All cell lines were authenticated at AstraZeneca cell banking using DNA fingerprinting short-tandem repeat assays and each bank is confirmed to be free from mycoplasma
Cells ordered from the global cell bank are cultured for up to 20 passages
Cell suspensions are counted using a haemocytometer and cells are re-suspended in full growth medium containing Pen/Strep to a final density for different cell line densities and for different seeding densities into 384-well cell culture plate
A volume of cells as determined by cell count and dependent on cell type was added to each well of a Greiner 384-well plate using a Multidrop Combi liquid handler and then incubated at 37 °C and 5% CO2 overnight in a rotating incubator
plates were shaken to distribute the cells more evenly at the bottom of the wells and left to stand on the bench for 1 h to allow even settling of cells
Drug combinations were screened with four combinations per 384-well plate in a 6-by-6 range of concentration format
The first row and first column in the 6-by-6 matrix are monotherapies of each drug in the combination
while the top left corner is the untreated control
Drug combinations therefore were tested in a 5-by-5 layout with comprehensively rescreening the monotherapy and control for each experiment to minimize batch effects
Drug concentrations ran from the highest dose to the lowest dose
All plates were dosed with drugs solubilized in DMSO or PBS
or DMSO alone to provide comparable treatment and max control wells
After 5 days of incubation 5 µl of 2 µM Sytox Green working solution was added to each well of the 384-well plates (0.133 µM final concentration) and the plates incubated for 1 h at room temperature
After incubation plates were read by the Acumen laser scanner to detect the number of Sytox Green stained cells
The total fluorescent intensity across the well was then read and the number of dead cells calculated by dividing this total fluorescence by the fluorescence of a single cell
The plates were re-read on the Acumen to give a total cell count
A live cell count was then determined by subtracting the dead cell count from the total cell count
A reference dose-response surface is then generated by Combenefit based on the Loewe model of additive combinations and the single drug dose-response curves
The experimental combination dose–response surface is then compared by the software to the model-generated one
resulting in a synergy distribution in concentration space
This synergy distribution is finally further summarized by integrating the synergy distribution in logarithmic concentration space
The procedure resulted in a single score (the result of this integration) for each combination
progressive disease-PD) for each combination-PDX pair were extracted and compared with monotherapy ‘Best Response’’ of each drug in the combination on the same PDX model
This was represented numerically where CR = 4
Synergy was assigned to a change of +2 or more
considering an element of experimental variability
Cases where best response has been observed as a range over time (PR→→PD)
the earliest response was considered as we hypothesize this to reflect in vitro response in a more realistic sense for comparison
The percent tumor volume change class definitions are as following:
Synergistic efficacy: Combination treatment leads to better tumor regression than either monotherapy
Synergistic non-efficacy: Combination response is better than either monotherapy but does not result in tumor regression
Additivity: Combination response same as the better of either monotherapy responses
Non-synergistic efficacy: Combination response weaker than the better of the monotherapy responses but results in tumor regression
Antagonism: Combination response weaker than both monotherapies
Response scores defined by the Loewe synergy model were considered in ordered to define in vitro response classes
The 85 cell lines were molecularly characterized
Mutations from whole exome sequencing with Illumina HiSeq 2000 Agilent SureSelect (EGAS00001000978)
Copy-number variants from Affymetrix SNP6.0 microarrays (EGAS00001000978)
Gene expression from Affymetrix Human Genome U219 array plates (E-MTAB-3610)
DNA methylation from Infinium HumanMethylation450 v1.2 BeadChip (GSE68379)
Variants were provided without further filtering
which are in total 75,281 mutations in 85 cell lines
or amplification of certain segments in a chromosome
One or multiple genes can fall within such segments
We reported copy number for the major and minor allele on gene and segment level
Gene expression for 83 cell lines across 17,419 genes (HGNC labels) was reported; no expression was available for MDA-MB-175-VII and NCI-H1437
resulting in a total of 26,313 CpG island based on either M or beta values
The Challenge consisted of two sub-challenges
SC1 had four leaderboard rounds that lasted 8
while SC2 had three leaderboard rounds that lasted 12
Participants were given a leaderboard dataset to build a model and generate three prediction files per leaderboard round
Scores were returned to participants so that they can improve their model throughout these rounds for their one submission to the final round
which was scored against a held-out dataset
which was then followed by a 9 week bonus round and 10 week collaborative round
participants were asked to predict drug synergy of 167 combinations in the panel of 85 cell lines
The synergy data of each drug combination was partitioned into three sets: a training dataset (3/6–50%)
and validation set (2/6–33%) of treated cell lines
SC2 leveraged data for remaining 740 drug combinations not overlapping with those used in SC1
although data for some of the same drugs (in combination with different drugs)
A leaderboard set (370 combinations) and a final validation set (370 combinations) were randomly split
which are mutually exclusive from each other
With synergy scores roughly normally distributed and and outliers truncated to −100 and 100 (Supplementary Fig. 2)
Pearson’s correlation was employed as the base measure of prediction accuracy within each drug combination
The primary metric was then the average weighted Pearson correlation (ρw) of the predicted vs
observed synergy scores across each individual drug combination
The weight for a given drug combination i was \(\sqrt {n_i - 1}\)where ni is the number of cell lines treated with the drug combination
This resulted in the following primary metric for SC1A&B
where N` = 167 were the tested drug combinations
The tie-breaking metric was identical to the primary metric Eq
1 except that it was applied to the subset of drug combinations that have at least one cell line with synergy score \(S_{ci} \ge 20\)in the held-out test set (Sci = synergy score at cell line c and drug combination i)
Neither the subset of drug combinations nor its size (N = 118) was revealed to participants prior to final evaluation
The primary metric was a sequential three-way ANOVA
which tested the separation of held-out synergy scores by predicted synergy (=1) and predicted non-synergy (=0)
In the sequential three-way ANOVA (type 1)
we controlled for systematic drug and cell line effects
and evaluated variance explained by a given team’s synergy predictions
where sgn is the sign of the effect size (positive or negative separation by prediction)
and p is the P-value (F-statistic) computed from the ANOVA distinguishing predicted synergy (=1) from predicted non-synergy (=0) across all experimentally measured synergy scores
This three-way ANOVA score can be interpreted via linear regression where the intercept is set to 0
the response variable y is the observed synergy
and there are three predictive features: dc = drug combination
cl = cell line and a teams binary synergy predictions x
\({\mathrm{SA}} = - {\mathrm{log}}_{10}(p.{\mathrm{value}}[\beta _3])x{\mathrm{sign}}(\beta _3)\)
measures the significance of a team’s predictions after controlling for variance associated with cell line and and drug combinations
we used balanced accuracy (BAC) using discretized synergy scores \(S_{ci} \ge 20\)to evaluate the binary classifiers submitted in this sub-challenge
This metric evaluates both the sensitivity and specificity of the classifiers while taking into account the low proportion of synergistic cases to un-synergistic
we estimated a Bayes Factor (BF) using a paired bootstrapped approach to determine whether a team’s score was statistically indistinguishable from another
In the event that a team’s scores were determined to be statistically equivalent
we sample with replacement from the M observations of the given sub-challenge and computing the primary metric (pm) for each team 1000 times
Where \(pm_{best,i}\)is the bootstrapped primary metric at iteration i for the team with the highest primary metric (non-bootstrapped)
Combinations defined as poorly predicted had an average predicted vs
observed Pearson correlation across teams in the range seen with a random predictor (SC1 Primary metric = −0.25 and 0.25)
well predicted combinations had an average Pearson correlation across teams of above 0.5
the total number of exact experiments (Drug A–Drug B–Cell line) overlapping is below 100
giving the participants a highly independent validation set for their prediction algorithms
This information was provided to best performing teams in the Challenge
along with a dictionary of curated chemical structures and putative targets for each
Prediction models were trained on the released Challenge dataset and made synergy score predictions on the O'Neil et al
Metrics for SC1 and SC2 were used to assess prediction performance
Full description and implementation of models used by teams in the final submission to DREAM can be downloaded from:
Random Aggregation is the traditional way that people aggregate models by giving equal weight to each method
We randomly pick n methods (do this ten times) and for n methods we compute the average BAC and the error
We calculated the P-value for each suggested association with an ANOVA correcting for tissue of origin and multiple hypothesis testing via Benjamini Hochberg
The effect sizes is the mean difference in synergy score between mutant and wild-type cell lines
We validated biomarkers in two different contexts
(i) for cell lines overlapping with AZ-DREAM
and (ii) cells non-overlapping for predictions on independent cell lines
synergy biomarker were derived from best performer models
Further information on research design is available in the Nature Research Reporting Summary linked to this article
Full description and source code of all participants in this Challenge can be downloaded from synapse.org/DrugCombinationChallenge[https://www.synapse.org/DrugCombinationChallenge]
Cancer drug resistance: an evolving paradigm
Looking beyond the cancer cell for effective drug combinations
An unbiased oncology drug screen to identify novel combination strategies
Combinatorial drug therapy for cancer in the post-genomic era
Modelling of drug combination effects and applications to efficacy and toxicity: state-of-the-art
A community computational challenge to predict the activity of pairs of drugs
High-throughput screening using patient-derived tumor xenografts to predict clinical trial drug response
Crowdsourcing biomedical research: leveraging communities as innovation engines
Effect of combinations : mathematical basis of problem
Combenefit: an interactive platform for the analysis and visualization of drug combinations
A Landscape of Pharmacogenomic Interactions in
The National Cancer Institute ALMANAC: A comprehensive screening resource for the detection of anticancer drug pairs with enhanced therapeutic activity
Wisdom of crowds for robust gene network inference
Ranking and combining multiple predictors without labeled data
KEGG as a reference resource for gene and protein annotation
Systematic identification of cancer driving signaling pathways based on mutual exclusivity of genomic alterations
OmniPath: guidelines and gateway for literature-curated signaling pathway resources
The regulatory crosstalk between kinases and proteases in cancer
Inconsistency in large pharmacogenomic studies
Synergistic combinations of signaling pathway inhibitors: mechanisms for improved cancer therapy
Drug Resistance mechanisms in colorectal cancer dissected with cell type–specific dynamic logic models
Clinical responses to ERK inhibition in BRAF(V600E)-mutant colorectal cancer predicted using a computational model
Network quantification of EGFR signaling unveils potential for targeted combination therapy
Cell-specific computational modeling of the PIM pathway in acute myeloid leukemia
Discovery of drug synergies in gastric cancer cells predicted by logical modeling
Adaptive resistance of melanoma cells to RAF inhibition via reversible induction of a slowly dividing de-differentiated state
A human B-cell interactome identifies MYB and FOXM1 as master regulators of proliferation in germinal centers
Interpreting transcriptional changes using causal graphs: new methods and their practical utility on public networks
Pan-cancer network analysis identifies combinations of rare somatic mutations across pathways and protein complexes
DIGGIT: a Bioconductor package to infer genetic variants driving cellular phenotypes
Inhibition of the PI3K/AKT pathway potentiates cytotoxicity of EGFR kinase inhibitors in triple-negative breast cancer cells
mTOR inhibition induces EGFR feedback activation in association with its resistance to human pancreatic cancer
Functional analysis of 44 mutant androgen receptors from human prostate cancer
The androgen receptor gene mutations database: 2012 update
Reciprocal feedback regulation of PI3K and androgen receptor signaling in PTEN-deficient prostate cancer
Androgen receptor and growth factor signaling cross-talk in prostate cancer cells
ADAM17-siRNA inhibits MCF-7 breast cancer through EGFR-PI3K-AKT activation
ADAM17 promotes breast cancer cell malignant phenotype through EGFR-PI3K-AKT activation
Feedback suppression of PI3Kα signaling in PTEN-mutated tumors is relieved by selective inhibition of PI3Kβ
Combination cancer therapy can confer benefit via patient-to-patient variability without drug additivity or synergy
Combine and conquer: challenges for targeted therapy combinations in early phase trials
An automated fitting procedure and software for dose-response curves with multiphasic features
The landscape of cancer genes and mutational processes in breast cancer
Pindel: a pattern growth approach to detect break points of large deletions and medium sized insertions from paired-end short reads
PICNIC: an algorithm to predict absolute allelic copy number variation with microarray cancer data
Affy–analysis of Affymetrix GeneChip data at the probe level
Comparison of Beta-value and M-value methods for quantifying methylation levels by microarray analysis
Estimating the accuracies of multiple classifiers without labeled data
Multi-omic measurement of mutually exclusive loss-of-function enriches for candidate synthetic lethal gene pairs
COSMIC: exploring the world’s knowledge of somatic mutations in human cancer
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We thank the Genomics of Drug Sensitivity in Cancer and COSMIC teams at the Wellcome Trust Sanger Institute for help with the preparation of the molecular data
and Katjusa Koler for help with matching drug names across combination screens
We thank AstraZeneca for funding and provision of data to the DREAM Consortium to run the challenge
and funding from the European Union Horizon 2020 research (under grant agreement No 668858 PrECISE to J.S.R.)
the Joint Research Center for Computational Biomedicine (which is partially funded by Bayer AG) to J.S.R.
National Institute for Health Research (NIHR) Sheffield Biomedical Research Center
Premium Postdoctoral Fellowship Program of the Hungarian Academy of Sciences
M.G lab is supported by Wellcome Trust (102696 and 206194)
Present address: Institute of Computational Biology
Helmholtz Zentrum München - German Research Center for Environmental Health
These authors contributed equally: Michael P
These authors jointly supervised this work: Justin Guinney
Sheffield Institute for Translational Neuroscience
Hungarian Academy of Sciences and Semmelweis University (MTA-SE)
Joint Research Center for Computational Biomedicine
Department of Computational Medicine and Bioinformatics
Department of Computer Science and Engineering
Independent Consultant in Computational Biology
Department of Genetics and Genomic Sciences
Department of Electrical and Computer Engineering
Department of Bioinformatics - BiGCaT NUTRIM Maastricht University
Genetics Bioinformatics and Computational Biology Virginia Tech
Institute for Molecular Medicine Finland FIMM
Zia-ur-Rehman Tanoli & Krister Wennerberg
Bioinformatics Research Center North Carolina State University
Costas Mitsopoulos & Carmen Rodriguez-Gonzalvez
Computational Bioscience Research Center (CBRC) KAUST
King Abdullah University of Science and Technology (KAUST)
Department of Computer Science Virginia Tech
University of North Carolina at Chapel Hill
Solna SciLifeLab Center for Molecular Medicine Karolinska Institute
Niranjan Nagarajan & Chayaporn Suphavilai
Center for Integrative Medical Sciences RIKEN Japan
CIMUS University of Santiago de Compostela
Bioinformatics and Computational Biology Unit
Department of Molecular and Translational Medicine
Department of Medical Epidemiology and Biostatistics
Barcelona Institute for Science and Technology
Korea Advanced Institute of Science and Technology (KAIST)
Departement de Biologie Structurale et Chimie Institut Pasteur Unite de Bioinformatique Structurale CNRS UMR
Clinical Bioinformatic Area Fundacion Progreso y Salud CDCA Hospital Virgen del Rocio
Dries Van Daele & Sergio Pulido Tamayo
Max Planck Institute for Developmental Biology
Konstantinos Votis & Alexandros Zamichos
Fatma-Elzahraa Eid & Haitham Elmarakeby
LaSIGE Faculdade de Ciencias Universidade de Lisboa Portugal
Center for Computational Biology and Bioinformatics
Norwegian University of Science and Technology
Oslo Centre for Biostatistics and Epidemiology
University of Oslo and Oslo University Hospital Norway
Department of Computer Science Aalto University
Marta Sales-Pardo & Marc Tarres-Deulofeu
Sanford Burnham Prebys Medical Discovery Institute
Mucosal and Salivary Biology Division King’s College London Dental Institute
MRC Biostatistics Unit University of Cambridge
Joint IRB-BSC-CRG Program in Computational Biology Institute for Research in Biomedicine
Petr Smirnov & Seyed Ali Madani Tonekaboni
Department of Mathematics University of Oslo
Institute of Machine Learning Johannes Kepler University Linz
Department of Tumor Biology Institute for Cancer Research
Department of Informatics University of Oslo
Wellcome Trust Centre for Human Genetics University of Oxford
Bioinformatics and Systems Biology Program
Department of Computer Science and Statistics
University of Texas Southwestern Medical Center
Columbia University in the City of New York
School of Public Health Shandong University China
Skolkovo Institute of Science and Technology
A.A.Kharkevich Institute for Information Transmission Problems
Algorithmic Dynamics Lab Unit of Computational Medicine
SciLifeLab Center for Molecular Medicine Karolinska Institute
Helmholtz Zentrum Munchen Institute of Health Economics and Health Care Management
The Ohio State University College of Medicine
SingHealth Duke-NUS Institute of Precision Medicine Singapore
Mathematics Medical Research Institute Tokyo Medical and Dental University
Bioinformatics Center Institute for Chemical Research Kyoto University
Helsinki Institute for Information Technology HIIT
Interuniversity Institute of Bioinformatics in Brussels
Marijke Van Moerbeke & Catharina Olsen
Ghent University Bogor Agricultural University
Department of Experimental and Life Sciences
University of Illinois at Urbana-Champaign Urbana
Bellvitge Biomedical Biomedical Research Institute (IDIBELL)
Institute for Integrated and Intelligent Systems Griffith University
Department of Electrical Electronic and Computer Engineering
Center for Quantitative Genetics and Genomics
Izel Fourie Soerensen & Peter Soerensen
Biological and Environmental Science and Engineering
Cancer Hospital of Chinese Academy of Sciences
Department of Clinical Chemistry and Hematology
University of Helsinki and Helsinki University Hospital Comprehensive Cancer Center
National Center for Advancing Translational Sciences National Institutes of Health
The top-performing approach was designed by Y.G
Data analysis for the top-performing approach was conducted by M.P.M,
The DREAM Consortium provided drug synergy and biomarker predictions
as well as method implementations and descriptions
performed analysis of challenge predictions
interpreted the results of the challenge and performed follow-up analyses for the manuscript
receives personal compensation from Eli Lilly and Company
receives research funding from AstraZeneca and has performed consultancy for Sanofi
The remaining authors declare no competing interests
Journal peer review information: Nature Communications thanks the anonymous reviewers for their contribution to the peer review of this work
Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations
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in collaboration with Suzanne Strom (WWU) and her lab
investigates the regulation of Heterosigma akashiwo blooms by protistan predators
akashiwo causes fish kills yearly in coastal waters of the Pacific
a raphidophyte that may have multiple modes of toxicity
Our study focuses on the interactions between H
We investigate the behaviors of both the HAB alga and potential predators to examine predator deterrence as a potential mechanism of bloom formation
This project provides the opportunity to utilize our ability to link small-scale behaviors with larger-scale phenomena to investigate the role of species interaction in driving HAB population dynamics
Harvey & Menden-Deuer 2011; Harvey & Menden-Deuer 2012; Strom et al
coast is known for its productive fisheries
which may be threatened by human activities
To decipher the contributions of natural and anthropogenic forcings and manage this intricate ecosystem
the National Science Foundation (NSF) has announced the selection of this critical ocean region for a new Long Term Ecological Research (LTER) site led by Woods Hole Oceanographic Institution (WHOI) along with researchers at the University of Massachusetts
LTER programs focus attention on specific sites representing major ecosystem types
and undertake long-term assessments of populations
The LTER science team will conduct four research cruises a year to observe the intensive cross-shelf study area using advanced automated equipment including imaging systems to assess phytoplankton and zooplankton populations and mass spectrometers to measure gases that trace production within the food web
They will also collect plankton for high-throughput DNA sequencing
These data will be integrated with physical and theoretical models as well as already existing data streams coming from the Martha’s Vinyard Coastal Observatory
Pioneer Array and fish stock surveys across the region by the National Oceanic and Atmospheric Administration’s Northeast Fisheries Science Center (NOAA-NMFSC)
The ultimate goal is to better understand interactions between physical and biological systems and the flow of energy through the ecosystem from phytoplankton to fish
illuminating how the food web is structured and shifts in response to environmental changes
The scientific efforts are complemented by intense data management and science outreach
including opportunities to participated in multifaceted education programs for graduate
son of the late Laymond and Elsie (Nee: Richter) Menden
Catherine’s High School “Class of 1952” and then served in the U.S
Matthews’s Catholic Church in Oak Creek he was united in marriage to Frances Nygren
Fred started his career as a model maker apprentice at In-Sink-Erator and retired as an engineer from Wrought Washer
During his career as an engineer he traveled to Japan
Mary’s By the Lake Catholic Church where he served on the parish council and as a trustee
Fred spent many hours assisting at prayer services at Villa Saint Ann
He was a member and past president of the Catholic Men’s Association and a member and past chairman of the Society of Manufacture Engineers
and taking trips to Las Vegas with friends and family
He enjoyed cooking for the family and if there were leftovers he’d comment
“You didn’t eat much… don’t you like my cooking?” Fred was a husband
grandfather and great grandfather who will be dearly missed
Michael and Marie Goulais; great granddaughters
JoAnn Luba; sister-in-law Betty Menden; in-laws
William and Doris Nygren; nieces and nephews and friends
with Reverend Stephen Stradinger officiating
Relatives and friends may meet with the family Friday at the church from 9:30 a.m
Private interment will be held at Holy Cross Cemetery
Memorials will be donated to Fred’s favorite charities and will be forwarded by the family
The family wishes to extend a special thank you to the care givers at the Adult day care located on Dominic Drive and the nurses and CNAs at Ridgewood Care Center 2 West for their loving and compassionate care
JavaScript is disabled. In order to use all of the features on meredithfuneralhome.com, enable JavaScript.Close
Alex explains: “I had the wonderful opportunity to present my first oral presentation at Benthic Ecology Meeting in SC
This project was sponsored by the National Oceanic and Atmospheric Administration’s (NOAA) through the NOAA Ernest F
My talk was titled “Assessing coral damage from super typhoon Mawar on guams reefs” and for this project I had the opportunity to live in Saipan for 2.5 months
During my time in Saipan I met a lot of wonderful people and with those people I swimming across the ocean for a 1.5 mile swim to a neighboring island named Managaha.”
Amanda recently attended the National Society of Women in Engineering (SWE) conference in Texas as a representative of the URI SWE chapter
This conference supports women in all engineering majors by providing education in engineering and life lessons such as managing finance
Amanda reports having had a wonderful time and being incredibly grateful for the opportunity to attend
Almost all of the Menden-Deuer lab was able to sail on this gorgeous summer cruise along the LTER transect
the group has shared excitement about an incredible journey with great data
It was fantastic to incorporate new procedures to test new hypotheses
and we are looking forward to more cutting edge research to follow this first round
CLINTON — Artist Jean Menden’s raw materials were created in the violent explosions of dying stars and in the tumultuous and molten depths of the earth
She transforms them into works of art in a quiet pinewood studio overlooking Big Stone Lake
It’s tucked into a wooded corner of the lake’s north end that is yet to be discovered by the many who visit this western Minnesota destination
“It’s OK that they don’t know,” Menden said with a smile
and her art demands the focus and concentration that her studio provides so well
intricate leaf you created out of silver becomes a tiny
glowing glob under the searing flame of your acetylene torch
Allow yourself to be distracted by the problems of the day
and that delicate balance of accentuating the beauty of a turquoise gem from the mountains of the West or an agate from the Black Hills with the subtle sheen of the sterling silver holding them can be compromised
Her first five years as a silversmith involved practice
practice and more practice as she learned the skills it requires
she did her share of unintentional melting
her works are appreciated for their beauty as much as their uncompromising perfection
These are not works meant to fill wall space
They are meant to complement the beauty of those who wear them
Menden first sketches each of her designs on paper to scale
Only then does she begin the process of transforming the metal that came from stars and the rock from the earth’s depths into wearable art
All of this can be traced back to her high school years
She was introduced to silversmithing while attending Richfield High School
She said her art instructor gave each student a square of silver
While most of her classmates kind of screwed around and whacked on it and tried to saw it
where she graduated from high school in 1968
It’s where she met the man she would marry
The high school sweethearts married while earning degrees in education in Winona
They moved to a rural farm place between Dawson and Boyd when her husband
took a teaching position with the Dawson-Boyd Schools
Their move to the shores of Big Stone Lake came after retirement when they decided that the cabin that had been their weekend escape would better serve as home
Many of those who know their relatively secluded location are those who purposely have made the trip in search of her work
Menden has been an artist with the Meander for 19 years now
She credits the Meander for helping introduce her art to many from around the state and beyond
No different than when she worked from the rural farm place outside of Boyd
she has also relied on the internet to connect customers with her creations
But she is quick to point out that marketing her works is her least favorite thing to do
Menden said she loves to spend her hours in her studio creating her works
she will set aside her time to create “signature” pieces
works that are one-of-a-kind and can only be described as inspired
she will devote her time to the more familiar jewelry pieces that people appreciate as well
While it’s the beauty of her works that customers appreciate most of all
for Menden it’s the creative process that she loves most of all
and then working the sterling silver to feature them in pieces that are balanced and natural are the joys found in her quiet studio
2013 at Golden Living Heritage Square in Hales Corners
son of the late Arthur and Catherine (Nee: Schlick) Menden
Marine Corps as a staff sergeant from 1951- 1954
Robert was employed with Hamilton Beach and then with Master Lock for twenty five years
Bob loved golfing in his Senior Golf Leagues at Ives Grove and Maplecrest
and recorded a hole-in-one twice in his life
Robert also enjoyed bowling and his casino trips with Elaine
he was a devoted husband and father who will be dearly missed
Sandy (Kelly) Menden; Kristi Menden all of Milwaukee; 3 brothers
Bob was also preceded in death by his sister
A Mass of Christian Burial will be celebrated at St
Entombment with Full Military Honors will follow at Holy Cross Cemetery
Lucy’s Catholic Church or to one’s favorite charity have been suggested
Volume 8 - 2021 | https://doi.org/10.3389/fmars.2021.716349
This article is part of the Research TopicPlastic Ingestion: Understanding Causes and ImpactsView all 8 articles
Microplastics are ubiquitous contaminants in marine ecosystems worldwide
Ingestion of microplastics by fish and large zooplankton has been documented
but there are few studies focusing on single-celled marine predators
the heterotrophic dinoflagellate species Oxyrrhis marina and Gyrodinium sp
readily ingested both algal prey and polystyrene microplastic spheres (2.5–4.5 μm)
Compared to algae-only fed dinoflagellates
those that ingested microplastics had growth rates reduced by 25–35% over the course of 5 days
Reduced growth resulted in a 30–50% reduction of secondary production as measured as predator biomass
Ingestion rates of algal prey were also reduced in the microplastic treatments
When given a mixture of microplastics and algal prey
marina displayed a higher selectivity for algal prey than Gyrodinium sp
Observations in the coastal ocean showed that phylogenetically diverse taxa ingested microplastic beads
and thus heterotrophic dinoflagellates could contribute to trophic transfer of microplastics to higher trophic levels
The results of this study may suggest that continued increase in microplastic pollution in the ocean could lead to reduced secondary production of heterotrophic protists due to microplastic ingestion
altering the flow of energy and matter in marine microbial food webs
entry of microplastics into marine microbial food webs could have far-reaching implications for marine food webs
Despite many attempts to quantify the abundance of microplastics in the surface ocean globally, the concentration of plastics smaller than 5 μm is not well known and varies widely from dilute to concentrated in coastal areas with high input from coastal runoff and accumulation in gyres (Eriksen et al., 2014; van Sebille et al., 2015)
As this study was designed as a scientific proof of concept
microplastic concentrations exceeding those observed in the environment today were used to determine if heterotrophic dinoflagellates with diverse feeding types could ingest microplastic particles
and if the effect of this ingestion could be quantified in the laboratory
Concentrations were not chosen to reflect in situ concentrations of microplastic particles
Understanding the effect of microplastics on grazing rates is imperative for predicting how the presence and inevitable increase of microplastics in the ocean could affect food web dynamics
the objectives of this study were to (1) investigate if microplastics are ingested by marine heterotrophic dinoflagellate species
(2) quantify heterotrophic dinoflagellate grazing rates when exposed to microplastics
and (3) determine if ingestion of microplastics affects heterotrophic dinoflagellate growth rates and secondary production
These questions were examined on three heterotrophic dinoflagellate species (e.g.
Oxyrrhis marina; Gyrodinium sp.; Protoperidinium bipes) in a laboratory setting
to examine if microplastic particle ingestion could be observed in diverse taxa in whole plankton community incubations in the coastal ocean
communities of zooplankton in natural seawater samples taken from the Northeast Atlantic Shelf waters were incubated in the presence of microplastics
All cultures were maintained in 125 mL polycarbonate (PC) flasks on a 12 h: 12 h light-dark cycle at 15°C and a salinity of 31.4 psu
Predators were incubated at a light intensity of 8–15 μmol photons m–2 s–1
while prey were incubated at a light intensity of 70–80 μmol photons m–2 s–1
Fluorescent yellow polystyrene (PS) microplastic particles ranging in diameter from 2.5 to 4.5 μm were used in all microplastic feeding experiments (Spherotech, FP-3052-2). This size range was chosen to mimic the size of the chosen algal prey species, as verified by microscopy (3–6 μm) (Menden-Deuer et al., 2020)
Microplastic particles were rinsed three times in DI water and resuspended in autoclaved
0.2 μm filtered seawater directly before use
High concentrations of microplastics exceeding current environmental observations were used to induce a high dinoflagellate encounter rate of both algal prey and microplastics
Initial (T0) and final (T5) abundances (mL–1) of heterotrophic dinoflagellates
and microplastics in each treatment of the 5-day microplastic ingestion experiments
Microplastic spiked experiments were run for 5 days and sampled daily
heterotrophic dinoflagellates were fed algal prey
or a mixture of microplastics and algal prey
and not fed again for the duration of the experiment
Samples of 3 mL were taken daily and fixed with 10% glutaraldehyde to a final concentration of 0.1% glutaraldehyde
Fixed samples were used to count heterotrophic dinoflagellates via light microscopy
Epifluorescence microscopy was used to verify plastic ingestion by dinoflagellate cells
subsamples of 10 mL were taken at T0 and every 24 h for 5 days
and microplastic particles were measured with a Beckman Coulter Multisizer 3 (Beckman Coulter) using a 100 μm aperture
All statistical analyses were performed in R (version 1.4.1106). The maximum abundances of heterotrophic dinoflagellates reached in each treatment were used as a first-order quantification of secondary production. Specific growth rates of prey, in the I. galbana control, and heterotrophic dinoflagellates, in all experimental treatments, were calculated by a linear regression of natural log-transformed abundance through time (ggpmisc; Aphalo, 2021)
Growth rates of heterotrophic dinoflagellates were calculated over the time span for which exponential growth occurred in the algal-only treatments
marina and days 1–5 for Gyrodinium sp
The slope of the line fit through the natural log-transformed abundance data for the given time range denotes the growth rate
Ingestion rates (I) were calculated via Equation 1 (Frost, 1972)
where Ni and Nf refer to the initial and final concentration of prey
The growth rate (μ) is calculated as described above from the predator-free I
P is the geometric mean of the zooplankton concentration
Ingestion rates of plastic were calculated in the same manner
based on the initial and final plastic concentrations
were investigated in short-term experiments lasting 3–4 h
The goal of this second set of experiments was to determine whether microplastics and prey were ingested at the same rate
or if dinoflagellates displayed a preference for either prey or microplastics
hereafter referred to as a “selectivity factor.”
The two dinoflagellate species that were found to ingest microplastics were separately subjected to two treatments: an algal prey only treatment and a treatment containing a 1:1 ratio of algal prey and microplastic particles
Total prey particle concentrations were equal between treatments at the start of the experiment
“total particles” will refer to the sum of all potential prey items
total particle abundance and abundance of algae are equal
In the algal prey and microplastics treatment
the total particle abundance is equal to the sum of algal prey and microplastic particles
A total of 13–15 concentrations of algal prey and microplastics were chosen to create a geometric spread of total possible prey particles (algal prey + microplastics) between 4,000 and 270,000 prey particles mL–1 (Berges et al., 1994; see Supplementary Table 1)
with 15 bottles containing the concentration gradient of algae
and the other 15 bottles containing the chosen array of combined algal prey and microplastics concentrations
The same was carried out for Gyrodinium sp
Each treatment contained 900–1,100 cells mL–1 of O
marina or 500–800 cells mL–1 of Gyrodinium sp
and was prepared to a final volume of 125 mL
Ingestion rates as a function of the prey concentration or the combined prey and microplastic concentration fit a Holling Type II relationship, equivalent to a Michaelis-Menten dependency (Michaelis and Menten, 1913; Monod, 1949; Holling, 1965) (Equation 2)
which iteratively determined the best fit curve by minimizing the sum of the squared residuals between the model values for the response and the experimental data
The model inputs included the average starting abundance of heterotrophic dinoflagellates
marina and 632 cells mL–1 for Gyrodinium sp.
and prey concentrations ranging from 0 to 300,000 cells mL–1
A selectivity factor for each species was calculated using a linear regression analysis between plastic ingestion rates and prey ingestion rates
Ingestion rates of plastic and of prey were calculated using Equation 1
with zero indicating no uptake of less-preferred prey or high selectivity
and 1 indicating equal uptake of all particle types reflecting no selectivity at all
Two-way ANOVA analyses were completed on ingestion rates or growth rates using time, treatment, and species as effects (AICcmodavg; Mazerolle, 2020)
Time was included as a categorical factor (i.e.
Time was included in the ANOVA analysis to avoid confounding effects
as it was known that ingestion rates would vary with time as algal concentrations were depleted
but this variation in time would not be identical between treatments
When significant interactions between effects were observed (p < 0.05)
Tukey’s HSD post hoc tests were carried out to identify the associated treatment factors
Samples were spiked with 1,000 fluorescent yellow polystyrene (PS) microplastic particles mL–1 (2.5–4.5 μm in size) and incubated for 24 h in deckboard surface seawater flow-through incubators
Fluorescent microplastic particles were chosen to avoid detection of potential contaminants present in the seawater
Concentrations of microplastics were chosen to ensure detectability of the plastic particles and do not reflect realistic concentrations of microplastics in the surface ocean
Once 24 h had elapsed, samples for organism and plastic particle imaging were taken and fixed with glutaraldehyde to a final concentration of 0.1%. Microscopy slides were prepared using a primuline yellow stain (Caron, 1983) to dye the phytoplankton and zooplankton cells and analyzed via epifluorescence microscopy for the identification of zooplankton phyla with and without microplastic ingestion
When fed a mixture of algal prey and microplastic particles, two of the three heterotrophic dinoflagellate species were able to ingest microplastics. When viewed under light and epifluorescence microscopy, both Gyrodinium sp. and O. marina cells contained ingested fluorescent microplastic particles (Figure 1)
bipes cells were found to have microplastic particles ingested
we will focus on the description of results pertaining to O
Micrographs of the heterotrophic dinoflagellates O
(right column) with microplastic beads (fluorescent green) ingested under light (a–d,i–l) and epifluorescence (e–h,m–p) illumination
Over the 5-day experiment, both O. marina and Gyrodinium sp. reached higher abundances in algae-only treatments than treatments with microplastics (Figure 2). Both a diet of algal prey only and a diet of combined microplastics and algal prey elicited positive growth rates in O. marina and Gyrodinium sp. (Figure 3)
For both heterotrophic dinoflagellate species
growth was slower in the treatment with microplastics
which subsequently resulted in a reduction in secondary production
Abundance of heterotrophic dinoflagellates in two feeding treatments
algae only (orange) and a mixture of microplastics with algal prey (blue) over time
with triplicate bottles of each treatment for each species
abundance of prey and microplastics for the respective predator treatments
Gray points represent the microplastic particle abundance in the treatments with microplastics
Error bars indicate one standard deviation of the mean
which is contained within the symbol for many measurements
Heterotrophic dinoflagellate growth rates during the exponential growth phase were higher when dinoflagellates were fed only algal prey (orange) and lower when fed a mixture of algal prey and microplastics (blue)
and error bars as the 95% confidence interval
O. marina had a 25% slower maximum growth rate in the presence of microplastics (0.43 ± 0.04 d–1) compared to when fed only algae (0.60 ± 0.03 d–1, p = 0.004) (Table 2)
This reduction in dinoflagellate growth rates led to a cell abundance average of just over 2,800 cells mL–1 by day 5 of the experiment in the microplastic-fed treatments
This is an accumulation almost 30% lower in the microplastics treatment than in the algae-only treatment
which reached nearly 4,000 cells mL–1
average ingestion rates of algal prey (cells predator–1 day–1)
and maximum ingestion rates of algal prey (cells predator–1 day–1) reached in each treatment of the long-term growth and grazing experiments
Gyrodinium sp. reached a maximum growth rate of 0.40 ± 0.04 d–1 in the algae-only treatment (Table 2)
reached a lower maximum growth rate of 0.27 ± 0.07 d–1 in the treatment with microplastics
growing on average 35% slower than in the algae-only treatment (p = 0.047)
This reduced growth rate led to a reduced dinoflagellate accumulation
cell abundances in the treatment with microplastics were 46%
of the cell abundances in algae-only treatment
A two-way ANOVA for both species confirmed that growth rates were statistically different across time (p = 0.0001) and between treatments (p = 0.0004)
the negative effect of microplastics on growth rates was significant
had an average ingestion rate of 45 ± 8 cells predator–1 day–1 in the algae-only treatment and only a slightly lower average ingestion rate of 41 ± 2 cells predator–1 day–1 in the treatment with microplastics
Maximum ingestion rates for both treatments were reached on day 1
with a maximum ingestion of 96 ± 12 cells predator–1 day–1 in the algae-only treatment and 114 ± 11 cells predator–1 day–1 in the treatment with microplastics
ingestion rates on any given day were up to 40% higher in the algae-only treatment than in the treatment with microplastics
Tukey’s HSD post hoc tests confirmed that
ingestion rates were statistically different across time and between treatments for day 2 (p = 0.0054)
when total prey particles were abundant enough to yield high grazing rates
Ingestion rates of algal prey through time over 5 days for O
ingestion rate decreased over time with decreasing prey particle concentration
The short-term experiments with only algae or with a 1:1 mixture of microplastics and prey showed a typical Type II functional response, with ingestion rates increasing up to a saturating prey density in both species of dinoflagellates (Figure 5)
Functional response curves from short-term
fit to the ingestion rate and total particle abundances for (A) O
or a mixture of algal prey and microplastics
Ingestion rates of algal prey (orange and black) as well as total ingestion of all particle types present (orange and blue) are shown for comparison
The relationship between the rate of plastic ingestion and rate of prey ingestion (C) when both prey types are at equal concentrations reveals the selectivity factor of each species between microplastic particles and algal prey
pink) showed higher selectivity for prey than Gyrodinium sp
there was less selectivity against microplastic particles for Gyrodinium sp
were relatively similar between the two treatments
The heterotrophic dinoflagellates in the algae-only treatment reached a maximum ingestion rate of 10 cells predator–1 h–1
The treatment with microplastics reached a maximum ingestion rate of algae of 7.4 cells predator–1 h–1
and an overall maximum ingestion rate of all particle types of 12 particles predator–1 h–1
When comparing overall prey ingestion rate to plastic ingestion rate
a selectivity factor of 0.662 was observed
Concentrations of microplastics ranged from 2,000 to 110,000 particles mL–1
and ingestion of microplastics was observed even at low concentrations by both heterotrophic dinoflagellate species
When prey and microplastics were at equal concentrations
2 microplastic particles for every 3 algal prey consumed
marina had a much higher selectivity factor
and on average consumed 1 microplastic particle for every 5 algal prey ingested
Both dinoflagellate species reached similar maximum ingestion rates of algal prey in the treatment with microplastics
marina’s higher ingestion rates when fed only algal prey
heterotrophic dinoflagellates preferentially selected for algae
but at lower total particle concentrations microplastics and prey were ingested at more similar rates
When coastal water communities from the Northeast Atlantic Shelf were incubated in the presence of microplastic particles for 24 h, ingestion was confirmed in several organisms. Plankton taxa with confirmed microplastic ingestion included many of the mixotrophic dinoflagellates of the genus Ceratium and ciliates (Figure 6)
Epifluorescence microscopy images of coastal marine microplankton
stained with primuline dye with confirmed microplastic ingestion (fluorescent spheres denoted by red arrows) after 24-h of exposure
it was not surprising that this particular species did not ingest microplastics
other dinoflagellate species could also readily ingest plastic particles in the same size range as their algal prey
Ingestion of plastic resulted in reduced growth for both O. marina and Gyrodinium sp. For both species, a reduction in maximum growth rate of approximately 30% was observed between the algae-only and microplastics treatments. Growth rates of these species have been reported in the range of 0.05–1.2 day–1, with increasing prey availability inducing a hyperbolic response in growth rates (Anderson and Menden-Deuer, 2017)
the microplastics-induced reduction in growth rate is on par with a 2–4-fold reduction in prey availability for Gyrodinium sp
Reduced secondary production curtails the trophic transfer of primary production to higher trophic levels
which could fundamentally alter the structure and function of planktonic marine food webs by causing a bottom-up cascade effect of reduced population sizes up the food chain
The weakening of this link between the microbial food web and the classical food chain could have implications for fisheries production
This implies that although presence of microplastics can be disruptive to heterotrophic dinoflagellate secondary production
the capacity of predators for selectivity could ameliorate plastics uptake
concentration-dependent and proportional uptake of microplastics is not to be expected
unaltered microplastics as used here likely represents a conservative estimate of feeding rates and could be enhanced when these particles acquire a chemical signature that draws zooplankton to plastic particles
these estimates do not include microplastics smaller than 300 μm
the concentration of small microplastics available for ingestion by heterotrophic dinoflagellates is an important unknown
the results of this study are important when determining the potential effects microplastic pollution can have on plankton communities in areas of high plastic contamination
Heterotrophic dinoflagellate growth and ingestion of algal prey was significantly and considerably (at least 30%) reduced when exposed to microplastic particles
If these processes are in effect in whole plankton communities under natural conditions
they would result in unrealized productivity for higher trophic levels and alterations to the abundance and composition of planktonic communities
Marine plastic pollution is a global problem and incorporating measures of the effect of microplastic pollution on the growth and ingestion rates of microzooplankton species
and their ramifications for food web structure and production
will be critical in tracking how the effects of plastic pollution could radiate from heterotrophic dinoflagellates at the base of the food web all the way up through the fishing and aquaculture industry
The datasets presented in this study have been submitted to the Biological and Chemical Oceanography Data Management Office (BCO-DMO) under the project Quantifying Temperature Dependence in Growth and Grazing Rates of Planktonic Herbivores (OCE-1736635). https://www.bco-dmo.org/project/739232
VF and SM-D collaborated on the inception of the project idea and experimental design
VF carried out experiments and data analysis and prepared the initial draft of the manuscript
Both authors contributed to the article and approved the submitted version
This work was supported by the grants from National Science Foundation
Further support came from grants for the North East Shelf Long Term Ecological Research project (NES-LTER) (1655686) and under the EPSCoR Research Infrastructure Improvement Award (#OIA-1655221)
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations
Any product that may be evaluated in this article
or claim that may be made by its manufacturer
is not guaranteed or endorsed by the publisher
We thank Jason Schaedler and Dawn Outram for culturing and logistical support
We thank Jacob Strock and Heather McNair for help with experimental design and valuable feedback
We are grateful to the reviewers and editor for their comments that improved this manuscript
The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fmars.2021.716349/full#supplementary-material
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Citation: Fulfer VM and Menden-Deuer S (2021) Heterotrophic Dinoflagellate Growth and Grazing Rates Reduced by Microplastic Ingestion
Copyright © 2021 Fulfer and Menden-Deuer. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY)
distribution or reproduction in other forums is permitted
provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited
in accordance with accepted academic practice
distribution or reproduction is permitted which does not comply with these terms
*Correspondence: Susanne Menden-Deuer, c21lbmRlbkB1cmkuZWR1
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
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Gary Alan Menden, Jr., 62, of Wyoming passed away on October 19, 2021
Gary enjoyed golf, fishing and rebuilding older cars.
Tribute Archive
December 12, 2020 - Just over three years ago, Borussia Dortmund were dealt a crippling blow in their title ambitions as they lost 5-1 to Stuttgart
Far from the bombastic Stuttgart side of 2023
this Stuttgart side had just returned to the Bundesliga under the stewardship of Pellegrino Matarazzo and the 5-1 victory came as a shock defeat to Lucien Favre’s side
The game proved to be definitive for Dortmund’s future
Lucien Favre was dismissed and Edin Terzic
a young scrappy-looking assistant coach who grew up 25 miles from the Westfalenstadion was appointed interim head coach
the Schwarzegelben have once again lost to Stuttgart
and continue to fall down the Bundesliga pecking order
the club saw Edin Terzic appointed as head coach twice
and the greatest title race in recent Bundesliga history – alongside an equally historic collapse
and generational talents like Jadon Sancho
Even the club’s sporting operation and philosophy has vastly changed with the departure of longtime sporting director
has been a rapidly changing club that has pinned its hopes
As questions about his tenure and legacy begin to mount
one must ask; who is Edin Terzic and how did we get to this point
Edin Terzic is the exact man who Dortmund fans have been clamoring for years
Terzic grew up as a Borussia Dortmund fan in the town of Menden
only a 30-minute drive away from the Westfalenstadion
but his upbringing strikes familiar chords with the tenets of Borussia Dortmund – his parents were blue-collar workers who migrated to the Rhineland amidst strife in their native Yugoslavia
Terzic even shared his bedroom with family members who had fled Yugoslavia – those who were lucky enough to escape the bloodshed
He began his footballing career as a teenager in one of Germany’s many amateur leagues and never progressed into professional football
he graduated with a degree in sports science at Ruhr University
when studying for his UEFA A coaching license
Terzic had a chance encounter with Dortmund’s then Chief Scout
Within months he was a member of Borussia Dortmund’s scouting department and youth academy setup where he was tasked with opposition analysis in addition to being an assistant coach for the club’s many youth teams
a 30-year-old Terzic reached out to then-Croatia coach
with a breakdown of Ireland’s play before Croatia’s opening match in the 2012 Euros
Croatia went on to win the occasion 3-1 and Bilić even praised Terzic in a subsequent press conference
When Slaven Bilić was offered the coaching job at Beşiktaş a year later
he brought Terzic with him as an assistant coach with Dortmund’s blessing
who has had a journeyman career as a coach
acted as a mentor to Terzic first at Beşiktaş and then at West Ham in 2015
Bilić let Terzic experiment – leading team meetings and tweaking the side’s tactics despite West Ham’s lackluster results
Terzic has also noted his time in the Premier League allowed him to see coaches like Jose Mourinho
Across the four years since he left Dortmund
Terzic refined his coaching aptitude and defined his man-management motivator philosophy as he often acted as Bilić’s orator to the team
ended in November of 2017 when West Ham sacked the entirety of the coaching staff
The German used the pause from club work to complete his UEFA Pro License in 2018 alongside other notable individuals including Graham Potter
It is undoubtable that Terzic was looking for the next opportunity to prove himself at this point and that opportunity came not long after
Terzic returned to Borussia Dortmund in 2018 as an assistant coach to Lucien Favre
Doing so saw him complete an unorthodox journey where he refined his coaching skills across three vastly different leagues
Terzic implemented the skills he had learned abroad and acted as a more motivational contrast to the soft-spoken Favre’s coaching philosophy
that Dortmund’s think-tank inclusive of Hans-Joachim Watzke
opted for Edin Terzic to take over on an interim basis when Lucien Favre’s time at Dortmund ran its course
With players and fans quickly turning on Lucien Favre
Edin Terzic presented Dortmund’s CEO with both the perfect interim coach and stop-gap
and liked by both the players and fans alike
There was minimal pressure on Terzic from anyone involved with the club – he was just expected to get through the season and
that Dortmund’s hierarchy were already courting his successor
No one saw a future for Terzic at Dortmund—except for him
further than any coach since Thomas Tuchel
and famously won the DFB Pokal against RB Leipzig to lift the first meaningful trophy since 2016/17
Edin Terzic’s popularity had quickly grown amongst the players
Hans-Joachim Watzke likely realized an opportunity in Edin Terzic – he could be the first coach to break out of the long shadow that Jürgen Klopp cast
No coach since Klopp left had the same fiery passion for the club
but his callousness proved to be too much for fans
and had won over fans not just with his success but with his personality
He contrasted the four coaches which came before him and represented an opportunity to spearhead Dortmund into an era where they challenged an aging Bayern
two months before Terzic’s DFB pokal victory and he was slated to take over from the interim Terzic in the 2021/22 season
Watzke’s solution to this was an interesting one
He established a technical director position and gave the role to Terzic in an unprecedented move for Borussia Dortmund
This position not only kept Terzic on the club’s payroll but also fought off interest from other top-flight entities
It also remains the strongest supporting evidence that Watzke had already determined Edin Terzic would succeed Marco Rose as coach of Borussia Dortmund
He had to protect his asset at all costs and then when Marco Rose’s stewardship faltered
The contingency plan went off without any issues
Marco Rose led Dortmund through a tumultuous and injury-plagued year that saw them fail to contest any trophy by the end of the season
Rose also failed to win over the board and was ‘mutually dismissed’ at the end of the season by Watzke
and newly appointed sporting director Sebastian Kehl
Rose’s swift dismissal came as a shock at the time
it now feels as if Dortmund’s board was waiting for the opportunity to place their prize asset into the head coach role
Edin Terzic was once again made head coach of Borussia Dortmund – this time permanently
Terzic’s season first season as permanent head coach was immediately beset with difficulty—high-profile signing Sebastién Haller was diagnosed with cancer a week into his tenure while injuries hampered Dortmund
all of which were brought in by Sebastian Kehl
showed promise but the likes of Karim Adeyemi and Anthony Modeste were struggling to produce goals
Terzic’s side slumped to sixth place by the season’s midway point and qualified for the Champions League knockout stages in lackluster fashion
it likely felt like years of planning coming to fruition while for every other Dortmund fan
The side put together a string of narrow victories and then went on a rampage
Victory after victory saw Dortmund climb into first place
While the team was humbled at times including an away defeat to Chelsea to be knocked out of the Champions League and the team’s routine defeat to Bayern
they were still on track to reclaim the Meisterschale for the first time in eleven years
it appeared Terzic became a miracle worker
Karim Adeyemi and Donyell Malen became two of the most lethal players in the league after struggling in the first half of the season while Emre Can had transformed into world-class defensive midfielder
was that Sebastién Haller was cancer-free and back to playing football
While it took him time to recover to full form
he became a centerpiece in Dortmund’s fairytale
All that was needed was a win at home against Mainz to reach the team’s ‘happily ever ending’
You do not need to be provided with the play-by-play of how Dortmund drew Mainz to lose the Bundesliga or rewatch Haller’s penalty miss over and over again
Those 90 minutes are not the reason Terzic’s support is wavering seven months later
and what this lengthy article seeks to contextualize
and Borussia Dortmund mishandled the aftermath of Matchday 34
the draw against Mainz was a setback but Dortmund’s resurgence served as a proof-of-concept
His years as a scout and assistant coach had come to fruition
and his motivational ethos enabled him to bring Dortmund to the final hurdle
For Hans-Joachim Watzke and Matthias Sammer, the match against Mainz was the opportunity they spent eight years building towards. After eight years, five coaches, and repeated defeats to Bayern Munich
Dortmund now had a coach who checked all the boxes they needed
They finally had a coach to build the team around who preached loyalty to Dortmund above all
Sebastian Kehl only recently ascended to the position of Sporting Director and the team needed to reconfigure its midfield following the astronomical sale of Jude Bellingham
Dortmund did what they thought was the right option and what turned out to be the biggest mistake in recent memories; they handed the keys to Edin Terzic
For a club that prided itself on Michael Zorc’s shrewd business and the ability to retain its identity across several coaches
handing the keys to Edin Terzic was always going to be a disaster
Terzic leaned into opposition analysis and coaching rather than talent identification
he vetoed key transfer decisions made by Kehl including Edson Alvarez
who looked shaky apart from the second half of the 2022/2023 season
but they doubled down and made him captain
the team brought in Felix Nmecha for a massive fee alongside Marcel Sabitzer
The last addition Was Niclas Füllkrug with the remainder of Dortmund’s budget despite the team only having three center-backs
These choices showcase Dortmund’s transfer business was building ‘Terzic’s Team’ to challenge for the Bundesliga once again
the club has prioritized physicality and experience over technical ability and potential sell-on value
This sharp change in squad building philosophy
but problematic signs are beginning to come to the forefront for both the players and fans
While Jürgen Klopp shared Terzic’s charisma
he also promised high-octane football that is yet to manifest for Dortmund this season under their new coach
The players Terzic is reliant on have also struggled
Both the new crop brought in to fit his identity and the veteran core that continues to age have been inconsistent
Equally important is that the expectations on Edin Terzic have never been higher
that Dortmund are struggling during the biggest transitionary period since Jürgen Klopp left
The players and fans will continue to ask questions of Terzic until he begins to replicate last season’s form
have put all their chips on the head coach
It is impossible to tell at what point they will have to give up on their hometown hero’s fairytale
the man from Menden has the reigns and the team’s future is intertwined with his
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Morung Express NewsDimapur | August 10Tanemi Pottery – ceramic studio and workshop in Dimapur
Nagaland is built with the purpose to introduce the art of pottery to our people which already is part of the Naga culture
Tanemi - a word of the Ao Naga language which is translated to “unhurried” implies that “in today’s fast-moving world
let’s focus our creative energies and create with perseverance to bring forth creation to the world.”
the young woman behind Tanemi and its visions
has always found inspirations through “words.” Marking the opening of her ceramic studio and workshop on August 10
Menden said that the inspirations for the products she creates come through words
it is translated into words and then transformed into objects or products
Menden recollected the one moment during her schooling days in Kolkata where she first come across the craft of pottery
when we visited an art live exhibition in Kolkata
I approached him and he allowed me to have first hand on experience of making pottery,” she shared
“It was an overwhelming experience and that feeling never left.”
Menden did not let go of that feeling and there on she started researching on pottery
She found her way to one of the “oldest” pottery training institutes in Gurgaon and started to nurture her love for pottery
When Menden came back to Nagaland after her training
She started teaching pottery in schools and other institutions
people started opening up to the idea of pottery
People of all age group were coming to learn
as Menden noted is already a part of the Naga culture
we have lost some attachments with pottery
pottery was always part of the Naga culture.’ “I don’t want pottery to be foreign
Contemporary pottery is progressing but we also have to keep our traditional pottery going
Every generation has to keep learning,” she asserted
but others should be able to come and learn from us,” she added.
“Today I have started a studio but my dream is to make it grow into an institution where people from different places and culture would come together and become part of learning and teaching about pottery,” she expressed.
On the rampant availability of ceramic products in the market
Menden raised awareness that it is important to know that all the raw materials she uses are “lead free.” Menden also observed that pottery is very expensive outside Nagaland
keeping in mind the complex economy of Nagaland state she informed that Tanemi offers reasonable fee structures
located in Kashiram road (opposite sub-jail) near Eden Medical Centre
is now open to take students and trainees and to create pottery products that make memories and tell stories.
Do you think social media platforms are strengthening or weakening journalism in Nagaland
The Morung Express is a people-oriented alternative newspaper based in Nagaland that was conceived from the Naga people’s historical realities and is guided by their voices and experiences
It emerged from the well-recognized concept that the core of a free press is based on “qualitative and investigative” journalism
Ensuring this is essential for contributing to an informed Naga public that makes sound decisions on issues that affect all spheres of life
Cynthia Beth Rubin, SMD lab artist in residence, gave a lightning talk at Creative Tech Week about her use of augmented reality in art. Check out this interview with Cynthia here from Creative Tech Week about her collaboration with the Menden-Deuer lab. Cynthia’s phenomenal work can be seen at her website
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Volume 6 - 2015 | https://doi.org/10.3389/fmicb.2015.01277
Motility is a key trait that phytoplankton utilize to navigate the heterogeneous marine environment
Quantifying both intra- and inter-specific variability in trait distributions is key to utilizing traits to distinguish groups of organisms and assess their ecological function
Because examinations of intra-specific variability are rare
here we measured three-dimensional movement behaviors and distribution patterns of seven genetically distinct strains of the ichthyotoxic raphidophyte
Strains were collected from different ocean basins but geographic distance between isolates was a poor predictor of genetic relatedness among strains
Observed behaviors were significantly different among all strains examined
with swimming speed and turning rate ranging from 33–115 μm s-1 and 41–110° s-1
Movement behaviors were consistent over at least 12 h
and in one case identical when measured several years apart
Movement behaviors were not associated with a specific cell size
These strain-specific behaviors resulted in algal populations that had distinct vertical distributions in the experimental tank
This study demonstrates that the traits of genetic identity and motility can provide resolution to distinguish strains of species
where variations in size or biomass are insufficient characteristics
Even small differences in movement behaviors between strains can have significant consequences for the population as a whole
a difference in swimming speed of 20 μm s-1 between two strains could result in net displacements of up to two body lengths per second or 1.7 m per day
even small differences can have considerable ramifications for the abundance and distribution of phytoplankton
Understanding the range in movement behaviors within a single species
and how these behaviors may shift in response to environmental conditions will provide an increased predictive capacity and understanding of phytoplankton population abundance and distributions in the marine environment and the biogeochemical implications
To date no study has examined whether individual-level genetic variation can be used to identify inherent behavioral diversity in phytoplankton
Such data would provide critical tools to link real-time
with the ecological ramifications of expressed behaviors
such as the distribution of motile species
cell–cell or cell-resource encounter rates
we wanted to quantify the strain-specific behavioral response to both high and low salinity conditions
High genetic and inherent behavioral diversity was observed among all strains of H
The diversity of swimming behaviors expressed resulted in unique
strain-specific vertical distributions of H
these swimming behaviors were found to be a persistent trait
and were observed over both short and longer temporal scales
These data provide further documentation of the persistent intra-specific variability in phytoplankton traits that need to be considered in order adequately characterize the ecosystem function of genetically diverse phytoplankton populations
Seven strains of H. akashiwo were used in these experiments; five strains isolated from the west coast of the United States and two strains from the east coast (Table 1)
Six strains originated from the National Center for Marine Algae and Microbiota
Strom at the Shannon Point Marine Center (SPMC 135)
we will refer to strains by their strain number
All strains were isolated within 4 years of one another
Strains 2808 and 2809 were isolated from the same water sample
single cells from all strains were re-isolated to ensure monocultures were used for both behavioral and genetic analyses
and carbon content (± standard deviation) for each Heterosigma akashiwo strain examined
Cultures were grown in 0.2 μm sterile-filtered autoclaved seawater enriched with f/2 nutrients minus silicate (f/2; Guillard, 1975)
Cultures were maintained under a 12:12 h light:dark cycle at 15°C
and a light intensity of 80–100 μmol photon m-2 s-1
Cultures were transferred every 7–10 days to maintain exponential growth
All experiments were conducted with exponentially growing cells
Cell counts were performed regularly to ensure exponential growth was maintained
cell concentrations were determined by microscope counts using samples fixed in 1% acid Lugol’s solution
genomic DNA was extracted from exponentially growing cells filtered onto a 47 mm
USA) using the DNeasy Plant Mini Kit (Qiagen
To confirm that all strains were identified correctly as H. akashiwo, the small subunit (18S) region of the ribosomal DNA was sequenced from each strain. Each 10 μl reaction mixture contained 5 μl BIO-X-ACT Short Mix (Bioline), 1 μl genomic DNA (∼3–5 ng), and 0.5 μmol L-1 each 18SA and 18SB universal primers (Medlin et al., 1988)
Thermocycling consisted of a 3 min denaturation step at 94°C
followed by one cycle at 72°C for 10 min
Amplicons were sequenced in both directions on an ABI 3130xl using the DS-33 Dye Set (Applied Biosystems)
Sequences were compared using CLC Workbench and Sequencher software programs
All sequences are available in GenBank (accession numbers: KT163009–KT163015)
Geographic distance between sampling sites was determined using the shortest ocean distance as calculated in Google Earth (Google Earth 7.1.2.2041)
Given the wide range in geographic distances sampled
and the need to show the data on a log scale
the two samples collected from the same water sample were set to a geographic distance of 1 km
TABLE 2. Heterosigma akashiwo microsatellite characteristics including microsatellite locus name (as in Nagai et al., 2006)
Strain specific carbon content was calculated from cell volume, assuming the shape of a prolate spheroid (Menden-Deuer and Lessard, 2000). For each strain, the length and width of 100 live cells were measured using a Nikon Eclipse E800 microscope equipped with image capture (Coriander) and image analysis software (ImageJ). Cells were measured live to avoid changes in cell size due to preservation (Menden-Deuer et al., 2001)
Differences in carbon content among strains were compared using a one-way ANOVA
Behavioral experiments were conducted similar to those reported in Harvey and Menden-Deuer (2011, 2012)
to quantify population distributions and movement behaviors
a linear salinity gradient from 0 to 30 psu was created in the chamber
Salinity decreased linearly from the bottom to the top of the tank
creating a stable water column not subject to convection
The same source water was used in all experiments and cultures
organisms were introduced at the bottom of the tank (at the equivalent salinity of 30 ppt) through silicone tubing with an internal diameter of 1 mm
Cells were introduced slowly at a rate of 10 mL min-1 to reduce stress to cells as well as disturbance to the water column
akashiwo was added to the tank for an average final concentration of 180 cells mL-1
and cells were allowed to acclimate for 10 min before filming started
Two infrared sensitive cameras (Pixelink) with Nikon 60-mm Micro Nikkor lenses monitored a two-dimensional (2D) field of view approximately 1 cm × 1 cm × 1.5 cm
The cameras were mounted at a 45° angle with maximally overlapping fields of view to enable reconstruction of three-dimensional (3D) movement behaviors
to eliminate the potential for light-mediated behavioral responses
the chamber was illuminated with infrared (960 nm) light-emitting diodes (LEDs)
Filming occurred at four evenly distributed vertical horizons
Swimming data from the lower and upper horizons were combined for analysis of high and low salinity swimming behaviors respectively
Each horizon was filmed for 1 min every hour for a 12 h period
and video was captured at 15 frames s-1 for a total of 1800 frames per observation
The order of filming the four horizons was initially randomized and then the same randomized order was used for all treatments
Cell abundances in video images were determined by averaging the number of tracks per frame over the duration of the video yielding an average number of cells per frame and variation estimated across the 1800 frames in each 1-min segment
and z velocity vectors and turning rates were calculated from 3D paths
Only trajectories that were longer than 3 s were used in the analysis
The upper and lower 1% tails of the frequency distributions of the swimming data were discarded before analysis to eliminate extreme outliers
The swimming behaviors and population abundances reported here are averages from the entire 12-h filming period averaged over the least (12 psu) or most (30 psu) saline portion of the tank respectively
The Kolmogorov–Smirnov test (K–S test) was used to determine significant differences among abundance data
as well as among distributions of swimming behaviors
A K–S test was conducted contrasting each swimming metric measured separately (speed
In order to test whether the variability in movement behaviors among H
akashiwo was a result of intrinsic variability or reflective of the sampling size
the coefficient of variation (CV) for swimming behaviors was calculated iteratively
increasing the number of track intervals included in each iteration
Calculations of the cumulative CV for each strain were conducted on individual track intervals from all tracks observed in all replicates
track intervals were chosen at random for the analysis
The abundance data are displayed graphically as the percent of the population at each horizon
calculated separately for each strain to allow for comparison between treatments
All statistical analyses were done on the absolute abundance data
the significance level was p < 0.05
In order to test whether the genetic and physiological data collected were correlated, a Mantel test (Mantel, 1967) using a Pearson product-momentum correlation was performed on pair-wise dissimilarity matrices of the physiological parameter of swimming speed and the genetic relatedness matrix described above
The dissimilarity matrix of swimming speed was created by taking the absolute differences between mean swimming speeds of two strains
999 permutations were run in R (using the vegan package)
and the average Mantel statistic and p-value was obtained
Regression analysis was used to quantify the relationship between genetic relatedness and geographic distance
as well as genetic relatedness and absolute difference of mean swimming speed
Model II regression (independent variable measured with error) was used for these comparisons
The 18S sequences of all seven strains were identical to each other (100% agreement) and to GenBank accessions of H
indicating that all strains used here represented the same species
Locus HaK17R was monomorphic and was excluded from the analysis. Of the remaining five loci, HaK37R and HaK3R were the most variable with seven alleles and six genotypes (Table 2)
There were no significant departures from Hardy–Weinberg equilibrium among loci (p > 0.05)
(A) Principal coordinate analysis of the genetic distance of all Heterosigma akashiwo strains examined
Strains do not cluster based on geographic origin (black squares – Pacific Northeast; gray triangles – Northwest Atlantic)
PC1 and PC2 explained 80% of the variance in the data
(B) Model II linear regression for geographic distance (km) by genetic distance of all H
Individuals within all seven strains exhibited significantly different distributions of swimming behaviors both among strains and with different salinities; all comparisons of swimming metrics between strains were significantly different (Figure 2; all p < 0.001
there was a nearly five-fold difference in average swimming speeds among strains
from 33 ± 6 (strain 3149) to 151 ± 4 μm s-1 (strain 3374)
Most strains had an average turning rate between 41 and 46 μm s-1 but strains 452 and 3149 had higher rates of 73 ± 4 and 110 ± 9 μm s-1
with both upward and downward swimming observed
ranging from -2.8 ± 0.3 (net downward swimming) to 11 ± 0.3 μm s-1 (net upward swimming)
including swimming speed (μm s-1; top row)
and vertical velocity (μm s-1; bottom row) in seven strains in high salinity (30 psu; left) and of five strains in low salinity (12 psu; right)
The asterisk next to strain 2809 indicates movement behavior data collected 2 years prior to the experiments conducted on all remaining strains
The dashed line separates strains isolated from the Northwest Atlantic (left of line) and from the Northeast Pacific (right of line)
Error bars represent one standard deviation from the mean
NA indicates that strain 2809 was not measured under these conditions
In the behavioral response to low salinity water (12 psu), there were marked differences between strains relative to swimming in high salinity waters (Figure 2)
Two strains (135 and 3374) avoided low salinity waters and
cell concentrations were too low for behavioral analysis
swimming speed in low salinity ranged from 85 ± 3 to 238 ± 10 μm s-1
turning rate from 24 ± 5 to 70 ± 2° s-1
and vertical velocity from 0.06 ± 0.1 to 81 ± 1.4 μm s-1
swimming speed increased ∼150% and turning rate decreased 43% in low salinity water
strain 3107 had virtually unchanged swimming behaviors irrespective of salinity
strain 3149 exhibited swimming speeds and turning rates that were more similar to the overall mean swimming behaviors expressed by all strains in high salinity
cells found in low salinity water displayed upward vertical velocities almost an order of magnitude larger than those observed in higher salinity
which displayed essentially no net vertical movement (0.06 ± 0.1 μm s-1)
indicating that a sub-sample of 1000 track intervals was sufficient to estimate the mean and associated inherent
Strain 3149 had the highest inherent variability
with a CV for swimming speed of almost 60%
whereas strain 452 had the lowest CV at ∼35%
Other strains had CVs that ranged between 37 and 50%
The CV as a function of sample size for other movement behaviors showed similar trends (data not shown)
turning rate and vertical velocity variability was higher than inherent variability in swimming speed
with CVs ranging between 74 and 103% for turning rate and CV > 100% for all strains for vertical velocity
This indicates that while swimming speed remained consistent throughout the experiment
turning rate and vertical movement were more variable over time
a plateau in CV was reached after ∼1000 track intervals for all strains
showing that the observed variability was inherent to the strains’ motility pattern and independent of sample size
akashiwo movement behaviors: (A) coefficient of variation (%) versus number of track increments and (B) average swimming speed (μm s-1) over time
Error bars (calculated as one standard error from the mean) were very small and are obscured by the symbols
The CV in turning rate and swimming speed between the two measurements of strain 2809 are 2 and 13%
This is smaller than the variability observed on an hourly time scale for this strain (15%) and indicates high consistency of movement behaviors over time
As a consequence of the variance in swimming behaviors among strains, unique distributions of cells throughout the experimental tank were observed (Figure 4
All strains had a higher mean abundance at the bottom
high salinity portion of the tank relative to the top
The abundance of the population ranged from 30 ± 5 to 63 ± 6% at the bottom of the tank and from 7 ± 2 to 25 ± 6% at the top of the tank
No two strains had identical vertical distributions
The CV in cell abundance among horizons ranged from 17% in strain 2809 that was relatively homogeneously distributed vertically to 102% in strain 135 that had a population skewed toward the bottom of the tank
akashiwo in the experimental tank over 12 h
Height in the tank is expressed as salinity
akashiwo strain as identified in the legend
The solid dark line represents the mean population distribution
and the width of each line represents one standard error of the mean; data was pooled from all time points and all three replicates
The high level of behavioral variability resulted in population-level variability in vertical distributions among strains
Cell length ranged from 10 to 25 μm, with a CV of 9%. Average carbon content of the strains ranged from 97 ± 2.6 to 162 ± 2.9 pgC cell-1 (Table 1)
The CV of carbon content among strains was 60%
whereas within strain CV was only 1–2%
Strains 3374 (97 ± 2.6 pgC cell-1) and 3149 (115 ± 3.1 pgC cell-1) had significantly lower carbon biomass than the other strains examined (p < 0.05 for all comparisons
and the remainder of the strains were not significantly different from at least one other strain
As carbon content is a function of cell biovolume, average carbon content and average swimming speed and turning rate were compared to determine if cell size could explain the variability in movement behaviors among the strains. There were no significant associations among average carbon content and average swimming speed or turning rate for any of the strains examined (Figures 5A,B)
Average swimming speed (μm s-1; A) and turning rate (deg s-1; B) in high salinity water of each strain of H
akashiwo in relation to its cell volume (μm3)
There were no associations between cell size and cell motility indicating that within-strain differences in motility were driven by mechanisms other than cell size
Error bars are one standard deviation from the mean
Model II linear regression for (A) absolute difference in swimming speed (μm s-1) and genetic relatedness (y = 44.2x+53.1
p = 0.66) and (B) absolute difference in swimming speed (μm s-1) and geographic distance (km) for all H
Trait-based approaches have been utilized increasingly in phytoplankton ecology to, amongst others, predict phytoplankton community organization (Litchman and Klausmeier, 2008)
revealing significant behavioral differences among genetically distinct strains of a single species
These results demonstrate that one strain cannot be considered representative of a species
and that each of these strains will have different distributions in the water column and thus
different encounter rates with resources and predators
Our results make clear the importance of not only investigating multiple isolates of a species to characterize the range of a particular phenotypic trait
but they also highlight the potential of motility as a persistent integral functional trait that can deliver high resolution distinction where broad characteristics
The microsatellite data revealed that pairwise genetic distance varied among strains
but strains were not equally differentiated from each other
genetic distance was greatest between strain 452 and the other strains examined
which was also sampled from the NW Atlantic
The genetic distance between 452 and all other strains may be related to the length of time 452 has been in culture (over 50 years) versus the remainder of the strains
which were all isolated within the last 4 years
Behavioral and genetic variation did not correlate among H. akashiwo strains; there was no association between the clustering of strains by movement traits and genetic relatedness. Lack of a correlation between defined genotypes and phenotypic diversity has been previously observed, in studies investigating the genetic and toxicity variability in the dinoflagellate, Alexandrium tamarense (Alpermann et al., 2010)
A lack of a correlation implies that the traits can be useful to characterize phenotypic variability in this species but are not linked such that one trait could be predicted from the other
As microsatellites and behavior do not correlate in our experiments
they both could be used as traits to identify specific strains
and provide a much finer resolution compared to cell size
which would not have allowed us to distinguish amongst the strains examined here
while movement behaviors are variable they are consistent and distinguish strains
the observed consensus of similar movement behaviors within the same strain over space and time
akashiwo behavioral differences are inherent and based on intrinsic genetic or physiological differences that are insensitive to peculiarities of the specific
culturing conditions and methods utilized by different researchers
This consistency suggests movement behaviors are a robust trait that reliably identifies a strain
while size may be an important metric in determining motility patterns over a large size range
it does not appear to dictate intra-specific patterns of variation
within the much smaller size range covered by strains of the same species
Motility metrics may be an additional trait
which could be valuable for use in trait-based models that seek to characterize phytoplankton community dynamics
A struggle in the formulation of trait-based phytoplankton population models lies in the difficulty involved with identifying traits that adequately resolve variability among individuals
allowing the ecological niche of a particular species to be defined
Here we show that both genetic differentiation and motility are highly variable in H
Determination of phytoplankton motility provided the opportunity to characterize phenotypic variation among individuals
and demonstrate that this variation has ramifications at the population level
for example for the population distribution in the water column
While routine measurements of swimming behaviors using current methodology may be prohibitive
future developments in coupling in situ camera systems (e.g.
in review) with ocean observing systems may afford the ability to make such measurements for the analysis of in situ plankton composition
These traits may be useful to characterize within-species variation where other metrics
fail to deliver the appropriate resolution
these traits may also prove useful in distinguishing among species
movement behaviors as well as genetic variability are high-resolution traits that can adequately capture intra-specific variability in order to better understand and predict the structure and function of plankton communities
This research was supported through funding from the National Science Foundation (Biological Oceanography) 0826205 to SM-D and 0727227 to TAR
This research is based in part upon work conducted using the Rhode Island Genomics and Sequencing Center and the Marine Science Research Facility
which is supported in part by the National Science Foundation under EPSCoR Grants No
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*Correspondence: Elizabeth L. Harvey, ZWxpemFiZXRoLmhhcnZleUBza2lvLnVnYS5lZHU=
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Nicole and Heather worked together with Susanne on the quantification of carbon and nitrogen phytoplankton biomass
they compared 3D cell volumes obtained using cutting-edge microscopy with the classic 2D biovolume estimates from classic microscopy
They also studied the impact of growth conditions on phytoplankton biovolume
This is the featured articles of the March/April 2021 issue of Journal of Plankton Research
nicely illustrated by the image processing performed by Cynthia Beth-Rubin
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German actress and Sea Shepherd ambassador Anne Menden joins the crew of the Emanuel Bronner to protect the critically endangered harbor porpoises in the Baltic Sea
This will be her third campaign for the protection of the oceans after previously participating in Sea Shepherd’s pilot whale defence campaigns Operation Grindstop 2014 and Operation Sleppid Grindini 2015 in the Danish Faroe Islands
“I'm looking forward to starting my third campaign with Sea Shepherd and I am proud to be part of Germany’s first campaign in the Baltic Sea
The problems our oceans are facing do not solely concern other countries
Action to protect marine wildlife is also needed on our very own doorstep”
“While I was preparing for this campaign I was quite shocked to learn that most people are not even aware of the fact that whales are native to German coasts
It therefore makes our campaign even more important as our harbor porpoises are critically endangered and there is an urgent need to get this situation under control
Among others this includes raising public awareness about the presence of these animals as well as investigating the causes for their endangerment.”
Alexander Menden enjoyed his dream job in London
their boys supporting England in the World Cup
But the disaster that is Brexit has changed all that
‘So you’re going home.” This is something I hear a lot when I tell people that my wife and I have decided to move to Germany after 14 years of living in London
This is our home.” We are moving to a country that my wife and I were born in and are citizens of
but which our children know only as a holiday destination
There was – and is – no burning desire on our part to live in Germany
control freakery and permanent moaning that I associate with much of German public life
level-headedness and tolerance (or at least benevolent indifference) have been largely replaced by uncompromising partisanship
The result of the EU referendum dismayed me
Ever since my time at Oxford University in the mid-90s
I had been aware of the deeply entrenched anti-EU sentiment
especially among politics graduate students – some of whom would go on to work with pro-Brexit politicians and in the media
What that time did not prepare me for was the absurd spectacle that post-referendum British politics has mutated into. There seems to be no fudge, no disaster, no incompetence to which Britain’s current, distressingly myopic and feckless batch of politicians refuse to stoop, be they in government or opposition. The unworkable white paper thrashed out at Chequers
parliamentary chaos and no-deal threats resulting from it
have thrown the current level of ineptitude in British politics into sharp relief
After the referendum, there was a shift in my journalistic remit. Before, I had what I will always consider the best job imaginable – reporting on the arts for the Süddeutsche Zeitung from the most culturally exciting and diverse city in the world
It was every arts journalist’s dream: I covered everything from the Turner prize to the Booker prize and interviewed artists such as Anish Kapoor
we would at best have to apply and pay to secure as a privilege something that free movement has so far guaranteed
Free movement is neither a privilege nor some kind of transactional immigration deal
It is a reciprocal arrangement between EU member states
which formed the legal basis of our move to Britain all those years ago
It has been changed unilaterally by the British government
Being used as bargaining chips for two years and then allowed to stay in our home for a fee
is hardly a democratic process – even though
The assertion that “nothing’s agreed until everything’s agreed”
recently reiterated by the trade secretary
we could be stuck in Britain with no legal status at all
it is surely better to jump than wait to be pushed
To those who are tempted to reassure us that “it won’t happen”, I can only say: look at the many instances over the past few years where you said the same, and then precisely that thing happened. Of course, Germany has its own problems. In her capricious interior minister, Horst Seehofer
Angela Merkel now has her own Boris Johnson-type loose cannon
in Germany at least we won’t be totally politically disenfranchised
EU citizens had no say in any of the Brexit decisions – Commonwealth citizens living in the UK were allowed to participate in the EU referendum
we weren’t; and we never had the vote in parliamentary elections
What our status would be in local elections (which we have been able to vote in so far) is up in the air
View image in fullscreenHeading for disaster
Theresa May discusses Brexit with her cabinet at Chequers last month
Photograph: Joel Rouse/Joel Rouse/MoD/Crown CopyrightI imagine reactions to our departure will range from
but we didn’t mean people like you” to “Good riddance
I would reply: it doesn’t matter; the damage is done
Brexit will affect all EU citizens in the UK (and UK citizens in the EU) equally
The country won’t suffer terribly from having one fewer foreign arts journalist
It will be harder to replace the rest of my family
and seven years old – have dual citizenship but are all UK-born and have never lived outside Cricklewood
All three were among the best students in their respective classes
and have visited (and in some cases been dragged to) more National Trust and English Heritage sites than you can shake a stick at
When a young and very likable England team beat Colombia in their World Cup penalty shoot-out
These were English boys supporting England
My children never had to choose between their German and British “identities” – a choice which I still hope they will never have to make
They have been very understanding about the reasoning behind the move
That doesn’t change the fact that they are leaving behind all their friends and
after a life shaped by the multiculturalism of one of the world’s great metropolises
now they will have to get used to an environment that is very different
during our visit to his new school in Germany
with some incredulity: “This is so weird – all the students are white!”
A parliamentary briefing by the British Medical Association noted that almost half of doctors from the European Economic Area surveyed were considering leaving the UK after the referendum
more than a third have made concrete plans – that is almost one in five EU doctors working in the NHS (18%)
A part of my wife’s job entails working with vulnerable children
and it remains unfilled - because the hospital so far has not been able to find a suitable replacement
Having listened to myself talking about all of this quite passionately to a British friend
I asked him: “Am I overthinking this?” “No,” he said
“You are overfeeling it.” I have never considered myself an Anglophile; hopefully
my response to this complex nation has been more nuanced than uncritical adoration
Our response to Brexit is as much emotional as a practical
considering that the leave vote was entirely rooted in emotion
It is not easy to stay calm and rational when faced with the visceral
jingoistic drivel that flows endlessly from some in the leave camp
nostalgic myth and is now falling prey to the resulting delusions
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Armed police deployed to town as children locked in classrooms during alert
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A false alarm has caused a German school to be put on lockdown amid fears of an armed man on the loose.
Children were instructed to lock themselves in classrooms as large numbers of armed police and helicopters arrived on the scene in Menden on Wednesday.
Police said no one had been injured in the incident and investigations were still underway into the source of the alert at the Hönne-Berufskolleg.
The local government in Arnsberg confirmed the incident was a false alarm and thanked the emergency services for their swift response.
A spokesperson previously urged people to follow security services' instructions over reports of an attacker.
Germany has seen a number of shootings at schools, including a 17-year-old student's murder of 15 people in Winnenden in 2009.
The country also remains on high alert following a wave of Isis-inspired terror attacks, prompting a nationwide crackdown on extremism.
A 35-year-old Russian citizen was arrested in Ingolstadt, Bavaria, on allegations of financially supporting Isis and drug dealing on Tuesday, while two men from Nigeria and Algeria are to be deported because of terror links.
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or browse Zappos while on the job may feel like a luxury
many crave more meaningful—and more demanding—responsibilities
The public work ethic had been wounded and in the days that followed the mayor of Menden lamented the incident
The municipality of Menden sent out a press release regretting that the employee never informed his superiors of his inactivity. In a lesser-known interview with the German newspaper Bild a month later
the former employee responded that his e-mail had been misconstrued
He had not been avoiding work for 14 years; as his department grew
his assignments were simply handed over to others
“There never was any frustration on my part
and I would have written the e-mail even today
but it’s not my problem if they don’t want them,” he said
The story of this German bureaucrat raised some questions about modern-day slacking
And what can be done to make employees less lazy—or is that even the right question to ask in a system that’s set up in the way that ours is
What is sometimes called “cyberloafing” has
(in which most work-time surveys are conducted)
Even if the percentage of workers who claim they are working at the pinnacle of their capacity all the time is slowly increasing, the majority still remains unaffected. In fact, the proportion of people who say they never work hard has long been far greater than those who say they always do
The articles and books about the stressed-out fraction of humanity can be counted in the thousands
but why has so little been written about this opposite extreme
The few books that have been written on this topic were written by slackers themselves. In Bonjour Paresse, French author Corinne Maier offers her own explanation for professional detachment. Maier opens the book (which eventually cost her a job) by declaring that social science has miserably failed to understand the mechanisms of office work: “Millions of people work in business
This is because the people who talk about it the most—and I mean the university professors—have never worked there; they aren’t in the know.” Having spent years as a bureaucrat at the utility Électricité de France
Maier contends that work is increasingly reduced to “make-believe,” that at the office
feigned obedience and fake commitment become so central to working that a deviation from those acts can result in embarrassment for everyone
I dared to say that the only reason I came to work was to put food on the table
‘travail,’ etymologically derives from an instrument of torture
that you are working because you are interested in your work.”
The gap between image and substance is also a recurring theme in the comic Dilbert
was inspired by his uninspiring stints in the working world
Adams questions not only the link between work and rationality
but also the relation between work and productivity: “Work can be defined as ‘anything you’d rather not be doing,’” he says
In the preface to the Dilbert collection This Is the Part Where You Pretend to Add Value
Adams openly gives his impressions of 16 years of employment at Crocker National Bank and Pacific Bell:
“If I had to describe my 16 years of corporate work with one phrase
it would be ‘pretending to add value.’ … The key to career advancement is appearing valuable despite all hard evidence to the contrary
… If you add any actual value to your company today
your career is probably not moving in the right direction
Real work is for people at the bottom who plan to stay there.”
Other office workers have presented similar accounts
David Bolchover rues “the dominance of image over reality
of politics over performance,” and in City Slackers
a disillusioned “business and communications expert,” gloomily declares: “In a society where presentation is everything
it’s about how you look like you’re doing it.”
and the sense of unreality—these are ingredients that often reappear in popular accounts of working life
The risk when they only appear in popular culture is that we begin regarding them as metaphors or exaggerations that may well apply to our own jobs but not to work in general
But what would happen if we started taking these “unserious” accounts of working life more seriously
it took them two days to notice that he was dead
None of them seemed to feel the loss of his labors; he was only found when a friend stopped by to have lunch with him
How could no one notice? I talked with over 40 people who spent half of their working hours on private activities—a phenomenon I call “empty labor.” I wanted to know how they did it, and I wanted to know why. "Why" turned out to be the easy part: For most people, work simply sucks. We hate Mondays and we long for Fridays—it's not a coincidence that evidence points towards a peak in cardiac mortality on Monday mornings
There are, of course, exceptional cases. According to a Gallup report from last year
13 percent of employees from 142 countries are “engaged” in their jobs
twice as many are “actively disengaged”—they’re negative and potentially hostile to their organizations
Foot-dragging, shirking, loafing, and slacking are ways of avoiding work within the frames of wage labor. In 1911, Frederick W. Taylor, the notorious founder of “scientific management,” called work avoidance “the greatest evil with which the working-people of both England and America are now afflicted.” His attempts to eradicate slacking set the course of a perpetual cat-and-mouse game
between the time-study men and the worker collective
that would live much longer than the industrial piece-work system
the project of making the labor process transparent was an important step towards efficiency—not only because it made the optimization of each operation possible
but also because it siphoned power from the worker collective
with its “natural” inclination towards “loafing,” and giving it to management
now that the labor process has become opaque in new ways
the “evil” of which Taylor once spoke may have returned for good
Something that would have surprised Taylor is that slacking is not always the product of discontent, but also of having too few tasks to fill the hours. According to repeated surveys by Salary.com
not having “enough work to do” is the most common reason for slacking off at work
The service sector offers new types of work in which periods of downtime are long and tougher to eliminate than on the assembly line: A florist watching over an empty flower shop
a logistics manager who did all his work between 2 and 3 p.m.
and a bank clerk responsible for a not-so-popular insurance program are some examples of employees I talked with who never actively strived to work less
but when the flow of assignments petered out
Many would say that the underworked should talk to their bosses
I spoke with a Swedish bank clerk who said he was only doing 15 minutes' worth of work a day
He asked his manager for more responsibilities
he was working three-hour days—there were laws that barred any workday shorter than that—and his intervention only added another 15 minutes to his workload
There's a widely held belief that more work always exists for those who want it
productivity has more than doubled since the '70s
Yet there has been no perceptible movement to reduce workers' hours in relation to this increased productivity; instead
the virtues of "creating jobs" are trumpeted by both Democrats and Republicans
The project of job creation hasn't been a complete failure
the jobs that are created often come up short on providing fulfillment
Involuntary slacking may first be conceived of as real bliss: “Hey
I don’t have to work!” one of my interviewees recalls
most of us will crave some type of meaningful activity
I interviewed an archivist who wrote his master’s thesis while at work and a subway-ticket collector who composed music in his little booth
these activities may be pursued within the frame of wage labor—but that's very hard to come by
Our economy produces inequalities in income and job security
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11 Sep 2023 • 3m read • View Author
Betti-Knut-s-e-e-d-a-new-sustainable-classroom-1732010171.png
They are sustainable. They are portable. They are biophilic. And they can maintain a comfortable indoor temperature all year around. They are s.e.e.d. – sustainable environmental education spaces – designed by architectural firm Betti & Knut for the German International School Sydney (GISS) in Terrey Hills, NSW and built using cross laminated timber (CLT) to the international Passive House standard.
Based on biophilic design principles, the three new classrooms were conceptualised by architect Knut Menden as an interim solution involving portable classrooms while working on the GISS masterplan.
“We saw this as a challenge to rethink the much established ‘demountables’, which are a common feature of nearly every school in Australia, and achieve a modern solution aligned to our strong advocacy for sustainability,” Menden says.
“The goal was to build sustainable portable classrooms at a cost and time-frame equivalent to traditional portable classrooms, whilst also aiming for the international Passive House standard and use of timber as the primary construction material.
“The result of our design is s.e.ed. - a prototype for a new sustainable environmental education space as the antidote to traditional demountables,” he adds.
Each mass timber classroom measuring 85 square metres was prefabricated and preassembled offsite, and craned into place in 5 modules in less than 90 minutes per building.
The students enjoy fresh, clean air and thermal comfort year-round in the airtight Passive House classrooms, with heating and cooling demand reducing by 90 per cent, compared to a regular building.
According to the architects, the use of timber counteracts humidity levels to reabsorb humidity during wet weather and release in dry weather, naturally helping to create a balanced indoor comfort. “The use of timber internally and externally connects the buildings to the surrounding bushland setting, providing a calm natural interior that supports a positive learning environment for the students,” Menden explains.
Heat recovery ventilation (HRV) units supply clean and fresh filtered air to the classrooms, helping maintain a comfortable room temperature in hot and cold months, while also benefiting students with allergies. The HRV units are particularly helpful during bushfire season by keeping CO2 levels below the critical 800 ppm level inside the building.
The mass timber classrooms have already won the 2022 Sustainability Award in the Education and Research category as well as two awards at the 2022 Australian Timber Design Awards.
“We are very proud that our new classrooms have won the prestigious Sustainability Award. At our school we encourage forward thinking and sustainability, so to see this project being awarded with the highest honour for sustainable design and innovation in Australia is very rewarding and motivating for us all,” GISS principal, Dr Lorenz Metzger said after the Sustainability Award win.
“Considering the continued demand for portable classrooms across Australia in the foreseeable future, we hope to see these s.e.ed.s become an integral part of a sustainable growth strategy within the education sector,” Menden adds.
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October 28 (MExN): The Okotso village and Mangmetong A Khel Pudu-Menden triennial meet 2022 was observed at Okotso village on October 28.
a joint press release issued by Okotso Village Council
Lima Wati said the house resolved that “no compensation shall be demanded for developmental works; the Doyang to Mangmetong road construction under PMGSY in particular in Mangmetong and Okotso village jurisdiction.”
It resolved to organise a mass social work for repair of the Mangmetong – Okotso stretch of PWD road jointly by the two villages
Celebrated between the two villages alternately every three years
the get-together was held at Community Hall
TL Merry and Dr I Lolen Imchen delivered speeches.
and cultural presentation by Nrimimo Ngullie & Co
Sulanthung Ngulie delivered the vote of thanks followed by mass prayer and benediction by Ezanthung Ngullie
The next triennial meeting will be held at Mangmetong village in 2025.