Before that, construction cranes will raise pieces of the new buildings into their place – a skyward signal of the forward progress being made at UCSF’s historic campus.
“It’s very exciting to see the vision start coming together,” said Kelly Lyon, project manager in UCSF Real Estate’s Campus Design and Construction
“It’s the moment where it gets real to see it going vertical like that
where the buildings are actually taking a physical shape in the skyline
It will be much more real for everyone.”
The first of those cranes arrived at Parnassus Heights last month.
It’s a 278-foot “T” shaped crane situated at the center of the site where the Bakar Research and Academic Building will sit on the western side of campus.
The state-of-the-art structure will house research programs for cancer, microbiology, diabetes, immunology and cell biology, be the new home of the UCSF School of Nursing and support graduate-level education across UCSF
The building’s innovative space is designed to encourage collaboration between researchers across scientific disciplines to advance discoveries in health and science.
It’s scheduled to open in early 2028.
“We are building it for the UCSF community
director of UCSF Real Estate’s Campus Design and Construction
“It obviously gives great pride to all of the architects
contractors and UCSF staff who are involved in designing and constructing this building
Many people from across the world have been involved in this project
It is a really exciting time for us.”
Twice the height of the neighboring Clinical Sciences Building
the crane will stay at the center of the building site as the steel structure rises up around it
then be dismantled from the inside once the exterior is completed roughly a year and a half from now.
Materials for the new research and academic building will be delivered to the crane using Koret Way
an elevated road that runs along Mount Sutro.
“You’ll be amazed when you see this crane in operation,” Blaj said
The team has been working at the site for about two years and was planning for the project another year before that
The work has included constructing a foundation system for the building and creating two shoring walls to “hold back the mountain and define the footprint of our site,” Lyon said.
the Bakar Research and Academic Building will be open to the public – part of UCSF's commitment to make the campus more accessible to all
“Many people from across the world have been involved in this project
the future home of the UCSF Health Helen Diller Hospital is beginning to take shape.
That’s where a pair of new construction cranes will soon sit
the first of which is expected to be installed this month with the second coming in May.
“It’s been hard to see the tremendous progress we’re making if you can’t see what’s happening behind the construction fences,” said Fred Whitney
Project Delivery for the new Helen Diller Hospital
“I think these tower cranes represent a significant milestone
really exciting for our clinicians and patients
who will begin to see the building that they’ll get their care at in the future.”
The pair are two of only 10 in the world that can perform the type of lifting operations needed for the hospital’s construction
built and shipped to San Francisco from Germany
weighted loads on this project,” Whitney said
we couldn’t put a crane in the middle of the project
We have to be able to reach long distances.”
Rendering of the tower cranes arriving at the UCSF Health Helen Diller Hospital project site
The first crane, listed at 280 feet tall, will sit adjacent to Parnassus Avenue on the north side of the hospital site. The second crane, a 260-foot structure, will be placed on the east side of Moffitt/Long Hospital
Both will reach as high as 400 feet when angled up during work hours.
The tower cranes will remain at the site for four and three years
Crews are nearly finished with basement excavation work and are on the verge of starting construction on the new hospital’s foundations.
“Once we start laying the hospital’s foundation
bringing in steel to build the structure and hoisting materials for the exterior and interior build out
That is why you’ll see them arriving soon.”
15-story hospital will aggregate some of the most complex care capacity in the country in one city block to serve San Francisco
the Bay Area and beyond for coming generations
It will incorporate the latest technologies in diagnostics
robotics and surgical procedures into complex specialty care
The hospital is scheduled to welcome its first patients in 2030.
who will begin to see the building that they’ll get their care at in the future.”
UCSF has used tower cranes on multiple projects, including several at UCSF Mission Bay.
Essential to support safe building development at both sites
tower cranes minimize the need to bring in multiple truck-mounted hydraulic cranes to lift from Parnassus Avenue
which would result in additional traffic and pedestrian disruptions
crews are following strict safety controls
guidelines for work hours and noise reduction efforts
The cranes are also subject to regular safety checks from Cal OSHA
which will check them prior to use and recertify the structures every six months.
All three Parnassus cranes will be pushed freely by wind when not in use – a common practice called “weathervaning.” That allows for external forces to push the top of the cranes 360 degrees in poor weather conditions
preventing damage to the tower cranes or the projects themselves.
people might see the horizontal part of the crane rotating,” Lyon said
but it's actually an indication that the right process is happening
It’s letting that wind pass through and move freely as opposed to generating a lot of force that’s met with resistance at the bottom.”
it’s clear the new tower cranes at Parnassus Heights are a temporary stop on the road to transform UCSF’s flagship campus and drive innovations in care delivery
discovery and health sciences education.
“We’re building something amazing that will be here a long time,” Whitney said.
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the Blaj family manufacturing business has been supplying special high-end screws and bolts that are critical to the function of a huge variety of machinery
TheBlaj bolts can be found in shipbuilding
hydroelectric power stations and machine building
The company combines the traditions of its founder Anton
most sophisticated engineering developments and innovations
They are investing heavily in technological production upgrades
developing their expert knowledge and optimizing logistics to provide customers with products they need
The list of customers includes large multinationals such as General Electric
Under the well-established Blaj Fasteners brand
the company develops and manufactures precision-engineered bolts and screws
used in some of the most complex machinery
Their exceptionally high product quality is confirmed by the miniscule number of customer complaints received over the past 10 years
he simply contacted the director of the company where he was employed and told him that he was “going solo.” “I leased a small space from the parish priest
set up a workshop and that’s how the whole thing started,” recalls Anton
since in those times the state severely restricted employment
they needed to expand their workforce and the Blaj family found their own solution
our son and daughter each registered five manufacturing crafts
in order to be able to hire five people each or 25 in total
while keeping separate books of accounts for each individual craft registered
this solution paid off and at that time I was the largest taxpayer in our valley,” proudly explains the ingenious founder
they built a manufacturing plant in Griže that is still used to this day
the law enabled companies to invest 40% of their profits
while an additional 20% was contributed by the municipality
Anton has learned that there is always potential for further improvement and he has always strived to prove himself
first proposed a move toward computer technology
The transition to computer-controlled production was made after Slovenia became independent
when they first began to pursue business abroad
“We made our first contacts with foreign markets in 1994 and from then on transferred our efforts exclusively to exports
I have always wanted to employ well-qualified staff
as this is the only way to compete with foreign companies
I also wanted to prove to the world that we were equal to them
Manufacturing top-quality screws and bolts is much more important recognition for me than payment,” says Anton
Their first foreign partner was the powerful wholesaler
”They were my first connection to foreign business,” describes Anton of their first steps outside Slovenia
they have no domestic competitors and stand side-by-side with large German companies
as much as 95% of profits are generated by exports
we are mostly involved in repair and overhaul
and almost our entire production is intended for the European market
The company is in the safe hands of a wider family
The Blaj company is synonymous with the family
since almost all members of the wider family are involved in running it
“My son Erih was involved in the company’s beginnings
while today both my daughters Blanka and Petra also work here
my daughter-in-law Justina and granddaughter Patricija
We are truly a family business,” proudly confirms Anton
has always been interested in the family business: “I have always wondered and found it intriguing to see how I could transfer the range of knowledge I have acquired over the years
I started to work in the finance department
while also continuing to attend further education
and training to promote the company’s growth and development
I assumed the position of Director; however
I continue to consult my father on key decisions.”
I joined the company after finishing school
When you set up a company you do not know whether it will develop into a family business or not
It’s mostly due to a set of circumstances and hard work that help you create something that will provide work for children
grandchildren and future generations,” says Blanka
the main advantage of their type of business is that family members commit to it completely
“You have to love the screws and bolts,” remembers Anton of the advice given to him by Bollhof
their business partner and adds: “When you look at it
You can make a top-quality product if you put your heart into it.”
The long-term safety of machinery operating with Blaj fasteners is essential and demands perfection in the production of screws and bolts
the company has proactively designed a sustainable development strategy
encompassing the ambition and commitment of the owners
management and key company experts in order to achieve unified and sustainable success
“This is what makes us successful: because everyone in the company knows
feels and is aware of this,” explains Petra of their commitment to sustainable development and the pursuit of continual improvement and quality
Customers recognize their passion for screws and bolts and turn to them not only for production of the fasteners
“Everyone in our company has a role where he or she can demonstrate their passion for work
The connection between family and non-family members
agility and rapid response to the needs of the market
It was my father who in fact built this strong infrastructure,” explains Petra
adding that she inherited her father’s philosophy of aiming for continuous improvement
as well as his passion for growth and development
“I’m happiest when we acquire a new customer or make a new product; when I see that after we have invested resources
time and effort in developing our solutions
of the member firms of Ernst & Young Global Limited
Metrics details
Muscle repair in dysferlinopathies is defective
Although macrophage (Mø)-rich infiltrates are prominent in damaged skeletal muscles of patients with dysferlinopathy
the contribution of the immune system to the disease pathology remains to be fully explored
Numbers of both pro-inflammatory M1 Mø and effector T cells are increased in muscle of dysferlin-deficient BlAJ mice
symptomatic BlAJ mice have increased muscle production of immunoproteasome
In vitro analyses using bone marrow-derived Mø of BlAJ mice show that immunoproteasome inhibition results in C3aR1 and C5aR1 downregulation and upregulation of M2-associated signaling
Administration of immunoproteasome inhibitor ONX-0914 to BlAJ mice rescues muscle function by reducing muscle infiltrates and fibro-adipogenesis
These findings reveal an important role of immunoproteasome in the progression of muscular dystrophy in BlAJ mouse and suggest that inhibition of immunoproteasome may produce therapeutic benefit in dysferlinopathy
reduction of muscle inflammation and macrophage-mediated vessel stability with consequent amelioration of muscle performance in dysferlinopathic BlAJ mice
A Volcano plot analysis of genes differentially expressed in 6 m BlAJ vs 12 m BlAJ muscles: red and yellow dots represent genes upregulated in 6 m BlAJ and 12 m BlAJ
with a p value < 0.05 (corresponding to a -Log10(p value) > 1.30)
B Gene ontology (GO) pathways enrichment in 6 m BlAJ and 12 m BlAJ mice
For GO analysis 837 genes upregulated in 6 m BlAJ
755 gene upregulated in 12 m BlAJ and 10,638 non-differentially expressed genes (based on RNA-seq data) were used
Only significant pathways (p value < 0.05) are shown
Redundant pathways are omitted from the figure
C Volcano plot analysis of genes involved in complement activation (Biological process; GO: 0006956) and complement receptor activity (Molecular function; GO: 000487)
Red and yellow dots represent genes upregulated in 6 m BlAJ and 12 m BlAJ
D GSEA plot for the annotated dataset “Hallmark_Complement” by the Molecular Signatures Database (MSigDB)
Geneset size: 143; Normalized enrichment score (NES): 1.43; False discovery rate (FDR) q value: 0.064
E WB expression of IP subunits and inflammatory mediators in psoas muscle of 12 mo BlAJ and 12 mo C57Bl mice
CD4+ and CD8+ T-lymphocytes and Tregs in skeletal muscles of 12 m BlAJ and C57Bl mice
G Representative FACS of CD4 and CD8 cell subpopulation profiles
The numbers within the panels indicate the percentage of each population of live cells
a gate of CD45-positive events defined infiltrating inflammatory cells
two populations were separated by the expression levels of CD4 or CD8
whose subpopulations were separated according to CD44 and CD62L.Within CD4+ cell population
effector memory (EM)—expressing CD4 and/or CD8 in the muscles of 12 m C57Bl and 12 m BlAJ
Data are presented as mean ± SD of n = 3 independent experiments with n = 3–12 animals/group
One-way ANOVA and Student t-test: *p < 0.05
Representative FACS analysis of thymic subpopulations of 12 m C57Bl and 12 m BlAJ (A) and of DN stages (B)
The amount of positively selected TCRβ+ CD69+ T cells and Tregs of 12 m C57Bl and 12 m BlAJ thymus (C)
Spleen weight (in grams) in 12 m C57Bl and 12 m BlAJ mice (D)
Representative FACS profile showing the percentage of each population of live cells: a gate of GR1-positive and F4/80 negative represents monocytes
further divided according to the expression of CD11b (E)
FACS analysis of spleen-derived IFNγ- and IL17/IFNγ-producing CD4+ and CD8+ T cells (G) and of CD4+ and CD8+ T cells (H)
The numbers within the panels indicate the percentage of each population of live cells: within the gate of CD4-positive or CD8-positive
two populations are separated by level of CD44 and CD62L expression (I)
effector memory (EM)—expressing CD4 and/or CD8 in the spleens of 12 m C57Bl and 12 m BlAJ (J)
Representative FACS profile showing the percentage of each population of live cells
two populations are separated by expression level of CD21 and CD23 (K)
CD21+) splenic B cells of 12 m C57Bl and 12 m BlAJ mice (L)
Subpopulations are separated according to B220 and CD19 expression (M)
FACS analysis of the percentage of mature B-cells (M) and evaluation of transitional T1 B (T1 B) and transitional T2 B (T2 B) splenic B cells of 12 m C57Bl and 12 m BlAJ mice (N)
Data are presented as mean ± SD of n = 3 independent experiments with n = 3–9 animals/group
All these findings demonstrated a distinct immune composition in dysferlin-deficient BlAJ mouse
Having demonstrated that inflammatory mediators including IP subunits are upregulated in 12 m BlAJ mice
we next explored the effect of PSMB8 inhibitor ONX-0914
Proteomic analysis of IP subunits (A); alarmins and inflammatory mediators (PTX3 and GPx1) (B); MAPK kinases and AKT1/2/3 and their phosphorylated isoforms (C) in psoas of 6 m BlAJ
PTX3 (in magenta) with nuclei stained in DAPI (blu) (scale bar: 10 μm) and its magnification (scale bar: 10 μm) with white arrows indicating cells co-expressing PTX3 and isolectin
The histogram represents the counting of PTX3 fluorescence (D)
Immunohistological staining of skeletal muscles for Iba1 (in red) and CD206 (in green)
Nuclei were counterstained with DAPI (blue)
Mac1 were stained with Iba1+ and Mac2 with CD206+ in 6 m BIAJ
Data are presented as mean ± SD of n = 3 independent experiments with n = 3–6 animals/group
Tukey multiple comparison test for WB and non-parametric test followed by Kruskal–Wallis test for PTX3+ cells’ and macrophages’ counting: *p < 0.05
To investigate whether IP activity of dysferlin-deficient Mø is of any functional relevance for macrophage polarization
we polarized monocytes isolated from 12 m BlAJ mice by treatment with TNFα
these data corroborate evidences that IP inhibition in dysferlin-deficient macrophages induces a differential signaling response to TNFα skewing the macrophage polarization toward the M2 phenotype
CD4+/CD8+ T-lymphocytes and Tregs infiltrating the 12 m BlAJ and 12 m BlAJ+ONX skeletal muscles (A)
Evaluation of muscle-derived CD4+ and CD8+ T-cell subsets (B)
RT-qPCR analysis of Th17-dependent ROR-γt in 12 m BlAJ and 12 m BlAJ+ONX skeletal muscles (C)
Determination of splenic weight in 12 m BlAJ and 12 m BlAJ+ONX mice (D)
FACS analysis assessing the percentage of splenic CD4+/CD8+ T cell subsets (E) and FoxP3+ CD25+ Tregs (F) of 12 m BlAJ and 12 m BlAJ+ONX mice
central memory and effector memory CD4+ and CD8+ cells (H) in the spleen of 12 m BlAJ and 12 m BlAJ+ONX mice
Evaluation of B-cell counts (I) and B-cell subsets (J) of 12 m BlAJ and 12 m BlAJ+ONX mice
Data are presented as mean ± SD of n = 3 independent experiments with n = 6 animals/group (and technical replicates for RT-qPCR)
Student t-test: *p < 0.05 and ***p < 0.001
Proteomic analysis of C3aR1 in psoas of 6 m BlAJ
Evaluation of C3 and C5 concentration in the serum of 6 m BlAJ
Representative images and quantification of psoas muscles from 6 m BlAJ
12 m C57Bl with big vessels co-stained with αSMA (in green) and C3aR1/CD88/CD93 (in red)
Nuclei were stained in DAPI (blue) (scale bar: 100 μm) (C)
12 m C57Bl with small vessels co-stained with isolectin (in green) and C3aR1/CD88/CD93 (in red)
Nuclei were stained in DAPI (blue) (scale bar: 50 μm) (D)
Tukey multiple comparison test for WB and non-parametric test followed by Kruskal–Wallis test for vessels’ count: *p < 0.05
Fluorescent staining of WGA+ (in green) and TR7+ (in red) while nuclei are in DAPI (blu) (scale bar: 50 μm) in psoas of 6 m BlAJ
Expression of pro-adipogenic mediators as PPARα (C)—in RT-qPCR—and perilipin
adiponectin and metalloproteinases (D)—in WB—was downregulated following ONX-0914 treatment
Data are presented as mean ± SD of n = 3 independent experiments with n = 3–6 animals/group (and technical replicates for RT-qPCR)
Tukey multiple comparison test for WB and non-parametric test followed by Kruskal–Wallis test for WGA+/TR7+ cells’ counting
Oil Red evaluation and RT-qPCR: *p < 0.05
Indeed, tetanic force of TA muscle of 12 m BlAJ+ONX was significantly increased related to age-matched BlAJ mice (Fig. 7I)
these findings propose the IP to be an interesting therapeutic target for the treatment of dysferlinopathy
we provide evidence that immune response in dysferlin-deficient BlAJ mice is driven by T cell and Mø activation
muscles from BlAJ mouse show a greater abundance of PSMB8 and PSMB9 IP subunits
The PSMB8 inhibitor ONX-0914 contributes to reduce the number of splenic and muscular CD4+/CD8+-effector T cells
ONX-0914 treatment targets macrophages polarization increasing the number of M2 Mø that are required for efficient muscle regeneration
Another effect of IP inhibition was the restoration of glucose and mitochondrial metabolism in affected 12 m dysferlin-deficient mice
This is consistent with modifications of AMPKα/p38 MAPK/mTOR signaling pathway
the metabolic reprogramming that we observed in 12 m BlAJ+ONX correlates with decreased adipogenesis
therefore explaining the amelioration in the extracellular matrix structure and the rescue of muscle performance
Dysferlinopathy is often associated with weakness
decreased muscle regeneration and increased fibro-adipogenesis
We show that IP inhibition by ONX-0914 increases the number of regenerating myofibers and reduces fibro-adipogenesis of dysferlinopathic muscle of BlAJ mice
we provide evidence of decrease of damaged alizarin red positive myofibers that was associated to a significant decrease of CpK levels in ONX-0914 treated 12 m BlAJ mice
mechanical analysis of intact muscles revealed that muscle force was strongly increased in ONX-0914 treated 12 m BlAJ mice and these data correlated to increased muscle performance
we provide the first evidence of IP subunits over-expression in affected dysferlin-deficient 12 m BlAJ muscles as a central target to prevent T cell and macrophage immune response
ameliorate vascular architecture defects and improve muscle force
We suggest that increasing our understanding of the contribution of aberrant IP expression to the pathophysiology of dysferlinopathy will ultimately lead to the development of novel therapeutic approaches
Even if side effects associated with their long-term use are not completely avoidable
the use of IP inhibitors could represent an encouraging starting point for the development of new immunotherapy for dysferlinopathy
The research procedures described were approved by the ethics committee of the University of Milan (CR937-G)
This study was performed in accordance with International Conference on Harmonisation of Good Clinical Practice guidelines
the Declaration of Helsinki (2008) and the European Directive 2001/20/EC
Procedures involving living animals were approved by local ethics committees
conforming to Italian law (D.L.vo 116/92 and subsequent additions)
This work was authorized by the Ministry of Health and Local University of Milan Committee with the protocol authorization numbers 10/10-2009/2010 and 6/13-2012/2013
6-month-old and 12-month-old dysferlinophatic (6 m BlAJ and 12 m BlAJ) mice were provided by Charles River (Calco
12-h dark) at a temperature between 2 and 24 °C
The mice had free access to clean water and food
The immunoproteasome inhibitor ONX-0914 (Clini Sciences
6 mg/Kg) was injected intraperitoneally into 12 m BlAJ for 5 weeks (two injections per week
Untreated age-matched BlAJ mice were used as control
Mice were sacrificed by cervical dislocation according to the Italian country Law
Randomization within blocks was performed to allocate the animals to different experimental procedures
To avoid that the effects of our treatments on mice had been overestimated thus diminishing the reliability of our results
the laboratory members that analyzed the mice were blinded regarding the treatment(s) that animals received
Animals that eventually suffered from clinical complications during each treatment (enhancement of stress
motor impairments) were excluded from the experimental plan
GSEA was performed via dedicated software (release 4.2.3) by Molecular Signatures Database (MSigDB)
The “Hallmark_Complement” annotated gene set (included in the “Hallmark” gene set collection v7.5.1) was used for analysis of ranked gene lists
For muscle: CD45 PerCp; CD4 PeCy7; CD8 efluor 450; CD44 FITC; CD62L PE; CD25 APC; B220 APC-Cy7
CD45 PerCp; CD4 Pacific Blue; CD25 APC; GITR PeCy7; CD3 FITC; B220 APC-Cy7
For spleen: CD4 PeCy7; CD8 efluor 450; CD44 FITC; CD62L PE
CD4 Pacific Blue; CD8 APC-Cy7; Foxp3 Alexa fluor 488; CD25 APC; CTLA4 PE; ICOS PerCP
CD19 PerCp; B220 APC-Cy7; CD21 Pacific Blue; CD23 PeCy7; IgD PE; IgM APC
Gr1 APC-Cy7; F4/80 PeCy7; CD11b PE; CD11c FITC
CD4 PAcific Blue; CD8 APC-Cy7; IL17 PE; IFNγ APC; Foxp3 Alexa Fluor 488
For thymus: CD4 Pacific Blue; CD8 APC-Cy7; CD44 FITC; CD25 APC
CD4 Pacific Blue; CD8 APC-Cy7; CD69 FITC; TCRβ PE; Qa2 APC
CD4 Pacific Blue; CD8 APC-Cy7; CD25 APC; Foxp3 Alexa fluor 488
All the antibodies were purchased from eBioscience (San Diego)
and TCRβ PE obtained from BD (New Jersey) and CD4 Pacific Blue from BioLegend (San Diego
Cells were isolated with A-FACS Aria machine (BD Bioscience
New Jersey); data were acquired with the Cytomics FC500 (Beckman-Coulter) machine and analyzed with CXP 2.1 software
Total proteins were obtained from skeletal muscles isolated from 12 m C57Bl
Samples were resolved on polyacrylamide gels (ranging from 6 to 12%)
transferred to nitrocellulose membranes (Bio-Rad Laboratories
USA) and overnight incubated with following antibodies: vinculin (1:600
Abcam); PSMB9 (1:500; Proteasome 20S LMP2 (EPR13785) ab184172
PA5-109467 Invitrogen); pAkt (Ser473)(1:600
Santa Cruz Biotechnology); C5aR1/CD88 (1:600
Filters were detected with peroxidase conjugated secondary antibodies (Agilent Technologies
USA) and developed by ECL (Amersham Biosciences
12 m BlAJ mice (n = 5) were anesthetized with isoflurane and sacrificed by cervical dislocation
Femur bones (with hip and knee joints intact)
briefly dipped in 70% ethanol to dehydrate any remaining muscle tissue
then rinsed in D-PBS without Ca++/Mg++ (Gibco) before cutting off the two extremities
The bone marrow was extracted into ice-cold PBS by pushing it out of the bone cavity with a syringe equipped with a 25G needle
centrifuged at 800 rpm for 5 min and resuspended in macrophage complete medium
Bone marrow precursor cells were differentiated into Mø in RPMI-1640 medium (Thermo Fisher Scientific) supplemented with 20 ng/ml recombinant M-CSF (PeproTech)
2mM L-glutamine (Thermo Fisher Scientific)
50 mm 2-Mercaptoethanol (Thermo Fisher Scientific)
Cells were routinely cultured at 37 °C in 21% O2 and 5% CO2 and regularly tested for the presence of mycoplasma
cells were seeded in 12-well plates onto 18 mm diameter coverslips
For western blot analysis cells were collected after trypsinization and lysed in NP-40 lysis buffer to obtain whole protein lysate
recombinant murine TNFα (Sigma-Aldrich) was added at a concentration of 20 and 40 ng/ml for 16 h
followed by the addition of ONX-0914 at a final concentration of 300 nM to the same wells
Mø polarization was monitored using an inverted phase contrast microscope (Nikon TS100)
and cells were generally cultured for ~48 h after the addition of TNFα
Oil Red O (ORO) staining was performed to determine the amount of lipids
sections were fixed with 4% paraformaldehyde for 10 min
permeabilized with 0.1% Triton X-100 for 10 min and incubated with 10% donkey serum to block non-specific binding for 1 h
Slides were then incubated with the primary antibodies (overnight at 4 °C) diluted in blocking solution at the following dilutions: PTX3 (MNB1) (1:50
Novus); Isolectin GS-IB4 Alexa Fluor™ 594 Conjugate (1:100
Thermo Fisher Scientific); WGA (Wheat Germ Agglutinin) Alexa Fluor 488™ Conjugated (1:50
Thermo Fisher Scientific); α-Smooth Muscle – FITC (1:100
Sigma-Aldrich); neuron-glial antigen 2 (NG2) (1:50
Fluorochrome-conjugated secondary antibodies were diluted 1:200 in PBS1X and added for 1 h at room temperature
Slides were then mounted with Prolong Gold® Antifade Reagent with DAPI (Thermo Fisher
Images were acquired by an inverted fluorescence microscope Dmi800
while Z-stack and tile reconstructions were acquired by confocal microscope Sp8 (Leica)
images were captured by Leica microdissector (CTR6000)
Quantification of fluorescence was performed by means of ImageJ Software (NIH)
Threshold color Plug in of ImageJ Software was used to quantify the amount of tissue stained with Alizarin Red and Oil red
Data were analyzed by GraphPad PrismTM and expressed as means ± SD
ImageJ software was used to estimate the percentage of Mac1 and Mac2 in n = 12 images from each mouse
quantification of immunoreactivity was performed in n = 11–15 images from each mouse
CPK analysis was performed on serum samples of 12 m BlAJ
12 m BlAJ+ONX and 12 m C57Bl mice with CPK kit (Cobas)
C3 and C5 serum levels of the same mice were measured using a commercially available mouse C3 ELISA Kit (catalog no
MBS135930; MyBioSource) and C5 ELISA kit (catalog no
ab264609; Abcam) according to the manufacturer’s instructions
The expression of MRF-4 (Mm00435126) was calculated with the Probe Mix by Applied Biosystem
To determine significance when comparing multiple groups’ means
we used one-way ANOVA followed by Tukey’s multiple comparison test; Student’s t-test was used to compare two groups assuming equal variances
statistical significance was calculated via simple linear regression
by testing for differences between slopes of best-fit lines
A 95% confidence band of each best-fit line is shown
the difference among groups was considered significant as follow: * at p < 0.05; ** at p < 0.01; *** at p < 0.001; **** at p < 0.0001
Sample size was determined by using a sample-size calculator freely available on internet
All the samples that did not rich quality control standards due to the presence of contaminants for RNA or to problems in freezing procedures for histological analysis were excluded
The data used to support the findings of this study are available from the corresponding author upon reasonable request
The limb-girdle muscular dystrophies and the dystrophinopathies
Muscle and Neuromuscular Junction Disorders):1954–77
Ferlins: regulators of vesicle fusion for auditory neurotransmission
Lipid accumulation in dysferlin-deficient muscles
Intracellular localization of dysferlin and its association with the dihydropyridine receptor
Unmasking potential intracellular roles for dysferlin through improved immunolabeling methods
A new role for the muscle repair protein dysferlin in endothelial cell adhesion and angiogenesis
Muscle inflammation and MHC class I up-regulation in muscular dystrophy with lack of dysferlin: an immunopathological study
MHC-I and C5b-9 involve the pathogenesis of dysferlinopathy
Complement and its role in innate and adaptive immune responses
and c1q-related molecules regulate macrophage polarization
Monitoring C3aR expression using a floxed tdTomato-C3aR reporter knock-in mouse
Complement C3a signaling facilitates skeletal muscle regeneration by regulating monocyte function and trafficking
Protective Role of C3aR (C3a Anaphylatoxin Receptor) against atherosclerosis in atherosclerosis-prone mice
Absence of T and B lymphocytes modulates dystrophic features in dysferlin deficient animal model
Activation of NF-kappaB by adherent Pseudomonas aeruginosa in normal and cystic fibrosis respiratory epithelial cells
Increased susceptibility to complement attack due to down-regulation of decay-accelerating factor/CD55 in dysferlin-deficient muscular dystrophy
Genetic ablation of complement C3 attenuates muscle pathology in dysferlin-deficient mice
Dysferlin-deficient muscular dystrophy and innate immune activation
C1q and HMGB1 reciprocally regulate human macrophage polarization
PTX3 predicts myocardial damage and fibrosis in duchenne muscular dystrophy
Complement activation triggers metalloproteinases release inducing cervical remodeling and preterm birth in mice
The complement C3a-C3aR axis promotes development of thoracic aortic dissection via regulation of MMP2 expression
The ubiquitin-proteasome pathway and pathogenesis of human diseases
20S proteasome and its inhibitors: crystallographic knowledge for drug development
Immunoproteasome assembly: cooperative incorporation of interferon gamma (IFN-gamma)-inducible subunits
Proteasome and peptidase function in MHC-class-I-mediated antigen presentation
An altered T cell repertoire in MECL-1-deficient mice
Immunoproteasomes down-regulate presentation of a subdominant T cell epitope from lymphocytic choriomeningitis virus
Immunoproteasomes shape immunodominance hierarchies of antiviral CD8(+) T cells at the levels of T cell repertoire and presentation of viral antigens
Role of the proteasome and NF-kappaB in streptococcal cell wall-induced polyarthritis
The proteasome as a lipopolysaccharide-binding protein in macrophages: differential effects of proteasome inhibition on lipopolysaccharide-induced signaling events
A selective inhibitor of the immunoproteasome subunit LMP7 blocks cytokine production and attenuates progression of experimental arthritis
Prevention of experimental colitis by a selective inhibitor of the immunoproteasome
The immunoproteasome in antigen processing and other immunological functions
Inhibiting the immunoproteasome exacerbates the pathogenesis of systemic Candida albicans infection in mice
Fibrosis rescue improves cardiac function in dystrophin-deficient mice and duchenne patient-specific cardiomyocytes by immunoproteasome modulation
Therapeutic potential of immunoproteasome inhibition in duchenne muscular dystrophy
Complement and macrophage crosstalk during process of angiogenesis in tumor progression
Complement-mediated inhibition of neovascularization reveals a point of convergence between innate immunity and angiogenesis
Dysferlinopathy promotes an intramuscle expansion of macrophages with a cyto-destructive phenotype
Muscular dystrophy in dysferlin-deficient mouse models
Efficient recovery of dysferlin deficiency by dual adeno-associated vector-mediated gene transfer
Mammalian Mss51 is a skeletal muscle-specific gene modulating cellular metabolism
Hypothalamic stearoyl-CoA desaturase-2 (SCD2) controls whole-body energy expenditure
Stearoyl-CoA desaturase 2 is required for peroxisome proliferator-activated receptor gamma expression and adipogenesis in cultured 3T3-L1 cells
Monocyte to macrophage differentiation goes along with modulation of the plasmalogen pattern through transcriptional regulation
Molecular characterization and function of tenomodulin
a marker of tendons and ligaments that integrate musculoskeletal components
NR1D1 modulates synovial inflammation and bone destruction in rheumatoid arthritis
Nuclear Receptor Subfamily 1 Group D Member 1 regulates circadian activity of NLRP3 inflammasome to reduce the severity of fulminant hepatitis in mice
The immunoproteasome controls the availability of the cardioprotective pattern recognition molecule Pentraxin3
The effects of MyD88 deficiency on disease phenotype in dysferlin-deficient A/J mice: role of endogenous TLR ligands
Dysferlin deficiency alters lipid metabolism and remodels the skeletal muscle lipidome in mice
P38alpha MAPK underlies muscular dystrophy and myofiber death through a Bax-dependent mechanism
AMPK complex activation promotes sarcolemmal repair in dysferlinopathy
Immunobiology of inherited muscular dystrophies
The effect of extreme cold temperatures on the risk of death in the two major Portuguese cities
Cellular interactions in thymocyte development
Unexpected role for the immunoproteasome subunit LMP2 in antiviral humoral and innate immune responses
Progressively impaired proteasomal capacity during terminal plasma cell differentiation
Bcl6 mediates the development of T follicular helper cells
Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells
Platelet-derived growth factor receptor-beta promotes early endothelial cell differentiation
Genetic and pharmacologic inhibition of complement impairs endothelial cell function and ablates ovarian cancer neovascularization
Regulation of mitochondrial biogenesis as a way for active longevity: interaction between the Nrf2 and PGC-1alpha signaling pathways
KDM3A senses oxygen availability to regulate PGC-1alpha-mediated mitochondrial biogenesis
Dynamin-related protein Drp1 is required for mitochondrial division in mammalian cells
Fibroadipogenic progenitors are responsible for muscle loss in limb girdle muscular dystrophy 2B
The role of autophagy in white adipose tissue function: implications for metabolic health
Role of metabolic stress and exercise in regulating fibro/adipogenic progenitors
AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy
Defective membrane repair in dysferlin-deficient muscular dystrophy
Dysferlin at transverse tubules regulates Ca(2+) homeostasis in skeletal muscle
Inflammasome up-regulation and activation in dysferlin-deficient skeletal muscle
The dual complexity of PTX3 in health and disease: a balancing act
The inflammatory pathology of dysferlinopathy is distinct from calpainopathy
Cross talk between the Akt and p38alpha pathways in macrophages downstream of Toll-like receptor signaling
The C5a/C5a receptor 1 axis controls tissue neovascularization through CXCL4 release from platelets
Pentraxins and atherosclerosis: the role of PTX3
Endothelial cell-derived pentraxin 3 limits the vasoreparative therapeutic potential of circulating angiogenic cells
Metabolic coordination of pericyte phenotypes: therapeutic implications
Metabolic regulation of macrophage activation
Oxidative metabolism and PGC-1beta attenuate macrophage-mediated inflammation
Pyruvate dehydrogenase kinase is a metabolic checkpoint for polarization of macrophages to the M1 phenotype
Activation of AMP-activated protein kinase prevents lipotoxicity in retinal pericytes
Inhibitory effects of antagonists of growth hormone-releasing hormone (GHRH) in thyroid cancer
Recombinant human IgA1 and IgA2 autoantibodies to type VII collagen induce subepidermal blistering ex vivo
Clinical features and short-term outcomes of 102 patients with coronavirus disease 2019 in Wuhan
Dynamics of inter-heavy chain interactions in human immunoglobulin G (IgG) subclasses studied by kinetic Fab arm exchange
A special population of regulatory T cells potentiates muscle repair
and purification of murine thymic epithelial cells
Defective dystrophic thymus determines degenerative changes in skeletal muscle
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This study was supported by the ERC 7th Framework Programme grant (FP7-HEALTH-2007-1.4-6; Optistem 223098)
Italian Ministry of Health (Ricerca Finalizzata RF-2009-1547384)
Ricerca corrente FR230 Policlinico Hospital and presents independent research funded by GRUPPO FAMILIARI BETA- SARCOGLICANOPATIE Odv (CONTR-ASPR20YTORR-01)
Funders of the study had no role in study design
Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico
Department of Pathophysiology and Transplantation
Laboratorio di Chimica Clinica e Microbiologia
Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
Department of Biotechnology and Biosciences
Department of Medical Biotechnologies and Translational Medicine
Humanitas Clinical and Research Center IRCCS
YT and AF conceived and designed the experiments
FF and FS interpreted and analyzed the data
LT and AF performed animal transplantation
FS and DM performed the experiments and acquired the data
All the authors stated were involved in the critical revision of the manuscript and approved the final version of the article
The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication
The authors declare no competing interests
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations
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DOI: https://doi.org/10.1038/s41419-022-05416-1
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A Riverside County correctional deputy who once led jail staff in overtime pay was fired after he fell asleep watching movies on duty – all while collecting $60 per hour during an overtime shift
was fired by the Riverside County Sheriff’s Department for neglect
But Blaj successfully appealed the termination last year
and now the sheriff's department is on the defensive
Agency attorneys filed a lawsuit this week asking a county judge to intervene so they don't have to put Blaj back on the jail staff
That lawsuit thrust Blaj’s case into the public eye
revealing the circumstances of his firing for the first time and calling into question the veracity of overtime pay he collected before he was fired
Blaj racked up $132,000 in overtime pay in 2013 and 2014
Blaj collected more overtime than any other correctional deputy in Riverside County
and was among the highest overtime collectors of thousands of California county jail guards
MORE: This cop was 'ready to snap.' Now he wants his job back.
The incident that led to Blaj’s firing began on Valentine’s Day 2015
while he was working a night shift in a security room that controls cell doors at the Temecula jail
jail staff became concerned because Blaj stopped answering his radio
so a supervisor went to investigate to ensure Blaj hadn’t been injured or taken hostage by inmates
the supervisor discovered that Blaj was just fine
he also noticed a charging cable plugged into a wall outlet and a portable speaker on the floor
Correctional officers are forbidden from bringing electronics into the jail out of concern they will fall into the hands of inmates
Blaj allegedly denied he had any electronics
then later admitted he had brought a tablet and a cell phone into the jail
According to sheriff’s department documents
has said that if Blaj had told his supervisor the truth
he would likely have received only an eight-hour suspension for falling asleep
watching movies and sneaking a cell phone into the jail
Raya felt “compelled to terminate,” documents state
MORE: Jailhouse toilet lawsuits could cost the county $330K
Those documents come from Blaj’s administrative appeal hearing
which is a confidential proceeding guaranteed to sheriff’s deputies as part of their union contract
Blaj did not deny he fell asleep or brought electronics into the jail
but argued that he didn’t lie about the electronics
saying the sheriff’s department should have given Blaj a 30-day suspension instead of firing him
Steinberg ordered the sheriff's department to reinstate Blaj and give him backpay amounting to about a year's salary
Blaj’s ability to patrol the jail was not compromised by just one lie
“While one singular lie is a dishonest act
and dishonesty is considered as taboo for a peace officer
not all lies are alike and not all peace officers are alike,” Steinberg wrote in his ruling
that ruling would bring an end to the case
the sheriff’s department has taken the unlikely step of challenging Steinberg’s ruling in court
The first court hearing has been set for May 5
The sheriff's department declined to comment
citing a policy against discussions of ongoing litigation
Blaj's appeal documents also mention that a second correctional deputy
was also caught with a cell phone in the security room on the same evening
It appears Alvarez was not fired and he is not a party in the ongoing lawsuit
Reporter Brett Kelman can be reached at 760 778 4642 or by email at brett.kelman@desertsun.com. You can also follow him on Twitter at @TDSbrettkelman
I want once again to greet all of you and all those whom I have met in the course of these days. I thank you for your warm welcome. I offer a respectful greeting to the President of the Republic and to the Authorities present here. I express my heartfelt gratitude for their generous cooperation in the planning and the unfolding of my visit. I am grateful to His Beatitude Patriarch Daniel
and to the clergy and faithful of the Romanian Orthodox Church for their fraternal welcome. May the Lord bless this ancient and illustrious Church and sustain it in its mission
I also offer a greeting full of affection and gratitude to His Beatitude Cardinal Lucian Mureşan. I greet the faithful of the Catholic Church: the Bishops
religious and lay faithful of Bucharest and Iaşi
together with the many pilgrims from Şumuleu Ciuc. I thank the Lord for giving me the opportunity to pray with you and to encourage your commitment to evangelization and your witness of charity. Here in Blaj
the sons and daughters of the Greek-Catholic Church
who for three centuries have borne witness to your faith with apostolic zeal
May the Virgin Mary bestow her maternal protection upon all the citizens of Romania who in the course of history have always trusted in her intercession. In entrusting all of you to her
I ask her to guide you on your journey of faith
as you advance towards a future of authentic progress and peace
and contribute to the building of an ever more just and fraternal homeland.
Regina Coeli…
Thank you for reading our article. You can keep up-to-date by subscribing to our daily newsletter. Just click here
opposing a system of totalitarian and coercive ideology," the pontiff told some 60,000 worshippers attending mass on a "Field of Liberty" in the small central town of Blaj
garnered for and left the Romanian people a precious heritage which we can sum up in two words: freedom and mercy," added Francis
while praising the "diversity of religious expression" in mainly Orthodox Romania
Regime officials detained the beatified bishops overnight on October 28
accusing them of "high treason" after they refused to convert to Orthodoxy
The Greek-Catholic Church was outlawed under 1948-89 Communist rule
others in confinement in an Orthodox monastery
They were then buried in secret -- to this day the whereabouts of four of their graves is unknown
The bars of the cells where they were held were symbolically incorporated into the throne built specially for the papal visit
The bishops followed the Eastern Rite Catholic Church which emerged from an Orthodox schism at the end of the 17th century when the central region of Transylvania was part of the Austro-Hungarian empire
While retaining Orthodox practices they recognised Roman Catholic papal authority -- unacceptable for the Communist regime which took power following World War II
Under a 1948 decree formally abolishing the Eastern Catholic churches
Greco-Catholics were forcibly obliged to return to the Orthodox fold
"This anti-faith hatred came from (Soviet leader) Joseph Stalin
who had in the same way liquidated the Ukrainian Greco-Catholic church," researcher Emanuel Cosmovici told AFP
Romania's Orthodox Church would itself face repression under the Communists -- albeit some senior prelates did collaborate with the party
most Romanian Catholics -- who numbered more than 1.5 million in 1948
abandoned their faith and their community has shrunk to around 200,000 today in a country of 20 million
almost nine in 10 of whom profess Orthodoxy
The politics which has seeped through Romania's modern religious history has poisoned inter-faith relations -- even if the papal visit has softened feelings to a degree
making up as much as 10 percent of the population
not hesitating to mention the fact during Francis' visit
"He will definitely speak about discrimination because we have no rights at all," said Ion
doors get closed," the former construction site worker told AFP ahead of Francis's arrival in Blaj
suffered around five centuries of slavery before the practice was formally abolished in 1856
But they remain a mainly poor and marginalised community -- even if recent years have seen roads paved and homes getting running water and electricity
Francis's arrival in Blaj to wind up his visit was part of his attempt at inclusiveness on his three-day visit to one of what remains Europe's poorest states
Although Romania has developed apace since obtaining EU membership in 2007 there remain some "urban or rural ghettos where nothing has changed," according to sociologist Gelu Duminica
who heads the anti-discrimination Impreuna (Together) association
Duminica and others in Blaj saw it as no coincidence that Francis
often seen as a defender of the rights of the most marginalised
to launch his appeal for tolerance and social inclusion
"The pope's visit is a message for those who are marginalised
disregarded or not accepted by others," said Mihai Gherghel
who supervised the construction of the Blaj church where Francis celebrated Sunday mass
Jn 9:2). The disciples’ question to Jesus triggers a series of actions and events that will accompany the entire Gospel account and clearly reveal what really blinds the human heart
Jesus
sees the man blind from birth. He acknowledges him and gives him his full attention. After making it clear that the man’s blindness was not the result of sin
he mixes dirt with his saliva and smears it on the man’s eyes. Then he tells him to wash in the pool of Siloam. After washing
the man blind from birth recovers his sight. It is significant that the miracle is recounted in just two verses; everything else has to do
not with the blind man who has recovered his sight
but with the arguments that followed his healing. It seems that his life and especially the story of his cure are of little interest
irritation and anger. The man healed of his blindness is questioned first by the astonished crowd
who also interrogate his parents. They question the identity of the man who was healed; then they deny the act of God
with the excuse that God does not work on the Sabbath. They even go so far as to doubt that the man was actually born blind
The whole scene and the arguments that follow show how hard it is to understand the actions and priorities of Jesus
who brings someone from the periphery into the centre. It is particularly hard for people who think that “the Sabbath” is more important than the love of the Father who wills all people to be saved (cf
1 Tim 2:4). The blind man had to live not only with his own blindness
but also with the blindness of those around him. We see the resistance and the hostility that can arise in the human heart when
which manage only to blind everything around them. The Lord’s approach is different: far from hiding himself behind inaction or ideological abstractions
he looks people in the eye. He sees their hurts and their history. He goes out to meet them and he does not let himself be sidetracked by discussions that fail to prioritize and put at the centre what is really important
These lands know well how greatly people suffer when an ideology or a regime takes over
setting itself up as a rule for the very life and faith of people
diminishing and even eliminating their ability to make decisions
their freedom and their room for creativity (cf
you were forced to endure a way of thinking and acting that showed contempt for others and led to the expulsion and killing of the defenceless and the silencing of dissenting voices. I think in particular of the seven Greek-Catholic Bishops whom I have had the joy of beatifying. In the face of fierce opposition from the regime
they demonstrated an exemplary faith and love for their people. With great courage and interior fortitude
they accepted harsh imprisonment and every kind of mistreatment
in order not to deny their fidelity to their beloved Church. These pastors
re-appropriated and handed down to the Romanian people a precious legacy that we can sum up in two words: freedom and mercy.
With regard to freedom
I cannot help but note that we are celebrating this Divine Liturgy in the “Field of Liberty”. This place
which is found in the diversity of its religious expressions. All these things constitute a spiritual patrimony that enriches and distinguishes Romanian culture and national identity. The new Beati endured suffering and gave their lives to oppose an illiberal ideological system that oppressed the fundamental rights of the human person. In that tragic period
the life of the Catholic community was put to a harsh test by a dictatorial and atheistic regime. All the Bishops and faithful of the Greek-Catholic Church and those of the Latin-rite Catholic Church were persecuted and imprisoned
sustained their people in confessing the faith without compromise or retaliation. The mercy they showed to their tormentors is a prophetic message
for it invites everyone today to conquer anger and resentment by love and forgiveness
and to live the Christian faith with consistency and courage.
Dear brothers and sisters
we witness the appearance of new ideologies that quietly attempt to assert themselves and to uproot our peoples from their richest cultural and religious traditions. Forms of ideological colonization that devalue the person
with alienating proposals as atheistic as those of the past
leaving them without roots from which they can grow (cf
78). Everything then becomes irrelevant unless it serves our immediate interests; people are led to take advantage of others and treat them as mere objects (cf
seek to cancel and bury the best that the history of these lands have bequeathed to you. I think
which forbade all forms of radicalism and was one of the first in Europe to promote an act of religious tolerance.
I would like to encourage you to bring the light of the Gospel to our contemporaries and to continue
to resist these new ideologies now springing up. It is up to us to resist now
allowing fraternity and dialogue to prevail over divisions
and fostering the fraternity of blood that arose in the period of suffering
drew closer and more united to one another. May the maternal protection of the Virgin Mary and the intercession of the new Beati accompany you on your journey
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Pope Francis gives the homily as he celebrates a Divine Liturgy and the beatification of seven martyred bishops of the Eastern-rite Romanian Catholic Church at Liberty Field in Blaj
By Junno Arocho Esteves • Catholic News Service • Posted June 3
Romania (CNS) — The memory and witness of Romania’s martyred bishops are a reminder that Christians are called to stand firm against ideologies that seek to stifle and suppress their cultural and religious traditions
the pope June 2 celebrated a Divine Liturgy during which seven Eastern-rite Catholic bishops
who died during a fierce anti-religious campaign waged by the communist regime in Romania
re-appropriated and handed down to the Romanian people a precious legacy that we can sum up in two words: freedom and mercy,” the pope said
an estimated 60,000 people filled Blaj’s Liberty Field
while some 20,000 people followed the liturgy on big screens set up in various squares around the city
the field — located on the grounds of Blaj’s Greek Catholic Theological Seminary — is both a symbol of national pride and sorrow
during the 100th anniversary of the Romanian nationalist revolution that communist authorities formerly dissolved the Eastern-rite Romanian Catholic Church
the apostolic administrator of Fagaras and Alba Iulia
which was perceived by his flock as a sign that they were called to remain steadfast in their faith and follow the path of persecution and martyrdom
held up images of the seven martyred bishops who gave their lives defending their faith: Bishop Suciu; Auxiliary Bishop Vasile Aftenie of Fagaras and Alba Iulia; Bishop Valeriu Traian Frentiu of Oradea Mare; Auxiliary Bishop Tit Liviu Chinezu of Fagaras and Alba Iulia; Bishop Ioan Balan of Lugoj; Bishop Alexandru Rusu of Maramures and Bishop Iuliu Hossu of Gherla
Paul VI “in pectore” or in his heart
withholding publication of his name until 1973
the pope remembered the sufferings of Eastern-rite Catholics who were forced to “endure a way of thinking and acting that showed contempt for others and led to the expulsion and killing of the defenseless and the silencing of dissenting voices.”
The martyred bishops left a “spiritual patrimony” for future generations demonstrated by their “exemplary faith and love for their people,” the pope said
was matched only by their willingness to suffer martyrdom “without showing hatred toward their persecutors and indeed responding to them with great meekness.”
“The mercy they showed to their tormentors is a prophetic message
and to live the Christian faith with consistency and courage,” the pope said
Pope Francis warned that even today there are new ideologies that “attempt to assert themselves and to uproot our peoples from their richest cultural and religious traditions.”
“Forms of ideological colonization that devalue the person
leaving them without roots from which they can grow.”
Catholics are called to bring the light of the Gospel to others and resist those ideologies rising in the world
“May you be witnesses of freedom and mercy
drew closer and more united to one another,” the pope said
On his final stop before departing for Rome
Pope Francis visited members of the Roma community living in the neighborhood of Barbu Lautaru
a newly erected church and pastoral center were built to assist the Roma community to fully integrated within the social fabric of the city of Blaj
there is room for everyone,” the pope told members of the community
“otherwise it would not be the church of Christ.”
The pope told the Roma community that his heart was heavy due to “the many experiences of discrimination
segregation and mistreatment experienced by your communities,” inflicted upon them
including by members of the Catholic Church
He asked forgiveness to them “for those times in history when we have discriminated
mistreated or looked askance at you” instead of defending them in their “uniqueness.”
“We are proud he is coming here in our community — a person like the pope
the Roma are “proud to be Gypsies.”
unless we are able to see the person before his or her actions
before our own judgments and prejudices,” the pope said
According to the Jesuit journal Civilta Cattolica
a 2011 census estimated that there are more than 620,000 Roma people in Romania
the figure may not reflect the actual numbers because many do not declare their ethnicity out of fear of discrimination
the pope encouraged them to not go down the path of vengeance and instead to choose the “way of Jesus” which brings peace and can heal the wounds of injustice
“May we not let ourselves be dragged along by the hurts we nurse within us; let there be no room for anger
no resentment is ever good for the heart and no rejection will ever bring us closer to others,” he said
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Lia Blaj-Ward is Associate Professor at Nottingham Trent University
Halfway through 2020, during a quiet week when undergraduate student teaching had just ended and master’s level students were about to begin their most substantial writing task for the year, I came across a piece about slow, caring scholarship
As an academic puzzling about my place on the recently developed Teaching & Scholarship career pathway
The pandemic-induced pivot to teaching online that year was fast
An ethics of care and a renewed appreciation of the value of slowed-down
underpinned the staff development experiences which made the pivot possible
with colleagues supporting each other to navigate the changed landscape
The same ethos underpinned the staff-student interaction in the spaces newly created to accommodate learning and teaching. It made intuitive sense that scholarship activity, which, as defined by Advance HE
captures and reflects on learning experiences for the purpose of enhancing them
discussion of academic roles is still dominated by the teaching/research (or TEF/REF) binary view
HESA’s categories of “academic employment function” reflect this
and inclusion among staff and therefore to greater quality of learning experiences for students
Teaching & Scholarship and Teaching & Practice
sit alongside the Teaching & Research pathway
Advance HE acknowledges that academic career progression is currently “a much more expansive and nuanced area than previously conceptualised” and invites reflection on how further expanse and nuance can be achieved
One avenue for this is to create an institutional environment which is supportive of slow
caring scholarship aligns with that of the anchor institution
and policies that drive sustainable development
They create a virtuous circle of investment in learning and growth that generate returns that help build capacity for further learning and growth – within the region in which they are based and in the communities their students and staff are connected to
The Teaching & Scholarship pathway at my university recognises the importance of anchoring learning and teaching in carefully designed pedagogic research
It promotes the value of scholarship outputs which push the boundaries of a body of peer-validated knowledge focused on learning and teaching experiences rather than subject discipline content
It offers a firmer basis for conversations about the role of higher education curricula in developing lifelong and lifewide learners
caring scholarship: “publish and flourish”
and considerate scholarship project design
and share insights which resonate with different audiences beyond the academic world
University teaching and learning that aim to prepare students successfully for lifelong and lifewide learning should be aligned to the variety of forms of teaching and learning which happen outside the campus walls
Progression along a pathway focusing on teaching and scholarship signals an institution’s commitment to creating collaborative learning environments not only for their students but also for their staff
projects I have been supported to develop speak to the value of collaborative working and learning
particularly across the academic / professional services divide
Collaboration with professional services colleagues who brought a rich perspective on student academic experiences at university has led to two co-authored outputs in reputable academic journals
An open access resource which celebrates innovation and resilience among colleagues in my field during the pandemic is co-edited with a colleague who is not in a formal teaching and learning role but who has an unparalleled depth of understanding of how university students should be supported to learn and develop in unusual circumstances
Considerate design of scholarship projects is a third and equally important principle of slow, caring scholarship. As Cora Xu emphasises
it is important not to burden contributors and participants in our pedagogic research projects with our scholarly ambitions
refraining from including them in our data sets at all costs
scholars of teaching and learning should set up projects which give contributors and participants an opportunity to engage on their terms
and to benefit in varied forms at all stages
throughout the process of generating insights
to the final output and impact planned beyond
My institution’s Trent Institute of Learning and Teaching builds capacity for considerate scholarship project design among staff through peer mentoring
and earmarking funding for student engagement in these
TILT application forms explicitly require an indication of how the project will generate value for applicants’ and contributors’ own learning and professional development
To reach Associate Professor stage on the Teaching & Scholarship pathway
and to develop as a more rounded higher education professional
I have benefited substantially from an institutional environment built on the ethos of slow
Two additional features of this environment stood out for me
Cross-functional mentoring: some of my most valuable mentors have been professional services colleagues who were not close to classroom practice but had a deep appreciation of the value of university experiences for students and for those around them now and in the future
These colleagues have made me aware of the value of learning experiences outside academia and of ways to bring them into my work in a university
Workloads which include space for “concept projects” with beneficial outcomes for all involved: to fine-tune my teaching so that it fully prepares my university students for a lifelong and lifewide learning experience
I used the volunteering allocation in my workload to host pre-18 participants on a work experience week at my university
Insights from designing and delivering this experience looped back into my teaching approach
and were validated through a Vice Chancellor’s Teaching Award
Diverse career pathways enable anchor institutions to grow their positive impact within and outside campus walls
To help build capacity to generate impactful learning (lifelong and lifewide) and growth
reflective conversations need to take place about the shape of academic roles on diverse pathways and about ways in which progression can occur
Great piece Lisa and congratulations on your promotion
I need more coffee before I do battle with autocorrect clearly
Excellent article and so pleased to see you go from strength to strength as an academic and a trusted voice in higher education
I have personally learned so much from you and enjoyed the process
We really must introduce this ethic of care into everything we do
A really interesting insight into you perspective of T&S at NTU
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daylight shootout in central Hamilton shut down several city blocks of the Gibson neighbourhood as the city’s police department scoured the area searching for clues
The initial shooting broke out shortly before 5 p.m
when police say “multiple 911 calls reporting gunfire” alerted them to the exchange taking place near Kinrade Avenue at Barton Street East
“We flooded the neighbourhood with officers on discovering that there were two males
and they were shooting at — at least — one other male in a vehicle,” Const
and it crashed into an uninvolved motorist travelling eastbound
Several witnesses reported to police that they had witnessed “several” individuals exchanging gunfire
investigators confirmed that bullets were found in “buildings
There have been no reported injuries at this time
police say they located an abandoned vehicle that they believe was involved in the incident
there have been no arrests made and the shooters remain at large
Police say it is too early in the investigation to release an accurate description of the suspects and will provide an update once one becomes available
This incident prompted a heavy response from the force
Authorities on scene called the cordoned-off area “extensive,” which spanned from Wilson Street and Birch Avenue to Cannon Street at Sherman Avenue
Police could be seen canvassing the neighbourhood for video Monday evening
and Blaj says he encourages anyone who may have seen anything or who has surveillance footage to come forward
residents with CCTV systems are asked to review footage between 4:30 p.m
Anyone with additional information that may assist police in the investigation is asked to contact them by phone at 905-546-4883 or by email at shootingresponseteam@hamiltonpolice.ca
tips can be submitted anonymously to Crime Stoppers
READ MORE: Hamilton police seek psychiatric patient who is ‘unlawfully at large’
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The German Bosch Group will invest EUR 120 million by 2013 in a new car component factory in Cluj and extending manufacturing facilities at its Blaj factory
almost doubling the number of employees to 2,000
after local sales rose 18 percent to EUR 188 million last year
Bosch will make a EUR 77 million greenfield investment in the Cluj plant
The production of electronic command units for the automotive industry will start in mid-2013 and employ 340 people in production and development
when around 1,600 people will be working there
The firm will also produce speed sensors for the automotive industry in Blaj
which will expand the Blaj factory by 21,000 sqm
Around 570 people currently work at the Blaj plant
which manufactures linear technology used in mechanical engineering
Building works at the Blaj center started in March and at the Cluj-Napoca plant in May. Romania has granted Bosch state aid to carry out the construction. The company said it wouldn’t have invested in Romania without the state aid.
The auto industry generates around 60 percent of Bosch’s turnover in Romania and worldwide
general director of Robert Bosch and group representative in Romania
The company estimates that sales in Romania will fall by 6 percent to EUR 176 million in 2012 due to Renault’s decision to move some processes to manufacturing lines to Russia and Morocco
It is active in the small appliances market
industrial technology and construction equipment
The group’s worldwide sales amounted to EUR 51.5 billion in 2011
Ovidiu Posirca
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“For Bosch it’s very important to support the Green Deal with a target of net zero emissions by 2050
It’s important for us because the management made a very bold decision to be carbon neutral
we have 400 locations worldwide with a carbon-neutral footprint
That’s a very bold step from an economic perspective
This shows our commitment towards stopping climate change and on meeting the Paris Agreement goals,“ Bernhard Gehlert
Bosch Automotive Blaj said during Sustainability Forum 2022 organized by The Diplomat-Bucharest
We have to invest in technologies which enable us to reduce consumption and also generate green electricity on our premises
This might not be sufficient to be carbon neutral
We have to rethink the entire supply chain
We have to think more about the impact of our products while they are used by our customers
it’s very important that we monitor the whole supply chain and by 2030 we want to reduce carbon emissions throughout our whole value chain
from purchasing to sales by further 15 percent
and it’s a necessary contribution to support this goal
The UE is a role-model for the whole world on how this transition can be managed
It takes a lot of effort to encourage everyone to stick to the rules and regulations which will be in place
I think this is a great opportunity for the rest of the world to follow this approach and implement maybe similar activities
electrification is the fastest way to reduce carbon emissions during the lifetime of the products
Electrification is a great way of reducing emissions by using green energy
We also believe hydrogen is a complementary technology to electrification
Both together could be one of the solutions for the future to make our products more sustainable
Hydrogen is a new technology and that means it will take some time for products to come to the market
Research is ongoing and the design of future products is in the making
This requires huge investments and a clear strategy
The power of technology helps to keep current living standards and have a plurality of different solutions
We need different solutions and a competition between them so that time will tell which one is the best
we don’t want to put all efforts in one technology
We must cover a certain range of technologies where we believe they have the biggest potential to solve the biggest problems the humanity is facing
In Romania we have production locations and development centres
We already implemented a lot of measures to reduce energy consumption because energy consumption is expensive
It’s a surprise to see how much potential companies have to reduce consumption.“
Full recording of the event: https://www.youtube.com/watch?v=g5TZ1M3tQnY
a 72-year-old retiree from Romania’s minority Roma community
doors get closed,” says the former construction site worker
But Pope Francis’ visit to his town Sunday to meet the Roma on the last day of his trip has given Ion new hope
“He will definitely speak about discrimination because we have no rights at all,” says Ion
Making up around 10 percent of Romania’s 20 million people
many Roma are marginalised and live in poverty
the daily life of Ion and his neighbours has improved due to initiatives by the town’s government: roads have been paved and their homes have received running water and electricity
still live mostly in precarious conditions on the periphery
“It’s always been like this for the areas where Roma live
It’s the same everywhere,” Petru Varga
Sociologist Gelu Duminica says conditions for the Roma have improved in line with the development of the country
but in the poorest communities in urban and rural areas alike “nothing has changed”
According to a study carried out last year by Duminica’s Impreuna (Together) association
nine percent of Roma in Romania don’t receive an income
compared to one percent for the rest of the population
compared to two percent for non-Roma Romanians
“It’s a vicious cycle where limited access to education leads to poor access to the labour market,” says Duminica
has chosen the Barbu Lautaru district of Blaj
where the majority of the inhabitants are Roma
to launch an appeal for tolerance and social inclusion
“The pope’s visit is a message for those who are marginalised
disregarded or not accepted by others,” says Mihai Gherghel
who supervised the construction of the Blaj church
“I think he will bring help to those who really need it,” said Gheorghe Halas
who has been promoting Protestantism in Blaj since 2005
many Roma have been attracted by neo-Protestantism in the last years
especially Pentecostalism — together with the aid that comes with it
“The conversion is an important moment for stigmatised people who finally feel respected for what they are,” Laszlo Foszto
“God doesn’t have any prejudices
he only sees their immaculate hearts.”
This attracts many Roma in search of recognition
away from the very conservative and powerful Orthodox church of Romania
which has never apologised for its central role in enslaving the Roma for hundreds of years until the mid-19th century
religious differences will be pushed aside
“All of Blaj will be a cathedral,” priest Mihai says
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no one knew besides Dan Ionescu that his daughter Sabrina would become one of the biggest names in the WNBA
Dan has been nothing short of a living motivation to Sabrina
her journey through the professional stage has been imbibed with her Romanian roots along the way
and aggression to make her mark on the court
Dan and Liliana too have an interesting story to tell
one that can keep one’s culture alive while not giving up on their hopes to live a better life with their loved ones
It was the 1989 Christmas Revolution in communist Romania when Dan Ionescu escaped his homeland to take political shelter in the U.S
and son Andrei to join him a few months later
the opportunity came after 6 years in 1995
Liliana gave birth to twins at a gap of 18 minutes
Dan had settled down in North Carolina amongst his extended family members
the two got talking about being Eastern European immigrants and basketball
DURHAM, NORTH CAROLINA – NOVEMBER 12: Sabrina Ionescu #6 of the US National Team looks on during an exhibition game against the Duke Blue Devils at Cameron Indoor Stadium on November 12, 2023 in Durham, North Carolina. The US National Team won 87-58. (Photo by Lance King/Getty Images)
Later on, he realized his American Dream by shifting from a taxicab job to owning a limousine service company called Premier Transportation. Today, it has been more than 3 decades since Dan started providing transportation services to corporate clients and private parties that include airport transportation, wine tours, and corporate functions.
Besides growing his business, Dan also played a major role in developing Sabrina’s and Edward’s balling skills.
Being the father of a first-generation athlete, Dan knew nothing about basketball. However, the sport was the perfect outlet for Sabrina’s aggression, confidence, and competitiveness, traits that come from her Romanian roots.
So, to channel all that energy, Dan Ionescu worked Sabrina and Edward into a competition, with one desperate purpose – ‘to exhaust the two and get them a peaceful night of sleep’ – as he put it, “When you have twins and they’re young, all you want is them to get tired.”
He found the solution at Larkey Park, which happened to be tennis and basketball courts and a sand volleyball pit. But they missed a soccer field there. Had it been there a soccer field, Dan would have surely pushed the twins into the game as well.
Eventually, Sabrina and Edward grew closer to basketball, with Larkey Park being their ultimate place to be. The two would team up and take down grown men in a quest for the ultimate spoil. “Some guys would be like, ‘If you beat us, we’ll get you guys a Slurpee,’ because there was a 7-Eleven right down the street. We’d beat them in H-O-R-S-E, or two-on-two, three-on-three, and they’d just go and get us a Slurpee and come back,” said Edward.
Individually, it was much more for Sabrina than just beating grown-up men for a cooler, as Dan put it, “The very first instinct for Sabrina was to be accepted by the boys. She wanted to be with the boys and always driven by that.”
Her competitive edge was on display in 2013 when, despite not being invited to the USA Basketball’s U16 tryouts in Colorado Springs, she went and was one of the two non-invitees to get selected, and the rest is history.
Native to Romania, the Ionescu family stayed connected with their roots. They didn’t want to lose their language but rather used it to their advantage. Whenever the twins played, Dan would shout his thoughts in their native language from the stands. Then Edwards would tell him to settle down.
While now Dan might tease that Sabrina Ionescu is not all that at times, he knows what she has done is nothing short of amazing.
Stay tuned for more such updates and join us for the exciting second episode of the “Dual Threat Show” as our host BG12 sits down with Georgia Bulldogs star and Mountain West All-Freshman Team Selection, Asia Avinger
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