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Nu Shu: The Secret Songs of Women was inspired by the remote Chinese village Nu Shu
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passed away peacefully on the evening of March 18th
Taiwan to Chi-wu Liu and Hsiu-lien Liu Chang
She found her greatest joy in singing praise and worship
dedicating her heart to both her family and church community
She earned a degree in International Trade from Chung Yuan Christian University (1992) in Taiwan before moving to the United States
where she obtained a Master’s in Accounting from the University of Missouri - Kansas City (1997)
She devoted 27 years of service to the City of Kansas City
they built a beautiful life in Kansas City
and faith alongside their three children— Grace
Charity’s deep devotion extended beyond her family to Emmanuel Chinese Baptist Church
where she found her spiritual home and served joyfully on the worship team
A service to celebrate Charity’s life will be held on Saturday, April 5th at Emmanuel Chinese Baptist Church and via livestream at 10am
Though she faced cancer with strength and bravery
and in eternal life with our Heavenly Father
Charity is deeply missed but will live on in the hearts of her family and those who knew her
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Taiwanese-British musician Shu-Wei Tseng has performed as both soloist and chamber musician across four continents in major concert halls on the piano and cello
Shu-Wei joined the Royal Conservatoire of Scotland faculty in 2010 and is a Global Ambassador of CU Boulder
with previous degrees from London's Royal Academy of Music
Alongside regular lectures/masterclasses and workshops she gives internationally
Shu-Wei is frequently featured as the musician representative for the Taipei Consulate and the Taiwan Ministry of Culture in the UK
as well as representing the UK at the D-Day Commemoration Concerts in Normandy
Shu-Wei is a newcomer to New York City since November 2023
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Templated DNA repair that occurs during homologous recombination and replication stress relies on RAD51
RAD51 activity is positively regulated by BRCA2 and the RAD51 paralogs
The Shu complex is a RAD51 paralog-containing complex consisting of SWSAP1
We demonstrate that SWSAP1-SWS1 binds RAD51
Using single-molecule confocal fluorescence microscopy combined with optical tweezers
we show that SWSAP1-SWS1 decorates RAD51 filaments proficient for homologous recombination
We also find SWSAP1-SWS1 enhances RPA diffusion on ssDNA
we show human sgSWSAP1 and sgSWS1 knockout cells are sensitive to pharmacological inhibition of PARP and APE1
we identify cancer variants in SWSAP1 that alter Shu complex formation
we show that SWSAP1-SWS1 stimulates RAD51-dependent high-fidelity repair and may be an important new cancer therapeutic target
how these RAD51 mediator complexes specifically function to promote homologous recombination and to counteract replication stress remains poorly defined
it is enigmatic why so many different RAD51 mediators are needed
The function of the human Shu complex in RAD51-dependent repair has yet to be mechanistically defined
plays multiple novel roles regulating RAD51 functions during high-fidelity repair in the presence of RPA
We show that SWSAP1-SWS1 forms a heterodimeric protein complex in solution that is positionally decorated throughout the RAD51 filament
We show that mechanistically SWSAP1-SWS1 binds to RAD51
and this enables stimulation of RAD51 D-loop reactions on RPA-coated ssDNA substrates
we find that SWSAP1-SWS1 stimulates RPA diffusion on ssDNA
We find that CRISPR/Cas9 SWSAP1 and SWS1 knockout cells are sensitive to the PARP inhibitor
uterine/endometrial and prostate cancers (TGCA
cBioportal) and mutations in SWSAP1 inhibit its binding to SWS1 by yeast-two-hybrid
This study provides novel mechanistic insights into how the RAD51 paralog complex SWSAP1-SWS1 modulates RAD51 and RPA activities and has implications in cancers containing genetic variants in this pathway
and Cy5-RAD51 (37 kDa) were run on SDS-PAGE gel and Coomassie stained or visualized by typhoon imaging (Cy3-RAD51 and Cy5-RAD51)
B SWSAP1-SWS1 were analyzed by size exclusion and the eluted fractions were analyzed by SDS-Page gel and Coomassie staining
C Quantitative analysis was performed to determine the size of SWSAP1-SWS1 (purple text) using known molecular standards and the partition coefficient was graphed vs the log of the molecular weight
The molecular standards used include Aprotinin (6.5 kDa)
and Thyroglobulin (669 kDa) run on a Superdex200 (10/300 GL) column
Partition coefficients (Kav) of low and high molecular weight protein standards are plotted vs the Log of the MW
Together these results support the notion that SWSAP1-SWS1 and RAD51 form protein complexes in solution
A FRET-based ssDNA binding assays were performed with a dT60 substrate with a Cy3 dye (FRET donor) and a Cy5 dye (FRET acceptor) separated by 30 nucleotides and increasing concentrations of RAD51 (black circles)
B FRET-based ssDNA binding assays were performed with a dT60 substrate with a Cy3 dye (FRET donor) and a Cy5 dye (FRET acceptor) separated by 30 nucleotides and increasing concentrations of SWSAP1-SWS1 (pink circles)
C FRET-based ssDNA binding assays with Cy3-dT60-Cy5 were performed with increasing concentrations of RAD51 alone or with SWSAP1-SWS1 at two different molar ratios (1:0.5 molar ratio in pink and 1:1 molar ratio in purple)
D Schematic of experimental setup for single-molecule studies of Cy3-RAD51 and Cy3-RAD51-HALO-SWSAP1-SWS1 experiments
In channel one lasers trap the streptavidin beads (CH1: beads)
then are moved to the second laminar flow channel which binds to biotin-labeled dsDNA (CH2: DNA)
then ssDNA is formed in channel three (CH3: Buffer) and moved to channel four containing Cy3-RAD51 or Cy3-RAD51-HALO-SWSAP1-SWS1 nuclear extract proteins (CH4: Protein)
E Representative kymograph showing Cy3-labeled RAD51 on lambda ssDNA under magnesium conditions
Cy3-RAD51 position was monitored over time
Cy3-RAD51 ATP hydrolysis occurs resulting in dwell times of ~1.5 s
F Representative kymograph showing Cy3-labeled RAD51 on lambda ssDNA under calcium conditions
The Cy3-labeled RAD51 and its position was monitored over time
Cy3-RAD51 ATP hydrolysis is inhibited resulting in increased dwell times and photobleaching time of ~11 min
G Representative kymograph showing Cy3-labeled RAD51 on lambda ssDNA complexed with HaloTag-JF503-SWSAP1 from nuclear extracts under calcium conditions
Positions of both RAD51 and SWSAP1 were monitored over time
Positional analysis and summation of fluorescent intensity were graphed relative to pixels in the kymograph
The length of the filament is indicated on the left of the image
H Each scan in the kymograph was summed and quantification of positional localization of SWSAP1 relative to the RAD51 filament [throughout the RAD51 filament (32 total; black bar)
on the end of the RAD51 filament (8 total; gray bar)
or SWSAP1 not present (2 total; white bar)] n = 42
I The Cy3-RAD51 filaments were traced and quantified for colocalization with HaloTag-JF503-SWSAP1
RAD51 and SWSAP1 colocalized in 76 events (purple bar) whereas 26 events had RAD51 (green bar) and 11 events had SWSAP1 alone (blue bar)
these results demonstrate that Cy3-labeled RAD51 protein is functional
our results show that SWSAP1-SWS1 binds RAD51
where it is located throughout the filament
SWSAP1-SWS1 could be incorporated within the RAD51 filament itself or decorated along the outside of the RAD51 filament through its interaction with RAD51
FITC-90mer ssDNA (yellow DNA with circle) was coated with RPA (green circles) for 5 min at 37 °C
or RAD51 with SWSAP1-SWS1 was added to the reaction for 5 min at 37 °C and then incubated with the pBluscript dsDNA template (supercoiled DNA) for 15 min at 37 °C
B FITC-90mer ssDNA coated with RPA (100 nM) was challenged with either RAD51 (0.25
1 μM) or RAD51 (0.25 μM) and increasing concentrations of SWSAP1-SWS1 as indicated
Then the reaction was begun by adding pBluescript dsDNA
DNA + RAD51 + RPA are controls (Lanes 1-6)
C Quantification of D-loop reaction products with recombinant SWSAP1-SWS1
and 125 nM) proteins and the values were normalized to RPA 100 nM and RAD51 250 nM
we observe a large enhancement of RPA diffusion in the presence of SWSAP1-SWS1
these data suggest that SWSAP1-SWS1 binding to RPA may cause some change that enhances the kinetic macroscopic and/or microscopic on and off rates of RPA on ssDNA
highlighting variants identified in breast
and prostate cancers from TCGA and cBioPortal
The Walker A and Walker B motifs are indicated in orange and blue
Summary of the yeast-2-hybrid results in (B) are highlighted with a red box (indicating a deficient yeast-2-hybrid interaction
yellow box (indicating a partial yeast-2-hybrid interaction
and a green box (indicating a proficient yeast-2-hybrid interactions
B Yeast-two-hybrid analysis of SWSAP1 variants from breast
and prostate cancers identified in COSMIC and cBioPortal
Wild-type SWSAP1 or the cancer variant were expressed in the GAL4-DNA binding domain vector (BD) and their interaction with SWS1
expressed in the GAL4-DNA activating domain (AD) was assessed by yeast-two-hybrid by assessing growth on selective medium (SC medium minus leucine
Equal cell plating was assessed by plating the yeast on SC medium minus leucine and tryptophan (SC-LT) medium
pGAD and pGBD empty vectors were used as negative controls
and colonies were quantified with ImageJ and normalized to the wild-type control
C AlphaFold models of SWSAP1 (purple) and SWS1 (pink) structures were fed into the HDOCK server to generate a combined model of SWSAP1-SWS1
The surface exposed cancer variants are highlighted in red
and sgSWS1 RPE-1 cells exposed to the indicated dose of Olaparib for approximately 14 days
The cells were fixed and stained with crystal violet before being photographed
E Quantification of (D) where cellular survival area of RPE-1
and sgSWS1 was normalized to untreated control and the colony area quantitated and the IC50 was calculated in Graphpad PRISM
Significance was determined by two-way ANOVA from three experiments (SWS1-C1 p = <0.0001
F Quantification of (D) where colony intensity of RPE-1
and sgSWS1 was normalized to untreated control and the colony intensity quantitated and the IC50 was calculated in Graphpad PRISM
Note that two independent clones were analyzed for each knockout
These results suggest that loss the human Shu complex
Our findings provide a rationale as to why so many RAD51 paralog-containing complexes exist and suggest that the Shu complex function is distinct from other RAD51 paralog complexes
It is plausible that binding to the end of a filament suggests inhibition of RAD51 disassembly
which is divergent from our FRET-based binding assays with SWSAP1-SWS1 and RAD51 which enable RAD51 filament assembly
One important difference between our studies and the RFS-1/RIP-1 work is that ssDNA was used instead of a dsDNA/ssDNA hybrid
a limitation of our single-molecule analysis is that other cofactors are present in the nuclear extracts used in the experiment
Future studies using recombinant proteins will enable independent validation of our findings
Schematic of our working model where replicating cells exposed to MMS cause fork-blocking lesions
within lagging strands of replication forks
The Shu complex binds to MMS-induced DNA damage or processing intermediates
which can stall replication leading to ssDNA gaps behind the fork
RPA-coated ssDNA protects the fork from collapse
SWSAP1-SWS1 interacts with RPA enabling its dissociation from the remodeled fork
RPA dissociation by SWSAP1-SWS1 would then promote RAD51-SWSAP1-SWS1 filament accumulation at these sites to enable template-switching and high-fidelity lesion bypass
it is also plausible that SWSAP1-SWS1 may have homologous recombination-independent functions during replication stress
Here we provide evidence that like the other RAD51 paralogs
the Shu complex plays an important and distinct role in RAD51 regulation
and whose disruption may have profound implications for human disease
All constructs used for infection of SF9 Insect Cells (Gibco) were codon optimized and cloned into vector pVL1393 (MTI Bio)
The 6XHIS-SWSAP1 and GST-SWS1 constructs were created and optimized for expression in SF9 insect cells (MTI Bio)
The pCH1-RAD51 vector was obtained from Dr
The human SWSAP1 and SWS1 proteins were purified from baculovirus infected SF9 insect cells (MTI Bio)
After infection of 2 × 107 SF9 (Gibco) with baculovirus (GST-SWS1 MOI = 5 and SWSAP MOI = 5) for 48 hrs
cells were centrifuged and pellets stored at −80 °C
solubilized in 50 mL of lysis buffer (Lysis Buffer: 100 mM Tris pH 8
30 μg/mL leupeptin) and lysed by sonication
Lysed supernatant was centrifuged for 2 hrs at 45,000 rpm at 4 °C
Then the supernatant was incubated with 20 mL of glutathione agarose beads for 1.5 hrs at 4 °C
Beads were washed with lysis buffer and low salt buffer (Low Salt Buffer: 40 mM Tris pH 8
Then protein was eluted with 10 mM reduced glutathione
Elution was then added with 250U biotin labeled thrombin (EMD Millipore) and dialyzed in 3,350 MW dialysis tubing o/n in 1 L Thrombin Dialysis Buffer (Thrombin Dialysis Buffer: 40 mM Tris pH 8
Cleaved GST and uncleaved GST-SWS1 was captured on a GST column by incubating with 20 mL of glutathione agarose beads for 1 hr at 4 °C
The elution was collected and added to 10 mL of StrepTactin beads for capture of biotinylated thrombin
Flow through containing cleaved SWSAP1-SWS1 was added to 20 mL of IMAC Sepharose charged with NiS04
and 15 mM Imidazole buffers and eluted with 100 mM Imidazole
Eluted fractions were run on a Superdex 200 size exclusion column in Size Exclusion Buffer (Size Exclusion Buffer: 40 mM Tris pH 8
The protein eluted as a heterodimer at the expected molecular weight
Protein was concentrated on a Mono Q column and dialyzed o/n into storage buffer (Storage Buffer: 40 mM Tris pH 8
Protein was flash frozen and stored at –80 °C
RAD51 was N-terminally labeled with either Cy3 or Cy5
Labeling was performed by incubating RAD51 protein that was dialyzed in buffer containing 250 mM NaPi (pH 7.0)
and 10% glycerol with Cy3-Mono-Reactive Dye or Cy5-Mono-Reactive Dye overnight (VWR Catalog# 95017-379)
The dye-labeled Cy3-RAD51 and Cy5-RAD51 was further purified as described above to remove any free dye in the protein prep
Labeling efficiency was determined by measuring the absorbance of RAD51 at 280 nm and of Cy5 at 550 nm using their respective (ε280 = 14,900 M−1cm−1 for RAD51 and ε550 = 150,000 M−1cm−1 for Cy3)
Labeling efficiency was determined to be 69% for Cy3-RAD51
Cy5-RAD51 was further purified as described
Labeling efficiency was determined by measuring the absorbance of RAD51 at 280 nm and of Cy5 at 650 nm using their extinction coefficients (ε280 = 14,900 M−1cm−1 for RAD51 and ε650 = 250,000 M−1cm−1 for Cy5)
Labeling efficiency was determined to be 40% for Cy5-RAD51
Size exclusion analysis was performed using a Superdex 10/300 GL Agarose Column (GE) equilibrated in buffer (20 mM Hepes KOH pH7.5
Molecular weight standards used from the Gel Filtration Calibration Kit HMW (GE/Cytiva) included Dextran
Small molecular weight proteins utilized for size calibration included Proteinase K (AMBION)
Proteins were run over column at 0.5 mL/min and 1 mL fractions were collected over a geometric column volume (Vc)of 24.19 with bed height of 30.8 mm
Dextran was utilized to calculate the void volume (Vo) and corresponded to 8.05 mL
The elution volume at max absorbance of the eluted protein (Ve) was determined and was used to calculate the partition coefficient (Kav)
Kav was calculated by (Kav = (Ve − Vo)/(Vc − Vo)
The known log of the molecular weights of protein standards were graphed vs their calculated Kav values and fit to a logarithmic function (y = m*ln(x)+b)
Binding to the Cy3-dT60-Cy5 substrate (10 nM) results in a change in FRET between the Cy3 and Cy5 dyes and an observed stoichiometric binding isotherm
RAD51 binding site size was determined by multiplying 10 nM of our Cy3-dT60-Cy5 substrate by the total number of nucleotides to obtain 600 nM nucleotides
Then we divided 600 nM nucleotides by the point at which the two lines meet (200 nM) to obtain a stoichiometry of 3
This means that a RAD51 protein binds to 3 nucleotides of ssDNA as expected
Cell lines were maintained in 5% CO2 at 37 °C
cells were washed with PBS and pelleted for nuclear extraction (Abcam Ab113474) on ice
Nuclear extracts were aliquoted and snap-frozen at −80 °C for storage
SDS-Page gels were run (without Coomassie dye) and imaged at the appropriate wavelength (488 nm) on the Typhoon Imager (GE)
MW bands at approximately 33.6 kDa were observed for the HaloTag-JF503-SWSAP1 protein
The HaloTag-JF503-SWSAP1 was quantified by using recombinant HALO-GFP protein standard (Promega) pre-incubated with JF503 at a 1:1 molar ratio and titrated into single molecule buffer (20 mM Tris pH 7.5
Nuclear extracts utilized were from six separate biological replicates
protein quantification was determined for each extract and typical yields ranged from 2–10 nM in 30 μL
C-trap data is a summation of > 4 nuclear extract preparations
Diffusivity was calculated based on a linear curve of pure diffusion by performing ordinary least squares
Then we challenged this complex with RAD51 (1 μM) or RAD51-SWSAP1-GST-SWS1 complexes at increasing concentrations (RAD51 250 nM: SWSAP1-GST-SWS1 5 nM
We initiated the reaction by adding pBluescript KG plasmid at 50 μM bp concentration for 15 min at 37 °C
stopped the reaction by incubation with SDS and Proteinase K
and ran the reaction products on an agarose gel
D-loops were visualized on a Typhoon instrument (GE) by imaging and exciting at Cy2 (495 nm)
% D-loops were quantified using the Typhoon software (GE) and normalized to RPA-RAD51 only reactions
Experiments were also performed with untagged SWSAP1-SWS1 where the GST was cleaved
The pGAD-SWS1 and pGBD-SWSAP1 plasmids were co-transformed into the S
cerevisiae PJ69-4a strain and plated on media selecting for yeast transformants expressing the two plasmids (SC-LEU-TRP) and grown for 48 h at 30°
3-4 individual colonies transformed with the according plasmids were selected and cultured overnight in selective media (SC-LEU-TRP)
The cultures were then diluted to OD600 0.5 and grown to early log phase (4 hrs)
They then were diluted to OD600 0.2 and 5 μL of the culture was spotted onto medium selecting for the plasmids (SC-LEU-TRP)
medium selecting for the expression of the HIS3 reporter gene (SC-LEU-TRP-HIS)
or medium selecting for the HIS3 reporter and stressing the strength of the interaction through the inclusion of a competitive inhibitor (SC-LEU-TRP-HIS + 3AT)
Plates were incubated for 3 days at 30 °C and photographed after 48 and 72 h
All Y2H images were adjusted identically for brightness and contrast using Adobe Photoshop
Human SWSAP1-SWS1 (4 & 6 μM) and RAD51 (7.5 μM) were incubated in a final volume of 20 μL for 10 min at RT in Native PAGE Sample Buffer (4x) (50 mM Bis Tris pH 7.2
0.5 μL of Native PAGE Sample G-250 Sample Additive (Invitrogen) was added to bind protein complexes for 5 min at 25 °C
Samples were then loaded and run on 4-16% native PAGE gel (Invitrogen) in 0.5% TBE buffer pH 8.5 at 4 °C for 3 hrs
The native PAGE gel was stained with Coomassie
and shifted bands were cut out for protein composition analysis using mass spectrometry
Excised bands corresponded to protein complexes of RAD51-SWSAP1-SWS1
Peptides for each corresponding protein were identified in each sample
The indicated cell lines were seeded into 6 well plates and then trypsinized and cell number counted using a Z Colter Counter (Beckman)
Approximately 200 cells were seeded into 60 mm dishes and exposed 25
or 100 µM of APE1 inhibitor (APE1 inhibitor III; Calbiochem) or 0
25 µM Olaparib for approximately 8–14 days
The cells were stained with crystal violet by first rinsing the cells with PBS twice
followed by crystal violet (0.5% crystal violet and 20% methanol) for 30 min
the colonies were counted and compared to the untreated control to calculate the relative survival or colony area and intensity using the ColonyArea ImageJ plugin
All cellular assays were performed in biological triplicate with different passages of both clones from each genetic knockout
The average relative survival for each clone was analyzed by two-way ANOVA by comparison to the corresponding RPE-1 treated cell line
Further information on research design is available in the Nature Portfolio Reporting Summary linked to this article
Authors can confirm that all relevant data are included in the published article in addition to supplementary information files. Source data are provided in this paper
The plasticity of DNA replication forks in response to clinically relevant genotoxic stress
Identification and purification of two distinct complexes containing the five RAD51 paralogs
Preferential binding to branched DNA strands and strand-annealing activity of the human Rad51B
Breast cancer-associated missense mutants of the PALB2 WD40 domain
hSWS1.SWSAP1 Is an evolutionarily conserved complex required for efficient homologous recombination repair
The human Shu complex functions with PDS5B and SPIDR to promote homologous recombination
Evolutionary and functional analysis of the invariant SWIM domain in the conserved Shu2/SWS1 protein family from Saccharomyces cerevisiae to Homo sapiens
Human RAD51 paralogue SWSAP1 fosters RAD51 filament by regulating the anti-recombinase FIGNL1 AAA+ ATPase
Roles for APRIN (PDS5B) in homologous recombination and in ovarian cancer prediction
The Shu complex promotes error-free tolerance of alkylation-induced base excision repair products
Mutations in homologous recombination genes rescue top3 slow growth in Saccharomyces cerevisiae
The Rad51 paralogs facilitate a novel DNA strand specific damage tolerance pathway
The Shu complex prevents mutagenesis and cytotoxicity of single-strand specific alkylation lesions
Structure and function of the RAD51B-RAD51C-RAD51D-XRCC2 tumour suppressor
Structural insights into BCDX2 complex function in homologous recombination
Visualizing RAD51-mediated joint molecules: implications for recombination mechanism and the effect of sequence heterology
Distinct pathways of homologous recombination controlled by the SWS1-SWSAP1-SPIDR complex
Visualization and quantification of nascent RAD51 filament formation at single-monomer resolution
Single-molecule imaging brings Rad51 nucleoprotein filaments into focus
Ca2+ activates human homologous recombination protein Rad51 by modulating its ATPase activity
Human RAD51 rapidly forms intrinsically dynamic nucleoprotein filaments modulated by nucleotide binding state
Differential Requirements for the RAD51 Paralogs in Genome Repair and Maintenance in Human Cells
Human Rad51 filaments on double- and single-stranded DNA: correlating regular and irregular forms with recombination function
Cryo-EM structures of human RAD51 recombinase filaments during catalysis of DNA-strand exchange
Purification and characterization of the human Rad51 protein
Srs2 prevents Rad51 filament formation by repetitive motion on DNA
High-resolution structure of the presynaptic RAD51 filament on single-stranded DNA by electron cryo-microscopy
FRET-based assays to monitor DNA binding and annealing by Rad52 recombination mediator protein
Tyrosine phosphorylation stimulates activity of human RAD51 recombinase through altered nucleoprotein filament dynamics
Contributions of the RAD51 N-terminal domain to BRCA2-RAD51 interaction
A non-canonical DNA structure enables homologous recombination in various genetic systems
and biochemical evaluation of human RAD51 protein
Single-molecule analysis of DNA-binding proteins from nuclear extracts (SMADNE)
Unlicensed origin DNA melting by MCV and SV40 polyomavirus LT proteins is independent of ATP-dependent helicase activity
Fluorescent human RAD51 reveals multiple nucleation sites and filament segments tightly associated along a single DNA molecule
Small-molecule inhibitors identify the RAD52-ssDNA interaction as critical for recovery from replication stress and for survival of BRCA2 deficient cells
A structural and dynamic model for the assembly of replication protein A on single-stranded DNA
Dynamic binding of replication protein a is required for DNA repair
Dynamic elements of replication protein A at the crossroads of DNA replication
Single-stranded nucleic acid binding and coacervation by linker histone H1
Replication fork activation is enabled by a single-stranded DNA gate in CMG helicase
Diffusion of human replication protein a along single-stranded DNA
A recurrent ZSWIM7 mutation causes male infertility resulting from decreased meiotic recombination
A novel homozygous variant in homologous recombination repair gene ZSWIM7 causes azoospermia in males and primary ovarian insufficiency in females
Prevalence of comprehensive DNA damage repair gene germline mutations in Chinese prostate cancer patients
Homologous recombination-deficient mutation cluster in tumor suppressor RAD51C identified by comprehensive analysis of cancer variants
RAD51D splice variants and cancer-associated mutations reveal XRCC2 interaction to be critical for homologous recombination
The HDOCK server for integrated protein-protein docking
HDOCK: a web server for protein-protein and protein-DNA/RNA docking based on a hybrid strategy
Suicidal cross-linking of PARP-1 to AP site intermediates in cells undergoing base excision repair
PARP1 changes from three-dimensional DNA damage searching to one-dimensional diffusion after auto-PARylation or in the presence of APE1
Sws1 is a conserved regulator of homologous recombination in eukaryotic cells
Single-molecule analysis reveals cooperative stimulation of Rad51 filament nucleation and growth by mediator proteins
Promotion of homologous recombination by SWS-1 in complex with RAD-51 paralogs in caenorhabditis elegans
Dynamics and selective remodeling of the DNA-binding domains of RPA
Mammalian RAD51 paralogs protect nascent DNA at stalled forks and mediate replication restart
Strand annealing and motor driven activities of SMARCAL1 and ZRANB3 are stimulated by RAD51 and the paralog complex
Exploiting replication gaps for cancer therapy
Functional and clinical characterization of variants of uncertain significance identifies a hotspot for inactivating missense variants in RAD51C
Long-term survival of an ovarian cancer patient harboring a RAD51C missense mutation
Raynard, S. & Sung, P. Assay for human Rad51-mediated DNA displacement loop formation. Cold Spring Harb Protoc. https://doi.org/10.1101/2Fpdb.prot5120 (2009)
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Luke Lavis for generously sharing the Janelia Farm HaloTag dyes
The authors would like to thank Artur Karczmarczyk from David Rueda’s lab for helping modulate their scripts to enable our blue and green data analysis
Shixin Liu (Rockefeller University) for providing the AlexaFluor488-RPA protein for use in these studies
is supported by the National Institutes of Health (R01 ES030335 and R01 ES031796)
is supported by the NIEHS [K99/R00-ES033738]
Hillman Postdoctoral Fellowship for Innovative Cancer Research (SRH) [2P30CA047904 to the UPMC Hillman Cancer Center]
and the American Cancer Society Postdoctoral Fellowship (133947-PF-19-132-01-DMC)
NIH [R35ES031638 to B.V.H.]; Hillman Postdoctoral Fellowship for Innovative Cancer Research (M.A.S.) [2P30CA047904 to the UPMC Hillman Cancer Center]
is supported by the National Institutes of Health MIRA R35GM131704
Lumicks C-trap supported by 1S10OD032158-01A1 (B.V.H.)
lab and Refyen TwoMP instrument were supported by the NIGMS R35GM131704 grant
is supported by the University of Pittsburgh Health Sciences Research Fellowship and the National Institute of General Medicine Sciences (1T32GM12274)
Department of Pharmacology and Chemical Biology
University of North Carolina at Chapel Hill
Department of Pathology and Laboratory Medicine
University of Pennsylvania School of Medicine
Department of Biochemistry and Molecular Biology
expressed and purified all recombinant proteins
and SDS-Page analysis of recombinant proteins
performed yeast-two hybrid and western blot analysis
provided C-trap training and aided with data analysis of single-molecule kymograph via shared scripts (Now on the harbor)
performed the clonogenic survival assays with APE1 inhibition
S.R.H and H.L.R performed the clonogenic survival assays with Olaparib
performed western blots of SWSAP1 from Y2H experiments
provided protocols for FRET-based RAD51-based assays and pCH1-RAD51 plasmid
performed mass photometry experiments in M.S
performed single-molecule experiments in B.V.H.'s laboratory using the Lumicks C-trap Instrument
performed cell culture colony quantification
performed cell culture assays to generate HALO-JF503-SWSAP1-SWS1 protein and performed ssDNA binding assays
The authors declare no competing interests
Nature Communications thanks the anonymous reviewer(s) 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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The materials scientist is a leading practitioner of biomimicry
or borrowing and modifying structures that occur organically to fit human needs—like taking inspiration from elephant skin for a new kind of heat-regulating stucco
Yang also developed an adhesive that’s strong enough to hold shelving on walls yet porous enough to be removed if the glue is remoistened
Snail secretion gave her a model to perfect the design
Yang, a materials scientist at the University of Pennsylvania
consults the natural world when looking to solve humanity’s problems
Pharmaceutical companies mine biology to develop drugs and vaccines
Could she do the same thing with engineering
She employs what’s called biomimicry: studying organically occurring structures and rethinking them to inspire new and often more sustainable solutions that meet human needs
Yang says her family didn’t have a lot of money
So by necessity she looked outside for entertainment
“There’s not too many things to explore other than nature,” Yang says
and her mother was a physical education teacher
“That’s why I’m also a sprinter,” Yang says of her prolific pace
While many scientists are wary of speaking about developing theories or unpublished work
Being open during the iterative process also allows her to collaborate with people who have expertise in other fields; she works with biologists
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Even though it may feel like something you can easily skip, to some of us, curling your eyelashes is just as important as putting on your shoes. Since eyelashes come in different textures and shapes
curling them is the best way to look more awake and open up the eye area
it might not be something that feels worth it
Over the years, our team has tried many, many eyelash curlers
To make sure you’re using the best curler out there
we spoke with some beauty experts to share their recommendations
you can also find the eyelash curler I’ve been using for three years straight
➼ Our top picks➼ More tried-and-true options➼ FAQs➼ Experts
2025: Updated prices and checked stock for all products
This one is loved by makeup artists because its eye bed is slightly wider and less round
so it works better on a variety of eye shapes
“It allows you to get up to the lash line without clamping on the eyelid because of its shape and is great for soft
Murphy has been recommending this curler for years and notes that the red band (the rounded crescent that helps shape lashes) enables you to see the lashes better while you curl them
Another great feature is that it comes with an extra red cushion
which will prolong the life of your curler
I agree with Sesnek: While the shape of this curler is wider
and I definitely noticed a more effortless curl after clamping down for about 20 seconds
The natural shape of the curl was something I hadn’t really noticed before with other options on the market
“This is the GOAT for a reason,” says Murphy. “It’s easy to use, and the shape allows you to get as close as possible to the base of the lashes. It has nice spring and is overall perfect.” As a longtime favorite of makeup artists
soft swoop to the lashes rather than an unnatural 90-degree angle
It’s a perfect starter lash curler if you want to try something comfortable that yields instant results
When it comes to rounded shapes, like Sesnek recommends, this sleek Dior curler is certainly a winner. Makeup artist Beau Nelson also swears by it
It’s wrapped on both sides to prevent pinching and pulling
and it’s a favorite among those with rounded and hooded eyes because it curls every single lash
Not only is the shape one of the best and most comfortable
I found myself having to focus on keeping my hand steady
but the rubber on this curler eliminates that issue
I instantly noticed a difference in my lashes after gripping the handles for about 20 seconds
I did a second round with a few extra pumps and I’d say this curler gave the most distinctly curvy shape to my lashes
as someone who prefers length to a complete curl
my lashes were so shaped that they were a bit shorter due to the more defined curl
depending on what you prefer in terms of lash definition
Tweezerman has an extensive line of affordably priced curlers that work just as well as the pricier ones
I found these curlers to be one of the most comfortable in my hands and easy to use
I love that the eyelash pad is silicone instead of rubber
making it a good option if you have sensitive eyes like me (thanks to bad allergies)
I found that it gave me a nice swooped lash after a few pumps
My lashes were curled and evenly coated—but still had a good length—when I applied mascara
The curler itself is a bit wider and does have less of an arch than the Dior or Kevyn Aucoin options above
Great eyelash curlers at a drugstore price point are hard to find
This is one of the best-reviewed and affordable ones on Amazon
with almost 700 reviews and close to a five-star rating
One thing I like about this curler is that the finger holes are made of rubber
which helps to give you that steadier hand
they instruct you to clamp your lashes for just five to ten seconds for the full effect
I think this option is best for daytime use
It creates natural-looking lashes but still gives a fluttery effect
I loved the sturdy grip of the Tower 28 curler
since it allows the best steady-hand precision when it comes to achieving the perfect curl
This is one of the curlers that I noticed an almost-instant wave in the lash upon the first use
it’s a great option for those with sensitive eyes since it’s designed with two hypoallergenic silicon pads that are gentle on the lashes
The first thing I loved about this curler was the ergonomic handles
which are very similar to the handles on the Dior curler
I knew right away that this curler would have a secure grip and perfect squeezing — and it did
The top of the curler features a contoured curve and stronger spring designed to make the curling process as swift as possible
centering my lashes between the top and bottom of the eyelash curler
I didn’t see any distinct results right away
so I did each eye twice (essentially 20 seconds total) and then noticed a subtle but natural swoop
the swoop was further enhanced and the shape held for the entire day
Amazon reviewers are positively ecstatic about this curler
There are close to 9,000 reviews all praising this one as being “the best.” Reviewers rate this one close to five stars and praise it for being easy to use and effective
Former Beauty Director Kathleen Hou describes this curler as “feeling like a hug.” The eye bed is formulated so that it delivers the best curl swoop
one that instantly opens the eye and makes you look more alert
It is so cushiony that it feels like your lashes are resting on their own special pillow (which Murphy calls a “luxurious experience”)
even the handle of the curler is different — it’s double-barreled
which is like a fail-safe that prevents you from over-squeezing or crimping your lashes
Sesnek says that this is their absolute favorite
and it’s clamp makes it easy to get all the lashes — my go-to since it debuted.”
This one has over 1,000 nearly five-star reviews on Sephora praising how well it works on a variety of eye types. Strategist writer Rio Viera-Newton likes it too
It gets close to the lash line without pulling and pinching and keeps lashes curled all day without tons of effort
If you’ve tried eyelash curlers before and have been frustrated at their lack of hold, try a heated one. As scary as they sound, they do hold a curl for longer and are ideal for extensions (mechanical eyelash curlers can damage them). This is one of the highest-ranked ones online, and it’s easy to use — it doesn’t become unbearably hot. You gently press it against the middle of your lashes to give yourself a lash lift
If you are determined to curl every single lash
it won’t snatch your lashes but it will precisely help you curl every single baby lash
even those close to your tear ducts or the edges of your eye
The pink curved section should go on the bottom
Makeup artist Molly Greenwald loves the Pro series from Tweezerman
Although both shapes from the series will work for everyone
she notes that the ProCurl is curvier and more comfortable on rounder eyes
this on-the-go eyelash curler from Japonesque can fit in most of your micro-bags so you’ll always be camera ready — the true definition of tiny but mighty
Behold the favorite eyelash curler of pro makeup artist Adrianna Dryniewicz
especially for smaller or hooded eye shapes
It allows for much more precise curling — perfect for lifting the outer corners or blending natural lashes with individuals
It really grabs all the hard to reach lashes.”
A good eyelash curler has a handle that comfortably fits your fingers and fits well with your eye shape. Makeup artist Quinn Murphy says to make sure all of your lashes fit into the curvature of the device
The best eyelash curler isn’t just comfortable; it ensures that your lashes don’t get pinched
The difference comes down to the eye bed — an inch-long curved strip (often made of silicone) that acts as a resting place for your lashes during the curling process
“It should feel stable and not wobbly when squeezed together
The pads should feel firm but bouncy and easy to use,” says Murphy
Makeup artist Robert Sesnek recommends paying attention to the metal part of the curler that’s opposite the eye bed
“Make sure it isn’t too sharp or thin,” Sesnek says
and rounded shapes tend to be better and safer for your lashes.”
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To devise such complex artworks, Sanxingdui’s artists employed methods new to Bronze Age China. Artisans from the Central Plains cast bronzes, which were mostly used as ritual vessels, in one piece. “The whole-casting method would not have worked for Sanxingdui,” says archaeologist Haichao Li of Sichuan University, “so people became creative.” To craft their more complicated pieces, the artisans of Sanxingdui first cast the artworks’ many individual parts and then welded them together.
The artifacts from Pits 5 and 6 resemble those found in Jinsha more than they resemble those in the other pits at Sanxingdui. This, along with the fact that Pit 6 seems to have been partially cut into Pit 7, has led some archaeologists to conclude that Pits 5 and 6 were likely dug after the other pits and may have served a different ritual purpose. Perhaps, says Ran, people symbolically sacrificed the artifacts in Pits 5 and 6 by burning them.
Lei is now mapping the trade networks that once connected Sanxingdui with the powerful states of the Central Plains to the east and the tribes and nomadic groups to the north. By determining where rare resources such as elephant tusks, gold, and cinnabar originated and tracing the routes used to bring them to Sanxingdui, he hopes to learn how the exchange of materials, technologies, and religious beliefs may have influenced the city’s history.
Slideshow: Unearthing the Sacred Precinct of China’s Lost Bronze Age City
Ling Xin is a writer based in Meigs County, Ohio.
Global Lead Partner
EN • EnglishDE • DeutschES • EspañolFR • FrançaisZH • 繁Welcome
the Net Art pioneer and self-described ‘badass of gender hacking’ has tips for the next generation","url":"https://www.artbasel.com/stories/shu-lea-cheang-tate-modern-performance-london-net-art","image":{"@type":"ImageObject","url":"https://d2u3kfwd92fzu7.cloudfront.net/asset/news/Shu_Lea_Cheang3.png","width":2400,"height":1500}}‘I became an artist accidentally
at the Whitney Museum of American Art in 1990 paved my way to “becoming” an artist
and I was very much supported by curators like John Hanhardt
who gave me a solo show for Those Fluttering Objects of Desire (1992)
which was then included in the Whitney Biennial in 1993
I developed a collaborative mode with performers of diverse racial and gender identities
was a mixed-media installation that featured three industrial washing machines and 12 performers of diverse racial backgrounds
and geek farming as a way to resource the land
‘I have been accepted as a multi-faceted artist
a badass of gender hacking and genre bending
I am blessed by the curators who have trusted me to dive into the “unknown.” When I’m asked what piece of advice I would give to a young artist
I always say: I keep six pots cooking on the stove
some can definitely be presented on the dining table with guests present to enjoy.’
Shu Lea Cheang and Dondon Hounwn, Hagay DreamingTate Modern
Shu Lea Cheang is represented by Project Native Informant (London).
Stephanie Bailey is Conversations Curator at Art Basel Hong Kong.
All photographs by Jan Kräutle for Art Basel.
Technology art pioneers Shu Lea Cheang and Tishan Hsu will join Lawrence Lek, whose immersive and often interactive work draws on gaming technology, to consider what tech and AI has taught them
AttendNFT Collector Matt Zhang on digital art collecting – and how to get involved‘If I could do it again, I would take my time, be more patient, see more art, and meet the artists first,’ says the entrepreneur
ReadShanghai through the eyes of BirdheadThe artist duo shares an exclusive photo essay on the city they are based in
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but that hasn’t stopped her from not just rewriting the record book for Harrison swimming
but adding continual edits on a book that she has near complete ownership of
Shu already owns the school record in five different events and this past Monday was one of the breakout stars of the Hudson County Meet of Champions
Shu left Bayonne’s Lincoln Community Pool with two gold medals
taking first place in both the 200 Yard Individual Medley (2:16.12) and the 500 Yard Freestyle (5:30.15)
who is believed to be the first Harrison girl to win a Hudson County swimming title
is The Observer Athlete of the Week for her latest record setting performances
“There was definitely some adrenaline when I stepped onto the pool deck since I didn’t really know who my competitors were,” said Shu
“She’s got enough experience where she just knew what she had to do and she’s proven that,” Harrison head coach Barry Mattern said
“She knows how to stand up to the take and she gets it done.”
Mattern saw Shu compete at the middle school level
so he knew that if she went to Harrison it would be a game-changer for the program
“I know she is ready to put in the work that it takes to be that good
Besides for the 200 Meter Individual Medley and the 500 Meter Freestyle
Shu also now owns the school records in 200 Yard Freestyle
the 100 Yard Butterfly and the 100 Yard Backstroke
Based on her times with her club program Scarlet Aquatics NJ-Wave
a nationally ranked program based out of Paramus
Shu only needed to take one glance at Harrison’s record board to know that it wouldn’t be long until her name was plastered all over it
I already knew I had the potential to break them since I’ve swum faster at club meets in the past,” Shu said
“It was an exciting moment to see it all come together and officially set those records.”
Shu has goals on the three remaining individual events she hasn’t claimed the records for yet
the 50 and 100 Yard Freestyles and the 100 Yard Breaststroke
her favorite events are the 200 Breast and 400 Individual Medley
but said she “never really took swimming seriously until I was 11.”
in addition to her time in the pool for Harrison
Shu’s times have her already qualified for the state individual tournament in February
but her goals for the rest of her freshman season go beyond individual marks
“My goals for the rest of the season is to help other swimmers improve their technique
There’s no denying that Shu is plenty motivated for the rest of the season and beyond
In case she needs any more in the future though
all she’ll have to do is take a look at the record board at the end of the season
That’s because for as impressive as the times she’s posted this season for the Blue Tide
those are not her own personal bests in those events
“I didn’t break any of my personal bests this season,” said Shu
“But the foundation I’ve built has definitely helped me succeed as a freshman.”
Jason Bernstein joined The Observer as its sports writer in March 2022
He has a wealth of sports-writing experience
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Manhattan shot +27 as a team and trail sixth-place Monmouth University by two strokes
John's University sits in first place at +4
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Air Force travels to Sacred Heart for AHA Quarterfinals
March 7-93/4/2025 9:49:00 AM | Men's Ice Hockey
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College of Arts and Sciences
Seton Hall University Astronomical Observatory
Reverend Forrest Pritchett Honored at SRTF Signature Event
Physician Assistant Graduate Leads with Advocacy and Service
Renovation for New Innovation Hub in Walsh Library
Charter Day: Honoring Service and St. Elizabeth Ann Seton
Chief Judge Michael A. Chagares' 87 Named Keynote Speaker
MaxBoxing caught up with Carrington at Vegas’ Knuckleheads Boxing Gym
Bruce “Shu Shu” Carrington recently moved to 15-0 (9 KOs)
he had an impressive win with a stoppage of rugged Enrique Vivas
More impressive was that Viva’s only 3 losses were to former title challengers
And that is fine with him as he wants to get back in the ring as soon as possible
he wants to contest for a world title before the year is over
MaxBoxing caught up with Carrington at Vegas’ Knuckleheads Boxing Gym a few days after his fight
his out-of-the-ring demeanour contrasts his intense
it was evident that Carrington has his eyes on the prize - that being a world title shot
“I hope to be back in June or July,” he said
“I’d love to have my next fight be for the title
but the way the other champions have fights lined up
realistically late fall or the end of the year is more likely”
then unify and be the first undisputed champion at featherweight," he said
I think (Britain’s undefeated WBA champ) Nick Ball would be a great
although I can adapt to any style and an aggressive guy like him who comes at me is suited to me and would make a great fight."
Carrington is hopeful that Top Rank can get a deal done this year for a world title shot and says he is more outspoken about calling out champions
Asked if he would go to England for a title shot
he welcomed the opportunity but would love to win his title at home
“Of course I’d go anywhere for a title shot”
Can you imagine winning the title in the big room at Madison Square Garden,” he said
STORRS – The quest for a Husky hat trick begins on Wednesday night when the No
3 UConn men's basketball team (0-0) lifts the lid on its 2024-25 campaign at Gampel Pavilion
The back-to-back defending national champions welcome in-state foe Sacred Heart (0-0) to campus for a 7 p.m
The contest will air in its entirety on FS1 with John Fanta and Sarah Kustok on the call
As part of opening night festivities on Wednesday
UConn will unveil its 2024 National Championship banner at Gampel in a pregame ceremony
The banner unveiling is presented by KeyBank*
For fans who are unable to attend the game
the full video of the ceremony will be posted on UConn+ and on the UConn social media channels
UConn Athletics is suggesting that fans be in their seats by 6:20 p.m
to not miss a moment of the banner ceremony
The first 3,500 fans in attendance on Monday night will receive a commemorative National Championship banner rally towel
Fans may purchase tickets on the secondary market through SeatGeek
the official fan to fan ticket marketplace of the Huskies
The Huskies sent four starters to the NBA following the 2024 title, but return a two-year title-winning starter in preseason All-American Alex Karaban (Southborough
Karaban averaged career-highs of 13.3 points and 5.1 rebounds per game and returns to Storrs after testing the NBA Draft waters with a chance to cement a collegiate legacy like no other in the modern era of the sport
Also back for Connecticut is Hassan Diarra (Queens, N.Y.), who emerged as a star in his role last season and won BIG EAST Sixth Man of the Year honors. Samson Johnson (Lome
Togo) returns in the frontcourt after setting a UConn single-season record with a 72.5 field goal percentage and ranking top-five in the country in dunks a season ago
Wash.) will all be relied to play larger roles this season after showing plenty of promise in limited action as freshmen
UConn welcomes five newcomers into the fold with the seven returners, including a pair of high-impact transfers in Aidan Mahaney (Lafayette, Calif.) and Tarris Reed Jr. (St
Mahaney was a two-time All-Conference selection in his two seasons at Saint Mary's and earned Preseason All-BIG EAST Third Team honors
Reed comes to Storrs after two years at Michigan
where he was a regular starter in the B1G as a sophomore
Pa.) round out the rookie class and enter the fray as consensus four-star recruits
Sacred Heart began its season on Monday night
Tanner Thomas led the Pioneers with 22 points and Bryce Johnson posted a 10-point
The Huskies will play another challenging non-league slate before conference play begins in late December
Connecticut will take part in the loaded 2024 Maui Invitational before facing top-10 foes Baylor and Gonzaga in December
The next home game after Wednesday's opener will be the XL Center debut on Saturday
KeyCorp's roots trace back nearly 200 years to Albany
Key is one of the nation's largest bank-based financial services companies
with assets of approximately $188 billion at September 30
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3at2Sacred Heart University
3/8/2025 8:45:00 PM | Men's Ice Hockey
1at4Sacred Heart University
3/9/2025 7:23:00 PM | Men's Ice Hockey
Listen to the latest episode of the “Detroit Evening Report” podcast
we’re reflecting on some of the stories we’ve reported on at WDET this year that show how special the people and places in our community truly are
We also share some news about what’s happening in the community over the holidays
Today, we hear some of WDET reporter Bre’Anna Tinsley’s conversation with Mama Shu — the founder and CEO of Avalon Village — about a summer program she started called “Hood Camp.”
Do you have a community story we should tell
Let us know in an email at detroiteveningreport@wdet.org
WDET is a community service of Wayne State University
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a fighter may evolve from being a touted prospect to a title contender
and hopefully from a champion with long-lasting success to an all-time legend
Each fighter approaches these transitions differently
with some able to leapfrog levels based on their skills
There are a few fighters ready to take a step
They have career trajectories and timelines to get championship opportunities very soon
We will focus on Bruce "Shu Shu" Carrington
who are scheduled to fight in the next two months
These are just six of the fighters that have recently graduated from prospects and find themselves at the critical place of contender status
Let's dive into each fighter's potential for the next phase of his journey to becoming world champion
like a chameleon skillfully changing its appearance to outwit predators
The combination of ring intelligence and technical insight distinguishes him as one of the most naturally talented fighters in the sport
Davis excels at physically manipulating his opposition's posture
forcing them into disadvantageous positions to punish them
He sets up attacks and flourishes off his educated jab
evading attacks with elusive head movement while delivering precise counters
allowing him to exploit openings created by his opponents when throwing punches
Davis can neutralize aggressive fighters through lateral traps
momentum-slowing clinches and punishing body punches to drain their resolve
sensing weakness or nervous energy in his opponents and capitalizing on it by finishing them abruptly when he chooses
His mastery of distance control and positioning further enhances his complexity as a fighter
His blend of intelligence and instinct sets him apart in boxing
Davis stands out as the top young contender
"Maturity" is the first word that comes to mind when I think of Carrington
a hotbed for boxing talent that has produced legends such as Mike Tyson
This maturity manifests in his decision to resist turning professional to allow his body to catch up with his mind
A wave of calmness can be witnessed from Carrington in his style
where many fighters fold under pressure and lack close-quarters combat skills
Carrington's ability to remain composed allows him to navigate tight spaces confidently
utilizing his catch-and-shoot skills to land powerful counters while evading incoming traffic
weaving and rolling shots showcases his defensive awareness and enhances his offensive capabilities
Carrington has earned must-watch contender status by delivering a combination of speed
power and technical proficiency that makes him a serious threat to any champion
His lightning-fast hands allow him to deliver devastating punches before opponents can react
while his exceptional positioning keeps him elusive and hard to hit
adapting to different styles and strategies and outmaneuvering seasoned opponents with flavor
remaining sharp and focused even in intense moments
which allows him to execute his game plan flawlessly
Carrington ensures he can maintain a high pace throughout the fight
wearing down his opposition and capitalizing on their tendencies
His reputation as a rising star makes him a force that champions cannot underestimate
Zayas has quickly transitioned into a highly-rated contender in the boxing world
His impressive average of 65 punches thrown per round (per CompuBox) embodies his acute thinking
conditioning and ability to maintain a high fight pace that keeps opponents on the defensive
delivered with precision to the body and head
adds a powerful dimension to his offensive arsenal
allowing him to break through tight defenses and turn the assumed brave opponents into respectable characters
His quick second-level step (a second transition of offense after offense) into range creates openings for follow-up attacks
enabling him to win 50/50 exchanges that can define the outcome of a battle
Zayas is well-taught at cutting angles and weaving under incoming punches
allowing him to land counters with efficiency
His ability to slip punches shows his understanding of timing and distance
which helps him draw reactions from opponents and set up his offense
This combination of attributes positions Zayas as one of the most sought-after contenders with the potential for championship glory
establishing himself as a force in the lightweight division with an aggressive style that combines top skills with remarkable physical attributes
with a long reach for the division that leverages his southpaw stance and helps him control distance while employing precise power punches
His hand speed complements his well-rounded arsenal
making him a dangerous fighter every second in the ring
With an instinct for timing and counterpunching
believing in his chin and anticipating their moves
often leaving opponents overwhelmed and open for his sharp
which he describes as an "appetite for smoke," reveals his mindset as a fighter who thrives under pressure and is always ready to take on the toughest challenges
Mason's trajectory in the division suggests he is on the fast track to becoming a top contender and then quickly a champion
tactical and technical style could soon lead him to the mountaintop against established names in the division such as Shakur Stevenson
Mason can make a huge impact and become one of the sport's new young superstars
the conqueror of the talented Keyshawn Davis in the amateurs (Cruz is 4-0 over Davis
including a win in the Tokyo Olympics final)
is making colossal waves in his boxing career as he transitions into the professional arena
father and trainer of welterweight champion Jaron "Boots" Ennis
Cruz is quietly honing his skills and improving his fighting style for the pro ranks
His unique "loose goose" style and approach leave opponents bewildered
as it seems they are getting hit by four hands instead of two as he maneuvers in and out of range
His approach is reminiscent of water flooding: swift
Cruz has already tackled the demanding challenge of fighting 10 rounds despite having only four professional fights
allowing him to outposition even the most seasoned veterans
Cruz has burst onto the scene with remarkable speed and established himself as a serious contender
Cruz's ability to seamlessly switch stances
As he continues to build and refine his craft
this lightweight sensation can elevate the sport to new heights
capturing attention and admiration as he trends upward in his boxing career
"The Transformer" Isley has undoubtedly improved and evolved into an under-the-radar contender in the middleweight division
Isley embodies the trait of a pocket fighter
exploding violently in the trenches with combinations while putting forth an eye-for-an-eye mentality
changing his tactics from slugger to boxer
and to break down opponents with skill and pinpoint accuracy created by his defense reveals his ring smarts
Isley compensates with an extraordinary heart and mental fortitude
allowing him to engage ferociously and take calculated risks
But what truly sets Isley apart is his mental toughness
honed through grueling seven-day-a-week workouts and a commitment to pushing his limits
He has transformed training challenges into strengths
developing into a fighter capable of dissecting opponents from a distance
His physical strength is a psychological weapon
Isley is coming up in the middleweight division
proving the doubters wrong with skill and heart
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Game Recap: Women's Basketball | 1/25/2025 10:57:00 PM
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You’re a badass #girlboss and we understand you’re always on the go
to help you get out of the house even faster
we’re bringing you the newest hair product that’ll change your life
It cuts your blow dry time down to basically nothing
and if that hasn’t convinced you… the below info will
What It’s Called: Shu Uemura Straightforward Time-Saving Blow Dry Oil
How Much Will It Set You Back? The cost of that on-sale scarf you’ve been coveting, or $39 available at shuuemuraartofhair-usa.com
Admit It, Teyonah Parris Had the Best Hair of 2015
Why You Care: This is the official time-saver for busy ladies like yourselves
This blow-dry oil was developed to cut your blowdrying time in half without sacrificing the end result
It’s *~special*~ because it uses the same gliding agents found in your foundation
The ingredients invisibly coat each strand—which allows your ‘do to look flat ironed
When to Use It: Use this product on wet or dry hair before you blow dry
What the Experts Are Saying: “Straightforward is the perfect aid to prep the hair fiber when a silky smooth, frizz free, soft blow dry is desired! The shine is beautiful and doesn’t weight the hair down—Black Cumin Oil truly nourishes the hair fiber and protects it from the blow drier and tools while sealing the cuticle down for a soft, radiant finish.” -Travis Valdez, senior stylist at Salon Thalia
The story originally appeared on MIMI.com
National Geographic has launched its inaugural 33 initiative
spotlighting 33 extraordinary individuals who are making strides toward solving the world’s most urgent challenges
This esteemed list includes a diverse group of trailblazers—climate activists
and athletes—recognized not only for their innovative ideas but also for their active efforts to create a better future for our planet
Among these honorees is Dr. Shu Yang
celebrated for her pioneering work in ocean conservation
Yang’s groundbreaking contributions in designing artificial reefs are helping to restore marine ecosystems
rebuild habitats damaged by coral degradation
and support biodiversity in areas facing environmental stress
Yang about this recognition and to learn about her work
Innovation & Tech Today: What does it mean to you to be chosen as one of National Geographic’s 33
especially for your work with reef structures and ocean conservation
super excited because we love National Geographic and all of their videos
I just can’t wait to be recognized as one of National Geographic’s 33
I&T Today: Can you explain how your artificial reefs work and how they help the ocean
Yang: This is actually a brand new project we just started about two years ago, in collaboration with architects. We had several other collaborations with architects, but this one started when GLE proposed a solicitation for carbon absorption in buildings
My architectural collaborator and I proposed the idea of printing carbon-absorbing concrete
which led to the development of this concrete printing project
we’re constantly thinking about what else we can do
We put together a proposal to focus on the reef
extreme weather and abnormal ocean tides have been causing damage to biodiversity on reefs
There are two main goals with our project:
We’re designing different types of reef structures, figuring out the right materials, and consulting with people from organizations like the Nature Conservancy to determine what will help corals and oysters grow
Corals and oysters need something hard to attach to
and we’re figuring out how to create materials that not only encourage attachment but also withstand extreme weather conditions and high waves
One of my PhD students got a grant from Florida to help develop these reef structures
and now I have a postdoc working on the 3D printing aspect
All these efforts are driven by a real need in society
and we’re excited to make a real impact
I&T Today: You mentioned 3D printing, which is awesome. Can you explain more about how that technology works for creating artificial reefs
Yang: 3D printing itself isn’t new; it’s been around for many years
3D printing with concrete is still a relatively new concept
Most 3D printing involves extruding polymers
it’s trickier because concrete requires water to mix with powder and form a paste
we use robotic arms to extrude the material in such a way that it retains its shape
This reduces the need for scaffolding and minimizes material waste
which are strong but use up to 30% less material
The goal is to use less material and reduce waste
while also developing concrete that can absorb CO2
We’ve already successfully 3D printed CO2-absorbing concrete
and we’re excited to see where we can take this technology next
I&T Today: What’s one thing you want people to understand better about your work after this recognition
I often feel the need to prioritize my own discipline
material science is highly interdisciplinary
and electrical engineering can all come together to create new materials
What I want to promote is the importance of material science
which is not just about the materials themselves but also about bringing people from diverse backgrounds together to drive innovation
I&T Today: What’s next for your research on artificial reefs
Is there any new technology you’re excited about
Yang: There are many different directions we’re exploring with the reefs
Reefs play an important role in both the economy and the ecosystem
We’re also looking at how to address issues like hurricanes
especially in places like New York City or Florida
I’m particularly interested in combining hard materials with soft biological systems to create a more robust ecosystem
oysters play a key role in cleaning the ocean
pristine oyster reefs are nearly nonexistent in the U.S
except in places like Hawaii and Australia
The future of reef conservation involves understanding the ecosystem
I’m especially excited to work with robotics experts who can send sensors or robots into the water to detect coral
which will help us develop better reef systems
We’re also exploring the idea of growing oysters vertically
which uses less space and might be more natural for their growth
I&T Today: What inspired you to work on artificial reefs
Yang: Our work on artificial reefs began with mechanical engineers
especially those who worked with microfluidics
We collaborated with engineers who could create systems to mimic the ocean and test the structures we designed
We also worked with biologists to understand how to seed the reefs with coral larvae or oysters
I believe material scientists play a central role in bringing people together
and others to understand their needs and collaborate toward a solution
Our work is truly interdisciplinary—there’s no single discipline that can solve these problems on its own
I&T Today: What advice would you give to young scientists or innovators who want to solve environmental problems
but you can make a meaningful difference by taking small steps
It’s important to stay motivated and excited about your work
Many ideas come from synthesizing your experiences and thoughts over time
It’s not about having a sudden “brilliant idea”; it’s about learning
Lindsey Feth is the Managing Editor for Innovation & Tech Today
She graduated with a degree in Journalism and Media Communications from Colorado State University
Lindsey specializes in writing about technology
A monthly overview of things you need to know as an architect or aspiring architect
View an example
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Live from the QCon San Francisco Conference
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emphasizing the importance of deploying ML models effectively
leveraging collaborative tools for prototyping
and aligning team roles with the ML life cycle to create scalable AI solutions
Solve your dev challenges with insights you can trust. Register now at InfoQ Dev Summit (June 9-10, 2025).
Roland Meertens: Welcome to The InfoQ Podcast. We are live at QCon in San Francisco, and I'm joined by Susan Shu Chang, who is working at Elastic as a principal data scientist.
At QCon San Francisco she is hosting the track AI and Machine Learning for Software Engineers: Foundational Insights. Welcome to The InfoQ Podcast.
Susan Shu Chang: Yes, thank you for having me.
Roland Meertens: So should we go over what the talks were, which you had in the track, and which ones you liked, or what's overall foundational insights you were hoping to instill in the attendees?
So just in summary, I wanted to cover various areas because the engineers here, they're working at all these companies that definitely use machine learning, and they have definitely been adjacent to it or heard of these techniques, but I wanted to help them bring concrete example from people who have been doing it on the machine learning side, but also help them understand, just behind the scenes, how this is working.
Roland Meertens: Yes, so there are, especially, for example, the recommender in search engines. I think the talk by Netflix was very interesting, about how to get better recommendations and really tailor them to specific people.
Roland Meertens: That was great. Also, you mentioned reinforcement learning. That was also very interesting, that some people who are working in Meta came up with an idea on how to use long-term interaction and see it as a reinforcement learning problem.
Roland Meertens: Are there any specific tools you would then recommend to people, or any specific topic you would recommend someone to look at first if they want to get into machine learning now?
Roland Meertens: Was it in your track that someone talked about how to actually get your model deployed? So-
Susan Shu Chang: Yes, the speaker from Grammarly was talking about common pitfalls that prevent machine learning models from getting into production. And actually a lot of the challenges have to do with finding the right problem, and communicating with management, and finding the right solutions as well. And that's actually something for me, as a principal data scientist, I do a lot at work too, which is find out what is overkill and what is more practical.
Roland Meertens: Yes. So do you think that in terms of AI machine learning nowadays, there's a lot of tools on the market, especially with this GenAI, everyone can call the GPT-4 API now, do you think it's still good to have a prior knowledge about AI, machine learning, specifically, understand how these models work? Or do you think it's now open to everyone?
Roland Meertens: Yes, but do you have a feeling that if people don't understand what's really happening, that it's setting them up for failure? So if someone doesn't understand what a embedding is, then maybe their retrieve for augmented generation becomes a bit harder-
Roland Meertens: ... if you just treat Elastic as a magical black box, which gives you some random documents back.
Susan Shu Chang: Yes, Yes, that's a good point. I think that's a good way you put it, which is it's easy to build an MVP. It's difficult to debug unless you know how it works. So I think that's where it's important to know about the fundamentals. It's important to know about how these various tools and techniques are working. Yes, so it was for if you want to tweak, tune and debug, that's where that comes in.
Roland Meertens: Yes. I think in general, often in software, the MVP is easy.
Roland Meertens: Actually getting it to deliver value to your customer seems to be the harder aspect.
Roland Meertens: So, Yes, given that you work at Elastic, are you then mostly working on tools for generative AI, or other aspects as well?
So that's thanks to the Elastic Common Schema and the fact that people love to ingest their data into Elastic. So that's one part that we own, and the other part is augmenting the AI assistant piece.
Susan Shu Chang: So as I mentioned that the engineering team we're able to build out the AI assistants by themselves, and then we'll conduct tasks like evaluation or research, R&D, into what other functionality can be added into this. We have to prove out that it actually works before we can add it into the product. Yes.
Roland Meertens: What do you mean that you have to prove that it works? How do you prove that it works?
So we did an R&D project where we grabbed real logs that we had, and then we did some data preprocessing. We tried different ways of preprocessing the data. We fed basically these logs through a large language model and see if the large language model's able to summarize from these logs that maybe the user SSH'd into here. They ran these commands. What did these commands do? They're not just spitting it out.
Roland Meertens: Yes, but these logs can be extremely large, right?
Roland Meertens: So the context window has to be very big as well.
Susan Shu Chang: Yes. That's one thing we had to do. We did a few things to narrow down the content that we're feeding into the language models. So at the time, of course, I think 4o, we're using GPT-4o, and then that had a larger window. Oh, and we tried the Gemini one, which had a huge, I forgot, 1 million, was it?
Roland Meertens: As in they would summarize what the user did in the session?
Susan Shu Chang: Yes. Yes, we had a bit of, almost like a survey, like what did you think that they did, or what do you think was the relevant piece in these logs? And things like that. And then we compared that to the response that the large language model was giving. Yes, so-
Roland Meertens: Yes, and also the AI tools and the AI methods are going so fast nowadays. It's really hard to know what the next big thing is, or how you have to adapt your database to make such work faster or better. It's quite difficult. Are there any specific algorithms or tools which you would recommend people to start with if they are starting with machine learning, or anything specifically they should try?
Susan Shu Chang: I think these days for creating some GenAI MVPs, I think a lot of people starting out, they're using the tools like Streamlit. So that's a, I guess it's a very... I don't know how to describe it.
Roland Meertens: It's a front-end for Python.
Susan Shu Chang: Yes. Yes, Yes. Very abstracted front-end, where they put all the boilerplate into... Wrapped it all up, so it can create-
Roland Meertens: Serving of your function as a website.
Susan Shu Chang: Yes. Yes, exactly. So people can create a interactive chatbot with a few lines of code. It could have a drop-down for some basic responses or built-in templates, and then you can have a input box. I don't know how it is in web dev terminology, where you type.
Roland Meertens: Yes, and also convincing other people to run a Python script and have the right dependencies always takes more time than just sending them the URL to your local Streamlits.
Susan Shu Chang: Yes. Yes, exactly. Yes. So that's a tool I think has been useful. Really, it's more at the toy learning, right? But it's got to start somewhere.
Susan Shu Chang: Yes, Yes, not building some gigantic, end-to-end for your learning project. Definitely not.
Roland Meertens: Yes. Yes, no, I also use it quite a lot. I really like it. Any other tools you recommend then, or-
Roland Meertens: Yes. Yes, and then also that way you can really have your Python function finally as a service, or as an API people can call.
Roland Meertens: That's quite nice. You also wrote a book, Machine Learning Interviews. How did you come up with the idea to write that?
Roland Meertens: Did you spend a full-time year on it, or did you do it during your spare time?
Susan Shu Chang: Yes. Yes, I think it's a lot of time management. So three to five hours a week, sometimes more, sometimes less. But I would say, I'm more like a slow and steady person, which is I just do a bit, do a bit, do a bit, and I prefer not to crunch on the book.
Susan Shu Chang: Yes, so it's less stressful, but it was a lot of time management and energy management too.
Roland Meertens: Yes. Interesting. So if people are listening to this and they have an interview upcoming, is there a fixed set of skills nowadays which everybody needs to master, or is it still, does it depend on where you're applying and what kind of machine learning job you're applying for?
Susan Shu Chang: Oh, I think one mistake that might be made is focusing maybe a lot on the specific tooling. So when I'm reviewing resumes and when I'm the interviewer, let's say, they mentioned they use PyTorch. So in my mind, I'm literally equating that to TensorFlow and some other tools.
Roland Meertens: Yes. Okay. So the tip is to not focus on specific tooling, but focus more on engineer skills.
Roland Meertens: Yes, and then maybe as a last question, if there are companies who are setting up the machine learning interview, do you have any tips for what questions they should ask, or what they should focus on, or how they should structure their interviews better?
Roland Meertens: They don't have a space for the unicorn.
Roland Meertens: Yes, so more like the breadth of skills rather than just a narrowness only on focusing model training.
And, oh, another thing, I have some more thoughts, actually, because for even larger companies, there's definitely more specialization happening. So let's say someone can go really, really deep on model training. They're a research scientist or something. So there's definitely exceptions where maybe they don't need to know as much about the deployment process, but it still differentiates them. It will differentiate them given another candidate with the exact same skills.
Susan Shu Chang: ... but our team has two broad sections. One requires more, let's say, ops skills, and one requires more of the ML modeling skills. So at each time we're hiring, we'll hire someone who might fit one profile more, the other profile more. So what makes an ideal candidate today might not be the ideal candidate next month if we're hiring for the other profile, because we know what we need on this team and we know what we're missing right now.
Roland Meertens: Yes, in terms of luck, it's just about too, is there a good fit, right?
Roland Meertens: And I think the fit is less clear for machine learning jobs than it is for development jobs.
Roland Meertens: But in that sense, maybe we just don't have enough specializations yet, unless people want to apply as prompt engineer, then... Yes.
Roland Meertens: Thank you very much, Susan, for joining The InfoQ Podcast and joining us at QCon San Francisco, and hope you have a good time.
Susan Shu Chang: Yes. Thanks again for having me.
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Battle for "SHU"premacy Monday in Walsh Gym12/8/2024 3:32:00 PM | Women's Basketball
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Connecticut-based Sacred Heart University officially opened its newly renovated and expanded campus here on March 28
This marks a significant milestone in the university’s two-decade-long commitment to higher education and community engagement in the region
The campus, known locally as Ollscoil An Chroí Naofa and informally as SHU Dingle
will welcome students into its new state-of-the-art facilities following years of sustained growth
Sacred Heart University has maintained a study abroad presence in Dingle since 2004 operating out of the Díseart Centre of Irish Spirituality and Culture
welcoming participants from Sacred Heart as well as from a variety of other U.S
Students engage in immersive semester-long and short-term study abroad programs taught largely by local instructors
Course offerings span such disciplines as Celtic religious traditions
SHU Dingle serves as a vital source of employment for faculty and staff, who not only provide high-quality instruction and administrative support but also engage in innovative research initiatives such as the Deep Maps Corca Dhuibhne project, the Dingle Watershed and Weather Tracking Project and the John Moriarty Institute
Sacred Heart University acquired the former Christian Brothers School in Dingle
undertaking a comprehensive restoration to transform the site into a premier higher education facility
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CNN (CNN) — Former Vice President Mike Pence said Sunday while receiving the John F
CNN (CNN) — Former Vice President Mike Pence said Sunday while receiving the John..
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