gebhart/patrepeval huggingface dataset:
Pathway-Enriched Gene Signature Associated with 53BP1 Response to PARP Inhibition in Triple-Negative Breast Cancer (2017)

Effective treatment of patients with triple-negative (ER-negative, PR-negative, HER2-negative) breast cancer remains a challenge. Although PARP inhibitors are being evaluated in clinical trials, biomarkers are needed to identify patients who will most benefit from anti-PARP therapy. We determined the responses of three PARP inhibitors (veliparib, olaparib, and talazoparib) in a panel of eight triple-negative breast cancer cell lines. Therapeutic responses and cellular phenotypes were elucidated using high-content imaging and quantitative immunofluorescence to assess markers of DNA damage (53BP1) and apoptosis (cleaved PARP). We determined the pharmacodynamic changes as percentage of cells positive for 53BP1, mean number of 53BP1 foci per cell, and percentage of cells positive for cleaved PARP. Inspired by traditional dose-response measures of cell viability, an EC<sub>50</sub> value was calculated for each cellular phenotype and each PARP inhibitor. The EC<sub>50</sub> values for both 53BP1 metrics strongly correlated with IC<sub>50</sub> values for each PARP inhibitor. Pathway enrichment analysis identified a set of DNA repair and cell cycle-associated genes that were associated with 53BP1 response following PARP inhibition. The overall accuracy of our 63 gene set in predicting response to olaparib in seven breast cancer patient-derived xenograft tumors was 86%. In triple-negative breast cancer patients who had not received anti-PARP therapy, the predicted response rate of our gene signature was 45%. These results indicate that 53BP1 is a biomarker of response to anti-PARP therapy in the laboratory, and our DNA damage response gene signature may be used to identify patients who are most likely to respond to PARP inhibition. <i>Mol Cancer Ther; 16(12); 2892-901. ©2017 AACR</i>.
Jet-like correlations with neutral pion triggers in pp and central Pb–Pb collisions at 2.76 TeV (2016)

We present measurements of two-particle correlations with neutral pion trigger particles of transverse momenta 8 < p trig T < 16 GeV/c and associated charged particles of 0.5 < p assoc T < 10 GeV/c versus the azimuthal angle difference at midrapidity in pp and central Pb-Pb collisions at s NN = 2.76 TeV with ALICE. The new measurements exploit associated charged hadrons down to 0.5 GeV/c, which significantly extends our previous measurement that only used charged hadrons above 3 GeV/c. After subtracting the contributions of the flow background, v 2 to v 5 , the per-trigger yields are extracted for | | < 0.7 on the near and for | | < 1.1 on the away side. The ratio of per-trigger yields in Pb-Pb to those in pp collisions, I AA , is measured on the near and away side for the 0-10% most central Pb-Pb collisions. On the away side, the per-trigger yields in Pb-Pb are strongly suppressed to the level of I AA 0.6 for p assoc T > 3 GeV/c, while with decreasing momenta an enhancement develops reaching about 5 at low p assoc T
Tessellation of a stripe (2006)

This paper describes enumeration of a class of topologically distinct periodic divisions of a stripe. Optimization of the geometry of these periodic tilings--optimization that yields minimum total perimeter of the tiles--gives a set of physically plausible periodic structures of monodisperse, two-dimensional foams bounded by two parallel walls. Evaluation of the minimum total perimeters of the lattices that we enumerated suggests two possible lower bounds for the mean perimeter of tiles forming periodic coverings of a stripe.
Block Truncation Coding (2009)

In block truncation coding (BTC), an image is segmented into n x n (typically, 4 x 4) nonoverlapping blocks of pixels, and a two-level (one-bit) quantizer is independently designed for each block. Both the quantizer threshold and the two reconstruction levels are varied in response to the local statistics of a block. Thus, encoding is essentially a local binarization process, and the representation of a block consists of an n x n bit map indicating the reconstruction level associated with each pixel and overhead information specifying the two reconstruction levels. Decoding is the simple process of placing the appropriate reconstruction value at each pixel location as per the bit map. A diagram of the basic BTC scheme is shown in Fig. 11.1.
Vaginal microbiome-host interactions modeled in a human vagina-on-a-chip (2022)

ABSTRACT Background A dominance of non-iners Lactobacillus species in the vaginal microbiome is optimal and strongly associated with gynecological and obstetric health, while the presence of diverse obligate or facultative anaerobic bacteria and a paucity in Lactobacillus species, similar to communities found in bacterial vaginosis (BV), is considered non-optimal and associated with adverse health outcomes. Various therapeutic strategies are being explored to modulate the composition of the vaginal microbiome; however, there is no human model that faithfully reproduces the vaginal epithelial microenvironment for preclinical validation of potential therapeutics or testing hypotheses about vaginal epithelium-microbiome interactions. Results Here, we describe an organ-on-a-chip (Organ Chip) microfluidic culture model of the human vaginal mucosa (Vagina Chip) that is lined by hormone-sensitive, primary vaginal epithelium interfaced with underlying stromal fibroblasts, which sustains a low physiological oxygen concentration in the epithelial lumen. We show that the Vagina Chip can be used to assess colonization by optimal L. crispatus consortia as well as non-optimal Gardnerella vaginalis -containing consortia, and to measure associated host innate immune responses. Co-culture of the L. crispatus consortia was accompanied by maintenance of epithelial cell viability, accumulation of D- and L-lactic acid, maintenance of a physiologically relevant low pH, and down regulation of proinflammatory cytokines. In contrast, co-culture of G. vaginalis- containing consortia in the Vagina Chip resulted in epithelial cell injury, a rise in pH, and upregulation of proinflammatory cytokines. Conclusion This study demonstrates the potential of applying human Organ Chip technology to create a preclinical model of the human vaginal mucosa that can be used to better understand interactions between the vaginal microbiome and host tissues, as well as to evaluate the safety and efficacy of live biotherapeutics products.
Real-time battery thermal management for electric vehicles (2014)

Electric vehicles (EVs) are powered by a large number of battery cells, requiring an effective battery management system (BMS) to maintain the battery cells in an operational condition while providing the necessary power efficiently. Temperature is one of the most important factors for battery operation, and existing BMSes have thus employed simple thermal management policies so as to prevent battery cells from very high and low temperatures which may likely cause their explosion and malfunction, respectively. In this paper, we study thermo-physical characteristics of battery cells, and design a battery thermal management system that achieves efficiency and reliability by active thermal controls. We first analyze the effect of a temperature change on the basic operation of a battery cell. We then show how it can cause thermal and general problems, e.g., a thermal runaway that results in explosion of battery cells, and unbalanced state of charge (SoC) that degrades battery cells' performance. Based on this understanding of thermal behavior, we finally develop temperature-control approaches which are then used to design a battery thermal management system. Our simulation results demonstrate that the proposed thermal management system improves battery performance by up to 58.4% without compromising reliability over the existing simple thermal management.
Transition from Excitonic Tunneling to Free Carrier Tunneling in GaAs/AlGaAs Double Quantum Wells (2007)

Nonresonant carrier tunneling has been studied as a function of temperature in GaAs/AlGaAs double quantum wells (DQWs). Time-resolved pump and probe reflectance measurements allow the direct observation of tunneling at any temperature between 15 K and room temperature. We found that for two DQWs with different barrier thicknesses, the tunneling time abruptly decreases above a critical temperature while it remains almost constant below the critical temperature. This critical temperature is shown to correspond to the exciton binding energy. Rate equation analysis explains this behavior as the thermalization of excitons into free electrons that have a faster tunneling time than excitons.
Interleukin-7 induces the proliferation of normal human B-cell precursors (1991)

In the present study, we investigated the effects of human recombinant interleukin-7 (IL-7) on the proliferation of enriched hematopoietic cells isolated from human adult and fetal bone marrow (BM). In cultures of CD34+ cells, IL-7 was found to induce dose-dependent incorporation of 3H-thymidine (3H-TdR), but had no demonstrable effect on the development of myeloid colony-forming cells. Numbers of B-cell precursors (BCP), initially present within CD34+ populations and which included a CD34+CD20+ subset, were significantly increased when CD34+ BM cells were cultured in the presence of IL-7. This effect was most striking on CD20+ BCP, and resulted at least partly from higher numbers of cycling cells as indicated by Hoechst 33342 fluorescence (Calbiochem, Behring Diagnostics, La Jolla, CA). These results indicate that IL-7 promotes the growth of BCP within the CD34+ compartment. In line with the B-lineage affiliation of CD34+ target cells, committed BCP (CD10+ CD19+ surface IgM-) isolated from BM were also found to proliferate in response to IL-7. Interestingly, this effect of IL-7 was strongly potentiated by the addition of IL-3. Taken together, and in accordance with previous observations on murine cells, our data indicate that IL-7 acts as a growth factor during the ontogeny of human B lymphocytes.
In utero gene editing for monogenic lung disease (2019)

Monogenic lung diseases that are caused by mutations in surfactant genes of the pulmonary epithelium are marked by perinatal lethal respiratory failure or chronic diffuse parenchymal lung disease with few therapeutic options. Using a CRISPR fluorescent reporter system, we demonstrate that precisely timed in utero intra-amniotic delivery of CRISPR-Cas9 gene editing reagents during fetal development results in targeted and specific gene editing in fetal lungs. Pulmonary epithelial cells are predominantly targeted in this approach, with alveolar type 1, alveolar type 2, and airway secretory cells exhibiting high and persistent gene editing. We then used this in utero technique to evaluate a therapeutic approach to reduce the severity of the lethal interstitial lung disease observed in a mouse model of the human <i>SFTPC<sup>I73T</sup></i> mutation. Embryonic expression of <i>Sftpc<sup>I73T</sup></i> alleles is characterized by severe diffuse parenchymal lung damage and rapid demise of mutant mice at birth. After in utero CRISPR-Cas9-mediated inactivation of the mutant <i>Sftpc<sup>I73T</sup></i> gene, fetuses and postnatal mice showed improved lung morphology and increased survival. These proof-of-concept studies demonstrate that in utero gene editing is a promising approach for treatment and rescue of monogenic lung diseases that are lethal at birth.
Long‐Lived States to Monitor Protein Unfolding by Proton NMR (2011)

The relaxation of long-lived states (LLS) corresponds to the slow return to statistical thermal equilibrium between symmetric and antisymmetric proton spin states. This process is remarkably sensitive to the presence of external spins and can be used to obtain information about partial unfolding of proteins. We detected the appearance of a destabilized conformer of ubiquitin when urea is added to the protein in its native state. This conformer shows increased mobility in the C-terminus, which significantly extends the lifetimes of proton LLS magnetisation in Ser-65. These changes could not be detected by conventional measurements of T(1) and T(2) relaxation times of protons, and would hardly be sensed by carbon-13 or nitrogen-15 relaxation measurements. Conformers with similar dynamic and structural features, as revealed by LLS relaxation times, could be observed, in the absence of urea, in two ubiquitin mutants, L67S and L69S.
A New Method of Preparing Monolayers on Silicon and Patterning Silicon Surfaces by Scribing in the Presence of Reactive Species (2001)

Here we describe a new and simple method for preparing alkyl monolayers on silicon, which consists of mechanically scribing oxide-coated silicon while it is wet with 1-alkenes or 1-alkynes (neat or in inert solvents) under ambient conditions. X-ray photoelectron spectroscopy, time-of-flight secondary ion mass spectrometry, wetting data, and stability tests suggest covalent bonding of unsaturated species to exposed silicon surfaces. Enclosures (hydrophobic corrals) made by scribing silicon that is wet with unsaturated hydrophobic species hold droplets of water and liquids with substantially lower surface tensions. Wetting tests suggest that 1-alkynes make better hydrophobic corrals than 1-alkenes, and theoretical results suggest it should be more difficult for alkyl chains of chemisorbed 1-alkenes to pack than those of 1-alkynes. Underivatized interior regions of hydrophobic corrals are functionalized with polyelectrolyte multilayers. Theoretical energies for water and methanol droplets (gravitational and surface) in hydrophobic corrals are calculated, and a model of failure of liquid droplets in hydrophobic corrals is presented.
Impact of similarity threshold on the topology of molecular similarity networks and clustering outcomes (2016)

We observed that the average clustering coefficient versus similarity threshold function can be characterized by the presence of a peak that covers a range of similarity threshold values. This peak is preceded by a steep decline in the number of edges of the similarity network. The maximum of this peak is well aligned with the best clustering outcome. Thus, if no reference set is available, choosing the similarity threshold associated with this peak would be a near-ideal setting for the subsequent network cluster analysis. The proposed method can be used as a general approach to determine the appropriate similarity threshold to generate the similarity network of large-scale molecular datasets.
Anti-(human immunodeficiency virus) activity of polyoxotungstates and their inhibition of human immunodeficiency virus reverse transcriptase (1995)

Heteropolyoxotungstates of the Keggin class containing different heteroatoms were tested for inhibition of two strains of human immunodeficiency virus 1 (HIV-1); they exhibited varying antiviral activity. Compounds containing boron were inactive, only one of those containing phosphorus showed selective anti-viral activity, whereas all silicon-containing compounds exhibited significant anti-viral activity in C8166 cells infected with the IIIB strain. Their effectiveness was some 10-fold higher in JM cells with selectivity indices of about 2000. The silicotungstates were effective inhibitors of HIV reverse transcriptase, showing greater inhibition with RNA/DNA template primers than with DNA/DNA template.primer. Kinetic analysis demonstrated that they inhibit the enzyme by different mechanisms, as, of the four compounds examined, two competed with template.primer and two competed with deoxynucleoside triphosphate. Inhibition of DNA polymerase activity by these compounds was compared using polymerases from different sources, including human; although not necessarily most specific for HIV-1 reverse transcriptase, they did not inhibit all DNA polymerases to a similar degree.
Highly reliable and fast nonvolatile hybrid switching ReRAM memory using thin Al 2 O 3 demonstrated at 54nm memory array (2011)

For the first time, very fast (10ns at even Reset) and high reliable (150°C 100h) ReRAM memory was demonstrated at 54 nm 256k bits array. Reset current successfully decreased up to 20uA using Al 2 O 3 which acts as a tunnel barrier and filament source in TiO 2 /Al 2 O 3 stack. From statistical analysis, the possibility of increasing array size and the key factor of resistance distribution were investigated.
B-26 Evaluation of load of lower limbs joints in Nordic Walking (2009)

Recent years have seen a worldwide increase in people participating in Nordic Walking with a heavy concentration in Northern Europe. This trend has led to abundant research in Nordic Walking. In these preliminary studies, however, whether the conclusions that this type of exercise is effective in reducing load on the lower limbs has been contradictory. To clarify the effects of reducing load on lower limb joint on Nordic Walking, this study measured the load on lower limbs joints during Nordic Waling on a level surface with three test conditions (free walking, speed constraint, speed and stride length constraint). Results revealed no significant differences between Nordic Walking and Ordinary Walking with speed constraint, speed and stride length constraint. Additionally, the effects of joint load resulting from difference of stride length were clarified.
Mission Profile Based Optimization of a Wearable Power System (2013)

A Wearable Power System (WPS) is a portable power source utilized primarily to power the modern soldier’s electronic equipment. Such a system has to satisfy output power demands in the range of 20 W...200 W, specified as a 4-day mission profile and has a weight limit of 4 kg. To meet these demands, an optimization of a WPS, comprising an internal combustion (IC) engine, permanent magnetic three-phase electrical motor/generator, inverter, Li-batteries, DC-DC converters, and controller, is performed in this paper. The mechanical energy extracted from the fuel by IC engine is transferred to the generator that is used to recharge the battery and provide the power to the electrical output load. The main objectives are to select the engine, fuel and battery type, to match the weight of fuel and the number of battery cells, to find the optimal working point of engine and to minimize the system weight. To provide the second output voltage level of 14 VDC, a separate DC-DC converter is connected between the battery and the load, and optimized for the specified mission profile. A prototype of the WPS based on the optimization presented in the paper results in a total system weight of 3.9 kg and fulfils the mission profile.
Molecular and Immunologic Characterization of a Highly Cross-Reactive Two EF-Hand Calcium-Binding Alder Pollen Allergen, Aln g 4: Structural Basis for Calcium-Modulated IgE Recognition (1998)

Serum IgE was used to isolate a cDNA coding for a 9.4-kDa two EF-hand calcium-binding allergen, Aln g 4, from a lambda gt11 expression cDNA library constructed from alder (Alnus glutinosa) pollen. rAln g 4 was overexpressed in Escherichia coli and purified to homogeneity. It reacted with serum IgE from 18% of pollen-allergic patients (n = 122); shared IgE epitopes with homologous allergens present in tree, grass, and weed pollens; and thus belongs to a family of highly cross-reactive pollen allergens. Exposure of two E. coli-expressed rAln g 4 fragments comprising amino acids 1-41 and 42-85 to patients' IgE Abs, as well as to a rabbit antiserum raised against purified rAln g 4, indicated that most of the B cell epitopes reside in the N-terminal portion of the protein. IgE recognition of Aln g 4 was strongly modulated by the presence or absence of calcium. Circular dichroism analysis of rAln g 4 revealed that the protein consisted mostly of alpha helical secondary structure and possessed a remarkable thermal stability and refolding capacity, a property that was greatly reduced after calcium depletion. Circular dichroism analysis of the calcium-bound and apo form of rAln g 4 indicated that calcium-induced modulation of IgE binding could be due to changes in the protein conformation. Purified rAln g 4 elicited dose-dependent basophil histamine release and immediate type skin reactions in sensitized patients. It may hence be useful for allergy diagnosis and for specific immunotherapy.
Comprehensive TCEP Assessment of Methods for Calculating MUAV Navigation Position Accuracy Based on Visual Measurement (2013)

in order to satisfy the positioning accuracy identification requirement of MUAV navigation system, the characteristics of visual navigation were analyzed, the existing navigation system accuracy assessment methods were summarized and the conversion relationship of each index were deduced. According to the Ethridge statistical algorithm for calculating circular error probability (CEP), navigation and positioning accuracy assessment scheme were designed. Finally, the time-CEP(TCEP) accuracy evaluation method based on visual measurement was put forward, which were verified by simulation using four group actual INS data .The results show that: the scheme is feasible, convenient and practical; the method can relatively comprehensive evaluate the positioning accuracy of navigation system and can make full use of the single trial data.
Detailed metabolic and genetic characterization reveals new associations for 30 known lipid loci (2011)

Almost 100 genetic loci are known to affect serum cholesterol and triglyceride levels. For many of these loci, the biological function and causal variants remain unknown. We performed an association analysis of the reported 95 lipid loci against 216 metabolite measures, including 95 measurements on lipids and lipoprotein subclasses, obtained via serum nuclear magnetic resonance metabolomics and four enzymatic lipid traits in 8330 individuals from Finland. The genetic variation in the loci was investigated using a dense set of 440 807 directly genotyped and imputed variants around the previously identified lead single nucleotide polymorphisms (SNPs). For 30 of the 95 loci, we identified new metabolic or genetic associations (P < 5 × 10(-8)). In the majority of the loci, the strongest association was to a more specific metabolite measure than the enzymatic lipids. In four loci, the smallest high-density lipoprotein measures showed effects opposite to the larger ones, and 14 loci had associations beyond the individual lipoprotein measures. In 27 loci, we identified SNPs with a stronger association than the previously reported markers and 12 loci harboured multiple, statistically independent variants. Our data show considerable diversity in association patterns between the loci originally identified through associations with enzymatic lipid measures and reveal association profiles of far greater detail than from routine clinical lipid measures. Additionally, a dense marker set and a homogeneous population allow for detailed characterization of the genetic association signals to a resolution exceeding that achieved so far. Further understanding of the rich variability in genetic effects on metabolites provides insights into the biological processes modifying lipid levels.
A 4th-order analog continuous-time filter designed using standard cells and automatic digital logic design tools (2016)

An inverter-transconductor-based continuous-time analog 4 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">th</sup> -order low-pass Butterworth filter was described entirely in Verilog hardware description language (HDL) using only standard cells. The physical design was synthesized with automated digital logic place-and-route (APR) CAD tools. APR was achieved in less than a minute making for an enormous improvement compared to traditional manual analog chip layout. A test chip was fabricated in a 0.18um CMOS technology and its performance was experimentally verified. The experimental results document excellent measured performance and a huge physical design timesaving thereby validating the proposed automated design methodology.