gebhart/patrepeval huggingface dataset:
Challenges to the Development of New Agents for Molecularly Defined Patient Subsets: Lessons From <i>BRCA1/2</i>-Associated Breast Cancer (2011)

Susan M. Domchek, University of Pennsylvania School of Medicine, Philadelphia, PA Gillian Mitchell, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia Geoffrey J. Lindeman, Walter and Eliza Hall Institute of Medical Research and Royal Melbourne Hospital, Melbourne, Victoria, Australia Nadine M. Tung, Beth Israel/Deaconess Medical Center, Boston, MA Judith Balmana, Vall d’Hebron University Hospital, Barcelona, Spain Steven J. Isakoff, Massachusetts General Hospital, Boston, MA Rita Schmutzler, University of Cologne, Cologne, Germany M. William Audeh, Cedars Sinai Medical Center, Los Angeles, CA Niklas Loman, Skane University Hospital, Malmo, Sweden Clare Scott, Walter and Eliza Hall Institute of Medical Research and Royal Melbourne Hospital, Melbourne, Victoria, Australia Michael Friedlander, Prince of Wales Cancer Centre, Sydney, New South Wales, Australia Bella Kaufman, The Chaim Sheba Medical Center, Tel Aviv, Israel Judy E. Garber, Dana-Farber Cancer Institute, Boston, MA Andrew Tutt, Guy’s Hospital, King’s Health Partners Academic Health Sciences Centre, London, United Kingdom Mark E. Robson, Memorial Sloan-Kettering Cancer Center, New York, NY
Validating the FSV Method using reverberation chamber measurements (2010)

The Feature Selective Validation (FSV) Method was originally developed as a standard technique to mimic an expert's opinion of concurrence between CEM and measurement datasets. It has recently expanded as a method to quantify agreement between various types of datasets. This paper presents a comparison of measurements obtained from different antenna positions in an overmoded cavity. Based on the field distributions within the usable area of the reverberation chamber these datasets should appear statistically similar. The objective is to present a credible evaluation of the FSV method using standard reverberation chamber theory.
Eta<sup>®</sup> Analysis of Portfolios: <i>The Economy Matters</i> (2012)

The authors introduce a macroeconomic factor model, the Eta model, and its various applications. The underlying message regarding the Eta model, be it for replication, wealth maximization, or wealth preservation, is that “the economy matters.” The core feature of the Eta model is its replication methodology, from which portfolios could be customized to fit the risk–reward preferences of investors with respect to the economy. They then evaluate the portfolios against the Dimensional Fund Advisors Core Equity 1 Portfolio, which adopts the methodology promoted by the Fama–French three-factor model. <b>TOPICS:</b>Factor-based models, portfolio construction, performance measurement
Efficiency of tetrofosmin versus sestamibi achieved through shorter injection-to-imaging times: A systematic review of the literature (2020)

Based on superior image quality, more accurate gated images, and lower radiation exposure to patients, Technetium-99m (Tc-99m) based tracers are preferred over Thallium-201 for SPECT myocardial perfusion imaging. The two Tc-99m tracers, sestamibi and tetrofosmin, have many similar characteristics but there are differences in blood and liver clearance rates, as well as the recommended time after injection for imaging to achieve optimal image quality. Because published peer-reviewed studies examining optimal times between injection and imaging are limited, it can be difficult to identify evidence-based opportunities to optimize imaging protocols. Using systematic literature review methods, this study was designed to identify and consolidate the available evidence on the use of sestamibi compared to tetrofosmin for variable injection to imaging times in regard to test efficiency, including test length and re-scan rates, and image quality, including overall quality and cardiac to extra-cardiac ratios. The composite of this data shows that earlier imaging with tetrofosmin is equivalent to later imaging with sestamibi when assessing subjective image quality or when quantifying heart-to-extra-cardiac ratios. Image quality and heart-to-extra-cardiac ratios comparing early versus later imaging with tetrofosmin were comparable if not equivalent to each other. The equivalency of the imaging quality occurs with 15 minutes (on average) earlier imaging compared to sestamibi and 30 minutes compared to standard time tetrofosmin. The subjective findings of equivalent image quality are also shown with objective measurements of heart-to-extra-cardiac ratios. In this review, the significantly shorter injection-to-acquisition times with tetrofosmin compared to sestamibi resulted in better efficiency and less waiting times for patients; in addition, significantly higher re-scan rates with sestamibi compared to tetrofosmin due to hepatic activity contributed to better throughput with tetrofosmin.
Arylsulfonylacetylenes as Alkynylating Reagents of CH Bonds Activated with Lithium Bases (2012)

Chameleon: a new strategy for the synthesis of a wide variety of alkynyl derivatives by the reaction of substituted arylsulfonylacetylenes with organolithium species is described. The high yields, the simplicity of the experimental procedure, the broad scope of this reaction, and the formation of C(sp)-C(sp2) bonds without using transition metals are the main features of this methodology.
SIS/PDGF-B promoter isolation and characterization of regulatory elements necessary for basal expression of the SIS/PDGF-B gene in U2-OS osteosarcoma cells. (1994)

Platelet-derived growth factor BB, encoded by the SIS/PDGF-B gene, is a potent mitogen for cells of mesenchymal origin, and the SIS/PDGF-B gene is expressed in a large percentage of human mesenchymal tumor cells establishing a growth-promoting, autocrine growth circuit. A 4-kb fragment, containing the SIS/PDGF-B promoter, was isolated from a human genomic library, and a series of 5'-nested deletions and linker-scanning mutants were used to identify positive regulatory elements that are necessary for the constitutive expression of this gene in human U2-OS osteosarcoma cells. A 250-bp fragment, lying immediately 5' to the SIS/PDGF-B mRNA initiation site (+1), retained full promoter activity, and positive regulatory elements at -228 to -219, -97 to -88 (SIS distal element) and -58 to -39 (SIS proximal element, SPE) were identified. Insertion of the 20-bp SPE into a heterologous, minimal promoter resulted in >5-fold transcriptional activation which was ablated by mutations to the SPE. High resolution mutagenesis within the 20-bp SPE, indicated the necessity of a CACCC motif for activity. Gel shift analysis of SPE-binding proteins in U2-OS nuclear extracts identified Sp1 and two additional binding factors that could be competed away from SPE binding by adding excess consensus Sp1 or CACC oligonucleotides. The individual and aggregate roles of the SPE and two weaker positive regulatory elements in regulating SIS/PDGF-B transcription in these tumor cells is considered.
Unstructured Grid Adaptation: Status, Potential Impacts, and Recommended Investments Towards CFD 2030 (2016)

International audience
Individuals With Weaker Antibody Responses After Booster Immunization Are Prone to Omicron Breakthrough Infections (2022)

Routine testing of anti-SARS-CoV-2 IgG antibodies and surrogate virus neutralization can quantify vaccine-induced humoral immune response and may help to identify subjects who are at risk for a breakthrough infection. The establishment of thresholds for SARS-CoV-2 IgG antibody levels identifying "non"-, "low" and "high"-responders may be used as an indication for re-vaccination.
2010. Volatile Organic Compounds Patterns in Breath, Plasma, and Stool in Patients with <i>Clostridium difficile</i> Infection: A Cross-Sectional Proof of Concept Study (2018)

Volatile organic compounds (VOCs) are hydrocarbon compounds which are end product metabolites of physiological and pathophysiological processes. Many disease processes can be identified by examining metabolome patterns in clinical samples from patients. The purpose of this study was to identify Clostridium difficile infection (CDI) based on differences in VOCs in stool, blood and breath of patients with CDI and controls without. Patients aged >18 years at Cleveland Clinic with CDI (> 3 watery stools in the preceding 24 hours and stool PCR positive for C. difficile), and matched controls (for age, sex, and date of PCR test) were included. Stool and plasma samples (within 24 hours of collection) and fresh breath samples were collected. Headspace gas from clinical samples was tested using selected ion flow tube mass spectrometry (SIFT-MS) on a VOICE200 instrument (Syft Technologies Ltd., Christchurch, New Zealand). The MS assay comprised of 22 common analytes: 2-propanol, acetaldehyde, acetone, acetonitrile, acrylonitrile, benzene, carbon disulfide, dimethyl sulfide, ethanol, isoprene, pentane, 1-decene, 1-heptene, 1-nonene, 1-octene, 3-methyl hexane, 2-nonene, ammonia, ethane, hydrogen sulfide, triethyl amine, and trimethyl amine. VOC analysis findings were classified as positive or negative using the K-nearest neighbors (KNN) method. Model accuracy was evaluated by k-fold cross-validation with 5-folds. Sensitivity and specificity were determined and receiver-operating characteristics curves generated for each sample type. Thirty-one patients with CDI and 31 controls were studied. The optimal KNN classifier model was achieved with k = 7, 5, and 9, for breath, plasma, and stool samples, respectively. The sensitivity/specificity for detection of CDI were 87.1%/77.4%, 66.7%/63.6%, and 61.3%/36.4%, for breath, stool, and plasma samples, respectively. Model accuracy was no better if positives were limited to those with C. difficile PCR CT <30 cycles. VOC analysis of fresh breath, but not plasma or stool samples ≤24 hours old, by the method studied had good sensitivity and moderate specificity for identifying patients with CDI. All authors: No reported disclosures.
APIR-DSP: An approximate PIR-DSP architecture for error-tolerant applications (2021)

In error-tolerant applications such as low-precision DNNs and digital filters, approximate arithmetic circuits can significantly reduce hardware resource utilization. In this work we propose an embedded block for field-programmable gate arrays, called APIR-DSP, which incorporates an approximate 9×9 hard multiplier based on the PIR-DSP architecture to improve speed and reduce area. In addition, a DSP unit evaluation platform based on Yosys and VPR which packs multiply accumulate operations into DSP blocks is developed. Using this tool we synthesis designs from Verilog implementations of matrix multiplication in DeepBench and the DoReFaNet low-precision neural network and show that APIR-DSP significantly reduces DSP resources and improves hardware utilization and performance compared with the Xilinx DSP48E2 embedded block. Compared with exact multiplication, it is shown that accuracy loss is optimized with the SNR of an FIR filter being reduced by 1.03 dB. For DNNs, accuracy loss for AlexNet is 0.31% on CIFAR10 dataset and no accuracy loss for LeNet on MNIST dataset is observed. Synthesis results show that the APIR-DSP enjoys an area reduction of 21.60%, critical path reduction of 4.85% and power consumption is reduced by 2.80%, compared with PIR-DSP.
Abundance of<i>Aeromonas</i>spp. in various components of pond ecoysystems in Dhaka, Bangladesh (1992)

Aeromonas spp. are considered to be waterborne agents of human gastroenteritis. A study was carried out in five ponds in Dhaka city over a period of one year to investigate the distribution and seasonality of these organisms in various components of pond ecosystems. Samples were collected from plants, water, phytoplankton and sediment every 15 days over 12 months and cultured for Aeromonas spp. using enrichment techniques. A. sobria, A. hydrophila and A. caviae were isolated from 199 (41.46%), 29 (6.04%) and 21 (4.38%) of the 480 samples, respectively. Two distinct peaks of A. sobria were observed in all components; one during the warmer months of May‐July and the other at the beginning of winter in November. Aeromonas spp. were isolated from all components from all ponds during the study period. This study gives some insight into the epidemiology of diarrhoea due to Aeromonas spp. in Bangladesh.
DNA: DNA‐Modification of Eukaryotic Cells (Small 2/2013) (2013)

The cover shows the modification of living cells with single-stranded DNA oligonucleotides. The method described by C. M. Niemeyer and co-workers on page 255 takes advantage of covalent modification of carbohydrate residues of membrane proteins, which are abundant on the surface of eukaryotic cells. Cis-diols of these carbohydrates are oxidatively cleaved to generate a carbonyl group, which undergoes a chemoselective oxime ligation with aminooxybiotin to produce biotinylated proteins. These are targeted by streptavidin covalently conjugated with DNA oligonucleotides. This method outperforms alternative chemistries for DNA coupling to cell surfaces because of its high labeling efficacy, specificity, and low impact on cell viability.
Keeping GBM in check by targeting CHK1-CIP2A axis. (2014)

2036 Background: Checkpoint kinase1 (CHK1) is constitutively active in many human cancers including Glioblastoma (GBM). Unfortunately CHK1 inhibitors, currently in clinical trials, have shown deleterious effects on normal cells, thus limiting their clinical utility. Therefore, identification and targeting of cancer specific effectors of CHK1 signaling, emerges as an attractive therapeutic alternative. Methods: Analysis of 906 gliomapatient samples was done. GBM cell lines (including primary) were used for mechanistic and functional studies. In vivo models of GBM were used to verify the findings. Results: Meta-analysis of key datasets revealed a strong positive correlation for CHK1 and CIP2A expression. By contrast, a negligible correlation was seen in normal samples. Importantly, high mRNA expression of both proteins associated with reduced overall survival in glioma patients and marked for a more aggressive form of the disease. CIP2A amplification, found in 14.72% cases in the REMBRANDT study, was associated with worse overall survival in GBM patients. Inhibition of CHK1, by siRNA and chemicals, resulted in decreased CIP2A expression both in vitro and in vivo. Functionally, both CHK1 and CIP2A promoted viability, clonogenicity and anchorage-independent growth of GBM cells. Strikingly, the CHK1-mediated reduction in the clonogenic potential was partially rescued by exogenous CIP2A expression in GBM cells. Mechanistically, we identify STAT3 as the transcriptional mediator for CHK1-mediated CIP2A regulation. Depletion of STAT3 resulted in decreased CIP2A expression in both, U251MG and primary GBM cells. Further, CHK1 promoted STAT3 phosphorylation in vitro and in vivo. Accordingly, higher CIP2A, pCHK1 and pSTAT3 levels were observed in de novo and patient-derived GBM samples, relative to normal human astrocytes. Analogously, 10- to 15-fold higher CHK1 and CIP2A mRNA expression was seen in the genetically engineered mouse models of human GBM. Finally, using xenograft mouse models we show that both CHK1 inhibitor and CIP2A depletion inhibit GBM growth. Conclusions: These results highlight CHK1 and CIP2A expression as potential diagnostic and prognostic markers in human GBMs and identify CIP2A as a relevant cancer specific therapeutic target.
Component‐resolved <i>in vitro</i> diagnosis of carrot allergy in three different regions of <scp>E</scp>urope (2012)

Component-resolved in vitro analyses revealed a significant difference in IgE sensitization pattern between geographical regions and in the prevalence of sensitization to carrot components between carrot allergic and carrot-tolerant but pollen sensitized patients.
Increased incidence of obstetric complications in women carrying mitochondrial <scp>DNA</scp> mutations: a retrospective cohort study in a single tertiary centre (2018)

Women heteroplasmic for mitochondrial DNA mutations have a higher incidence of obstetric complications, compared with the control group.
Optimization of Hammerhead Ribozymes for the Cleavage of S100A4 (CAPL) mRNA (2001)

Previously, suppression of the S100A4 mRNA by an endogenously expressed ribozyme in osteosarcoma cells was shown to inhibit their metastasis in rats. As a prelude to performing similar studies with exogenous, synthetic ribozymes, we compared a series of hammerhead ribozymes targeted against different sites in the mRNA. The ribozymes differed only in the 7-base flanking sequences complementary to the substrate and were protected against nucleases by chemical modification. Cleavage efficiency varied widely and was not obviously related to the predicted secondary structure of the target RNA. The most active ribozyme of the series was chosen for further optimization. Lengthening its flanking sequences was counterproductive and reduced cleavage even when using excess ribozyme. Using excess substrate (multiple-turnover kinetics), cleavage was fastest with the (6+8) ribozyme having 6 nucleotides (nt) in stem III and 8 nt in stem I. Although these stems strongly influence ribozyme performance, their optimization is still empirical. Faster cleavage was obtained by adding facilitator oligonucleotides to ribozymes with shorter stems of (6+6) and (5+5) nt. Stimulation was particularly strong in the case of the (5+5) ribozyme, which was poorly active by itself. The enhancement caused by different facilitator oligonucleotides paralleled their expected ability to hybridize to RNA as a function of length and chemical modification.
Structural insight into the viscoelastic behaviour of elastomeric polyesters: effect of the nature of fatty acid side chains and the degree of unsaturation (2020)

Increase in unsaturation of fatty acid side chains results in decrease of zero-shear viscosity, degree of entanglement and resilience of polyesters. <italic>Cis</italic> double bonds act as kinks that prevent molecular packing of polymer chains.
Human exhaled air diagnostic markers for respiratory tract infections in subjects receiving mechanical ventilation (2022)

Diagnosing respiratory tract infections (RTIs) in critical care settings is essential for appropriate antibiotic treatment and lowering mortality. The current diagnostic method, which primarily relies on clinical symptoms, lacks sensitivity and specificity, resulting in incorrect or delayed diagnoses, putting patients at a heightened risk. In this study we developed a noninvasive diagnosis method based on collecting non-volatile compounds in human exhaled air. We hypothesized that non-volatile compound profiles could be effectively used for bacterial RTI diagnosis. Exhaled air samples were collected from subjects receiving mechanical ventilation diagnosed with or without bacterial RTI in intensive care units at the Johns Hopkins Hospital. Truncated proteoforms, a class of non-volatile compounds, were characterized by top-down proteomics, and significant features associated with RTI were identified using feature selection algorithms. The results showed that three truncated proteoforms, collagen type VI alpha three chain protein, matrix metalloproteinase-9, and putative homeodomain transcription factor II were independently associated with RTI with the<i>p</i>-values of 2.0 × 10<sup>-5</sup>, 1.1 × 10<sup>-4</sup>, and 1.7 × 10<sup>-3</sup>, respectively, using multiple logistic regression. Furthermore, a score system named 'TrunScore' was constructed by combining the three truncated proteoforms, and the diagnostic accuracy was significantly improved compared to that of individual truncated proteoforms, with an area under the receiver operator characteristic curve of 96.9%. This study supports the ability of this noninvasive breath analysis method to provide an accurate diagnosis for RTIs in subjects receiving mechanical ventilation. The results of this study open the doors to be able to potentially diagnose a broad range of diseases using this non-volatile breath analysis technique.
Incorporation of Second-Tier Biomarker Testing Improves the Specificity of Newborn Screening for Mucopolysaccharidosis Type I (2020)

Enzyme-based newborn screening for Mucopolysaccharidosis type I (MPS I) has a high false-positive rate due to the prevalence of pseudodeficiency alleles, often resulting in unnecessary and costly follow up. The glycosaminoglycans (GAGs), dermatan sulfate (DS) and heparan sulfate (HS) are both substrates for α-l-iduronidase (IDUA). These GAGs are elevated in patients with MPS I and have been shown to be promising biomarkers for both primary and second-tier testing. Since February 2016, we have measured DS and HS in 1213 specimens submitted on infants at risk for MPS I based on newborn screening. Molecular correlation was available for 157 of the tested cases. Samples from infants with MPS I confirmed by <i>IDUA</i> molecular analysis all had significantly elevated levels of DS and HS compared to those with confirmed pseudodeficiency and/or heterozygosity. Analysis of our testing population and correlation with molecular results identified few discrepant outcomes and uncovered no evidence of false-negative cases. We have demonstrated that blood spot GAGs analysis accurately discriminates between patients with confirmed MPS I and false-positive cases due to pseudodeficiency or heterozygosity and increases the specificity of newborn screening for MPS I.