gebhart/patrepeval huggingface dataset:
General linear-time inference for Gaussian Processes on one dimension. (2020)

Gaussian Processes (GPs) provide a powerful probabilistic framework for interpolation, forecasting, and smoothing, but have been hampered by computational scaling issues. Here we prove that for data sampled on one dimension (e.g., a time series sampled at arbitrarily-spaced intervals), approximate GP inference at any desired level of accuracy requires computational effort that scales linearly with the number of observations; this new theorem enables inference on much larger datasets than was previously feasible. To achieve this improved scaling we propose a new family of stationary covariance kernels: the Latent Exponentially Generated (LEG) family, which admits a convenient stable state-space representation that allows linear-time inference. We prove that any continuous integrable stationary kernel can be approximated arbitrarily well by some member of the LEG family. The proof draws connections to Spectral Mixture Kernels, providing new insight about the flexibility of this popular family of kernels. We propose parallelized algorithms for performing inference and learning in the LEG model, test the algorithm on real and synthetic data, and demonstrate scaling to datasets with billions of samples.
Inactivation of human immunodeficiency virus (HIV)-1 envelope-specific CD8+ cytotoxic T lymphocytes by free antigenic peptide: a self-veto mechanism? (1996)

Free peptide has been found to inhibit cytotoxic T lymphocyte (CTL) activity, and veto cells bearing peptide-major histocompatibility complex (MHC) complexes have been found to inactivate CTL, but the two phenomena have not been connected. Here we show that a common mechanism may apply to both. CD8+ CTL lines or clones specific for a determinant of the human immunodeficiency virus (HIV) 1 IIIB envelope protein gp160, P18IIIB, are inhibited by as little as 10 min exposure to the minimal 10-mer peptide, I-10, within P18IIIB, free in solution, in contrast to peptide already bound to antigen-presenting cells (APC), which does not inhibit. Several lines of evidence suggest that the peptide must be processed and presented by H-2Dd on the CTL itself to the specific T cell receptor (TCR) to be inhibitory. The inhibition was not killing, in that CTL did not kill 51Cr-labeled sister CTL in the presence of free peptide, and in mixing experiments with CTL lines of different specificities restricted by the same MHC molecule, Dd, the presence of free peptide recognized by one CTL line did not inhibit the activity of the other CTL line that could present the peptide. Also, partial recovery of activity could be elicited by restimulation with cell-bound peptide, supporting the conclusion that neither fratricide nor suicide (apoptosis) was involved. The classic veto phenomenon was ruled out by failure of peptide-bearing CTL to inactivate others. Using pairs of CTL lines of differing specificity but similar MHC restriction, each pulsed with the peptide for which the other is specific, we showed that the minimal requirement is simultaneous engagement of the TCR and class I MHC molecules of the same cell. This could occur in single cells or pairs of cells presenting peptide to each other. Thus, mechanistically, the inhibition is analogous to veto, and might be called self-veto. As a clue to a possible mechanism, we found that free I-10 peptide induced apparent downregulation of expression of specific TCR as well as interleukin 2 receptor, CD69, lymphocyte function-associated antigen 1, and CD8. This self-veto effect also has implications for in vivo immunization and mechanisms of viral escape from CTL immunity.
Broad-Spectrum Antimicrobial Effects of Photocatalysis Using Titanium Dioxide Nanoparticles Are Strongly Potentiated by Addition of Potassium Iodide (2016)

Photocatalysis describes the excitation of titanium dioxide nanoparticles (a wide-band gap semiconductor) by UVA light to produce reactive oxygen species (ROS) that can destroy many organic molecules. This photocatalysis process is used for environmental remediation, while antimicrobial photocatalysis can kill many classes of microorganisms and can be used to sterilize water and surfaces and possibly to treat infections. Here we show that addition of the nontoxic inorganic salt potassium iodide to TiO2 (P25) excited by UVA potentiated the killing of Gram-positive bacteria, Gram-negative bacteria, and fungi by up to 6 logs. The microbial killing depended on the concentration of TiO2, the fluence of UVA light, and the concentration of KI (the best effect was at 100 mM). There was formation of long-lived antimicrobial species (probably hypoiodite and iodine) in the reaction mixture (detected by adding bacteria after light), but short-lived antibacterial reactive species (bacteria present during light) produced more killing. Fluorescent probes for ROS (hydroxyl radical and singlet oxygen) were quenched by iodide. Tri-iodide (which has a peak at 350 nm and a blue product with starch) was produced by TiO2-UVA-KI but was much reduced when methicillin-resistant Staphylococcus aureus (MRSA) cells were also present. The model tyrosine substrate N-acetyl tyrosine ethyl ester was iodinated in a light dose-dependent manner. We conclude that UVA-excited TiO2 in the presence of iodide produces reactive iodine intermediates during illumination that kill microbial cells and long-lived oxidized iodine products that kill after light has ended.
A Four-Gene Signature Predicts Disease Progression in Muscle Invasive Bladder Cancer (2011)

There are no reliable criteria to handle disease progression of muscle invasive bladder cancer (MIBC), which strongly influences patient survival. Therefore, an accurate predicting method to identify progressive MIBC patients is greatly needed. The aim of this study was to identify a genetic signature associated with disease progression in MIBC. To address this issue, we analyzed three independent cohorts (a training set, test set 1 and test set 2) comprising a total of 128 MIBC patients. Microarray gene expression profiling, including gene network analysis, was performed in the training set to identify a gene expression signature associated with disease progression. The prognostic value of the signature was validated in test set 1 and test set 2 by microarray and real-time reverse transcriptase polymerase chain reaction (RT-PCR), respectively. The determination of gene expression patterns by microarray data analysis identified 1,320 genes associated with disease progression. Gene network analysis of the 1,320 genes suggested that IL1B, S100A8, S100A9 and EGFR were important mediators of MIBC progression. We validated this putative four-gene signature in two independent cohorts (log-rank test, P < 0.05 each, respectively) and estimated the predictive value of the signature by multivariate Cox regression analysis (hazard ratio [HR], 6.24; 95% confidence interval [CI], 1.58-24.61; P = 0.009). Finally, signature-based stratification demonstrated that the four-gene signature was an independent predictor of MIBC progression. In conclusion, a molecular signature defined by four genes represents a promising diagnostic tool for the identification of MIBC patients at high risk of progression.
Investigating the contribution of hyaluronan (HA) to the breast tumour microenvironment using multiparametric MRI and histology (2023)

The impact of HA on tumour characteristics measured by MRI/E is not fully understood. We evaluated relationships between MRI biomarkers and histology in saline (HA present) and PEGPH20 treated (HA absent) breast tumours. ADC had the strongest association with HA, reaffirming that ADC is the most sensitive biomarker of tumour response to PEGPH20. MTR negatively correlated with HA, likely due to a HA-mediated dilution of MT-inducing components including collagen. MRE-derived elasticity (G d ) did not directly correlate with HA, however, HA degradation reduced the contribution of collagen to tumour viscoelasticity and may shift the sensitivity of G d to the cellular compartment.
Improved performance second order time delay digital tanlock loop (2010)

This paper presents a second order time delay digital tanlock loop with improved locking as well as acquisition performance. The former is achieved through replacement of the delay unit of the TDTL by a variable one whose phase error is controlled by the output of the phase detector. This approach maintains the quadrature relationship between the two TDTL channels and hence results in a linearized phase detector characteristics. Fast acquisition is obtained through modification of the free running sampling frequency of digital controlled oscillator (DCO) in order to speed up the loop digital filter response. This improved architecture was tested using various input signals including FSK (frequency shift keying) and the results show an enhanced performance when compared with the original TDTL system.
<title>New ferroelectric liquid crystal host materials for use in optoelectronic applications</title> (1994)

Ferroelectric smectic C* liquid crystals (FLCs) have been shown to exhibit high speed electrooptic response when incorporated into the surface stabilized ferroelectric liquid crystal light valve. An important component of the FLC material used in devices is the smectic C host, which imparts many of the important characteristics to the final mixture, allowing customization to a specific type of device. A new class of FLC materials based on a cyclohexenyl core is reported and their properties evaluated in both the pure material and mixtures.
DNA ploidy and survival of patients with clinically localized prostate cancer treated without intent to cure (1998)

Flow cytometric determined nondiploidy was associated with disease-specific death in patients with clinically localized prostate cancer, but DNA ploidy provided additional prognostic information in patients with low-grade tumors only.
Rapid Sample Processing for Detection of Food-Borne Pathogens via Cross-Flow Microfiltration (2013)

This paper reports an approach to enable rapid concentration and recovery of bacterial cells from aqueous chicken homogenates as a preanalytical step of detection. This approach includes biochemical pretreatment and prefiltration of food samples and development of an automated cell concentration instrument based on cross-flow microfiltration. A polysulfone hollow-fiber membrane module having a nominal pore size of 0.2 μm constitutes the core of the cell concentration instrument. The aqueous chicken homogenate samples were circulated within the cross-flow system achieving 500- to 1,000-fold concentration of inoculated Salmonella enterica serovar Enteritidis and naturally occurring microbiota with 70% recovery of viable cells as determined by plate counting and quantitative PCR (qPCR) within 35 to 45 min. These steps enabled 10 CFU/ml microorganisms in chicken homogenates or 10(2) CFU/g chicken to be quantified. Cleaning and sterilizing the instrument and membrane module by stepwise hydraulic and chemical cleaning (sodium hydroxide and ethanol) enabled reuse of the membrane 15 times before replacement. This approach begins to address the critical need for the food industry for detecting food pathogens within 6 h or less.
Generation and manipulation of domain walls using a thermal gradient in a ferrimagnetic TbCo wire (2015)

We demonstrate the ability to create, control the propagation, and annihilate domain walls in 25-nm thick Tb22Co78 ferrimagnetic alloy wires using a temperature gradient under a constant applied field. The temperature gradient is generated by passing a current through the wire, and the domain wall properties are imaged using Kerr microscopy. The manipulation of the domain wall is made possible by creating a temperature gradient such that the temperature at one end of the wire is above the compensation temperature for the TbCo alloy, while the other end remains below the compensation temperature. By tuning the intensity of the applied magnetic field and the current flowing inside the wire, it is possible to carefully control the domain wall position that can then be stabilized under zero applied field and current.
Internal photoemission spectroscopy determination of barrier heights between Ta-based amorphous metals and atomic layer deposited insulators (2019)

The energy barrier heights between two recently reported Ta-based amorphous metals (TaWSi and TaNiSi), TaN, and atomic layer deposited Al2O3 and HfO2 insulators are measured in metal/insulator/metal (MIM) structures with Au top electrodes using internal photoemission (IPE) spectroscopy. For Al2O3, the Ta-based metal barrier heights, φBn, increase with increasing metal work function, ΦM, for TaN, TaWSi, and TaNiSi, respectively. For HfO2, however, the barrier heights are relatively constant for all three metals φBn,TaNiSi ≈ φBn.TaWSi ≈ φBn.TaN. The difference between HfO2 and Al2O3 is attributed to enhanced Fermi-level pinning due to a larger dielectric constant. The slope parameter, S, was found to be roughly 0.89 and 0.44–0.69 for Al2O3 and HfO2, respectively. For devices with a TaWSi bottom electrode, a comparison was also made between Al and Au top electrodes. Significantly, smaller barrier heights were obtained with an Au top electrode than with an Al top electrode, 0.6 eV and 0.8 eV lower for HfO2 and Al2O3, respectively. IPE energy barriers are found consistent with current-voltage asymmetry of MIM diodes, whereas Schottky model predictions of barrier heights were inconsistent.
The Padova Type 2 Diabetes Simulator from Triple-Tracer Single-Meal Studies: In Silico Trials Also Possible in Rare but Not-So-Rare Individuals (2020)

<b><i>Background:</i></b><i>In silico</i> trials in type 2 diabetes (T2D) would be useful for testing diabetes treatments and accelerating the development of new antidiabetic drugs. In this study, we present a T2D simulator able to reproduce the variability observed in a T2D population. The simulator also allows to safely experiment on virtual subjects with severe (and possibly rare) pathological conditions. <b><i>Methods:</i></b> A meal simulation model of glucose, insulin, and C-peptide systems, made of 15 differential equations and 39 parameters, has been identified using a system decomposition and forcing function Bayesian strategy on data of 51 T2D subjects undergoing a single triple-tracer mixed meal. One hundred T2D <i>in silico</i> subjects have been generated from the joint distribution of estimated model parameters. A case study is presented to illustrate the simulator use for testing a virtual drug (improving insulin action and secretion) in a subpopulation of rare, extremely impaired, T2D subjects. <b><i>Results:</i></b> The model well fitted T2D data and parameters were estimated with precision. Simulated plasma glucose, insulin, and C-peptide well matched the data (e.g., median [25<sup>th</sup>-75<sup>th</sup> percentile] glucose area under the curves of 6.9 [6.1-8.5] 10<sup>4</sup> mg/dL·min <i>in silico</i> vs. 7.0 [5.6-8.2] 10<sup>4</sup> mg/dL·min <i>in vivo</i>). The potential use of the simulator was shown in a case study, in which the (virtual) antidiabetic drug dose was optimized for very insulin-resistant T2D subjects. <b><i>Conclusions:</i></b> We have developed a T2D simulator that captures the behavior of T2D population during a meal, both in terms of average and intersubject variability. The simulator represents a cost-effective way to test new antidiabetic drugs, before moving to human trials.
SPARC: Development of Pigs with mCherry‐CRE Recombinase Fusion Proteins in Cholinergic Neurons (2020)

Large animals are increasingly utilized in biomedical research and offer an advantage in that their anatomy and physiology closely parallel humans. Yet despite these advantages, rodent models dominate many areas of research, including neuroscience. This might be due in part to the greater number of technologies available to rodent researchers. Here we describe the development of pigs with mCherry and CRE‐recombinase proteins expressed in cholinergic neurons. We first cloned a 5,972 bp DNA fragment containing the predicted choline acetyltransferase (ChAT) promoter from porcine genomic DNA and placed into a pGlow TOPO™ TA expression system. We then tested for promoter activity by transfecting the expression system into porcine hippocampal slices and assessed for green fluorescent protein (GFP). We observed GFP at 60–72 hours post transfection. Confirmation of specificity was achieved by using antibody detection of ChAT. To optimize the expression system, we relied upon proven strategies used in rodents, and added an additional 535 bp of predicted promoter to the 5’ end. We then used this sequence to drive production of a mCherry‐P2A‐CRE recombinase fusion protein (ChAT‐mCherry‐P2A‐CRE). We transfected brain slice cultures from the pig hippocampus, striatum and brainstem with ChAT‐mCherry‐P2A‐CRE. Approximately 60 hours later, we isolated RNA and froze brain slices from transfected and non‐transfected samples. qRT‐PCR revealed mCherry and CRE recombinase mRNA in all transfected tissues. Expression of mCherry protein was also visible in discreet subsets of neurons in transfected samples. Studies are ongoing to confirm mCherry expression in cholinergic neurons. Key next steps include engineering our ChAT‐mCherry‐P2A‐CRE to contain GGTA1 homology arms for placement into the GGTA1 safe harbor in the pig genome, providing in vivo validation of ChAT‐mCherry‐P2A‐CRE using lentivirus pseudotyped with rabies glycoprotein, and targeting porcine fetal fibroblasts for somatic cell nuclear transfer. If successful, this model will allow for simultaneous visualization of neurons (and their innervation), and the ability to control or monitor neural activity through CRE‐mediated recombination. Support or Funding Information HL119560, 1OT2OD026582
Accuracy of Very Low Pretest Probability Estimates for Pulmonary Embolism Using the Method of Attribute Matching Compared with the Wells Score (2010)

Attribute matching categorizes over one-quarter of patients tested for PE as having a pretest probability of <2.5%, and the observed rate of VTE within 45 days in this subset was <2.5%.
Spontaneous copolymerization of 1,3‐cyclohexadiene with polar vinyl monomers (1981)

Abstract In the reactions of 1,3‐cyclohexadiene(1,3‐CHD) with polar vinyl monomers, CH 2 C(X)Y (X is ‐CN and CO 2 CH 3 ; Y is CI, H, and CH 3 ), the two α‐chlorosubstituted monomers underwent rapid spontaneous copolymerization, accompanied by the formation of a small amount of cycloadduct. Both polar monomers also gave predominantly copolymers in the reaction with 1,3‐cycloheptadiene(1,3‐CHpD) in lower yield. 1,3‐Cyclooctadiene (1,3‐COD) reacted only with α‐chloroacrylonitrile (CAN) to give a copolymer, while only cycloaddition took place in systems involving cyclopentadiene(CPD) as diene. The charge–transfer (CT) complex formation of 1,3‐CHD with CAN and methyl α‐chloroacrylate(MCA) was confirmed by ultraviolet spectroscopic studies and the equilibrium constants estimated were 0.18 and 0.07 liter/mole, respectively, at 25°C in chloroform as solvent. The activation energies for the copolymerizations of 1,3‐CHD with CAN and MCA in benzene were determined to be ca. 6.6 and 9.6 kcal/mole, respectively. In the system composed of 1,3‐CHD and CAN, only the copolymerization was affected by solvents used and oxygen. Although addition of ZnCl 2 to the system resulted in the acceleration of the both reactions, the variation in the product ratio of copolymer to cycloadduct with ZnCl 2 concentration showed a maximum. Based on the results in the present and preceding studies for systems involving 1,3‐cyclodienes and acceptor monomers, the relationship between the cycloaddition and the spontaneous copolymerization is discussed.
Induction de molécules de classe II du CMH après infection de cellules endothéliales de cerveau de bovin par <em>Cowdria ruminantium</em> (1993)

Les molécules de classe II du complexe majeur d’histocompatibilité(CMH) jouent un rôle clé dans l’induction de l’immunité. Chez le bovin, les molécules de classe II du CMH, codées par les loci DR et DQ, sont constituées par deux chaînes protéiques, α et β, qui sont associées à une chaîne invariante (I) durant leur transport intracellulaire. Des cellules endothéliales bovines (BBEC) de microvaisseaux cérébraux peuvent être cultivées in vitro et n’expriment pas de manière constitutive des molécules de classe II du MHC. Néanmoins, après traitement avec de l’interféron γ bovin (INFγ), les BBEC synthétisent des protéines de classe II du CMH. Une infection in vitro des BBEC par C. ruminantium a été effectuée sur des cellules traitées ou non par l’INFγ. L’expression des molécules de classe II a été suivie, au niveau des ARN, par analyse de “northern blot”. Quarante huit heures après l’infection, des transcrits correspondant à la chaîne I ont été détectés sur toutes les cellules infectées. Deux ARNmDQα de 1,3 et 1,5 kb sont présents sur les cellules infectées et traitées à l’INFγ, alors qu’un simple transcrit DQα de 1,5 kb a été observé sur les cellules seulement infectées. D’autre part, les cellules traitées mais non infectée sont montré un simple ARNmDQα de 1,3 kb. La nature et la fonctionnalité de l’espèce moléculaire de 1,5 kb demeurent inconnues, mais elle pourrait représenter un ARNmDQα polyadénylé en un deuxième site en aval du premier site de polyadénylation. En contraste de l’expression précoce des chaînes I et DQα, les ARNmDRα n’ont été détectés que sept jours après l’infection. Il est important de noter qu’une lyse totale des BBEC infectées n’a été obtenue qu’au treizième jour de l’infection, alors que les cellules infectées et traitées par l’INFγ ont montré un effet cytopathogène plus précoce et plus marqué. Les résultats présentés ici montrent que les molécules de classe II du CMH peuvent être induites sur les BBEC après infection par C. ruminantium, ce qui nous mène à l’hypothèse que les cellules endothéliales de cerveau peuvent exercer une fonction immune spéciﬁque, comme la présentation d’antigènes. Des expériences supplémentaires doivent être accomplies de manière à évaluer si oui ou non ces cellules infectées peuvent spécifiquement stimuler des cellules T.
β-N-Acetylhexosaminidases HEXO1 and HEXO3 Are Responsible for the Formation of Paucimannosidic N-Glycans in Arabidopsis thaliana (2011)

Most plant glycoproteins contain substantial amounts of paucimannosidic N-glycans instead of their direct biosynthetic precursors, complex N-glycans with terminal N-acetylglucosamine residues. We now demonstrate that two β-N-acetylhexosaminidases (HEXO1 and HEXO3) residing in different subcellular compartments jointly account for the formation of paucimannosidic N-glycans in Arabidopsis thaliana. Total N-glycan analysis of hexo knock-out plants revealed that HEXO1 and HEXO3 contribute equally to the production of paucimannosidic N-glycans in roots, whereas N-glycan processing in leaves depends more heavily on HEXO3 than on HEXO1. Because hexo1 hexo3 double mutants do not display any obvious phenotype even upon exposure to different forms of abiotic or biotic stress, it should be feasible to improve the quality of glycoprotein therapeutics produced in plants by down-regulation of endogenous β-N-acetylhexosaminidase activities.