gebhart/patrepeval huggingface dataset:
Whole-Genome Patterns of Common DNA Variation in Three Human Populations (2005)

Individual differences in DNA sequence are the genetic basis of human variability. We have characterized whole-genome patterns of common human DNA variation by genotyping 1,586,383 single-nucleotide polymorphisms (SNPs) in 71 Americans of European, African, and Asian ancestry. Our results indicate that these SNPs capture most common genetic variation as a result of linkage disequilibrium, the correlation among common SNP alleles. We observe a strong correlation between extended regions of linkage disequilibrium and functional genomic elements. Our data provide a tool for exploring many questions that remain regarding the causal role of common human DNA variation in complex human traits and for investigating the nature of genetic variation within and between human populations.
Niemann-Pick disease: a frequent missense mutation in the acid sphingomyelinase gene of Ashkenazi Jewish type A and B patients. (1991)

Although the A and B subtypes of Niemann-Pick disease (NPD) both result from the deficient activity of acid sphingomyelinase (ASM; sphingomyelin cholinephosphohydrolase, EC 3.1.4.12) and the lysosomal accumulation of sphingomyelin, they have remarkably distinct phenotypes. Type A disease is a fatal neurodegenerative disorder of infancy, whereas type B disease has no neurologic manifestations and is characterized primarily by reticuloendothelial involvement and survival into adulthood. Both disorders are more frequent among individual of Ashkenazi Jewish ancestry than in the general population. The recent isolation and characterization of cDNA and genomic sequences encoding ASM has facilitated investigation of the molecular lesions causing the NPD subtypes. Total RNA was reverse-transcribed, and the ASM cDNA from an Ashkenazi Jewish type A patient was specifically amplified by the polymerase chain reaction (PCR). Molecular analysis of the PCR products revealed a G----T transversion of nucleotide 1487, which occurred at a CpG dinucleotide and predicted an Arg----Leu substitution in residue 496. Hybridization of PCR-amplified genomic DNA with allele-specific oligonucleotides indicated that the proband was homoallelic for the Arg----Leu substitution and that both parents and several other relatives were heterozygous. This mutation was detected in 32% (10 of 31) of the Ashkenazi Jewish NPD type A alleles studied and occurred in only 5.6% (2 of 36) of ASM alleles from non-Jewish type A patients. Of interest, the Arg----Leu substitution occurred in one of the ASM alleles from the two Ashkenazi Jewish NPD type B patients studied and in none of the ASM alleles of 15 non-Jewish type B patients. In contrast, the mutation was not present in 180 ASM alleles from normal individuals of Ashkenazi Jewish descent. These findings identify a frequent missense mutation among NPD patients of Ashkenazi Jewish ancestry that results in neuronopathic type A disease when homoallelic and can result in the nonneuronopathic type B phenotype when heteroallelic. The identification of this ASM mutation in Ashkenazi Jewish patients should facilitate the prevention of NPD in this population by carrier detection with molecular diagnostic techniques.
Metabotropic glutamate receptors mediate expression of LTP in slices of rat visual cortex (2002)

Long-term-potentiation (LTP) can be induced by application of a standard theta-burst stimulation protocol in slice preparations of the neocortex. This type of LTP is known to be dependent on the activation of NMDA receptors. The present study used specific experimental conditions to evoke a non-NMDA receptor mediated type of LTP. By use of weak theta-burst stimulation (wTBS) we describe a non-NMDA receptor dependent LTP in rat visual cortex in vitro, which is sensitive to an antagonist of metabotropic glutamate receptors (mGluR). In slices of the visual cortex we stimulated ascending inputs in cortical layer IV and recorded extracellular field potentials (FPs) from cortical layers II/III. In disinhibited slices (with 1 microm picrotoxin), a wTBS induced LTP to 138% of control. The expression of this potentiation was insensitive to the NMDA-receptor antagonist, D-AP5, but could be abolished by application of the mGluR antagonist MCPG. These data suggest an NMDA-independent mechanism for LTP induction in the visual cortex which can be observed in layer II/III neurons.
Chronic leucine supplementation improves glycemic control in etiologically distinct mouse models of obesity and diabetes mellitus (2010)

Chronic leucine supplementation significantly improves glycemic control in multiple mouse models of obesity and diabetes with distinct etiologies. The metabolic benefits of leucine supplementation are likely mediated via multiple mechanisms in different tissues, but are not necessarily dependent of weight reduction.
Microfluidic Approach to Create Three-Dimensional Tissue Models for Biofilm-Related Infection of Orthopaedic Implants (2010)

With conventional in vitro culture methods, it is difficult to study complex interactions of host cells with pathogens and drugs in physiologically relevant microenvironments. To simulate orthopaedic implant-associated infection, a multi-channel microfluidic device was used to (1) observe in real-time the development of osteoblasts into three-dimensional (3D) tissue-like structures and (2) study how this development was influenced by phenotypes of Staphylococcus epidermidis. In the absence of bacteria, osteoblasts formed a confluent layer on the bottom channel surface, gradually migrated to the side and top surfaces, and formed calcified 3D nodular structures in 8 days. The delivery timing and concentration of an antibiotic were controlled to produce small colony variants, sessile biofilms, or dead cells of S. epidermidis. In the presence of the small colony variants, osteoblasts initially adhered, and spread, but were killed within 2 days. In contrast, the sessile biofilms and dead bacteria cells did not significantly interfere with the formation of tissue-like structures. The results suggest the possibility of creating in vitro tissue-biofilm-biomaterial interfaces and therefore 3D tissue models, as an entirely new method of studying biofilm-related infection of orthopaedic implants with physiological relevance.
Expression of c‐myc, c‐raf‐1, and c‐Ki‐ras in azaserine‐induced pancreatic carcinomas and growing pancreas in rats (1990)

Abstract We examined the pattern of expression of several proto‐oncogenes during nonneoplastic growth and in acinar cell neoplasms in the rat pancreas. The levels of c‐ myc , c‐ raf ‐1, and c‐Ki‐ ras mRNAs were increased in regenerating pancreata following surgical partial pancreatectomy and following administration of camostat. We also investigated proto‐oncogene expression associated with the progression of pancreatic cancers in azaserine‐treated rats. Injection of a single dose (30 mg/kg) of azaserine (O‐diazoacetyl‐L‐serine) to 14‐d‐old rats leads to a variety of neoplastic lesions in the rat pancreas. Total RNA was isolated from lesions in various stages of tumor progression, including adenomas, carcinomas in situ, and invasive carcinomas. We observed increased expression of c‐ myc , c‐ raf ‐1, and c‐Ki‐ ras in azaserine‐induced adenomas and carcinomas. Actin expression was also increased in these tissues, whereas amylase expression was variable. However, when compared to the normal growing pancreas, the level of proto‐oncogene expression in the adenomas and carcinomas was disproportionate to the degree of cellular division in those tissues. Thus, the alterations induced by azaserine apparently caused a deregulated increase in expression of cellular oncogenes associated with growth regulation.
Functionalization and characterization of InAs and InP surfaces with hemin (2007)

Chemical functionalization of hemin molecules onto InAs and InP is reported. X-ray photoelectron spectroscopy (XPS), atomic force microscopy, and spectroscopic ellipsometry (SE) analyses are used to characterize the III-V surfaces. One notable feature of the C 1s core level spectra is a peak at ∼284eV observed for the functionalization chemistries, which is attributed to CN bonding within the porphyrin molecule. This is corroborated by the observation of N 1s, Fe 2p, and other distinguishable chemical bonding peaks. For example, in the As 3d and P 2p core levels, –COOH bonding is observed to the As and P anion in the InAs and InP samples, respectively, which implies chemisorption of the functional groups to the material surfaces. Another result of the XPS analysis is the impact of the surface functional group on the electronic state of the surface causing upward band bending of the valence band maximum, indicating surface charge transfer as explored in previous work [Garcia et al., Appl. Phys. Lett. 88, 013506 (2006)]. SE analysis on the functionalization process provides data for the effect of hemin and benzoic acid solution concentrations. The authors discuss the dependence of the band bending, surface coverage, and hemin layer thickness as determined by XPS and SE.
Quantum electrodynamics in photonic band gaps: atomic-beam interaction with a defect mode (1993)

A structural defect in a two-dimensionally periodic dielectric structure may form a local field mode within a photonic band gap in which no other E-polarized field modes exist. We show that such a defect mode can give rise to new quantum-electrodynamic effects in resonant field–atom interaction, owing to the spatially modulated standing-wave character of its field. Atomic-beam motion is considered (a) along an interplanar defect and (b) through a spherical defect. The resonant interaction of a moving two-level atom with the quantized field of these defects can yield hitherto unknown features—oscillatory patterns of the atomic population inversion, fluorescence spectra, and nonclassical field states—that are essentially different from their counterparts in the standard Jaynes–Cummings model, which holds for atomic-beam motion in a spatially uniform single-mode field.
Retroviral vector-mediated transfer of the bacterial neomycin resistance gene into fetal and adult sheep and human hematopoietic progenitors in vitro (1990)

We compared the efficiency of retroviral vector (N2)-mediated transfer of the bacterial neomycin resistance gene (NeoR) into adult and fetal hematopoietic progenitors of sheep and humans by assessing their ability to form colonies in the presence of lethal doses of the neomycin analogue G418 in vitro. Fetal cells from both sheep and humans exhibited a higher degree of NeoR transfer than adult cells. The overall level of NeoR expression was significantly higher for sheep than human cells. The transfer/expression of NeoR into adult human bone marrow hematopoietic progenitors was not affected by the presence or absence of T cells and monocyte/macrophages. The efficiency of NeoR transfer into both adult and fetal human cells, however, was improved when transduction was carried out in the presence of recombinant human interleukin-3 and granulocyte-macrophage colony-stimulating factor. These results demonstrate the greater efficiency of NeoR gene transfer into fetal hematopoietic progenitors, which may provide a basis for the relatively higher efficiency of the in utero approach to gene therapy.
Bayesian analysis for fault location in homogeneous distributed systems (2002)

A simple and practical probabilistic comparison-based model, employing multiple incomplete test concepts, for handling fault location in distributed systems using a Bayesian analysis procedure is proposed. This approach is more practical and complete than previous ones since it does not assume any conditions such as permanently faulty units, complete tests, perfect environments, or non-malicious environments. Fault-free systems are handled without overhead; hence, the test procedure may be used to monitor a functioning system. Given a system S with a specific test graph, the corresponding conditional distribution between the comparison test results (syndrome) and the fault patterns of S can be generated. To avoid the complex global Bayesian estimation process, a simple bitwise Bayesian algorithm is developed for fault location in S, which locates system failures with linear complexity, suitable for hard real-time systems.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Psychology of Reading (2012)

The last 20 years have witnessed a revolution in reading research. Cognitive psychologists, using high-speed computers to aid in the collection and analysis of data, have developed tools that have begun to answer questions that were previously thought unanswerable. These tools allow for a "chronometric," or moment-to-moment, analysis of the reading process. Foremost among them is the use of the record of eye movements to help reveal the underlying perceptual and cognitive processes of reading. This volume provides a coherent framework for the research accomplished on the reading process over the past 15 years. It emphasizes how readers go about extracting information from the printed page and how they comprehend the text.
Cystic Fibrosis (2005)

This review of the genetics and molecular mechanisms of cystic fibrosis emphasizes recent progress and recounts the historical background that made these new advances possible.
Notch1 Expression Is Spatiotemporally Correlated with Neurogenesis and Negatively Regulated by Notch1-Independent Hes Genes in the Developing Nervous System (2006)

In the developing nervous system, neural stem cells initially proliferate by a symmetric cell division and then undergo an asymmetric cell division, which makes one neuron (or neuronal precursor) and one progenitor. It remains to be determined how the switch from the symmetric to asymmetric cell divisions is regulated. Here, we found that Notch1 is expressed in the regions where neurogenesis occurs actively but not in the regions where neurogenesis does not yet occur. Furthermore, in Hes-mutant mice where neurogenesis is accelerated, Notch1 expression is also accelerated. Thus, Notch1 expression is negatively regulated by Hes genes and is spatiotemporally correlated with neurogenesis, suggesting that the neural stem cells that undergo asymmetric cell divisions express Notch1, whereas those that undergo symmetric cell divisions do not. We propose that initiation of Notch1 expression is one of the key features for switch from the symmetric to asymmetric cell divisions of neural stem cells and that this process is negatively regulated by Notch1-independent Hes genes.
Clinical impact and functional aspects of tenascin‐C expression during glioma progression (2002)

The extracellular matrix protein tenascin-C is expressed in processes like embryogenesis and wound healing and in neoplasia. Tenascin-C expression in gliomas has been described previously; however, the relation to clinical data remains inconsistent. Generally, analysis of tenascin-C function is difficult due to different alternatively spliced isoforms. Our studies focus on changes in tenascin-C expression in human gliomas, correlating these changes with tumor progression and elucidating the functional role of the glioma cell-specific tenascin-C isoform pool. Eighty-six glioma tissues of different World Health Organization (WHO) grades were analyzed immunohistochemically for tenascin-C expression. The influence of the specific tenascin-C isoforms produced by glioblastoma cells on proliferation and migration was examined in vitro using blocking antibodies recognizing all isoforms. In general, tenascin-C expression increased with tumor malignancy. Perivascular staining of tenascin-C around tumor-supplying blood vessels was observed in all glioblastoma tissues, whereas in WHO II and III gliomas, perivascular tenascin-C staining appeared less frequently. The appearance of perivascular tenascin-C correlated significantly with a shorter disease-free time. Analysis of proliferation and migration in the presence of blocking antibodies revealed an inhibition of proliferation by around 30% in all 3 glioblastoma cell cultures, as well as a decrease in migration of 30.6-46.7%. Thus we conclude that the endogenous pool of tenascin-C isoforms in gliomas supports both tumor cell proliferation and tumor cell migration. In addition, our data on the perivascular staining of tenascin-C in WHO II and III gliomas and its correlation with a shorter disease-free time suggest that tenascin-C may be a new and potent prognostic marker for an earlier tumor recurrence.
CosFace: Large Margin Cosine Loss for Deep Face Recognition (2018)

Face recognition has made extraordinary progress owing to the advancement of deep convolutional neural networks (CNNs). The central task of face recognition, including face verification and identification, involves face feature discrimination. However, the traditional softmax loss of deep CNNs usually lacks the power of discrimination. To address this problem, recently several loss functions such as center loss, large margin softmax loss, and angular softmax loss have been proposed. All these improved losses share the same idea: maximizing inter-class variance and minimizing intra-class variance. In this paper, we propose a novel loss function, namely large margin cosine loss (LMCL), to realize this idea from a different perspective. More specifically, we reformulate the softmax loss as a cosine loss by $L_2$ normalizing both features and weight vectors to remove radial variations, based on which a cosine margin term is introduced to further maximize the decision margin in the angular space. As a result, minimum intra-class variance and maximum inter-class variance are achieved by virtue of normalization and cosine decision margin maximization. We refer to our model trained with LMCL as CosFace. Extensive experimental evaluations are conducted on the most popular public-domain face recognition datasets such as MegaFace Challenge, Youtube Faces (YTF) and Labeled Face in the Wild (LFW). We achieve the state-of-the-art performance on these benchmarks, which confirms the effectiveness of our proposed approach.
Prostacyclin-dependent Apoptosis Mediated by PPARδ (2001)

Prostacyclin (PGI(2)) plays important roles in hemostasis both as a vasodilator and an endogenous inhibitor of platelet aggregation. PGI(2) functions in these roles through a specific IP receptor, a G protein-coupled receptor linked to G(s) and increases in cAMP. Here, we report that intracellular prostacyclin formed by expressing prostacyclin synthase in human embryonic kidney 293 cells promotes apoptosis by activating endogenous peroxisome proliferator-activated receptor delta (PPAR delta). In contrast, treatment of cells with extracellular prostacyclin or dibutyryl cAMP actually reduced apoptosis. On the contrary, treatment of the cells with RpcAMP (adenosine 3',5'-cyclic monophosphothioate, Rp-isomer), an antagonist of cAMP, enhanced prostacyclin-mediated apoptosis. The expression of an L431A/G434A mutant of PPAR delta completely blocked prostacyclin-mediated PPAR delta activation and apoptosis. These observations indicate that prostacyclin can act through endogenous PPAR delta as a second signaling pathway that controls cell fate.
Synthesis and Evaluation of Water‐Soluble Prodrugs of Ursodeoxycholic Acid (UDCA), an Anti‐apoptotic Bile Acid (2013)

Ursodeoxycholic acid (UDCA) is a bile acid with demonstrated anti-apoptotic activity in both in vitro and in vivo models. However, its utility is hampered by limited aqueous solubility. As such, water-soluble prodrugs of UDCA could have an advantage over the parent bile acid in indications where intravenous administration might be preferable, such as decreasing damage from stroke or acute kidney injury. Five phosphate prodrugs were synthesized, including one incorporating a novel phosphoryloxymethyl carboxylate (POMC) moiety. These prodrugs were highly water-soluble, but showed significant differences in chemical stability, with oxymethylphosphate prodrugs being the most unstable. In a series of NMR experiments, the POMC prodrug was bioactivated to UDCA by alkaline phosphatase (AP) faster than a prodrug containing a phosphate directly attached to the alcohol at the 3-position of UDCA. Both of these prodrugs showed significant anti-apoptotic activity in a series of in vitro assays, although the POMC prodrug required the addition of AP for activity, while the other compound was active without exogenous AP.
The Golden Age of Transfer Hydrogenation (2015)

ADVERTISEMENT RETURN TO ISSUEPREVReviewThe Golden Age of Transfer HydrogenationDong Wang* and Didier Astruc*View Author Information ISM, Université de Bordeaux, 351 Cours de la Libération, 33405 Talence Cedex, France*E-mail: [email protected]*E-mail: [email protected]Cite this: Chem. Rev. 2015, 115, 13, 6621–6686Publication Date (Web):June 10, 2015Publication History Received8 April 2015Published online10 June 2015Published inissue 8 July 2015https://pubs.acs.org/doi/10.1021/acs.chemrev.5b00203https://doi.org/10.1021/acs.chemrev.5b00203review-articleACS PublicationsCopyright © 2015 American Chemical SocietyRequest reuse permissionsArticle Views44377Altmetric-Citations1452LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Alcohols,Catalysts,Hydrogen,Ketones,Ligands Get e-Alerts
Lysophosphatidic Acid Is Constitutively Produced by Human Peritoneal Mesothelial Cells and Enhances Adhesion, Migration, and Invasion of Ovarian Cancer Cells (2006)

Lysophosphatidic acid (LPA) is both a potential marker and a therapeutic target for ovarian cancer. It is critical to identify the sources of elevated LPA levels in ascites and blood of patients with ovarian cancer. We show here that human peritoneal mesothelial cells constitutively produce LPA, which accounts for a significant portion of the chemotactic activity of the conditioned medium from peritoneal mesothelial cells to ovarian cancer cells. Both production of LPA by peritoneal mesothelial cells and the chemotactic activity in the conditioned medium can be blocked by HELSS [an inhibitor of the calcium-independent phospholipase A(2) (iPLA(2))] and AACOCF(3) [an inhibitor of both cytosolic PLA(2) (cPLA(2)) and iPLA(2)]. Moreover, cell-based enzymatic activity assays for PLA(2) indicate that peritoneal mesothelial cells have strong constitutive PLA(2) activity. Receptors for LPA, LPA(2), and LPA(3) are involved in the conditioned medium-induced chemotactic activity. Invasion of ovarian cancer cells into peritoneal mesothelial cells has also been analyzed and shown to require PLA(2), LPA receptors, and the mitogen-activated protein/extracellular signal-regulated kinase kinase/extracellular signal-regulated kinase signaling pathway. Thus, we show here, for the first time, that human peritoneal mesothelial cells constitutively produce bioactive lipid signaling molecules, such as LPA, via iPLA(2) and/or cPLA(2) activities. Conditioned medium from peritoneal mesothelial cells stimulate migration, adhesion, and invasion of ovarian cancer cells, and may play similar roles in vivo.