gebhart/patrepeval huggingface dataset:
Cardiomyocytes differentiated in vitro from embryonic stem cells developmentally express cardiac-specific genes and ionic currents. (1994)

Cardiomyocytes differentiated in vitro from pluripotent embryonic stem (ES) cells of line D3 via embryo-like aggregates (embryoid bodies) were characterized by the whole-cell patch-clamp technique during the entire differentiation period. Spontaneously contracting cardiomyocytes were enzymatically isolated by collagenase from embryoid body outgrowths of early, intermediate, and terminal differentiation stages. The early differentiated cardiomyocytes exhibited an outwardly rectifying, transient K+ current sensitive to 4-aminopyridine and an inward Ca2+ current but no Na+ current. The Ca2+ current showed all features of L-type Ca2+ current, being highly sensitive to 1,4-dihydropyridines but not to omega-conotoxin. Cardiomyocytes of intermediate stage were characterized by the additional expression of cardiac-specific Na+ current, the delayed K+ current, and If current. Terminally differentiated cardiomyocytes expressed a Ca2+ channel density about three times higher than that of early stage. In addition, two types of inwardly rectifying K+ currents (IK1 and IK,Ach) and the ATP-modulated K+ current were found. During cardiomyocyte differentiation, several distinct cell populations could be distinguished by their sets of ionic channels and typical action potentials presumably representing cardiac tissues with properties of sinus node, atrium, and ventricle. Reverse transcription polymerase chain reaction revealed the transcription of alpha- and beta-cardiac myosin heavy chain (MHC) genes synchronously with the first spontaneous contractions. Transcription of embryonic skeletal MHC gene at intermediate and terminal differentiation stages correlated with the expression of Na+ channels. The selective expression of alpha-cardiac MHC gene in ES cell-derived cardiomyocytes was demonstrated after ES cell transfection of the LacZ construct driven by the alpha-cardiac MHC promoter region followed by ES cell differentiation and beta-galactosidase staining. In conclusion, our data demonstrate that ES cell-derived cardiomyocytes represent a unique model to investigate the early cardiac development and permit pharmacological/toxicological studies in vitro.
Estimating the number of unseen variants in the human genome (2009)

The different genetic variation discovery projects (The SNP Consortium, the International HapMap Project, the 1000 Genomes Project, etc.) aim to identify as much as possible of the underlying genetic variation in various human populations. The question we address in this article is how many new variants are yet to be found. This is an instance of the species problem in ecology, where the goal is to estimate the number of species in a closed population. We use a parametric beta-binomial model that allows us to calculate the expected number of new variants with a desired minimum frequency to be discovered in a new dataset of individuals of a specified size. The method can also be used to predict the number of individuals necessary to sequence in order to capture all (or a fraction of) the variation with a specified minimum frequency. We apply the method to three datasets: the ENCODE dataset, the SeattleSNPs dataset, and the National Institute of Environmental Health Sciences SNPs dataset. Consistent with previous descriptions, our results show that the African population is the most diverse in terms of the number of variants expected to exist, the Asian populations the least diverse, with the European population in-between. In addition, our results show a clear distinction between the Chinese and the Japanese populations, with the Japanese population being the less diverse. To find all common variants (frequency at least 1%) the number of individuals that need to be sequenced is small ( approximately 350) and does not differ much among the different populations; our data show that, subject to sequence accuracy, the 1000 Genomes Project is likely to find most of these common variants and a high proportion of the rarer ones (frequency between 0.1 and 1%). The data reveal a rule of diminishing returns: a small number of individuals ( approximately 150) is sufficient to identify 80% of variants with a frequency of at least 0.1%, while a much larger number (> 3,000 individuals) is necessary to find all of those variants. Finally, our results also show a much higher diversity in environmental response genes compared with the average genome, especially in African populations.
Presence of double-strand breaks with single-base 3' overhangs in cells undergoing apoptosis but not necrosis. (1996)

Apoptotic cells in rat thymus were labeled in situ in paraffin-embedded and frozen tissue sections by ligation of double-stranded DNA fragments containing digoxigenin or Texas red. Two forms of double-stranded DNA fragments were prepared using the polymerase chain reaction: one was synthesized using Taq polymerase, which yields products with single-base 3' overhangs, and one using Pfu polymerase, which produces blunt-ended products. Both types of fragment could be ligated to apoptotic nuclei in thymus, indicating the presence in such nuclei of DNA double-strand breaks with single-base 3' overhangs as well as blunt ends. However, in nuclei with DNA damage resulting from a variety of nonapoptotic processes (necrosis, in vitro autolysis, peroxide damage, and heating) single-base 3' overhangs were either nondetectable or present at much lower concentrations than in apoptotic cells. Blunt DNA ends were present in such tissues, but at lower concentrations than in apoptotic cells. In contrast, in all of these forms of DNA damage, nuclei contained abundant 3'-hydroxyls accessible to labeling with terminal deoxynucleotidyl transferase. Thus, although single-base 3' overhangs and blunt ends are present in apoptotic nuclei, the specificity of the in situ ligation of 3'-overhang fragments to apoptotic nuclei indicates that apoptotic cells labeled in this way can readily be distinguished from cells with nonapoptotic DNA damage. These data are consistent with the involvement of an endonuclease similar to DNase I in apoptosis, which is predicted to leave short 3' overhangs as well as blunt ends in digestion of chromatin.
Piet Mondrian’s trees and the evolution in understanding multiple sclerosis, Charcot Prize Lecture 2011 (2013)

Four questions were posed about multiple sclerosis (MS) at the 2011 Charcot Lecture, Oct. 22, 2011. 1. The Male/Female Disparity: Why are women developing MS so much more frequently than men? 2. Neuronal and Glial Protection: Are there guardian molecules that protect the nervous system in MS? 3. Predictive Medicine: With all the approved drugs, how can we rationally decide which one to use? 4. The Precise Scalpel vs. the Big Hammer for Therapy: Is antigen-specific therapy for demyelinating disease possible? To emphasize how our views on the pathogenesis and treatment of MS are evolving, and given the location of the talk in Amsterdam, Piet Mondrian's progressive interpretations of trees serve as a heuristic.
Stimulation of Mature Canine Intervertebral Disc by Growth Factors (1991)

Although the role of growth factors in the regulation of phenotype, maintenance, and repair of cartilaginous tissues has been extensively evaluated, the response of intervertebral disc to growth factors has not been investigated. A tissue culture system for annular, transitional, and nuclear regions of mature canine intervertebral disc was devised to assess the proliferative response, as determined by 3H-thymidine incorporation, and the biosynthetic response, assayed by 35S-sulfate incorporation into proteoglycan, of these tissues to growth factors. The culture system achieved steady-state conditions in serum-free mediums at 4 days and was perturbed by plasma-derived equine serum, fetal calf serum, insulin-like growth factor-1, epidermal growth factor, fibroblast growth factor, and transforming growth factor-beta. Incorporation rates by the tissue regions of up to five times the control rate were recorded; the nucleus and transition zone responded more than anulus. Transforming growth factor-beta and epidermal growth factor elicited greater responses than fibroblast growth factor; insulin-like growth factor-1 produced a marginally significant response in the nucleus and no response in the anulus and transition. The intervertebral disc appeared to respond to the growth factors differently than cartilage, and this may represent inherent differences in cell biology. The biologic significance and basis of these responses require further evaluation. However, the responses observed, particularly in the nucleus and transition zone suggest the possibility that disc repair can be modulated by growth factors. A therapeutic approach to degenerative disc disease involving enhanced tissue repair by exogenous growth factors would be of great clinical significance.
A truncated form of fibroblast growth factor receptor 1 inhibits signal transduction by multiple types of fibroblast growth factor receptor. (1992)

A truncated form of the type 1 fibroblast growth factor receptor (FGFR1) lacking most of its cytoplasmic domain was tested for its ability to inhibit signal transduction by each of three different wild-type FGFRs (FGFR1, 2, and 3). When the truncated FGFR1 was expressed in Xenopus oocytes in excess of each wild-type FGFR, mobilization of intracellular calcium mediated by the wild-type FGFRs was completely blocked. The truncated FGFR did not inhibit signal transduction by the co-expressed platelet-derived growth factor beta-receptor. A form of truncated FGFR1 which lacked the first immunoglobulin-like domain also inhibited signal transduction by wild-type FGFRs. Truncated FGFR formed complexes with wild-type FGFR in the presence of basic FGF in intact cells. These observations were consistent with the hypothesis that the truncated FGFR interacted with wild-type FGFRs to form nonfunctional heterodimers, thus eliminating the signaling by the wild-type FGFRs. The observation that signaling by multiple types of FGFR can be blocked by a single type of truncated FGFR suggests that the different types of FGFR can interact with each other in ligand-mediated complexes. These findings provide a molecular basis for inhibiting the actions of FGFs in vivo.
Automatic Paper Chromatography (1949)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAutomatic Paper ChromatographyR. H. Müller and D. L. CleggCite this: Anal. Chem. 1949, 21, 9, 1123–1125Publication Date (Print):September 1, 1949Publication History Published online1 May 2002Published inissue 1 September 1949https://pubs.acs.org/doi/10.1021/ac60033a032https://doi.org/10.1021/ac60033a032research-articleACS PublicationsRequest reuse permissionsArticle Views1057Altmetric-Citations129LEARN 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 Get e-Alerts
Oxygen-deficient metal oxide nanostructures for photoelectrochemical water oxidation and other applications (2012)

This review presents highlights of the latest results of studies directed at developing oxygen-deficient metal oxides, including TiO(2), WO(3), and α-Fe(2)O(3), nanostructures as electrode materials, which show significantly enhanced performance in applications for photoelectrochemical water oxidation. The enhanced photoelectrochemical performance is attributed to improved electrical conductivities by controlled incorporation of oxygen vacancies as shallow donors for metal oxides. We also discuss the potential of these oxygen-deficient metal oxides for other energy conversion and storage applications, such as photocatalytic reactions and charge storage.
A novel bioassay for human somatogenic activity in serum samples supports the clinical reliability of immunoassays (2002)

Because the results of the Elegance ELISA and the bioassay correlate well, even though there is greater bioactivity at higher hormone concentrations, it is evident that an appropriate immunoassay is able to act as a reliable indicator for clinical assessment. In those rare cases where bio-inactive GH exists, our bioassay should provide an appropriate means to demonstrate this.
Deletion of NLRX1 increases fatty acid metabolism and prevents diet-induced hepatic steatosis and metabolic syndrome (2018)

NOD-like receptor (NLR)X1 (NLRX1) is an ubiquitously expressed inflammasome-independent NLR that is uniquely localized in mitochondria with as yet unknown effects on metabolic diseases. Here, we report that NLRX1 is essential in regulating cellular metabolism in non-immune parenchymal hepatocytes by decreasing mitochondrial fatty acid-dependent oxidative phosphorylation (OXPHOS) and promoting glycolysis. NLRX1 loss in mice has a profound impact on the prevention of diet-induced metabolic syndrome parameters, non-alcoholic fatty liver disease (NAFLD) progression, and renal dysfunction. Despite enhanced caloric intake, NLRX1 deletion in mice fed a western diet (WD) results in protection from liver steatosis, hepatic fibrosis, obesity, insulin resistance, glycosuria and kidney dysfunction parameters independent from inflammation. While mitochondrial content was equal, NLRX1 loss in hepatocytes leads to increased fatty acid oxidation and decreased steatosis. In contrast, glycolysis was decreased in NLRX1-deficient cells versus controls. Thus, although first implicated in immune regulation, we show that NLRX1 function extends to the control of hepatocyte energy metabolism via the restriction of mitochondrial fatty acid-dependent OXPHOS and enhancement of glycolysis. As such NLRX1 may be an attractive novel therapeutic target for NAFLD and metabolic syndrome.
Lung Pattern Classification for Interstitial Lung Diseases Using a Deep Convolutional Neural Network (2016)

Automated tissue characterization is one of the most crucial components of a computer aided diagnosis (CAD) system for interstitial lung diseases (ILDs). Although much research has been conducted in this field, the problem remains challenging. Deep learning techniques have recently achieved impressive results in a variety of computer vision problems, raising expectations that they might be applied in other domains, such as medical image analysis. In this paper, we propose and evaluate a convolutional neural network (CNN), designed for the classification of ILD patterns. The proposed network consists of 5 convolutional layers with 2 × 2 kernels and LeakyReLU activations, followed by average pooling with size equal to the size of the final feature maps and three dense layers. The last dense layer has 7 outputs, equivalent to the classes considered: healthy, ground glass opacity (GGO), micronodules, consolidation, reticulation, honeycombing and a combination of GGO/reticulation. To train and evaluate the CNN, we used a dataset of 14696 image patches, derived by 120 CT scans from different scanners and hospitals. To the best of our knowledge, this is the first deep CNN designed for the specific problem. A comparative analysis proved the effectiveness of the proposed CNN against previous methods in a challenging dataset. The classification performance ( ~ 85.5%) demonstrated the potential of CNNs in analyzing lung patterns. Future work includes, extending the CNN to three-dimensional data provided by CT volume scans and integrating the proposed method into a CAD system that aims to provide differential diagnosis for ILDs as a supportive tool for radiologists.
Application of Combinatorial Libraries and Protein Engineering to the Discovery of Novel Anti-Thrombotic Drugs (1995)

Combinatorial libraries and protein engineering represent two new powerful tools in drug discovery and development. The application of a combinatorial ssDNA library to thrombin led to the discovery of a sequence-specific nucleotide-based thrombin inhibitor (thrombin aptamer). The thrombin aptamer has a novel tertiary structure revealed by NMR and shows potent rapid anticoagulation with a short half-life in vivo. It has been used successfully to replace heparin in a canine cardiopulmonary bypass model. Functional mapping of the surface residues of thrombin led to the generation of a modified thrombin with markedly diminished procoagulant properties while retaining its ability to activate protein C. This engineered thrombin functions as a protein C activator and demonstrates potent anticoagulation in vivo without prolongation of the bleeding time.
Generation of polyclonal plasmablasts from peripheral blood B cells: a normal counterpart of malignant plasmablasts (2002)

A new way to identify tumor-specific genes is to compare gene expression profiles between malignant cells and their autologous normal counterparts. In patients with multiple myeloma, a major plasma cell disorder, normal plasma cells are not easily attainable in vivo. We report here that in vitro differentiation of peripheral blood B lymphocytes, purified from healthy donors and from patients with multiple myeloma, makes it possible to obtain a homogeneous population of normal plasmablastic cells. These cells were identified by their morphology, phenotype, production of polyclonal immunoglobulins, and expression of major transcription factors involved in B-cell differentiation. Oligonucleotide microarray analysis shows that these polyclonal plasmablastic cells have a gene expression pattern close to that of normal bone marrow-derived plasma cells. Detailed analysis of genes statistically differentially expressed between normal and tumor plasma cells allows the identification of myeloma-specific genes, including oncogenes and genes coding for tumor antigens. These data should help to disclose the molecular mechanisms of myeloma pathogenesis and to define new therapeutic targets in this still fatal malignancy. In addition, the comparison of gene expression between plasmablastic cells and B cells provides a new and powerful tool to identify genes specifically involved in normal plasma cell differentiation.
Brivaracetam, but not ethosuximide, reverses memory impairments in an Alzheimer’s disease mouse model (2015)

Our data confirm an intriguing therapeutic role of anticonvulsant drugs targeting synaptic vesicle protein 2A across AD mouse models. Chronic ethosuximide dosing did not reverse spatial memory impairments in APP/PS1 mice, despite reduction of SWDs. Our data indicate that SWDs are not a reliable surrogate marker of appropriate target engagement for reversal of memory dysfunction in APP/PS1 mice.
Transport properties of undoped and NH3-doped polycrystalline SnO2 with low background electron concentrations (2004)

A series of polycrystalline 1 μm thick SnO2 films were deposited onto borosilicate glass substrates by atmospheric pressure chemical vapor deposition. Unintentionally doped as-grown SnO2 layers had electron concentrations and mobility of 2–4×1017cm−3 and 25–30cm2∕Vs, respectively. Potential barriers and trap concentrations were calculated to be 30 meV and 2.3×1012cm−2, respectively. Upon N2∕vacuum annealing at 670 K for 15–20 min, the potential barrier height decreased to 8 meV and the electron mobility increased to 58cm2∕Vs. When doped with ammonia, the mobility of as-grown samples decreased to 0.5cm2∕Vs. The magnitude of the potential barriers varied, with ammonia doping, from 175 to 31 meV with trap densities of 4.7–1.2×1012cm−3, respectively. Upon vacuum∕N2 annealing at 670 K for 20 min, the electron mobilities of ammonia doped films recovered to 50–71cm2∕Vs, whereas the height of the potential barriers decreased to 3–4 meV with trap concentrations of 8–9×1011cm−2. The observed changes in the electrical properties are well described by a double back-to-back Schottky barrier model.
The Molecular Inflammatory Process in Aging (2006)

Emerging pathological evidence indicates that major chronic aging-related diseases such as atherosclerosis, arthritis, dementia, osteoporosis, and cardiovascular diseases, are inflammation-related. In this review, inflammation is examined as a possible underlying basis for the molecular alterations that link aging and agerelated pathological processes. A proposal for the molecular inflammation hypothesis of the aging views the redox derangement that occurs during aging as the major factor for increased risk for age-related inflammation. Accumulated data strongly indicate the activation of redox-sensitive transcription factors and dysregulated gene expression under the age-related oxidative stress seems to be the major culprits. Key players involved in the inflammatory process are the age-related upregulation of NF-κB, IL-1β, IL-6, TNFα, cyclooxygenase-2, adhesion molecules, and inducible NO synthase. Furthermore, data are presented on the molecular events involved in age-related NF-κB activation and phosphorylation by IκB kinase/NIK and MAPKs. Experimental data on antiaging calorie restriction (CR) for its antiinflammatory efficacy by suppressing the upregulated proinflammatory mediators will be reviewed. Also, the involvement of another super family of transcription factors, PPARs (PPARα, γ) as regulators of proinflammatory responses and NF-κB signaling pathway is described as well as a discussion on the physiological significance of a well-maintained balance between NF-κB and PPARs.
Inhibition of human immunodeficiency virus 1 protease in vitro: rational design of substrate analogue inhibitors. (1989)

Inhibitors of the protease from human immunodeficiency virus 1 (HIV-1) were designed, synthesized, and kinetically characterized. Analogues of a heptapeptide substrate of HIV-1 protease with sequence similar to the p17-p24 cleavage site in the natural substrate, Pr55gag, were synthesized in which the scissile dipeptide bond was replaced with bonds from six categories of stable mimics of an aspartic proteolysis transition state or intermediate. These mimics included an analogue of statine, hydroxyethylene isosteres, two categories of phosphinic acids, a reduced amide isostere, and an alpha,alpha-difluoroketone. The resulting peptide analogues were linear competitive inhibitors of purified recombinant HIV-1 protease with inhibition constants ranging from 18 nM to 40 microM depending on the type of inhibitor. A truncated inhibitor, an analogue of a hexapeptide, retained full inhibitory potency. The most potent inhibitors, containing the hydroxyethylene isostere, effectively blocked the proteolytic processing of a recombinant form of Pr55gag by HIV-1 protease in a cell-free assay.
Presence and subcellular localization of tyrosine aminotransferase and p-hydroxyphenyllactate dehydrogenase in epimastigotes ofTrypanosoma cruzi (1992)

Cell-free extracts of epimastigotes of Trypanosoma cruzi contain tyrosine aminotransferase (TAT) and p-hydroxyphenyllactate dehydrogenase (pHPLDH). The TAT activity could be separated from aspartate aminotransferase (ASAT) by polyacrylamide gel electrophoresis or DEAE-cellulose chromatography; the latter procedure also allowed complete separation of pHPLDH. The subcellular localization of both T. cruzi enzymes, as determined by digitonin extraction, subcellular fractionation by differential centrifugation, and isopycnic ultracentrifugation in sucrose gradients, was mainly cytosolic, with low mitochondrial activities.