gebhart/patrepeval huggingface dataset:
Characterization of Anti-Advanced Glycation End Product Antibodies to Nonenzymatically Lysine-Derived and Arginine-Derived Glycated Products (2009)

N(epsilon)-(carboxymethyl)lysine (CML) and N(epsilon)-(carboxyethyl)lysine (CEL) termed advanced glycation end products (AGEs) are known to be produced by nonenzymatic glycation between bovine serum albumin (BSA) and D-glucose. This study is to characterize the immunoreactivity of anti-AGE antibodies including anti-CML and anti-CEL antibodies. Using AGE-modified BSA (AGE-BSA) as an immunogen, a polyclonal anti-AGE immunoglobulin G (IgG) was produced. The anti-AGE IgG could strongly detect AGEs formed on BSA, at least in part, AGEs produced on both residues Lys and Arg due to its immunoreaction with Lys-derived and Arg-derived AGEs produced by NaCNBH(3), a reducing agent, in amino acid glycation analysis, but the pre-immune serum could not. As the anti-CML antibody could also strongly react with AGE-BSA, this suggests that CML is a major nonenzymatically glycated product cross-linked to BSA. Furthermore, CEL is associated with distinguishable polymerization of BSA from CML polymerization of BSA, though weaker than CML and was not produced by Lys glycation analysis. These results indicate that the anti-AGE antibody is effective for detecting both Lys-derived and Arg-derived AGEs, and CML and CEL distinctively polymerize albumin as major AGEs present on AGE-BSA.
Evaluation of urinary metanephrine and normetanephrine enzyme immunoassay (ELISA) kits by comparison with isotope dilution mass spectrometry (1997)

Determination of urinary 3-O-methylated catecholamines (metanephrines) is generally considered a principal test for the clinical chemical diagnosis of pheochromocytoma and is currently performed predominantly with chromatographic techniques such as gas-liquid chromatography and HPLC. Enzyme immunoassays based on microtiter plate technology have recently been developed for the quantitative determination of urinary metanephrine (M) and normetanephrine (NM). We compared the results for urinary M and NM determined by these ELISA methods with those obtained by a recently developed isotope dilution mass spectrometric method. From this comparative study we can conclude that the investigated ELISA methods are applicable in the quantification of urinary M and thus can be successfully used to establish the diagnosis of pheochromocytoma. These relatively simple methods can be executed in any clinical laboratory and in time may replace the present, more complicated, chromatographic techniques.
A Heptad Motif of Leucine Residues Found in Membrane Proteins Can Drive Self-assembly of Artificial Transmembrane Segments (1999)

Specific interactions between alpha-helical transmembrane segments are important for folding and/or oligomerization of membrane proteins. Previously, we have shown that most transmembrane helix-helix interfaces of a set of crystallized membrane proteins are structurally equivalent to soluble leucine zipper interaction domains. To establish a simplified model of these membrane-spanning leucine zippers, we studied the homophilic interactions of artificial transmembrane segments using different experimental approaches. Importantly, an oligoleucine, but not an oligoalanine, se- quence efficiently self-assembled in membranes as well as in detergent solution. Self-assembly was maintained when a leucine zipper type of heptad motif consisting of leucine residues was grafted onto an alanine host sequence. Analysis of point mutants or of a random sequence confirmed that the heptad motif of leucines mediates self-recognition of our artificial transmembrane segments. Further, a data base search identified degenerate versions of this leucine motif within transmembrane segments of a variety of functionally different proteins. For several of these natural transmembrane segments, self-interaction was experimentally verified. These results support various lines of previously reported evidence where these transmembrane segments were implicated in the oligomeric assembly of the corresponding proteins.
Objective-Reinforced Generative Adversarial Networks (ORGAN) for Sequence Generation Models (2017)

In unsupervised data generation tasks, besides the generation of a sample based on previous observations, one would often like to give hints to the model in order to bias the generation towards desirable metrics. We propose a method that combines Generative Adversarial Networks (GANs) and reinforcement learning (RL) in order to accomplish exactly that. While RL biases the data generation process towards arbitrary metrics, the GAN component of the reward function ensures that the model still remembers information learned from data. We build upon previous results that incorporated GANs and RL in order to generate sequence data and test this model in several settings for the generation of molecules encoded as text sequences (SMILES) and in the context of music generation, showing for each case that we can effectively bias the generation process towards desired metrics.
Attenuated, Replication-Competent Herpes Simplex Virus Type 1 Mutant G207: Safety Evaluation in Mice (2000)

Herpes simplex virus type 1 (HSV-1) mutants that are attenuated for neurovirulence are being used for the treatment of cancer. We have examined the safety of G207, a multimutated replication-competent HSV-1 vector, in mice. BALB/c mice inoculated intracerebrally or intracerebroventricularly with 10(7) PFU of G207 survived for over 20 weeks with no apparent symptoms of disease. In contrast, over 80% of animals inoculated intracerebrally with 1.5 x 10(3) PFU of HSV-1 wild-type strain KOS and 50% of animals inoculated intracerebroventricularly with 10(4) PFU of wild-type strain F died within 10 days. Similarly, after intrahepatic inoculation of G207 (3 x 10(7) PFU) all animals survived for over 10 weeks, whereas no animals survived for even 1 week after inoculation with 10(6) PFU of KOS. After intracerebroventricular inoculation, LacZ expression was initially observed in the cells lining the ventricles and subarachnoid space; expression decreased until almost absent within 5 days postinfection, with no apparent loss of ependymal cells. G207 DNA could be detected by PCR in the brains of mice 8 weeks after intracerebral inoculation; however, no infectious virus could be detected after 2 days. As a model for latent HSV in the brain, we used survivors of an intracerebral inoculation of HSV-1 KOS at the 50% lethal dose. Inoculation of a high dose of G207 at the same stereotactic coordinates did not result in reactivation of detectable infectious virus or symptoms of disease. We conclude that G207 is safe at or above doses that were efficacious in mouse tumor studies.
Sulfonylurea and K+-Channel Opener Sensitivity of KATP Channels (1999)

The sensitivity of K(ATP) channels to high-affinity block by sulfonylureas and to stimulation by K(+) channel openers and MgADP (PCOs) is conferred by the regulatory sulfonylurea receptor (SUR) subunit, whereas ATP inhibits the channel through interaction with the inward rectifier (Kir6.2) subunit. Phosphatidylinositol 4, 5-bisphosphate (PIP(2)) profoundly antagonized ATP inhibition of K(ATP) channels expressed from cloned Kir6.2+SUR1 subunits, but also abolished high affinity tolbutamide sensitivity. By stabilizing the open state of the channel, PIP(2) drives the channel away from closed state(s) that are preferentially affected by high affinity tolbutamide binding, thereby producing an apparent loss of high affinity tolbutamide inhibition. Mutant K(ATP) channels (Kir6. 2[DeltaN30] or Kir6.2[L164A], coexpressed with SUR1) also displayed an "uncoupled" phenotype with no high affinity tolbutamide block and with intrinsically higher open state stability. Conversely, Kir6. 2[R176A]+SUR1 channels, which have an intrinsically lower open state stability, displayed a greater high affinity fraction of tolbutamide block. In addition to antagonizing high-affinity block by tolbutamide, PIP(2) also altered the stimulatory action of the PCOs, diazoxide and MgADP. With time after PIP(2) application, PCO stimulation first increased, and then subsequently decreased, probably reflecting a common pathway for activation of the channel by stimulatory PCOs and PIP(2). The net effect of increasing open state stability, either by PIP(2) or mutagenesis, is an apparent "uncoupling" of the Kir6.2 subunit from the regulatory input of SUR1, an action that can be partially reversed by screening negative charges on the membrane with poly-L-lysine.
Stochastic Models Inspired by Hybridization Theory for Short Oligonucleotide Arrays (2005)

High density oligonucleotide expression arrays are a widely used tool for the measurement of gene expression on a large scale. Affymetrix GeneChip arrays appear to dominate this market. These arrays use short oligonucleotides to probe for genes in an RNA sample. Due to optical noise, nonspecific hybridization, probe-specific effects, and measurement error, ad hoc measures of expression that summarize probe intensities can lead to imprecise and inaccurate results. Various researchers have demonstrated that expression measures based on simple statistical models can provide great improvements over the ad hoc procedure offered by Affymetrix. Recently, physical models based on molecular hybridization theory have been proposed as useful tools for prediction of, for example, nonspecific hybridization. These physical models show great potential in terms of improving existing expression measures. In this paper, we suggest that the system producing the measured intensities is too complex to be fully described with these relatively simple physical models, and we propose empirically motivated stochastic models that complement the above-mentioned molecular hybridization theory to provide a comprehensive description of the data. We discuss how the proposed model can be used to obtain improved measures of expression useful for the data analysts.
Fate of endogenous stem/progenitor cells following spinal cord injury (2006)

The adult mammalian spinal cord contains neural stem and/or progenitor cells that slowly multiply throughout life and differentiate exclusively into glia. The contribution of adult progenitors to repair has been highlighted in recent studies, demonstrating extensive cell proliferation and gliogenesis following central nervous system (CNS) trauma. The present experiments aimed to determine the relative roles of endogenously dividing progenitor cells versus quiescent progenitor cells in posttraumatic gliogenesis. Using the mitotic indicator bromodeoxyuridine (BrdU) and a retroviral vector, we found that, in the adult female Fisher 344 rat, endogenously dividing neural progenitors are acutely vulnerable in response to T8 dorsal hemisection spinal cord injury. We then studied the population of cells that divide postinjury in the injury epicenter by delivering BrdU or retrovirus at 24 hours after spinal cord injury. Animals were euthanized at five timepoints postinjury, ranging from 6 hours to 9 weeks after BrdU delivery. At all timepoints, we observed extensive proliferation of ependymal and periependymal cells that immunohistochemically resembled stem/progenitor cells. BrdU+ incorporation was noted to be prominent in NG2-immunoreactive progenitors that matured into oligodendrocytes, and in a transient population of microglia. Using a green fluorescence protein (GFP) hematopoietic chimeric mouse, we determined that 90% of the dividing cells in this early proliferation event originate from the spinal cord, whereas only 10% originate from the bone marrow. Our results suggest that dividing, NG2-expressing progenitor cells are vulnerable to injury, but a separate, immature population of neural stem and/or progenitor cells is activated by injury and rapidly divides to replace this vulnerable population.
Methylides from trimethylsilylmethylsulfonium, -ammonium, -immonium, and -phosphonium salts (1979)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMethylides from trimethylsilylmethylsulfonium, -ammonium, -immonium, and -phosphonium saltsE. Vedejs and G. R. MartinezCite this: J. Am. Chem. Soc. 1979, 101, 21, 6452–6454Publication Date (Print):October 1, 1979Publication History Published online1 May 2002Published inissue 1 October 1979https://pubs.acs.org/doi/10.1021/ja00515a061https://doi.org/10.1021/ja00515a061research-articleACS PublicationsRequest reuse permissionsArticle Views803Altmetric-Citations140LEARN 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
Synthesis and Gas Sorption Properties of a Metal-Azolium Framework (MAF) Material (2009)

A new strut containing an imidazolium tetracarboxylic acid core has been successfully incorporated into a microporous material using paddlewheel-coordinated copper(II) ions as nodes. Sorption studies conducted on this permanently microporous material imply that it can separate carbon dioxide from methane with high selectivity.
C1-inhibitor in patients with severe sepsis and septic shock: Beneficial effect on renal dysfunction (2002)

C1-inhibitor administration attenuated renal impairment in patients with severe sepsis or septic shock.
Reduced transcriptional activity in the p53 pathway of senescent cells revealed by the MDM2 antagonist nutlin-3 (2009)

The p53 tumor suppressor plays a key role in induction and maintenance of cellular senescence but p53-regulated response to stress in senescent cells is poorly understood. Here, we use the small-molecule MDM2 antagonist, nutlin-3a, to selectively activate p53 and probe functionality of the p53 pathway in senescent human fibroblasts, WI-38. Our experiments revealed overall reduction in nutlin-induced transcriptional activity of nine p53 target genes and four p53-regulated microRNAs, indicating that not only p53 protein levels but also its ability to activate transcription are altered during senescence. Addition of nutlin restored doxorubicin-induced p53 protein and transcriptional activity in senescent cells to the levels in early passage cells but only partially restored its apoptotic activity, suggesting that changes in both upstream and downstream p53 signaling during senescence are responsible for attenuated response to genotoxic stress.
Delineation of molecular mechanisms of sensitivity to lapatinib in breast cancer cell lines using global gene expression profiles (2007)

Lapatinib (GW572016) is a small-molecule dual inhibitor of epidermal growth factor receptor (ErbB1) and ErbB2 receptor kinase activities currently in phase III clinical trials. We used phosphoprotein and microarray analyses to carry out targeted pathway studies of phosphorylation and gene expression changes in human breast cancer cell lines in the presence or absence of lapatinib. Studies were done in four breast cancer cell lines, two of which were responsive and two of which were nonresponsive to lapatinib. Responsive cell lines, BT474 and SKBr3, constitutively overexpress ErbB2 and show an IC(50) of 25 or 32 nmol/L for lapatinib, respectively. In contrast, nonresponsive MDA-MB-468 and T47D cells expressed a low basal level of ErbB2 and showed IC(50) values in the micromolar range. Cells responsive to lapatinib exhibited strong differential effects on multiple genes in the AKT pathway. After 12 h of exposure to 1.0 micromol/L of lapatinib, AKT1, MAPK9, HSPCA, IRAK1, and CCND1 transcripts were down-regulated 7- to 25-fold in responsive BT474 and SKBr3 cells. In contrast, lapatinib weakly down-regulated the AKT pathway in nonresponsive breast cancer cell lines (<5-fold down-regulation of most genes in the pathway). Furthermore, the proapoptotic gene FOXO3A, which is negatively regulated by AKT, was up-regulated 7- and 25-fold in lapatinib-responsive SKBr3 and BT474 cells, respectively. Phosphorylated Akt and Akt-mediated phosphorylation of FOXO3A also decreased in responsive breast cancer cell lines exposed to lapatinib. Gene expression profiling also revealed that lapatinib stimulated the expression of estrogen and progesterone receptors and modulated the expression of genes involved in cell cycle control, glycolysis, and fatty acid metabolism. In BT474 and T47D cells, which expressed moderate basal levels of the estrogen and progesterone receptors, 1.0 micromol/L of lapatinib induced expression by 7- to 11-fold. These data provide insight into the mechanism of action of lapatinib in breast cancer cells.
The influence of the right to refuse treatment on precommitment patients. (1988)

The unplanned extension of the right to refuse treatment to the precommitment period is described in this paper. This extension of the right to refuse treatment has important public policy implications for the civil commitment process. These implications, as well as the pros and cons of the extension of the right to refuse treatment, are discussed.
Linear Differentiation of Cytotoxic Effectors into Memory T Lymphocytes (1999)

A central question in immunology is the origin of long-lived T cell memory that confers protection against recurrent infection. The differentiation of naïve T cell receptor transgenic CD8+ cells into effector cytotoxic T lymphocytes (CTLs) and memory CD8+ cells was studied. Memory CD8+ cells that were generated after strong antigenic stimulation were the progeny of cytotoxic effectors and retained antigen-specific cytolytic activity 10 weeks after adoptive transfer to antigen-free recipient mice. Thus, potential vaccines based on CTL memory will require the differentiation of naïve cells into post-effector memory T cells.
The Anchors Hierarchy: Using the Triangle Inequality to Survive High Dimensional Data (2000)

This paper is about metric data structures in high-dimensional or non-Euclidean space that permit cached sufficient statistics accelerations of learning algorithms. It has recently been shown that for less than about 10 dimensions, decorating kd- trees with additional &amp;quot;cached sufficient statistics &amp;quot; such as first and second moments and contingency tables can provide satisfying acceleration for a very wide range of statistical learning tasks such as kernel regression, locally weighted regression, k-means clustering, mixture modeling and Bayes Net learning. In this paper, we begin by defining the anchors hierarchy---a fast data structure and algorithm for localizing data based only on a triangle-inequality-obeying distance metric. We show how this, in its own right, gives a fast and effective clustering of data. But more importantly we show how it can produce a well-balanced structure similar to a Ball-Tree (Omohundro, 1991) or a kind of metric tree (Uhlmann, 1991;...
Facet Formation in Selective Silicon Epitaxial Growth (1985)

Facets observed adjacent to insulator films in selective silicon epitaxial growth were studied. The facet formation depended on the crystallographic orientation of the openings, and facets did not appear adjacent to the SiO 2 sidewall parallel to the [100] direction. Facet formation could also be suppressed by using a polysilicon-coated sidewall. Defects in the selective epi-layers were examined using transmission electron microscopy, and facet-free and defect-free epilayers were obtained.
Crystal engineering – nucleation, the key step (2002)

In the world of crystal engineering in which the focus of effort is on the assembly of molecular species by crystallisation, surprisingly little attention has been paid to the actual nucleation and crystallisation processes involved. This Highlight explores the structural aspects of the nucleation process in a range of small molecule systems. It uses a combination of thermodynamic, structural and modelling approaches in order to progress our understanding of the link between liquid phase molecular assemblies, which constitute crystal growth units, and their solid state counterparts, the supramolecular synthons.
Bioorthogonal Reactions for Labeling Proteins (2014)

ADVERTISEMENT RETURN TO ISSUEPREVIn FocusNEXTBioorthogonal Reactions for Labeling ProteinsKathrin Lang* and Jason W. Chin*View Author Information Medical Research Council - Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, U.K.*E-mail: [email protected]*E-mail: [email protected]Cite this: ACS Chem. Biol. 2014, 9, 1, 16–20Publication Date (Web):January 17, 2014Publication History Published online17 January 2014Published inissue 17 January 2014https://pubs.acs.org/doi/10.1021/cb4009292https://doi.org/10.1021/cb4009292newsACS PublicationsCopyright © 2014 American Chemical SocietyRequest reuse permissionsArticle Views21202Altmetric-Citations453LEARN 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:Addition reactions,Chemical reactions,Kinetic parameters,Labeling,Peptides and proteins Get e-Alerts
Pomalidomide plus low-dose dexamethasone in myeloma refractory to both bortezomib and lenalidomide: comparison of 2 dosing strategies in dual-refractory disease (2011)

Pomalidomide at doses of 2 or 4 mg/d has demonstrated excellent activity in patients with multiple myeloma (MM). We opened 2 sequential phase 2 trials using the pomalidomide with weekly dexamethasone (Pom/dex) regimen at differing doses to study the efficacy of this regimen in patients who have failed both lenalidomide and bortezomib. Pomalidomide was given orally 2 or 4 mg daily with dexamethasone 40 mg weekly. Thirty-five patients were enrolled in each cohort. Confirmed responses in the 2-mg cohort consisted of very good partial response (VGPR) in 5 (14%), partial response (PR) in 4 (11%), minor response (MR) in 8 (23%) for an overall response rate of 49%. In the 4-mg cohort, confirmed responses consisted of complete response (CR) in 1 (3%), VGPR in 3 (9%), PR in 6 (17%), MR in 5 (14%) for an overall response rate of 43%. Overall survival at 6 months is 78% and 67% in the 2- and 4-mg cohort, respectively. Myelosuppression was the most common toxicity. This nonrandomized data suggests no advantage for 4 mg over the 2 mg daily. Pomalidomide overcomes resistance in myeloma refractory to both lenalidomide and bortezomib. This trial is registered at http://ClinicalTrials.gov, number NCT00558896.