gebhart/patrepeval huggingface dataset:
Accurate and reproducible invasive breast cancer detection in whole-slide images: A Deep Learning approach for quantifying tumor extent (2017)

With the increasing ability to routinely and rapidly digitize whole slide images with slide scanners, there has been interest in developing computerized image analysis algorithms for automated detection of disease extent from digital pathology images. The manual identification of presence and extent of breast cancer by a pathologist is critical for patient management for tumor staging and assessing treatment response. However, this process is tedious and subject to inter- and intra-reader variability. For computerized methods to be useful as decision support tools, they need to be resilient to data acquired from different sources, different staining and cutting protocols and different scanners. The objective of this study was to evaluate the accuracy and robustness of a deep learning-based method to automatically identify the extent of invasive tumor on digitized images. Here, we present a new method that employs a convolutional neural network for detecting presence of invasive tumor on whole slide images. Our approach involves training the classifier on nearly 400 exemplars from multiple different sites, and scanners, and then independently validating on almost 200 cases from The Cancer Genome Atlas. Our approach yielded a Dice coefficient of 75.86%, a positive predictive value of 71.62% and a negative predictive value of 96.77% in terms of pixel-by-pixel evaluation compared to manually annotated regions of invasive ductal carcinoma.
Comparison of stable human Treg and Th clones by transcriptional profiling (2009)

From cancerous and non-cancerous patients, we derived stable clones of CD4(+) Treg, defined as clones that expressed high CD25 at rest, were anergic in vitro, and suppressed the proliferation of co-cultured CD4(+) cells. A conserved region of FOXP3 intron 1 was demethylated in all Treg clones, whereas it was methylated in non-regulatory Th and CTL clones. In our panel of human clones, this stable epigenetic mark correlated better with suppressive activity than did FOXP3 mRNA or protein expression. We used expression microarrays to compare Treg and Th clones after activation, which is required for suppressive function. The transcriptional profile that is specific of activated Treg clones includes a TGF-beta signature. Both activated Treg and Th clones produced the latent form of TGF-beta. However, SMAD2 phosphorylation was observed after activation in the Treg but not in the Th clones, indicating that only activated Treg clones produced the bioactive form of TGF-beta. A TGF-beta signature was also displayed by a Th clone "suppressed" by a Treg clone. In conclusion, the hallmark of our panel of activated human Treg clones is to produce bioactive TGF-beta which has autocrine actions on Tregs and can have paracrine actions on other T cells.
Polycyclotrimerization of Dinitriles: A New Polymerization Route for the Construction of Soluble Nitrogen-Rich Polytriazines with Hyperbranched Structures and Functional Properties (2013)

A new synthetic route to nitrogen-rich hyperbranched polymers is developed. The polycyclotrimerizations of dinitriles [NC–C6H4–O(CH2)4O–C6H4–CN and NC–C6H4–O(CH2)4O–Ar–O(CH2)4O–C6H4–CN Ar = isopropylidenebis(1,4-phenylene), 9,9-fluorenylenebis(1,4-phenylene) and 1,2-diphenylethenylenebis(1,4-phenylene)] catalyzed by trifluoromethanesulfonic acid proceed smoothly in 1,2-dichlorobenzene at room temperature, affording hyperbranched poly(triazine)s with high degree of branching (DB ∼63%) in high yields (up to 74.7%). All the polymers are soluble and film-forming. The polymers are thermally and morphologically stable, showing high thermal-degradation and glass-transition temperatures up to 363 and 126.5 °C, respectively. They are optically transparent, allowing almost all visible and IR lights to transmit through. The polymer thin films show high refractive indices (n = 1.7456–1.5857) in a wide spectral region (400–1600 nm) as well as high Abbe numbers (νD′ up to 187.4) and low optical dispersions (D′ down to 0.005). Polymerization of tetraphenylethene-containing dinitrile generates a polymer with aggregation-induced emission characteristic, enabling it to be utilized as a sensitive and selective fluorescent chemosensor for ruthenium(III) ion detection.
Incretins and other peptides in the treatment of diabetes (2007)

Glucagon-like peptide-1 (7-36) amide (GLP-1) is a gut hormone, released postprandially,which stimulates insulin secretion and insulin gene expression as well as pancreatic B-cell growth. Together with glucose-dependent insulinotropic polypeptide (GIP), it is responsible for the incretin effect which is the augmentation of insulin secretion following oral administration of glucose. Patients with Type 2 diabetes have greatly impaired or absent incretin-mediated insulin secretion which is mainly as a result of decreased secretion of GLP-1. However,the insulinotropic action of GLP-1 is preserved in patients with Type 2 diabetes,and this has encouraged attempts to treat Type 2 diabetic patients with GLP-1.GLP-1 also possesses a number of potential advantages over existing agents for the treatment of Type 2 diabetes. In addition to stimulating insulin secretion and promoting pancreatic B-cell mass, GLP-1 suppresses glucagon secretion,delays gastric emptying and inhibits food intake. Continuous intravenous and subcutaneous administration significantly improves glycaemic control and causes reductions in both HbA1c and body weight. However, GLP-1 is metabolized extremely rapidly in the circulation by the enzyme dipeptidyl peptidase IV(DPP-IV). This is the probable explanation for the short-lived effect of single doses of native GLP-1, making it an unlikely glucose-lowering agent. The DPP-IV resistant analogue, exenatide, has Food and Drug Administration (FDA) approval for the treatment of Type 2 diabetes and selective DPP-IV inhibitors are underdevelopment. Both approaches have demonstrated remarkable efficacy in animal models and human clinical studies. Both are well tolerated and appear to have advantages over current therapies for Type 2 diabetes, particularly in terms of the effects on pancreatic B-cell restoration and potential weight loss.
16,16-Difluoro Steroid Hormone Analogs1 (1963)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT16,16-Difluoro Steroid Hormone Analogs1C. H. Robinson, N. F. Bruce, and E. P. OlivetoCite this: J. Org. Chem. 1963, 28, 4, 975–980Publication Date (Print):April 1, 1963Publication History Published online1 May 2002Published inissue 1 April 1963https://pubs.acs.org/doi/10.1021/jo01039a024https://doi.org/10.1021/jo01039a024research-articleACS PublicationsRequest reuse permissionsArticle Views64Altmetric-Citations10LEARN 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
Mycobacterium sp. as a Possible Cause of Hypersensitivity Pneumonitis in Machine Workers (1999)

Hypersensitivity pneumonitis (HP) in workers exposed to metal removal fluids (MRFs) is increasing. This study supports the hypothesis that aerosolized mycobacteria colonizing the MRFs likely cause the disease. Three case studies of HP outbreaks among metal workers showed potentially high exposures to a rare and newly proposed Mycobacterium species. Retrospective review of samples submitted to our laboratory showed an association between presence of mycobacteria and HP.
Glycosylation Focuses Sequence Variation in the Influenza A Virus H1 Hemagglutinin Globular Domain (2010)

Antigenic drift in the influenza A virus hemagglutinin (HA) is responsible for seasonal reformulation of influenza vaccines. Here, we address an important and largely overlooked issue in antigenic drift: how does the number and location of glycosylation sites affect HA evolution in man? We analyzed the glycosylation status of all full-length H1 subtype HA sequences available in the NCBI influenza database. We devised the "flow index" (FI), a simple algorithm that calculates the tendency for viruses to gain or lose consensus glycosylation sites. The FI predicts the predominance of glycosylation states among existing strains. Our analyses show that while the number of glycosylation sites in the HA globular domain does not influence the overall magnitude of variation in defined antigenic regions, variation focuses on those regions unshielded by glycosylation. This supports the conclusion that glycosylation generally shields HA from antibody-mediated neutralization, and implies that fitness costs in accommodating oligosaccharides limit virus escape via HA hyperglycosylation.
Regulation of sulphotransferase expression in the endometrium during the menstrual cycle, by oral contraceptives and during early pregnancy (1999)

The endometrium plays a key role in reproduction, and this function is tightly regulated by endogenous and xenobiotic steroids. Sulphation, catalysed by members of the sulphotransferase (SULT) enzyme family, is a major deactivating mechanism for steroid hormones and we have investigated the expression and regulation in vivo of SULT in the human endometrium. In the normal cycling endometrium, expression of the phenol sulphotransferases SULT1A1 and SULT1A3 and the oestrogen sulphotransferase SULT1E1 were observed, with SULT1A1 and SULT1E1 expression being higher in the luteal phase than in the follicular phase. No expression of the hydroxysteroid sulphotransferase SULT2A1 was detected at any time in the endometrium. In endometrium from women taking the combined oral contraceptive pill (OCP), SULT1E1 expression was virtually absent, and SULT1A1 expression was substantially reduced. Similarly, in early pregnancy (i.e. first trimester) endometrium, SULT1E1 expression was absent, although SULT1A1 and SULT1A3 expression were unaffected. Our results with normal endometrium support in-vitro data showing that SULT1E1 expression is regulated by progesterone. However, the data obtained from OCP and early pregnancy endometrium suggest that factors other than the concentration of circulating progesterone are involved in the regulation of the expression of this important enzyme in the endometrium.
Curcumin-induced inhibition of microglial activation (2000)

Conference Abstract| October 01 2000 Curcumin-induced inhibition of microglial activation K. K. Jung; K. K. Jung 15 Nokbun Dong Eunpyung Gu, Seoul, Republic of Korea Search for other works by this author on: This Site PubMed Google Scholar S. W. Yi; S. W. Yi 15 Nokbun Dong Eunpyung Gu, Seoul, Republic of Korea Search for other works by this author on: This Site PubMed Google Scholar S. Y. Kang; S. Y. Kang 15 Nokbun Dong Eunpyung Gu, Seoul, Republic of Korea Search for other works by this author on: This Site PubMed Google Scholar T. G. Kim; T. G. Kim 15 Nokbun Dong Eunpyung Gu, Seoul, Republic of Korea Search for other works by this author on: This Site PubMed Google Scholar J. H. Kang; J. H. Kang 15 Nokbun Dong Eunpyung Gu, Seoul, Republic of Korea Search for other works by this author on: This Site PubMed Google Scholar J. H. Lee; J. H. Lee 15 Nokbun Dong Eunpyung Gu, Seoul, Republic of Korea Search for other works by this author on: This Site PubMed Google Scholar S. H. Kim; S. H. Kim 15 Nokbun Dong Eunpyung Gu, Seoul, Republic of Korea Search for other works by this author on: This Site PubMed Google Scholar H. M. Han H. M. Han 15 Nokbun Dong Eunpyung Gu, Seoul, Republic of Korea Search for other works by this author on: This Site PubMed Google Scholar Biochem Soc Trans (2000) 28 (5): A305. https://doi.org/10.1042/bst028a305a Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter LinkedIn Cite Icon Cite Get Permissions Citation K. K. Jung, S. W. Yi, S. Y. Kang, T. G. Kim, J. H. Kang, J. H. Lee, S. H. Kim, H. M. Han; Curcumin-induced inhibition of microglial activation. Biochem Soc Trans 1 October 2000; 28 (5): A305. doi: https://doi.org/10.1042/bst028a305a Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Society Transactions Search Advanced Search This content is only available as a PDF. © 2000 Biochemical Society2000 Article PDF first page preview Close Modal You do not currently have access to this content.
Posttranscriptional regulation of hsp70 expression in human cells: effects of heat shock, inhibition of protein synthesis, and adenovirus infection on translation and mRNA stability. (1987)

We have examined the posttranscriptional regulation of hsp70 gene expression in two human cell lines, HeLa and 293 cells, which constitutively express high levels of HSP70. HSP70 mRNA translates with high efficiency in both control and heat-shocked cells. Therefore, heat shock is not required for the efficient translation of HSP70 mRNA. Rather, the main effect of heat shock on translation is to suppress the translatability of non-heat shock mRNAs. Heat shock, however, has a marked effect on the stability of HSP70 mRNA; in non-heat-shocked cells the half-life of HSP70 mRNA is approximately 50 min, and its stability increases at least 10-fold upon heat shock. Moreover, HSP70 mRNA is more stable in cells treated with protein synthesis inhibitors, suggesting that a heat shock-sensitive labile protein regulates its turnover. An additional effect on posttranscriptional regulation of hsp70 expression can be found in adenovirus-infected cells, in which HSP70 mRNA levels decline precipititously late during infection although hsp70 transcription continues unabated.
Low expression of GluR2 AMPA receptor subunit protein by human motor neurons (1999)

Disturbance of glutamate neurotransmission may contribute to motor neuron injury in amyotrophic lateral sclerosis. There is evidence that human motor neurons may express a specific profile of glutamate receptors, with low or absent expression of mRNA for the GluR2 AMPA receptor subunit, which has a crucial role in controlling calcium permeability. This study, using an immunocytochemical approach with a GluR2 specific antibody, shows that human upper and lower motor neurons have a very low/absent expression of GluR2 protein, in contrast to many other neuronal groups. Thus, it is likely that human motor neurons express a high proportion of atypical, calcium permeable AMPA receptors which may contribute to selective vulnerability and may allow cell-specific modulation of the actions of glutamate.
High efficiency transformation of E.coli by high voltage electroporation (1988)

E. coli can be transformed to extremely high efficiencies by subjecting a mixture of cells and DNA to brief but intense electrical fields of exponential decay waveform (electroporation). We have obtained 10(9) to 10(10) transformants/micrograms with strains LE392 and DH5 alpha, and plasmids pUC18 and pBR329. The process is highly dependent on two characteristics of the electrical pulse: the electric field strength and the pulse length (RC time constant). The frequency of transformation is a linear function of the DNA concentration over at least six orders of magnitude; and the efficiency of transformation is a function of the cell concentration. Most of the surviving cells are competent with up to 80% transformed at high DNA concentration. The mechanism does not appear to include binding of the DNA to the cells prior to entry. Possible mechanisms are discussed and a simple procedure for the practical use of this technique is presented.
Ph. Cibois, L'analyse des données en sociologie, Paris, P.U.F., 1984 (1985)

Genet Jean-Philippe. Ph. Cibois, L'analyse des données en sociologie, Paris, P.U.F., 1984. In: Le médiéviste et l'ordinateur, N°13, printemps 1985. Le livre médiéval et l'informatique. p. 22.
Nucleotide sequences of the mRNA's encoding the vesicular stomatitis virus N and NS proteins (1981)

The complete nucleotide sequences of the vesicular stomatitis virus (VSV) mRNA's encoding the N and NS proteins have been determined from the sequences of cDNA clones. The mRNA encoding the N protein is 1,326 nucleotides long, excluding polyadenylic acid. It contains an open reading frame for translation which extends from the 5'-proximal AUG codon to encode a protein of 422 amino acids. The N and mRNA is known to contain a major ribosome binding site at the 5'-proximal AUG codon and two other minor ribosome binding sites. These secondary sites have been located unambiguously at the second and third AUG codons in the N mRNA sequence. Translational initiation at these sites, if it in fact occurs, would result in synthesis of two small proteins in a second reading frame. The VSV and mrna encoding the NS protein is 815 nucleotides long, excluding polyadenylic acid, and encodes a protein of 222 amino acids. The predicted molecular weight of the NS protein (25,110) is approximately one-half of that predicted from the mobility of NS protein on sodium dodecyl sulfate-polyacrylamide gels. Deficiency of sodium dodecyl sulfate binding to a large negatively charged domain in the NS protein could explain this anomalous electrophoretic mobility.
Vascular endothelial growth factor and substrate mechanics regulate in vitro tubulogenesis of endothelial progenitor cells (2009)

Endothelial progenitor cells (EPCs) in the circulatory system have been suggested to maintain vascular homeostasis and contribute to adult vascular regeneration and repair. These processes require that EPCs break down the extracellular matrix (ECM), migrate, differentiate and undergo tube morphogenesis. Evidently, the ECM plays a critical role by providing biochemical and biophysical cues that regulate cellular behaviour. Using a chemically and mechanically tunable hydrogel to study tube morphogenesis in vitro, we show that vascular endothelial growth factor (VEGF) and substrate mechanics co-regulate tubulogenesis of EPCs. High levels of VEGF are required to initiate tube morphogenesis and activate matrix metalloproteinases (MMPs), which enable EPC migration. Under these conditions, the elasticity of the substrate affects the progression of tube morphogenesis. With decreases in substrate stiffness, we observe decreased MMP expression while increased cellular elongation, with intracellular vacuole extension and coalescence to open lumen compartments. RNAi studies demonstrate that membrane type 1-MMP (MT1-MMP) is required to enable the movement of EPCs on the matrix and that EPCs sense matrix stiffness through signalling cascades leading to the activation of the RhoGTPase Cdc42. Collectively, these results suggest that coupled responses for VEGF stimulation and modulation of substrate stiffness are required to regulate tube morphogenesis of EPCs.
A subset of HLA-B27 molecules contains peptides muchlonger than nonamers. (1994)

An unusual monoclonal antibody (MARB4) directed against HLA-B27 that reacts with only approximately 5-20% of the cell surface HLA-B27 was used for large-scale purification of these molecules. Subsequent mass spectrometry of HLA-B27-bound peptides showed that the minor MARB4-reactive population contained peptides primarily from 900 to 4000 Da in size (approximately 8-33 amino acid residues), whereas the major HLA-B27 population contained peptides in the mass range of 900-1400 Da (approximately 8-12 amino acid residues). Thus, a subset of HLA-B27 molecules binds to peptides much longer than nonamers. Typical HLA-B27-binding peptides contain arginine in position 2. Further analysis by Edman sequencing of the pooled bound peptides revealed that the major population contained substantial amounts of arginine at positions 1 and 9 (40-50%) and exclusively arginine at position 2, as expected. The minor population of peptides also contained detectable amounts of arginine at these positions, but at the level of only approximately 10%; no marked enrichment at any position was observed. These long HLA-B27-bound peptides could represent either intermediates in the formation of nonamers or adventitiously bound peptides. Lastly, in the TAP2 mutant cell line BM36.1 transfected with HLA-B*2705, MARB4-reactive HLA-B27 molecules were absent from the cell surface, indicating that the peptide transporter was required for delivery of the long peptides. Thus, during the folding of class I heavy chains, peptides of diverse lengths are available and participating.
Dual α2-Adrenergic Agonist and α1-Adrenergic Antagonist Actions of Dexmedetomidine on Human Isolated Endothelium-Denuded Gastroepiploic Arteries (2002)

The actions of dexmedetomidine (DEX) on human vascular smooth muscle are unclear. We investigated its effects on isolated, endothelium-denuded human gastroepiploic arteries in vitro and compared them with clonidine (CLO). DEX had little direct effect on resting tension, whereas CLO produced small contractile responses, an effect which is blocked by the α1-adrenergic antagonist prazosin. DEX markedly enhanced the high K+ (40 mmol/L)-induced contraction, and this effect was reversed by the α2-adrenergic antagonists yohimbine and rauwolscine but unaffected by prazosin. However, CLO had little effect on the K+ contractions. Interestingly, larger concentrations (>10−7 mol/L) of both α2-adrenergic stimulants significantly inhibited the contractions elicited by the α1-adrenergic agonist phenylephrine (10−6 mol/L) and, to a lesser extent, those elicited by the α1/α2-agonist norepinephrine (10−6 mol/L). These results suggest the possibility that DEX and CLO each have a high affinity for α1-adrenoceptors in human isolated gastroepiploic arteries, resulting in a reduced efficacy of α1-adrenergic activation by α-agonists. The differing affinities of the drugs for α1- and α2-adrenoceptors may help explain their additional actions: 1) DEX enhances the high K+-induced contraction presumably through α2-adrenoceptor activation, and 2) CLO acts on α1-adrenoceptors as a partial agonist when present alone.
Second-Generation Antibacterial Benzimidazole Ureas: Discovery of a Preclinical Candidate with Reduced Metabolic Liability (2014)

Compound 3 is a potent aminobenzimidazole urea with broad-spectrum Gram-positive antibacterial activity resulting from dual inhibition of bacterial gyrase (GyrB) and topoisomerase IV (ParE), and it demonstrates efficacy in rodent models of bacterial infection. Preclinical in vitro and in vivo studies showed that compound 3 covalently labels liver proteins, presumably via formation of a reactive metabolite, and hence presented a potential safety liability. The urea moiety in compound 3 was identified as being potentially responsible for reactive metabolite formation, but its replacement resulted in loss of antibacterial activity and/or oral exposure due to poor physicochemical parameters. To identify second-generation aminobenzimidazole ureas devoid of reactive metabolite formation potential, we implemented a metabolic shift strategy, which focused on shifting metabolism away from the urea moiety by introducing metabolic soft spots elsewhere in the molecule. Aminobenzimidazole urea 34, identified through this strategy, exhibits similar antibacterial activity as that of 3 and did not label liver proteins in vivo, indicating reduced/no potential for reactive metabolite formation.