gebhart/patrepeval huggingface dataset:
Therapeutic Outcome of Epstein-Barr Virus Positive T/NK Cell Lymphoma in the Upper Aerodigestive Tract (2002)

Expression of the natural killer (NK) cell antigen CD56 is uncommon in malignant lymphoma, but when it is, it is almost exclusively of the non-B cell lineage and show a preference for the nasal and nasopharyngeal region. T/NK cell lymphoma is known to be aggressive and refractory to treatment. It is highly associated with the Epstein-Barr Virus (EBV), but clinical investigations are rarely reported, that is until recently. We report here, on the clinical features and therapeutic outcomes of patients with T/NK cell lymphomas and its association with EBV. We reviewed fifty-four cases with peripheral T cell lymphomas in the upper aerodigestive tract between Jan. 1987 and Aug. 1998 from the Severance Hospital, Yonsei University College of Medicine. The diagnosis of T/NK cell lymphoma was made according to the expression of the NK cell markers, CD56 antigen and cytoplasmic CD3epsilon, in tumor specimens, by immunohistochemistry. Epstein-Barr early region (EBER) RNA was detected using in situ hybridization on paraffin-embedded sections. Among the 54 cases with malignant lymphomas occurring in the upper aerodigestive tract, 20 had T/NK cell lymphoma (37%). The primary sites of T/NK cell lymphomas were the nasal cavity, 12 cases (60%), the tonsils, 4 cases (20%), the nasopharynx, 2 cases (10%), and the oropharynx, 2 case (10%). There were no differences between the features, at diagnosis or therapeutic modalities for patients with T/NK cell lymphoma and non-T/NK cell lymphoma. The complete remission rate of T/NK cell lymphomas was lower than non-T/NK cell lymphomas (65% vs 85%, p=0.02). The overall survival of T/NK cell lymphomas was 13 months (1-74 month), which was significantly lower than non-T/NK cell lymphomas [60.6% with a median follow up of 22 months (1-101 month, p=0.02)]. Disease free survival of T/NK cell lymphomas was 22 months (4-66 month), significantly lower than non-T/NK cell lymphomas [73.8% with a median follow up of 22 months (2-95 month), p=0.04]. The overall survival rates for T/NK cell lymphomas were significantly lower than for EBV positive non-T/NK cell lymphomas (p=0.018). EBER RNA was detected in the paraffin-embedded tissue sections of all T/NK cell lymphomas, compared to only 17.6% (6 of 34 cases) for non- T/NK cell lymphomas. In conclusion, as patients with T/NK cell lymphomas showed poor clinical outcomes, and a high association with EBV positivity, clinical trials with more investigational therapeutic strategies, and further research into the relationship of EBV infection with pathogenesis of T/NK cell lymphoma is warranted.
Genetic Ablation in Transgenic Mice with an Attenuated Diphtheria Toxin A Gene (1990)

We have previously generated microphthalmic mice lacking lens fiber cells by targeting the expression of the diphtheria toxin A (DT-A) gene in transgenic mice with regulatory sequences associated with the mouse gamma 2-crystallin gene. Because of the extreme toxicity of DT to animal cells and the potential leakiness of many tissue-specific regulatory regions, we investigated whether there might be an experimental advantage in using a mutant, attenuated form of the DT-A gene (tox-176) fused to gamma 2-crystallin regulatory sequences to ablate fiber cells in the ocular lens. In contrast to the microphthalmia observed in transgenic animals carrying the native DT-A gene, independent lines of mice transgenic for the gamma 2tox176 construct displayed predominantly cataracts or clinical anophthalmia. These contrasting phenotypes were transmitted within each pedigree, although for some lines some phenotypic heterogeneity among offspring was noted. The difference in phenotype between cataractous and clinically anophthalmic transgenic lines could not be ascribed to differences in the transgene copy number. Instead, the results suggest that transgene expression and hence the extent of genetic ablation are modulated by the site of chromosomal integration and, to a lesser extent, by epigenetic events. They also suggest that the attenuated gamma 2tox176 construct can integrate into chromosomal regions that are particularly favorable for expression without compromising embryological development and therefore that the tox-176 gene may be more versatile and effective than the wild-type DT-A gene for achieving genetic ablation with a broad range of cell- or tissue-specific regulatory sequences.
Pathogen Burden, Inflammation, Proliferation and Apoptosis in Human In-Stent Restenosis (2004)

Pathogenic events leading to in-stent restenosis (ISR) are still incompletely understood. Among others, inflammation, immune reactions, deregulated cell death and growth have been suggested. Therefore, atherectomy probes from 21 patients with symptomatic ISR were analyzed by immunohistochemistry for pathogen burden and compared to primary target lesions from 20 stable angina patients. While cytomegalovirus, herpes simplex virus, Epstein-Barr virus and Helicobacter pylori were not found in ISR, acute and/or persistent chlamydial infection were present in 6/21 of these lesions (29%). Expression of human heat shock protein 60 was found in 8/21 of probes (38%). Indicated by distinct signals of CD68, CD40 and CRP, inflammation was present in 5/21 (24%), 3/21 (14%) and 2/21 (10%) of ISR cases. Cell density of ISR was significantly higher than that of primary lesions (977 +/- 315 vs. 431 +/- 148 cells/mm(2); p < 0.001). There was no replicating cell as shown by Ki67 or PCNA. TUNEL(+) cells indicating apoptosis were seen in 6/21 of ISR specimens (29%). Quantitative analysis revealed lower expression levels for each intimal determinant in ISR compared to primary atheroma (all p < 0.05). In summary, human ISR at the time of clinical presentation is characterized by low frequency of pathogen burden and inflammation, but pronounced hypercellularity, low apoptosis and absence of proliferation.
Consistency analysis and improvement for single-camera localization (2012)

In this paper, we study the problem of estimator inconsistency in single-camera simultaneous localization and mapping (MonoSLAM) from a standpoint of system observability. Specifically, we postulate that a leading cause of inconsistency is the gain of spurious information along unobservable directions, resulting in smaller uncertainties, larger estimation errors, and divergence. Moreover, we introduce an Observability-Constrained MonoSLAM (OC-MonoSLAM) approach, which explicitly enforces the unobservable directions of the system, hence preventing spurious information gain and reducing inconsistency. Our analysis, along with the proposed method for reducing inconsistency, are validated with simulation trials and real-world experimentation.
50 Years of computer architecture: From the mainframe CPU to the domain-specific tpu and the open RISC-V instruction set (2018)

IBM had four incompatible computer lines. Each had its own unique instruction-set architecture (ISA); I/O system; system software (assemblers, compilers, libraries); and market niches (business, scientific, real time). IBM engineers bet that they could invent a single ISA that would work for customers of all four lines. Moreover, the same program would run correctly on any implementation of that ISA, though at different speed and cost. That vision required a new way to build computers that would be binary compatible from the cheapest 8-bit model to the fastest 64-bit version.
The effect of fluid shear stress upon cell adhesion to fibronectin‐treated surfaces (1990)

Cell attachment to and spreading upon a surface is mediated by adhesion molecules, such as fibronectin. The role of fibronectin in maintaining cell adhesion was examined by measuring cell attachment following exposure of cells to laminar flow in a parallel-plate flow channel. 3T3 fibroblasts were allowed to adhere to glass slides with or without preadsorbed fibronectin for 2 h before exposure to shear stresses ranging from 5 to 140 dyne/cm2. For cells which adhered to glass surfaces, cell loss was biphasic with a significant loss of cells during the first 2 min of flow, followed by a much slower decline in the number of attached cells with time. Following exposure to shear stresses greater than 5 dyne/cm2, the number of attached cells decreased exponentially as the shear stress increased. The distribution of adhesive stresses among the population of cells was log-normal with a median of 50 dyne/cm2, a mean of 82 dyne/cm2 and a standard deviation of 108 dyne/cm2. After exposure to flow for 2 h, the adhesive stress of the remaining cells decreased to a mean value of 50 dyne/cm2. Cell adhesion after exposure to flow was increased by preadsorbing fibronectin to the glass surface. The initial loss of cells from fibronectin-treated glass following exposure to flow correlated with the degree of cell spreading. Preadsorbed fibronectin resulted in a greater number of bonds between the surface and the cell, which in turn promoted cell spreading and increased the adhesive strength of the cell.
Artificial intelligence approach to structure-activity studies. Computer automated structure evaluation of biological activity of organic molecules (1984)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTArtificial intelligence approach to structure-activity studies. Computer automated structure evaluation of biological activity of organic moleculesGilles KlopmanCite this: J. Am. Chem. Soc. 1984, 106, 24, 7315–7321Publication Date (Print):November 1, 1984Publication History Published online1 May 2002Published inissue 1 November 1984https://pubs.acs.org/doi/10.1021/ja00336a004https://doi.org/10.1021/ja00336a004research-articleACS PublicationsRequest reuse permissionsArticle Views967Altmetric-Citations343LEARN 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
Hydrogen peroxide-inducible proteins in Salmonella typhimurium overlap with heat shock and other stress proteins. (1986)

Hydrogen peroxide treatment induces the synthesis of 30 proteins in Salmonella typhimurium. Five of these proteins are also induced by heat shock, including the highly conserved DnaK protein. The induction of one of these five proteins by heat shock is dependent on oxyR, a positive regulator of hydrogen peroxide-inducible genes, while the induction of the other four by heat shock is oxyR independent. Five of the 30 hydrogen peroxide-inducible proteins have been identified, and their structural genes have been mapped. Other stresses such as nalidixic acid, ethanol, or cumene hydroperoxide treatment also induce subsets of the 30 hydrogen peroxide-inducible proteins as well as additional proteins. Hydrogen peroxide-inducible proteins are shown to be largely different from those proteins induced by aerobiosis. In addition, the expression of the katG (catalase) gene is shown to be regulated by oxyR at the level of mRNA.
Efficient Derivation of Lateral Plate and Paraxial Mesoderm Subtypes from Human Embryonic Stem Cells Through GSKi-Mediated Differentiation (2013)

The vertebrae mesoderm is a source of cells that forms a variety of tissues, including the heart, vasculature, and blood. Consequently, the derivation of various mesoderm-specific cell types from human embryonic stem cells (hESCs) has attracted the interest of many investigators owing to their therapeutic potential in clinical applications. However, the need for efficient and reliable methods of differentiation into mesoderm lineage cell types remains a significant challenge. Here, we demonstrated that inhibition of glycogen synthase kinase-3 (GSK-3) is an essential first step toward efficient generation of the mesoderm. Under chemically defined conditions without additional growth factors/cytokines, short-term GSK inhibitor (GSKi) treatment effectively drives differentiation of hESCs into the primitive streak (PS), which can potentially commit toward the mesoderm when further supplemented with bone morphogenetic protein 4. Further analysis confirmed that the PS-like cells derived from GSKi treatment are bipotential, being able to specify toward the endoderm as well. Our findings suggest that the bipotential, PS/mesendoderm-like cell population exists only at the initial stages of GSK-3 inhibition, whereas long-term inhibition results in an endodermal fate. Lastly, we demonstrated that our differentiation approach could efficiently generate lateral plate (CD34(+)KDR(+)) and paraxial (CD34(-)PDGFRα(+)) mesoderm subsets that can be further differentiated along the endothelial and smooth muscle lineages, respectively. In conclusion, our study presents a unique approach for generating early mesoderm progenitors in a chemically directed fashion through the use of small-molecule GSK-3 inhibitor, which may be useful for future applications in regenerative medicine.
Antimicrobial susceptibility testing in 90 min by bacterial cell count monitoring (2012)

The rise in antimicrobial resistance has become a serious global health problem. Restrictive use of antibiotics seems the only option to temper this accession since research in new antibiotics has halted. Antimicrobial stewardship programmes rely on quick access to susceptibility data. This study evaluated the concept of bacterial cell count monitoring as a fast method to determine susceptibility. Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus strains were tested for amoxicillin/piperacillin and gentamicin by three conventional methods (VITEK2(®) , Etest(®) and broth-macrodilution). Bacterial cell count monitoring reliably predicted susceptibility after 90 min for Escherichia coli and after 120 min for Pseudomonas aeruginosa and Staphylococcus aureus without any minor, major or very major discrepancies. Time-to-result was reduced by 74%, 83% and 76%, respectively. Bacterial cell count monitoring shows great potential for rapid susceptibility testing.
Efficient and simultaneous generation of hematopoietic and vascular progenitors from human induced pluripotent stem cells (2012)

The hematopoietic and vascular lineages are intimately entwined as they arise together from bipotent hemangioblasts and hemogenic endothelial precursors during human embryonic development. In vitro differentiation of human pluripotent stem cells toward these lineages provides opportunities for elucidating the mechanisms of hematopoietic genesis. We previously demonstrated the stepwise in vitro differentiation of human embryonic stem cells (hESC) to definitive erythromyelopoiesis through clonogenic bipotent primitive hemangioblasts. This system recapitulates an orderly hematopoiesis similar to human yolk sac development via the generation of mesodermal-hematoendothelial progenitor cells that give rise to endothelium followed by embryonic primitive and definitive hematopoietic cells. Here, we report that under modified feeder-free endothelial culture conditions, multipotent CD34⁺ CD45⁺ hematopoietic progenitors arise in mass quantities from differentiated hESC and human induced pluripotent stem cells (hiPSC). These hematopoietic progenitors arose directly from adherent endothelial/stromal cell layers in a manner resembling in vivo hematopoiesis from embryonic hemogenic endothelium. Although fibroblast-derived hiPSC lines were previously found inefficient in hemato-endothelial differentiation capacity, our culture system also supported robust hiPSC hemato-vascular differentiation at levels comparable to hESC. We present comparative differentiation results for simultaneously generating hematopoietic and vascular progenitors from both hESC and fibroblast-hiPSC. This defined, optimized, and low-density differentiation system will be ideal for direct single-cell time course studies of the earliest hematopoietic events using time-lapse videography, or bulk kinetics using flow cytometry analyses on emerging hematopoietic progenitors.
Serial analysis of gene expression in HIV‐1‐infected T cell lines (1999)

The gene expression profile of the HIV-1 infection state was analyzed in the human T cell line MOLT-4. Using the serial analysis of gene expression (SAGE) method, a total of 142¿ omitted¿603 SAGE tags were sequenced and identified, representing 43¿ omitted¿581 unique mRNA species. Comparison of expression patterns revealed that 53 cellular genes were differentially expressed upon HIV-1 infection. Northern blot and RT-PCR analyses confirmed the altered expression of the genes in both MOLT-4 and MT-4 cells. Up-regulated genes were mainly composed of transcription factors and genes related to T cell activation, whereas down-regulated genes were comprised of mitochondrial proteins, actin-related factors and translational factors. These findings indicate that persistent T cell activation, which may accelerate HIV-1 replication, and the disruption of cellular housekeeping genes including those involved in anti-apoptotic systems, may play an important role in HIV-1-induced pathogenesis.
Role of Dietary Supplements/Nutraceuticals in Chemoprevention through Induction of Cytoprotective Enzymes (2007)

ADVERTISEMENT RETURN TO ISSUEPREVOpen ForumNEXTRole of Dietary Supplements/Nutraceuticals in Chemoprevention through Induction of Cytoprotective EnzymesJed W. Fahey and Thomas W. KenslerView Author Information Departments of Pharmacology and Molecular Sciences, International Health, and Environmental Health Sciences, Johns Hopkins University, Baltimore, Maryland 21205 Cite this: Chem. Res. Toxicol. 2007, 20, 4, 572–576Publication Date (Web):March 16, 2007Publication History Received9 February 2007Published online16 March 2007Published inissue 1 April 2007https://pubs.acs.org/doi/10.1021/tx7000459https://doi.org/10.1021/tx7000459discussionACS PublicationsCopyright © 2007 American Chemical SocietyRequest reuse permissionsArticle Views557Altmetric-Citations43LEARN 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:Food,Peptides and proteins,Phytochemistry,Plant derived food,Plants Get e-Alerts
Structure-Function Analysis of Inositol Hexakisphosphate-induced Autoprocessing of the Vibrio cholerae Multifunctional Autoprocessing RTX Toxin (2008)

Vibrio cholerae secretes a large virulence-associated multifunctional autoprocessing RTX toxin (MARTX(Vc)). Autoprocessing of this toxin by an embedded cysteine protease domain (CPD) is essential for this toxin to induce actin depolymerization in a broad range of cell types. A homologous CPD is also present in the large clostridial toxin TcdB and recent studies showed that inositol hexakisphosphate (Ins(1,2,3,4,5,6)P(6) or InsP(6)) stimulated the autoprocessing of TcdB dependent upon the CPD (Egerer, M., Giesemann, T., Jank, T., Satchell, K. J., and Aktories, K. (2007) J. Biol. Chem. 282, 25314-25321). In this work, the autoprocessing activity of the CPD within MARTX(Vc) is similarly found to be inducible by InsP(6). The CPD is shown to bind InsP(6) (K(d), 0.6 microm), and InsP(6) is shown to stimulate intramolecular autoprocessing at both physiological concentrations and as low as 0.01 microm. Processed CPD did not bind InsP(6) indicating that, subsequent to cleavage, the activated CPD may shift to an inactive conformation. To further pursue the mechanism of autoprocessing, conserved residues among 24 identified CPDs were mutagenized. In addition to cysteine and histidine residues that form the catalytic site, 2 lysine residues essential for InsP(6) binding and 5 lysine and arginine residues resulting in loss of activity at low InsP(6) concentrations were identified. Overall, our data support a model in which basic residues located across the CPD structure form an InsP(6) binding pocket and that the binding of InsP(6) stimulates processing by altering the CPD to an activated conformation. After processing, InsP(6) is shown to be recycled, while the cleaved CPD becomes incapable of further binding of InsP(6).
Cysteine-Rich Peptide Family with Unusual Disulfide Connectivity from Jasminum sambac (2015)

Cysteine-rich peptides (CRPs) are natural products with privileged peptidyl structures that represent a potentially rich source of bioactive compounds. Here, the discovery and characterization of a novel plant CRP family, jasmintides from Jasminum sambac of the Oleaceae family, are described. Two 27-amino acid jasmintides (jS1 and jS2) were identified at the gene and protein levels. Disulfide bond mapping of jS1 by mass spectrometry and its confirmation by NMR spectroscopy revealed disulfide bond connectivity of C-1-C-5, C-2-C-4, and C-3-C-6, a cystine motif that has not been reported in plant CRPs. Structural determination showed that jS1 displays a well-defined structure framed by three short antiparallel β-sheets. Genomic analysis showed that jasmintides share a three-domain precursor arrangement with a C-terminal mature domain preceded by a long pro-domain of 46 residues and an intron cleavage site between the signal sequence and pro-domain. The compact cysteine-rich structure together with an N-terminal pyroglutamic acid residue confers jasmintides high resistance to heat and enzymatic degradation, including exopeptidase treatment. Collectively, these results reveal a new plant CRP structure with an unusual cystine connectivity, which could be useful as a scaffold for designing peptide drugs.