gebhart/patrepeval huggingface dataset:
Subversion of Cellular Autophagosomal Machinery by RNA Viruses (2005)

Infection of human cells with poliovirus induces the proliferation of double-membraned cytoplasmic vesicles whose surfaces are used as the sites of viral RNA replication and whose origin is unknown. Here, we show that several hallmarks of cellular autophagosomes can be identified in poliovirus-induced vesicles, including colocalization of LAMP1 and LC3, the human homolog of Saccharomyces cerevisiae Atg8p, and staining with the fluorophore monodansylcadaverine followed by fixation. Colocalization of LC3 and LAMP1 was observed early in the poliovirus replicative cycle, in cells infected with rhinoviruses 2 and 14, and in cells that express poliovirus proteins 2BC and 3A, known to be sufficient to induce double-membraned vesicles. Stimulation of autophagy increased poliovirus yield, and inhibition of the autophagosomal pathway by 3-methyladenine or by RNA interference against mRNAs that encode two different proteins known to be required for autophagy decreased poliovirus yield. We propose that, for poliovirus and rhinovirus, components of the cellular machinery of autophagosome formation are subverted to promote viral replication. Although autophagy can serve in the innate immune response to microorganisms, our findings are inconsistent with a role for the induced autophagosome-like structures in clearance of poliovirus. Instead, we argue that these double-membraned structures provide membranous supports for viral RNA replication complexes, possibly enabling the nonlytic release of cytoplasmic contents, including progeny virions, from infected cells.
Urokinase-type plasminogen activator, receptor, and inhibitor correlating with gelatinase-B (MMP-9) contribute to inflammation in gouty arthritis of the knee. (2006)

These results show a correlation of the PA/plasmin system and MMP-9 in SF from patients with gouty arthritis, resulting in increased PA catalytic activity and contributing to inflammation in gouty arthritis.
Super-resolution from image sequences-a review (2002)

Growing interest in super-resolution (SR) restoration of video sequences and the closed related problem of construction of SR still images from image sequences has led to the emergence of several competing methodologies. We review the state of the art of SR techniques using a taxonomy of existing techniques. We critique these methods and identified areas which promise performance improvements.
Cotreatment with the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) enhances imatinib-induced apoptosis of Bcr-Abl–positive human acute leukemia cells (2003)

Here we demonstrate that treatment with SAHA (suberoylanilide hydroxamic acid), a known inhibitor of histone deacetylases (HDACs), alone induced p21 and/or p27 expressions but decreased the mRNA and protein levels of Bcr-Abl, which was associated with apoptosis of Bcr-Abl-expressing K562 and LAMA-84 cells. Cotreatment with SAHA and imatinib (Gleevec) caused more down-regulation of the levels and auto-tyrosine phosphorylation of Bcr-Abl and apoptosis of these cell types, as compared with treatment with either agent alone (P <.05). This finding was also associated with a greater decline in the levels of phospho-AKT and Bcl-x(L). Significantly, treatment with SAHA also down-regulated Bcr-Abl levels and induced apoptosis of CD34(+) leukemia blast progenitor cells derived from patients who had developed progressive blast crisis (BC) of chronic myelocytic leukemia (CML) while receiving therapy with imatinib. Taken together, these findings indicate that cotreatment with SAHA enhances the cytotoxic effects of imatinib and may have activity against imatinib-refractory CML-BC.
A Comparison of Gene Expression Signatures from Breast Tumors and Breast Tissue Derived Cell Lines (2001)

Cell lines derived from human tumors have historically served as the primary experimental model system for exploration of tumor cell biology and pharmacology. Cell line studies, however, must be interpreted in the context of artifacts introduced by selection and establishment of cell lines in vitro. This complication has led to difficulty in the extrapolation of biology observed in cell lines to tumor biology in vivo. Modern genomic analysis tool like DNA microarrays and gene expression profiling now provide a platform for the systematic characterization and classification of both cell lines and tumor samples. Studies using clinical samples have begun to identify classes of tumors that appear both biologically and clinically unique as inferred from their distinctive patterns of expressed genes. In this review, we explore the relationships between patterns of gene expression in breast tumor derived cell lines to those from clinical tumor specimens. This analysis demonstrates that cell lines and tumor samples have distinctive gene expression patterns in common and underscores the need for careful assessment of the appropriateness of any given cell line as a model for a given tumor subtype.
The ArcB Sensor Kinase of Escherichia coli : Genetic Exploration of the Transmembrane Region (2000)

The Arc two-component signal transduction system of Escherichia coli regulates the expression of numerous operons in response to respiratory growth conditions. Cellular redox state or proton motive force (Delta(H(+))) has been proposed to be the signal for the membrane-associated ArcB sensor kinase. This study provided evidence for a short ArcB periplasmic bridge that contains a His47. The dispensability of this amino acid, the only amino acid with a pK in the physiological range, renders the Delta(H(+)) model unlikely. Furthermore, results from substituting membrane segments of ArcB with counterparts of MalF indicate that the region does not play a stereospecific role in signal reception.
Oncofetal antigen 5T4 expression as a prognostic factor in patients with gastric cancer. (2002)

The assessment of 5T4 expression may be useful in identifying gastric cancer patients with a poor prognosis.
Software-to-hardware conversion: automating the process (1994)

Design automation has become an increasingly important link in the development of integrated circuits. CAD/CAE systems have enabled designers to reduce the overall project time, errors and thereby cost. The automation has been limited to development tools capable of emulating hardware, synthesizing the appropriate structures and performing the layout of these structures and routing the interconnections. Generally each tool operates independently while generating outputs that are not readily useable by other CAD tools. The development of a process by which a design team may convert software to a hardware platform would enhance the available automated CAD/CAE tools. The development of such an automated design process is proposed and will be verified by converting a standard algorithm for voice coding from software to hardware. Several main features of this proposal will be the ability of the designer to perform an accurate feasibility study of the power and area requirements of the algorithm once implemented in hardware. The performance of the algorithm under the restriction of hardware will also be verified before commitment to silicon.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
HIV protease inhibitors restore impaired T-cell proliferative response in vivo and in vitro: a viral-suppression–independent mechanism (2000)

In 99 adults infected with human immunodeficiency virus type 1 (HIV-1) who received highly active antiretroviral therapy (HAART) (including 2 nucleoside analogues and 1 or 2 protease inhibitors) for 1 year, CD4+ and CD8+ T cells (including memory and naive subsets) increased similarly among patients with sustained plasma viral load decrease, transient decrease, or no decrease. A linear correlation was observed between the decrease in serum β2-microglobulin concentration (an independent surrogate marker of HIV disease) and the increase in peripheral blood T-cells (CD4+ and CD8+) counts. In vitro, HIV protease inhibitors indinavir and saquinavir (but not nucleoside analogues) enhanced the survival of patients' peripheral blood T cells at doses that are at least 30-fold lower than those required for achieving 90% viral inhibition in the same cultures. This enhanced T-cell survival (which is similar for CD4 and CD8 cells) was associated with a restoration of T-cell proliferative response to immune stimuli. However, neither TCR/CD3-ligation– nor Fas-ligation–triggered apoptosis was affected by either of the 2 protease inhibitors. A reduction in apoptosis observed after prolonged culture of patient T cells in the presence of the protease inhibitors could result from restored T-cell proliferation. These findings explain the discrepancies between virologic and immunologic responses that are increasingly reported in patients receiving HAART, and may provide insights into the pathogenesis of HIV infection.
Variation in RNA-Seq Transcriptome Profiles of Peripheral Whole Blood from Healthy Individuals with and without Globin Depletion (2014)

Globin depletion appears to meaningfully improve the quality of peripheral whole blood RNA-Seq data, and may improve our ability to detect true biological variation. Some concerns remain, however. Key amongst them the significant reduction in RNA yields following globin depletion. More generally, our investigation of technical and biological variation with and without globin depletion finds that high-throughput sequencing by RNA-Seq is highly reproducible within a large dynamic range of detection and provides an accurate estimation of RNA concentration in peripheral whole blood. High-throughput sequencing is thus a promising technology for whole blood transcriptomics and biomarker discovery.
Cooperative inhibitory effect of ZD1839 (Iressa) in combination with 17‐AAG on glioma cell growth (2006)

ZD1839 ("Iressa") is an orally active, selective epidermal growth factor (EGF) receptor-tyrosine kinase inhibitor. We evaluated the antitumor activity of ZD1839 in combination with HSP90 antagonist, 17-AAG in malignant human glioma cell lines. ZD1839 independently produced a dose-dependent inhibition of cellular proliferation in glioma cells grown in culture with time- and dose-dependent accumulation of cells in G(1) phase of the cell cycle on flow cytometric analysis, although the concentrations required for optimal efficacy were at or above the limits of clinically achievable levels. Because the heat shock protein (HSP) is involved in the conformational maturation of a number of signaling proteins critical to the proliferation of malignant glioma cells, we hypothesized that the HSP90 inhibitor 17-AAG would potentiate ZD 1839-mediated glioma cytotoxicity by decreasing the activation status of EGF receptor, as well as down regulating the levels of other relevant signaling effectors. We, therefore, examined the effects of ZD1839 and 17-AAG, alone and in combination, on signal transduction and apoptosis in a series of malignant glioma cell lines. Simultaneous exposure to these inhibitors significantly induced cell death and quantitative analysis revealed that interaction between ZD1839 and 17-AAG-induced cytotoxicity was synergistic, leading to a pronounced increase in active caspase-3 and PARP cleavage. No significant growth inhibition or caspase activation was seen in control cells. The enhanced cytotoxicity of this combination was associated with diminished Akt activation and a significant downregulation of EGFR receptor, Raf-1 and mitogen activated protein kinase (MAPK). Cells exposed to 17-AAG and ZD1839 displayed a significant reduction in cell cycle regulatory proteins, such as CDK4 and CDK6. Taken together, these findings suggest that ZD1839, an EGF receptor tyrosine kinase inhibitor, plays a critical role in regulating the apoptotic response to 17-AAG and that multi-site targeting of growth signaling and cell survival pathways could provide a potent strategy to treat patients with malignant gliomas.
Rationale of anti-CD19 immunotherapy: an option to target autoreactive plasma cells in autoimmunity (2012)

Anti-CD20 therapy using rituximab directly targeting B cells has been approved for treatment of non-Hodgkin lymphoma, rheumatoid arthritis and anti-neutrophil cytoplasmic antibody-associated vasculitides and has led to reappreciation of B-lineage cells for anti-rheumatic treatment strategies. Moreover, blocking B-cell activating factor with belimumab, a drug that is licensed for treatment of active, seropositive systemic lupus erythematosus (SLE), represents an alternative, indirect anti-B-cell approach interfering with proper B-cell development. While these approaches apparently have no substantial impact on antibody-secreting plasma cells, challenges to improve the treatment of difficult-to-treat patients with SLE remain. In this context, anti-CD19 antibodies have the promise to directly target autoantibody-secreting plasmablasts and plasma cells as well as early B-cell differentiation stages not covered by anti-CD20 therapy. Currently known distinct expression profiles of CD19 by human plasma cell subsets, experiences with anti-CD19 therapies in malignant conditions as well as the rationale of targeting autoreactive plasma cells in patients with SLE are discussed in this review.
Expression of Antisense to DNA Methyltransferase mRNA Induces DNA Demethylation and Inhibits Tumorigenesis (1995)

Many tumor cell lines overexpress DNA methyltransferase (MeTase) activity; however it is still unclear whether this increase in DNA MeTase activity plays a causal role in naturally occurring tumors and cell lines, whether it is critical for the maintenance of transformed phenotypes, and whether inhibition of the DNA MeTase in tumor cells can reverse transformation. To address these basic questions, we transfected a murine adrenocortical tumor cell line Y1 with a chimeric construct expressing 600 base pairs from the 5' of the DNA MeTase cDNA in the antisense orientation. The antisense transfectants show DNA demethylation, distinct morphological alterations, are inhibited in their ability to grow in an anchorage-independent manner, and exhibit decreased tumorigenicity in syngeneic mice. Ex vivo, cells expressing the antisense construct show increased serum requirements, decreased rate of growth, and induction of an apoptotic death program upon serum deprivation. 5-Azadeoxycytidine-treated cells exhibit a similar dose-dependent reversal of the transformed phenotype. These results support the hypothesis that the DNA MeTase is actively involved in oncogenic transformation.
A parallel processor architecture for graphics arithmetic operations (1987)

Interactive 3D graphics applications require significant arithmetic processing to handle complex models, particularly if realistic rendering techniques are used. Current semiconductor technology cannot provide the necessary performance without some form of multi-processing.This paper describes a graphics processor architecture which can be configured with an arbitrary number of identical processors operating in parallel. Each of the parallel processors can be programmed identically as if it were a single processor system, substantially simplifying software development and allowing complex rendering functions to take advantage of the multiple processors. The architecture described is able to achieve extremely high performance while allowing the price/performance of the system to be optimized for a given application.Techniques are described for handling graphics command distribution, sequencing of commands which must be processed in order, parallel processing of graphics primitive picking, and handling inquiry (read-back) commands.
PERCUTANEOUS RADIO FREQUENCY ABLATION OF SMALL RENAL TUMORS: INITIAL RESULTS (2002)

Percutaneous radio frequency ablation of small renal tumor is well tolerated and minimally invasive. It will remain experimental until procedural and imaging parameters that correlate with tumor destruction are validated.
Improved low molecular weight Myc-Max inhibitors (2007)

Compounds that selectively prevent or disrupt the association between the c-Myc oncoprotein and its obligate heterodimeric partner Max (Myc-Max compounds) have been identified previously by high-throughput screening of chemical libraries. Although these agents specifically inhibit the growth of c-Myc-expressing cells, their clinical applicability is limited by their low potency. We describe here several chemical modifications of one of these original compounds, 10058-F4, which result in significant improvements in efficacy. Compared with the parent structure, these analogues show enhanced growth inhibition of c-Myc-expressing cells in a manner that generally correlates with their ability to disrupt c-Myc-Max association and DNA binding. Furthermore, we show by use of a sensitive fluorescence polarization assay that both 10058-F4 and its active analogues bind specifically to monomeric c-Myc. These studies show that improved Myc-Max compounds can be generated by a directed approach involving deliberate modification of an index compound. They further show that the compounds specifically target c-Myc, which exists in a dynamic and relatively unstructured state with only partial and transient alpha-helical content.
Therapeutic potential of new hydrogen sulfide-releasing hybrids (2010)

A new class of hydrogen sulfide (H(2)S)-donating hybrids combined with pharmacologically active compounds is presented in this article. The pharmacological profiles of some hybrid lead compounds in the areas of inflammation, H(2)S-donating diclofenac (ACS 15); cardiovascular, H(2)S-donating aspirin (ACS 14); urology, H(2)S-donating sildenafil (ACS 6); and neurodegenerative, H(2)S-donating latanoprost (ACS 67) for glaucoma treatment and H(2)S-donating levodopa (ACS 84) for Parkinson's disease, are described. The new H(2)S-releasing hybrids demonstrate remarkable improvement in activity and tolerability as compared with the related parent compounds, suggesting an active pharmacological role for H(2)S. Finally the mechanism(s) of action of glutathione-dependent and independent, and of gas (H(2)S) release (spontaneous or enzymatic) and its implications for clinical pharmacology perspectives will be also discussed.
Detection of bcr - abl Fusion in Chronic Myelogeneous Leukemia by in Situ Hybridization (1990)

Chronic myelogeneous leukemia (CML) is genetically characterized by fusion of the bcr and abl genes on chromosomes 22 and 9, respectively. In most cases, the fusion involves a reciprocal translocation t(9;22)(q34;q11), which produces the cytogenetically distinctive Philadelphia chromosome (Ph 1 ). Fusion can be detected by Southern (DNA) analysis or by in vitro amplification of the messenger RNA from the fusion gene with polymerase chain reaction (PCR). These techniques are sensitive but cannot be applied to single cells. Two-color fluorescence in situ hybridization (FISH) was used with probes from portions of the bcr and abl genes to detect the bcr - abl fusion in individual blood and bone marrow cells from six patients. The fusion event was detected in all samples analyzed, of which three were cytogenetically Ph 1 -negative. One of the Ph 1 -negative samples was also PCR-negative. This approach is fast and sensitive, and provides potential for determining the frequency of the abnormality in different cell lineages.
The Glucagon-Like Peptides (1999)

I. Introduction II. History of the Incretin Concept: Discovery of Gastric Inhibitory Polypeptide III. Discovery of GLP-1 IV. Structures of GLPs and Family of Glucagon-Related Peptides V. Tissue Distribution of the Expression of GLPs A. Pancreatic α-cells B. Intestinal L cells C. Central nervous system VI. Proglucagon Biosynthesis A. Organization/structure of the proglucagon gene B. Regulation of glucagon gene expression C. Posttranslational processing of proglucagon VII. Regulation of GLP Secretion A. Overview B. Intracellular signals C. Carbohydrates D. Fats E. Proteins F. Endocrine G. Neural H. GLP-2 VIII. Metabolism of GLPs A. GLP-1 B. GLP-2 IX. Physiological Actions of GLPs A. Overview B. Pancreatic islets C. Counterregulatory actions of GLP-1 and leptin on β-cells D. Stomach E. Lung F. Brain G. Liver, skeletal muscle, and fat H. Pituitary, hypothalamus, and thyroid I. Cardiovascular system J. GLP-2 X. GLP Receptors A. Structure B. Signaling C. Distribution D. Regulation E. GLP-2 XI. Pathophysiology o...
Pricing-To-Market In Korean Manufacturing Exports (1995)

This paper shows that pricing-to-market behavior is prevalent is sixteen Korean manufacturing export industries. Since Korea is a relatively country, its pricing-to-market can be explained by the market power asymmetry between home and export markets. This explanation yields two empirical predictions that are examined here. First, pricing-to-market is affected by export market shares. Second, export prices are effected by the exchange rate of a dominant third country. The date provide support for the first prediction. [D4,E3]
Biomimetic EMG-prosthesis-hand (2002)

The purpose of this study is to develop a myoelectric prosthetic hand that simulates fundamental dynamic properties of the neuromuscular control system of human hand. In particular, this prosthetic hand mimics the property that both muscle viscoelasticity and gain of the stretch reflex vary linearly with the activity of muscle. Those nonlinear properties of the neuromuscular control system were realized by using a position control system of the finger movement, force feedback and variable gain which was modulated by amplitude of rectified and smoothed EMG signals. The prosthetic hand consisted of a processing unit of surface EMG signals, a digital servo system of DC motor and a mechanical hand of one-degree-of-freedom with three fingers. Usefulness of the developed prosthetic hand was shown in myoelectric control experiments with an amputated subject. Both the finger-angle and the stiffness of the hand were voluntarily controlled with EMG signals and soft objects were grasped smoothly.
Chronic sinusitis. Relationship of computed tomographic findings to allergy, asthma, and eosinophilia (1994)

We present a system for quantitation of disease extent using computed tomographic scans of patients with chronic sinusitis. The well-accepted associations of chronic sinusitis with asthma and allergy appear to be restricted to the group with extensive disease. The presence of peripheral eosinophilia in patients with sinusitis indicates a high likelihood of extensive disease.