gebhart/patrepeval huggingface dataset:
Cholesteryl-Conjugated Phosphorothioate Oligodeoxynucleotides Modulate CYP2B1 ExpressionIn Vivo (1995)

5' cholesteryl-conjugated phosphorothioate oligodeoxynucleotides with sequence complementary to the rat CYP2B1 mRNA were evaluated in adult male Sprague-Dawley rats for their pharmacokinetic properties, toxicity, and ability to modulate CYP2B1 expression in vivo. Following intraperitoneal administration of 35S-labelled oligodeoxynucleotides, volume of distribution for the phosphorothioate was 0.33 l/kg while the 5' cholesteryl-conjugate oligodeoxynucleotide was 0.12 l/kg. The elimination half-life was 23.2 and 55.4 hrs for cholesteryl-modified and unmodified oligodeoxynucleotides, respectively. Cholesteryl-conjugate oligodeoxynucleotide toxicity was detected at a dose of 1.0 mg/kg and consisted primarily of midzonal liver cell enlargement and increased total RNA. Hexobarbital sleep times, a measure of CYP2B1 enzyme activity in vivo, increased from 21.9 minutes in saline-treated animals to 29.5 minutes in cholesterol oligodeoxynucleotide-treated animals. A significant decrease in liver microsomal pentoxyresorufin O-dealkylase enzyme activity, a CYP2B1/2 specific assay, was observed but not a change in p-nitrophenol hydroxylase activity, a specific CYP2E1 assay. These data indicate that in vivo modulation of the CYP2B1 gene can be accomplished with synthetic phosphorothioate oligodeoxynucleotides in a sequence-specific manner. Further, cholesteryl conjugation to the 5' end of the oligodeoxynucleotide enhanced potency despite lesser bioavailability.
MicroRNAs (miR)-221 and miR-222, both overexpressed in human thyroid papillary carcinomas, regulate p27Kip1 protein levels and cell cycle (2007)

We have recently reported that MicroRNAs (miR)-221 and miR-222 were up-regulated in human thyroid papillary carcinomas in comparison with the normal thyroid tissue. Bioinformatic analysis proposed the p27(Kip1) protein, a key regulator of cell cycle, as a candidate target for the miR-221/222 cluster. Here, we report that the enforced expression of miR-221 and miR-222 was able to reduce p27(Kip1) protein levels in thyroid carcinoma and HeLa cells in the absence of significant changes in specific p27(Kip1) mRNA levels. This effect is direct as miR-221 and miR-222 negatively regulate the expression of the 3'-untranslated region-based reporter construct from the p27(Kip1) gene, and is dependent on two target sites in this region. Consistent with these results, an enforced expression of the miR-221 and miR-222 induced the thyroid papillary carcinoma cell line (TPC-1) to progress to the S phase of the cell cycle. It is likely that the negative regulation of p27(Kip1) by miR-221 and miR-222 might also have a role in vivo since we report an inverse correlation between miR-221 and miR-222 up-regulation and down-regulation of the p27(Kip1) protein levels in human thyroid papillary carcinomas. Therefore, the data reported here demonstrate that miR-221 and miR-222 are endogenous regulators of p27(Kip1) protein expression, and thereby, the cell cycle.
High Mobility Group Box–1 as a Therapeutic Target Downstream of Tumor Necrosis Factor (2003)

The discovery of tumor necrosis factor (TNF) as a necessary and sufficient mediator of systemic inflammation started a new field of research to rationally modulate cytokine responses to therapeutic advantage. However, the early kinetics of the TNF response during infection defined an extremely narrow window of opportunity during which anti-TNF therapeutics are efficacious, hampering clinical development for severe sepsis. Because death from severe sepsis often occurs as a late phenomenon, we began a search began for putative "late" mediators that could be targeted after the onset of infection. We have now identified high mobility group box-1 (HMGB1) as a late mediator of endotoxemia and sepsis. HMGB1 is released by activated macrophages, induces the release of other proinflammatory mediators, and mediates lethality when overexpressed. Administration of anti-HMGB1 antibodies inhibit systemic inflammation, even in established cases, because HMGB1 activity is elevated at significantly later time points than TNF or interleukin-1. It will now be important to determine whether this wider window of activity can be translated into therapeutic advantage for human inflammatory disease.
Application Of Recurrent Iterated Function Systems To Images (1988)

A new fractal technique for the analysis and compression of digital images is presented. It is shown that a family of contours extracted from an image can be modelled geometrically as a single entity, based on the theory of recurrent iterated function systems (RIFS). RIFS structures are a rich source for deterministic images, including curves which cannot be generated by standard techniques. Control and stability properties are investigated. We state a control theorem - the recurrent collage theorem - and show how to use it to constrain a recurrent IFS structure so that its attractor is close to a given family of contours. This closeness is not only perceptual; it is measured by means of a min-max distance, for which shape and geometry is important but slight shifts are not. It is therefore the right distance to use for geometric modeling. We show how a very intricate geometric structure, at all scales, is inherently encoded in a few parameters that describe entirely the recurrent structures. Very high data compression ratios can be obtained. The decoding phase is achieved through a simple and fast reconstruction algorithm. Finally, we suggest how higher dimensional structures could be designed to model a wide range of digital textures, thus leading our research towards a complete image compression system that will take its input from some low-level image segmenter.
Histone Deacetylase (HDAC) Inhibition as a Novel Treatment for Diabetes Mellitus (2011)

Both common forms of diabetes have an inflammatory pathogenesis in which immune and metabolic factors converge on interleukin-1β as a key mediator of insulin resistance and β-cell failure. In addition to improving insulin resistance and preventing β-cell inflammatory damage, there is evidence of genetic association between diabetes and histone deacetylases (HDACs); and HDAC inhibitors (HDACi) promote β-cell development, proliferation, differentiation and function and positively affect late diabetic microvascular complications. Here we review this evidence and propose that there is a strong rationale for preclinical studies and clinical trials with the aim of testing the utility of HDACi as a novel therapy for diabetes.
Neurotensin Is a Lipid-Induced Gastrointestinal Peptide Associated with Visceral Adipose Tissue Inflammation in Obesity (2018)

Neurotensin (NT) is a 13-amino acid peptide localized in the neuroendocrine cells of the small intestine, which promotes fat absorption and fatty acids translocation in response to lipid ingestion. NT-knock-out mice fed with a high-fat diet are protected from obesity, fatty liver, and the development of insulin-resistance. In humans, higher plasma levels of pro-NT, which is the stable circulating precursor of NT, predict obesity, type 2 diabetes (T2D), and cardiovascular disease. In obesity, the presence of visceral adipose tissue (VAT) inflammation leads to unfavorable metabolic outcomes and is associated with the development of T2D and non-alcoholic fatty liver disease (NAFLD). In this study, we investigated the relationship between plasma pro-NT levels and the presence of VAT inflammation in biopsies from 40 morbidly obese subjects undergoing bariatric surgery. We demonstrated that higher proNT levels are significantly associated with greater macrophages infiltration, HIF-1&alpha;, WISP-1, and UNC5B expression in VAT (all <i>p</i> < 0.01) due to the diagnosis of T2D and NAFLD. The overall results show that, in obesity, pro-NT is a biomarker of VAT inflammation and insulin-resistance. Additionally, NT may be involved in the development of dysmetabolic conditions likely mediated by increased gut fat absorption and the presence of a proinflammatory milieu in the adipose tissue.
Essential differences in oncogene involvement between primary nodal and extranodal large cell lymphoma (1991)

Large cell lymphomas (LCLs) are heterogeneous in morphology, clinical presentation, and behavior. We studied 52 de novo LCLs of B-cell type for rearrangements of the bcl-2 and c-myc oncogenes by Southern blot analysis and related these data to the primary site of presentation, stage, and cytomorphology. Thirteen tumors had comigrating rearrangements of JH and bcl-2, indicative of a t(14;18). Far more primary nodal lymphomas than extranodal lymphomas carried a t(14;18) (40% v less than 5%). Additionally, almost all lymphomas with a t(14;18) versus 41% of the tumors without a bcl-2 rearrangement presented with lymphadenopathy. c-myc rearrangements were seen in 35% of the extranodal lymphomas and 5% of the nodal lymphomas. No differences were observed in bone marrow involvement and staging according to Ann Arbor. bcl-2 rearrangements were found in 50% of the LCLs with cleaved nuclei, whereas c-myc rearrangements were relatively frequent (25%) in the noncleaved subtype. Our data support the hypothesis that primary nodal and extranodal lymphomas have a different genetic origin.
Charge neutrality violation in quantum-dot lasers (1997)

Theory of quantum-dot (QD) lasers is augmented to include, in a self-consistent manner, the QD-layer charge. The electron- and hole-level occupancies in QDs are obtained through the solution of the problem for the electrostatic-field distribution across the junction. They are shown to differ from each other. As a result, the local neutrality is broken down in each QD, i.e., the QD layer is charged. The key dimensionless parameters controlling the difference of the hole- and electron-level occupancies are revealed. The detailed analysis of the gain and spontaneous radiative recombination current density is given, having regard to the fact of violation of the charge neutrality in QDs. The gain-current density dependence is calculated, The voltage dependences of the electron- and hole-level occupancies, gain, and current density are obtained. Particular emphasis is given to the transparency and lasing threshold characteristics. Optimization of the QD-laser structure is carried out. The optimum surface density of QDs, minimizing the threshold current density, is shown to be distinctly higher than that calculated without regard for the lack of the charge neutrality in QDs.
Treatment of metastatic prostate carcinoma with radiolabeled antibody CC49. (1994)

CC49 had a high frequency of tumor localization with evidence of anti-tumor effects (pain relief).
Epistatic Interaction Maps Relative to Multiple Metabolic Phenotypes (2011)

An epistatic interaction between two genes occurs when the phenotypic impact of one gene depends on another gene, often exposing a functional association between them. Due to experimental scalability and to evolutionary significance, abundant work has been focused on studying how epistasis affects cellular growth rate, most notably in yeast. However, epistasis likely influences many different phenotypes, affecting our capacity to understand cellular functions, biochemical networks adaptation, and genetic diseases. Despite its broad significance, the extent and nature of epistasis relative to different phenotypes remain fundamentally unexplored. Here we use genome-scale metabolic network modeling to investigate the extent and properties of epistatic interactions relative to multiple phenotypes. Specifically, using an experimentally refined stoichiometric model for Saccharomyces cerevisiae, we computed a three-dimensional matrix of epistatic interactions between any two enzyme gene deletions, with respect to all metabolic flux phenotypes. We found that the total number of epistatic interactions between enzymes increases rapidly as phenotypes are added, plateauing at approximately 80 phenotypes, to an overall connectivity that is roughly 8-fold larger than the one observed relative to growth alone. Looking at interactions across all phenotypes, we found that gene pairs interact incoherently relative to different phenotypes, i.e. antagonistically relative to some phenotypes and synergistically relative to others. Specific deletion-deletion-phenotype triplets can be explained metabolically, suggesting a highly informative role of multi-phenotype epistasis in mapping cellular functions. Finally, we found that genes involved in many interactions across multiple phenotypes are more highly expressed, evolve slower, and tend to be associated with diseases, indicating that the importance of genes is hidden in their total phenotypic impact. Our predictions indicate a pervasiveness of nonlinear effects in how genetic perturbations affect multiple metabolic phenotypes. The approaches and results reported could influence future efforts in understanding metabolic diseases and the role of biochemical regulation in the cell.
Proteomic Analysis of the Spore Coats of Bacillus subtilis and Bacillus anthracis (2003)

The outermost proteinaceous layer of bacterial spores, called the coat, is critical for spore survival, germination, and, for pathogenic spores, disease. To identify novel spore coat proteins, we have carried out a preliminary proteomic analysis of Bacillus subtilis and Bacillus anthracis spores, using a combination of standard sodium dodecyl sulfate-polyacrylamide gel electrophoresis separation and improved two-dimensional electrophoretic separations, followed by matrix-assisted laser desorption ionization-time of flight and/or dual mass spectrometry. We identified 38 B. subtilis spore proteins, 12 of which are known coat proteins. We propose that, of the novel proteins, YtaA, YvdP, and YnzH are bona fide coat proteins, and we have renamed them CotI, CotQ, and CotU, respectively. In addition, we initiated a study of coat proteins in B. anthracis and identified 11 spore proteins, 6 of which are candidate coat or exosporium proteins. We also queried the unfinished B. anthracis genome for potential coat proteins. Our analysis suggests that the B. subtilis and B. anthracis coats have roughly similar numbers of proteins and that a core group of coat protein species is shared between these organisms, including the major morphogenetic proteins. Nonetheless, a significant number of coat proteins are probably unique to each species. These results should accelerate efforts to develop B. anthracis detection methods and understand the ecological role of the coat.
Control of Smooth Muscle Cell Proliferation – The Role of the Basement Membrane (1999)

In atherogenesis and in response to vessel injury, arterial smooth muscle cells (SMCs) are activated from a quiescent, differentiated state into an actively proliferating and synthetic phenotype which migrate into the intima where the cells participate in the formation of a fibrous plaque or intimal hyperplasia. The mechanisms involved in the control of SMC function are not clear and no preventive therapy against SMC activation is available. Interactions between SMCs and the extracellular matrix have been shown to influence SMC structure and function through integrin-mediated signaling processes. The SMC basement membrane is a specific form of extracellular matrix which seems to be crucial for the maintenance of SMC quiescence and the disruption of these interactions is part of cellular activation after atherogenic or traumatic stimuli. This concept of "negative growth control" may constitute a future target for the development of new strategies in the prevention of SMC activation in atherogenesis and restenosis formation.
Beyond the pale of MAC and DAC-defining new forms of access control (1990)

Examples of DoD/intelligence data protection requirements are described that cannot be handled through traditional mandatory (MAC) or discretionary (DAC) access controls, and two new forms of access controls to respond to these problems are proposed. First, a user attribute-based access control for enforcement of dissemination controls is introduced. Second, a type of access control known as owner-retained access control is described, to provide a privilege-based form of access control that, unlike DAC, prevents access to data being extended to others without the owner's concurrence. For both types of controls, the access control rules to be enforced and the implications of providing automated enforcement of these controls are discussed. The two forms of control are compared, and an informal model is presented that provides a common framework for representing both. In conclusion, the benefits and drawbacks of this approach are discussed, and some areas for future work are identified.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Amplified In Situ Hybridization With Peptide Nucleic Acid Probes for Differentiation ofMycobacterium tuberculosisComplex and NontuberculousMycobacteriumSpecies on Formalin-Fixed, Paraffin-Embedded Archival Biopsy and Autopsy Samples (2001)

The aim of this study was to evaluate sensitivity and specificity of in situ hybridization (ISH) using peptide nucleic acid (PNA) probes and tyramide-based amplification for the differentiation between Mycobacterium tuberculosis (MTB) and mycobacteria other than tuberculosis (MOTT) on formalin-fixed, paraffin-embedded tissue samples. We performed ISH simultaneously with both probes on 86 specimens from different organs: 70 obtained at autopsy and 16 by biopsy, all with a histologic evidence of mycobacterial infection confirmed by Ziehl-Neelsen-positive staining. Taking culture as the "gold standard," the sensitivity and the specificity of the MTB probe were 100% (41/41) and 95% (38/40), respectively. In only 2 cases ISH failed to identify mycobacteria. Culture results were not available in 3 cases. We propose ISH as a relatively simple and rapid method to differentiate mycobacteria on formalin-fixed, paraffin-embedded specimens (it is more specific than usual histologic stains) and as an alternative to polymerase chain reaction, allowing the morphologic evaluation of positive bacilli.
Thrombin Receptors Activate Go Proteins in Endothelial Cells to Regulate Intracellular Calcium and Cell Shape Changes (2002)

Thrombin receptors couple to G(i/o), G(q), and G(12/13) proteins to regulate a variety of signal transduction pathways that underlie the physiological role of endothelial cells in wound healing or inflammation. Whereas the involvement of G(i), G(q), G(12), or G(13) proteins in thrombin signaling has been investigated extensively, the role of G(o) proteins has largely been ignored. To determine whether G(o) proteins could contribute to thrombin-mediated signaling in endothelial cells, we have developed minigenes that encode an 11-amino acid C-terminal peptide of G(o1) proteins. Previously, we have shown that use of the C-terminal minigenes can specifically block receptor activation of G protein families (). In this study, we demonstrate that G(o) proteins are present in human microvascular endothelial cells (HMECs). Moreover, we show that thrombin receptors can stimulate [(35)S]guanosine-5'-O-(3-thio)triphosphate binding to G(o) proteins when co-expressed in Sf9 membranes. The potential coupling of thrombin receptors to G(o) proteins was substantiated by transfection of the G(o1) minigene into HMECs, which led to a blockade of thrombin-stimulated release of [Ca(2+)](i) from intracellular stores. Transfection of the beta-adrenergic kinase C terminus blocked the [Ca(2+)](i) response to the same extent as with G(o1) minigene peptide, suggesting that this G(o)-mediated [Ca(2+)](i) transient was caused by Gbetagamma stimulation of PLCbeta. Transfection of a G(i1/2) minigene had no effect on thrombin-stimulated [Ca(2+)](i) signaling in HMEC, suggesting that Gbetagamma derived from G(o) but not G(i) could activate PLCbeta. The involvement of G(o) proteins on events downstream from calcium signaling was further evidenced by investigating the effect of G(o1) minigenes on thrombin-stimulated stress fiber formation and endothelial barrier permeability. Both of these effects were sensitive to pertussis toxin treatment and could be blocked by transfection of G(o1) minigenes but not G(i1/2) minigenes. We conclude that the G(o) proteins play a role in thrombin signaling distinct from G(i1/2) proteins, which are mediated through their Gbetagamma subunits and involve coupling to calcium signaling and cytoskeletal rearrangements.
Analysis of EGFR signaling pathway in nasopharyngeal carcinoma cells by quantitative phosphoproteomics (2011)

The data not only can extend our knowledge of canonical EGFR signaling, but also will be useful to understand the molecular mechanisms of EGFR in NPC pathogenesis and search therapeutic targets for NPC.
Induction of lipid peroxidation during heavy metal stress in Saccharomyces cerevisiae and influence of plasma membrane fatty acid unsaturation (1997)

The degree of plasma membrane fatty acid unsaturation and the copper sensitivity of Saccharomyces cerevisiae are closely correlated. Our objective was to determine whether these effects could be accounted for by differential metal induction of lipid peroxidation. S. cerevisiae S150-2B was enriched with the polyunsaturated fatty acids (PUFAs) linoleate (18:2) and linolenate (18:3) by growth in 18:2- or 18:3-supplemented medium. Potassium efflux and colony count data indicated that sensitivity to both copper (redox active) and cadmium (redox inactive) was increased in 18:2-supplemented cells and particularly in 18:3-supplemented cells. Copper- and cadmium-induced lipid peroxidation was rapid and associated with a decline in plasma membrane lipid order, detected by fluorescence depolarization measurements with the membrane probe trimethylammonium diphenylhexatriene. Levels of thiobarbituric acid-reactive substances (lipid peroxidation products) were up to twofold higher in 18:2-supplemented cells than in unsupplemented cells following metal addition, although this difference was reduced with prolonged incubation up to 3 h. Conjugated-diene levels in metal-exposed cells also increased with both the concentration of copper or cadmium and the degree of cellular fatty acid unsaturation; maximal levels were evident in 18:3-supplemented cells. The results demonstrate heavy metal-induced lipid peroxidation in a microorganism for the first time and indicate that the metal sensitivity of PUFA-enriched S. cerevisiae may be attributable to elevated levels of lipid peroxidation in these cells.
Diagnostic accuracy of shoulder ultrasound performed by a single operator (2007)

Both diagnostic ultrasound and magnetic resonance imaging (MRI) are used for investigation of the presence and severity of rotator cuff lesions. There is no consensus as to which is the more accurate and cost-effective study. We sought to examine the sensitivity of ultrasound, when used by one experienced radiologist with modern equipment. We compared the ultrasound and surgical results obtained from 68 patients. Ultrasound showed a sensitivity of 89% and specificity of 100% (Positive Predictive Value 100%) for full-thickness tears, and a sensitivity of 79% and specificity of 94% (Positive Predictive Value 87%) for partial-thickness tears. We found that shoulder ultrasound, in the hands of an experienced radiologist with the use of modern high-resolution equipment, is highly sensitive in differentiating complete tears and partial-thickness tears. Our results are similar to the best published results for MRI and given that ultrasound is significantly cheaper and more available, ultrasound by an experienced radiologist should be considered as a primary diagnostic tool for imaging the rotator cuff.