gebhart/patrepeval huggingface dataset:
c- fos -induced growth factor/vascular endothelial growth factor D induces angiogenesis in vivo and in vitro (1999)

c-fos-induced growth factor/vascular endothelial growth factor D (Figf/Vegf-D) is a secreted factor of the VEGF family that binds to the vessel and lymphatic receptors VEGFR-2 and VEGFR-3. Here we report that Figf/Vegf-D is a potent angiogenic factor in rabbit cornea in vivo in a dose-dependent manner. In vitro Figf/Vegf-D induces tyrosine phosphorylation of VEGFR-2 and VEGFR-3 in primary human umbilical cord vein endothelial cells (HUVECs) and in an immortal cell line derived from Kaposi's sarcoma lesion (KS-IMM). The treatment of HUVECs with Figf/Vegf-D induces dose-dependent cell growth. Figf/VEGF-D also induces HUVEC elongation and branching to form an extensive network of capillary-like cords in three-dimensional matrix. In KS-IMM cells Figf/Vegf-D treatment results in dose-dependent mitogenic and motogenic activities. Taken together with the previous observations that Figf/Vegf-D expression is under the control of the nuclear oncogene c-fos, our data uncover a link between a nuclear oncogene and angiogenesis, suggesting that Figf/Vegf-D may play a critical role in tumor cell growth and invasion.
Sequence of events in angina at rest: primary reduction in coronary flow. (1980)

To investigate the events that lead to acute myocardial ischemia we monitored continuously the ECG, the left ventricular (four patients) or aortic (two patients) pressure and the great cardiac vein oxygen saturation (CSO2S) by a fiberoptic catheter in six patients with frequent anginal attacks at rest. We recorded 137 transient ischemic episodes (10 with chest pain) characterized by ST-segment elevation in 28 episodes, depression in three episodes and by pseudonormalization of previously inverted or flat T waves in 106 episodes. The onset of electrocardiographic and hemodynamic changes was preceded by a large drop in CSO2S in all 135 episodes with ST-T changes in the anterior leads but not in two episodes with ST elevation on inferior leads. The fall in CSO2S, consistently followed by signs of left ventricular function impairment and never preceded by any detectable increase in the hemodynamic determinants of myocardial oxygen consumption, probably reflects a reduction in regional perfusion. Thus, a reduction in coronary flow may cause transient ischemia in patients with angina at rest. These episodes may be associated with variable, often minor electrocardiographic changes and occasionally with anginal pain.
Synthesis of C 5 -dicarboxylic acids from C 2 -units involving crotonyl-CoA carboxylase/reductase: The ethylmalonyl-CoA pathway (2007)

Fifty years ago, Kornberg and Krebs established the glyoxylate cycle as the pathway for the synthesis of cell constituents from C2-units. However, since then, many bacteria have been described that do not contain isocitrate lyase, the key enzyme of this pathway. Here, a pathway termed the ethylmalonyl-CoA pathway operating in such organisms is described. Isotopically labeled acetate and bicarbonate were transformed to ethylmalonyl-CoA by cell extracts of acetate-grown, isocitrate lyase-negative Rhodobacter sphaeroides as determined by NMR spectroscopy. Crotonyl-CoA carboxylase/reductase, catalyzing crotonyl-CoA + CO2 + NADPH --> ethylmalonyl-CoA- + NADP+ was identified as the key enzyme of the ethylmalonyl-CoA pathway. The reductive carboxylation of an enoyl-thioester is a unique biochemical reaction, unprecedented in biology. The enzyme from R. sphaeroides was heterologously produced in Escherichia coli and characterized. Crotonyl-CoA carboxylase/reductase (or its gene) can be used as a marker for the presence of the ethylmalonyl-CoA pathway, which functions not only in acetyl-CoA assimilation. In Streptomyces sp., it may also supply precursors (ethylmalonyl-CoA) for antibiotic biosynthesis. For methylotrophic bacteria such as Methylobacterium extorquens, extension of the serine cycle with reactions of the ethylmalonyl-CoA pathway leads to a simplified scheme for isocitrate lyase-independent C1 assimilation.
Quasi-Phase-Matched Parametric Fluorescence in a Periodically Inverted GaP Waveguide (2009)

We have fabricated periodically-inverted GaP/AlGaP waveguiding devices and succeeded in achieving quasi phase matching in an optical parametric interaction for the first time. Quasi-phase-matched parametric fluorescence signals at 1.6 and 3.1 µm were generated from 1.064 µm pump, and the estimated efficiency agreed with the theoretical one. The temperature tuning rates of type-I quasi-phase-matched interaction are -0.5 nm/K for signal in 1.6 µm range and 2.0 nm/K for idler in 3.1 µm range, respectively.
A Noncatalytic Domain Conserved among Cytoplasmic Protein-Tyrosine Kinases Modifies the Kinase Function and Transforming Activity of Fujinami Sarcoma Virus P130gag-fps (1986)

Proteins encoded by oncogenes such as v-fps/fes, v-src, v-yes, v-abl, and v-fgr are cytoplasmic protein tyrosine kinases which, unlike transmembrane receptors, are localized to the inside of the cell. These proteins possess two contiguous regions of sequence identity: a C-terminal catalytic domain of 260 residues with homology to other tyrosine-specific and serine-threonine-specific protein kinases, and a unique domain of approximately 100 residues which is located N terminal to the kinase region and is absent from kinases that span the plasma membrane. In-frame linker insertion mutations in Fujinami avian sarcoma virus which introduced dipeptide insertions into the most stringently conserved segment of this N-terminal domain in P130gag-fps impaired the ability of Fujinami avian sarcoma virus to transform rat-2 cells. The P130gag-fps proteins encoded by these transformation-defective mutants were deficient in protein-tyrosine kinase activity in rat cells. However v-fps polypeptides derived from the mutant Fujinami avian sarcoma virus genomes and expressed in Escherichia coli as trpE-v-fps fusion proteins displayed essentially wild-type enzymatic activity, even though they contained the mutated sites. Deletion of the N-terminal domain from wild-type and mutant v-fps bacterial proteins had little effect on autophosphorylating activity. The conserved N-terminal domain of P130gag-fps is therefore not required for catalytic activity, but can profoundly influence the adjacent kinase region. The presence of this noncatalytic domain in all known cytoplasmic tyrosine kinases of higher and lower eucaryotes argues for an important biological function. The relative inactivity of the mutant proteins in rat-2 cells compared with bacteria suggests that the noncatalytic domain may direct specific interactions of the enzymatic region with cellular components that regulate or mediate tyrosine kinase function.
Inflammatory Responses to Biomaterials (1995)

Implanted biomedical devices are of increasing importance in modern medical care. However, surprisingly little is known of the factors that determine biocompatibility of the materials used in these devices. These materials, although generally inert and non-toxic, can mediate a variety of adverse reactions, including inflammation, fibrosis, coagulation, and infection. This brief review focuses on the inflammatory responses (including fibrosis) that commonly occur around implanted biomaterials. Host proteins that spontaneously associate with implant surfaces are important determinants of the acute inflammatory response. In this regard, adsorbed fibrinogen appears particularly pro-inflammatory. Chronic inflammatory processes, in many cases in response to fragments of implanted biomaterials, may cause implant failure. In the case of silicone-filled mammary prostheses, the extravasation of silicone gel has been held responsible for a number of complications, including silicone granuloma, synovitis, connective-tissue disease, and lymphadenopathy. In some instances, material-mediated inflammatory responses may even cause degradation of the material itself (via oxidative products released by implant-associated inflammatory cells). Overall, there is insufficient knowledge of the determinants and mechanisms of host: implant responses. A clear understanding of tissue:biomaterial interactions will be required both to explain the pathogenesis of many implant-mediated complications and to aid in the development of more biocompatible materials for implantable devices.
Alkyl glycoside detergents: a simpler synthesis and their effects on kinetic and physical properties of cytochrome c oxidase (1980)

Octyl glucoside is an effective, nonionic, solubilizing agent for membrane proteins with the advantage of ease of removal by dialysis. In order to study the detergent-sensitive activity of cytochrome c oxidase, we chose this detergent because of its simple structure and the possibility of synthesizing analogues to test the structural dependence of the detergent specificity. A procedure was therefore developed that facilitates large-scale preparation of octyl glucoside and related alkyl glycosides, improving on previous methods by eliminating crystallization steps and employing a one-step purification of the final product on Dowex 1. This new purification procedure is particularly important for achieving the level of purity required to obtain the disaccharide, longer alkyl chain detergents in soluble form. Of the alkyl glycosides prepared (octyl beta-D-glucopyranoside, octyl beta-D-lactopyranoside, dodecyl beta-D-lactopyranoside, dodecyl beta-D-cellobiopyranoside, and dodecyl beta-D-maltopyranoside), lauryl (dodecyl) maltoside was found to be the most successful as an activator of purified beef and Neurospora cytochrome oxidase, giving two- to tenfold higher activities than octyl glucoside and other commercially available detergents, Tween-20 and Triton X-100. Kinetic studies using two different steady-state assay systems indicate that the activity changes are not the result of altered binding of the substrate but rather reflect a detergent effect on the state of association of the enzyme (as a monomer, dimer, or polymer) as well as on its intrinsic activity. By gel filtration procedures, lauryl maltoside and octyl glucoside were found to exist as monodisperse populations of micelles of 50 000 and 8000 daltons, respectively. The small uniform micelles and chemically well-defined structures of lauryl maltoside and octyl glucoside make them superior to other nonionic detergents for the study of membrane proteins in general and cytochrome oxidase in particular, since its activity in lauryl maltoside most closely approaches that of the physiological state.
Biomedical Differences Between Human and Nonhuman Hominids: Potential Roles for Uniquely Human Aspects of Sialic Acid Biology (2011)

Although humans are genetically very similar to the evolutionarily related nonhuman hominids (chimpanzees, bonobos, gorillas, and orangutans), comparative studies suggest a surprising number of uniquely human differences in the incidence and/or severity of biomedical conditions. Some differences are due to anatomical changes that occurred during human evolution. However, many cannot be explained either by these changes or by known environmental factors. Because chimpanzees were long considered models for human disease, it is important to be aware of these differences, which appear to have been deemphasized relative to similarities. We focus on the pathophysiology and pathobiology of biomedical conditions that appear unique to humans, including several speculative possibilities that require further study. We pay particular attention to the possible contributions of uniquely human changes in the biology of cell-surface sialic acids and the proteins that recognize them. We also discuss the metabolic incorporation of a diet-derived nonhuman sialic acid, which generates a novel xeno-autoantigen reaction, and chronic inflammation known as xenosialitis.
Multiplexing molecular diagnostics and immunoassays using emerging microarray technologies (2006)

Enzyme-linked immunosorbent assays (ELISA) are frequently used for quantitative measurement of the presence of protein, for single-analyte testing, in a sample. The application of ELISA in a microarray format has the potential to simultaneously measure the presence and/or concentrations of numerous proteins, in multiplex testing, all contained in a small drop of test fluid. Microspot microarray technology, in combination with protein biomarkers and nucleic acid diagnostics, appears to be the future high-performance analytical platform of choice. Validation of a large number of disease markers in both molecular and protein diagnostics has paved the way for the emergence of the multiplex assay. Initially, simple low-throughput multiplex assays were tested using the immunoassay format. These were followed by low-level multiplexing and high-throughput array-based immunoassays. More recently, two types of high-level multiplexing and high-throughput diagnostic methods using microspot arrays and bead arrays have been successfully developed to complement single-analyte assays. The value in rapid diagnostic evaluation for high-throughput multiplex, diagnostic test systems based on sound assay design must take into account data screening, normalization and statistical evaluation of possible concentration measurement, data errors and automated operation. Benefits of using multiplex array platforms include improved-quality patient care, as well as cost effectiveness and time saving. These multiplex methods also set the stage for future protein/nucleic acid codetection. Currently, the one analyte at a time test scheme is still dominant; nonetheless, the multiplex microspot microarray tests evaluated in a single multiassay analyzer are expected to become a significant part of clinical diagnostic testing within the next 5-10 years. This review is focused on microspot array and bead array methods for providing high throughput and a high degree of multiplexing in diagnostic testing.
Reversal of Nonalcoholic Hepatic Steatosis, Hepatic Insulin Resistance, and Hyperglycemia by Moderate Weight Reduction in Patients With Type 2 Diabetes (2005)

To examine the mechanism by which moderate weight reduction improves basal and insulin-stimulated rates of glucose metabolism in patients with type 2 diabetes, we used (1)H magnetic resonance spectroscopy to assess intrahepatic lipid (IHL) and intramyocellular lipid (IMCL) content in conjunction with hyperinsulinemic-euglycemic clamps using [6,6-(2)H(2)]glucose to assess rates of glucose production and insulin-stimulated peripheral glucose uptake. Eight obese patients with type 2 diabetes were studied before and after weight stabilization on a moderately hypocaloric very-low-fat diet (3%). The diabetic patients were markedly insulin resistant in both liver and muscle compared with the lean control subjects. These changes were associated with marked increases in IHL (12.2 +/- 3.4 vs. 0.6 +/- 0.1%; P = 0.02) and IMCL (2.0 +/- 0.3 vs. 1.2 +/- 0.1%; P = 0.02) compared with the control subjects. A weight loss of only approximately 8 kg resulted in normalization of fasting plasma glucose concentrations (8.8 +/- 0.5 vs. 6.4 +/- 0.3 mmol/l; P < 0.0005), rates of basal glucose production (193 +/- 7 vs. 153 +/- 10 mg/min; P < 0.0005), and the percentage suppression of hepatic glucose production during the clamp (29 +/- 22 vs. 99 +/- 3%; P = 0.003). These improvements in basal and insulin-stimulated hepatic glucose metabolism were associated with an 81 +/- 4% reduction in IHL (P = 0.0009) but no significant change in insulin-stimulated peripheral glucose uptake or IMCL (2.0 +/- 0.3 vs. 1.9 +/- 0.3%; P = 0.21). In conclusion, these data support the hypothesis that moderate weight loss normalizes fasting hyperglycemia in patients with poorly controlled type 2 diabetes by mobilizing a relatively small pool of IHL, which reverses hepatic insulin resistance and normalizes rates of basal glucose production, independent of any changes in insulin-stimulated peripheral glucose metabolism.
Efficient transduction of neural cells in vitro and in vivo by a baculovirus-derived vector (2000)

Gene delivery to the central nervous system is central to the development of gene therapy for neurological diseases. We developed a baculovirus-derived vector, the Bac-CMV-GFP vector, containing a reporter gene encoding for the green fluorescent protein (GFP) under the control of the cytomegalovirus (CMV) promoter. Two neuroblastomal cell lines and three human primary neural cultures could be efficiently transduced. In all cases, addition of butyrate, an inhibitor of histone deacetylase, increased the level of expression in terms of the number of GFP-expressing cells and the intensity of fluorescence. The level of expression in a human telencephalic culture was over 50% of transduced cells with a multiplicity of infection of 25. GFP expression was demonstrated to be genuine expression and not pseudotransduction of the reporter protein. Most interestingly, Bac-CMV-GFP could transduce neural cells in vivo when directly injected into the brain of rodents and was not inactivated by the complement system. Thus, baculovirus is a promising tool for gene transfer into the central nervous system both for studies of the function of foreign genes and the development of gene therapy strategies.
Defined-size DNA triple crossover construct for molecular electronics: modification, positioning and conductance properties (2011)

We present a novel, defined-size, small and rigid DNA template, a so-called B-A-B complex, based on DNA triple crossover motifs (TX tiles), which can be utilized in molecular scale patterning for nanoelectronics, plasmonics and sensing applications. The feasibility of the designed construct is demonstrated by functionalizing the TX tiles with one biotin-triethylene glycol (TEG) and efficiently decorating them with streptavidin, and furthermore by positioning and anchoring single thiol-modified B-A-B complexes to certain locations on a chip via dielectrophoretic trapping. Finally, we characterize the conductance properties of the non-functionalized construct, first by measuring DC conductivity and second by utilizing AC impedance spectroscopy in order to describe the conductivity mechanism of a single B-A-B complex using a detailed equivalent circuit model. This analysis also reveals further information about the conductivity of DNA structures in general.
The Death Penalty in New York: An Historical Perspective (1995)

3 State Assemblyman Frank Barbaro stated that he believes his constituents voted for Governor George Pataki primarily
Design and Synthesis of Pyrrolo-[2,1-c][1,4]benzodiazepine (PBD)-Polyaminoalkyl Conjugates by the Use of SNAr Reaction of 2-Nitro-5-fluorobenzoate Precursor as Key Reaction (2004)

The design and synthesis of a series of pyrrolo[2,1c][l,4]benzodiazepine (PBD)-polyaminoalkyl conjugates as DNA minor groove binders are described.To introduce polyaminoalkyl groups to the pyrrolo[2,1c][1,4]benzodiazepine pharmacophore, S N Ar reactions between 2-nitro-5fluorophenyl ketone or 2-nitro-3-pehenyl ketone and polyaminoalkyl side chains were developed.
VCIP135, a novel essential factor for p97/p47-mediated membrane fusion, is required for Golgi and ER assembly in vivo (2002)

NSF and p97 are ATPases required for the heterotypic fusion of transport vesicles with their target membranes and the homotypic fusion of organelles. NSF uses ATP hydrolysis to dissociate NSF/SNAPs/SNAREs complexes, separating the v- and t-SNAREs, which are then primed for subsequent rounds of fusion. In contrast, p97 does not dissociate the p97/p47/SNARE complex even in the presence of ATP. Now we have identified a novel essential factor for p97/p47-mediated membrane fusion, named VCIP135 (valosin-containing protein [VCP][p97]/p47 complex-interacting protein, p135), and show that it binds to the p97/p47/syntaxin5 complex and dissociates it via p97 catalyzed ATP hydrolysis. In living cells, VCIP135 and p47 are shown to function in Golgi and ER assembly.
The Cholesterol Requirement for Sindbis Virus Entry and Exit and Characterization of a Spike Protein Region Involved in Cholesterol Dependence (1999)

ABSTRACT Semliki Forest virus (SFV) and Sindbis virus (SIN) are enveloped alphaviruses that enter cells via low-pH-triggered fusion in the endocytic pathway and exit by budding from the plasma membrane. Previous studies with cholesterol-depleted insect cells have shown that SFV requires cholesterol in the cell membrane for both virus fusion and efficient exit of progeny virus. An SFV mutant, srf-3 , shows efficient fusion and exit in the absence of cholesterol due to a single point mutation in the E1 spike subunit, proline 226 to serine. We have here characterized the role of cholesterol in the entry and exit of SIN, an alphavirus quite distantly related to SFV. Growth, primary infection, fusion, and exit of SIN were all dramatically inhibited in cholesterol-depleted cells compared to control cells. Based on sequence differences within the E1 226 region between SFV, srf-3 , and SIN, we constructed six SIN mutants with alterations within this region and characterized their cholesterol dependence. A SIN mutant, SGM , that had the srf-3 amino acid sequence from E1 position 224 to 235 showed increases of ∼100-fold in infection and ∼250-fold in fusion with cholesterol-depleted cells compared with infection and fusion of wild-type SIN. Pulse-chase analysis demonstrated that SGM exit from cholesterol-depleted cells was markedly more efficient than that of wild-type SIN. Thus, similar to SFV, SIN was cholesterol dependent for both virus entry and exit, and the cholesterol dependence of both steps could be modulated by sequences within the E1 226 region.
Developmental analysis of the facets, a group of intronic mutations at the Notch locus of Drosophila melanogaster that affect postembryonic development (1991)

The activity of the Notch locus of Drosophila melanogaster during embryogenesis is necessary for the correct segregation of neural from epidermal lineages. The action of Notch is not confined to embryogenesis but is also essential for normal development during the postembryonic stages. Its action is pleiotropic, as revealed by the existence of several classes of mutations which affect various imaginal structures. Here, we examine a group of six recessive mutations, the facets (fa, fa3, fag, fag-2, fafx and fasw), which affect eye and optic lobe morphology and have been previously shown to be associated with the insertion of transposable elements into an intronic region of Notch. Using both somatic recombination and gynandromorph analysis, we find that their behavior in a mosaic analysis is not identical. While in the majority of alleles abnormal Notch function in the retina is sufficient to induce optic lobe abnormalities, in the case of fag-2, a considerable number of individuals having mosaic retinas exhibit normal optic lobe structure. All the facet alleles appear to behave in a cell-autonomous manner. A developmental analysis of the eye and optic lobe defects associated with the facet mutations support the contention that Notch may be involved not only in the formation of certain structures but also in their maintenance.