gebhart/patrepeval huggingface dataset:
Oncogenes and tumor angiogenesis: differential modes of vascular endothelial growth factor up-regulation in ras-transformed epithelial cells and fibroblasts. (2000)

A possible link between oncogenes and tumor angiogenesis has been implicated by the finding that expression of various oncogenes, particularly mutant ras, can lead to a marked induction of a potent paracrine stimulator of angiogenesis, vascular endothelial growth factor (VEGF). We sought to determine how oncogenic ras induction of VEGF is mediated at the molecular level and whether the mechanisms involved differ fundamentally between transformed epithelial cells and fibroblasts. Our results suggest that in a subline (called RAS-3) of immortalized nontumorigenic rat intestinal epithelial cells (IEC-18) that acquired a tumorigenic phenotype upon transfection of mutant ras, up-regulation of VEGF occurs in the absence of an autocrine growth factor circuit. The expression of VEGF mRNA and protein by RAS-3 cells was strongly suppressed in the presence of LY294002, an inhibitor of phosphatidylinositol 3'-kinase, but remained largely unaffected in the same cells treated with an inhibitor (PD98059) of mitogen-activated protein/extracellular signal-regulated kinase kinase 1 (MKK/MEK-1). This is consistent with the observation that overexpression of a constitutively activated mutant of MEK-1 (AN3/ S222D) in the parental IEC-18 cells did not result in up-regulation of VEGF production. The impact of mutant ras on VEGF expression was also significantly amplified at high cell density, conditions under which RAS-3 cells became less sensitive to LY294002-induced VEGF down-regulation. In marked contrast to cells of epithelial origin, ras-transformed murine fibroblasts (3T3RAS) up-regulated VEGF in a manner that was strongly inhibitable by MEK-1 blockade (ie. treatment with PD98059), whereas these cells were relatively unaffected by treatment with the phosphatidylinositol 3'-kinase inhibitor LY294002. In addition, VEGF was up-regulated by 2-3-fold in NIH3T3 cells overexpressing mutant MEK-1. Collectively, the data suggest that the stimulatory effect of mutant ras on VEGF expression is executed in a nonautocrine and cell type-dependent manner and that it can be significantly exacerbated by physiological/ environmental influences such as high cell density.
Intensity discrimination as the driving force for loudness. Application to pure tones in quiet (1990)

Loudness functions and their associated neural-count functions are derived for steady-state tones at 250 and 1000 Hz from measurements of intensity discrimination obtained under gated and continuous conditions. The calculations are based on a multichannel generalization of the McGill-Goldberg counting model [J. Acoust. Soc. Am. 44, 576-581 (1968)]. Using the data for just noticeable differences (jnd) in intensity as input, the generalized version gives an integral relation between the neural-count function N(x) and the intensity-jnd function, where x = I/I0 and I0 is the reference intensity. Loudness functions are generated through the prescription L(x) = AN(x)--B. To determine how the detailed shapes of the intensity-jnd functions affect the form of the loudness function within the model, integration was performed over the intensity-jnd functions with and without a power-function approximation. Over a range of intensity levels from 20-95 dB, the best agreement between the calculated and measured loudness functions is obtained from the unaltered intensity-jnd functions. Consistent with psychophysical evidence and several models of intensity coding, the results predict that the output of the whole auditory nerve is unnecessary to maintain the large dynamic range observed for loudness and intensity discrimination.
Extracellular Matrix Regulates Apoptosis in Mammary Epithelium through a Control on Insulin Signaling (1999)

Adherent epithelial cells require interactions with the extracellular matrix for their survival, though the mechanism is ill-defined. In long term cultures of primary mammary epithelial cells, a laminin-rich basement membrane (BM) but not collagen I suppresses apoptosis, indicating that adhesion survival signals are specific in their response (. J. Cell Sci. 109:631-642). We now demonstrate that the signal from BM is mediated by integrins and requires both the alpha6 and beta1 subunits. In addition, a hormonal signal from insulin or insulin-like growth factors, but not hydrocortisone or prolactin, is necessary to suppress mammary cell apoptosis, indicating that BM and soluble factors cooperate in survival signaling. Insulin induced autophosphorylation of its receptor whether mammary cells were cultured on collagen I or BM substrata. However, both the tyrosine phosphorylation of insulin receptor substrate-1 and its association with phosphatidylinositol 3-kinase were enhanced in cells cultured on BM, as was the phosphorylation of the phosphatidylinositol 3-kinase effector, protein kinase B. These results suggest a novel extracellular matrix-dependent restriction point in insulin signaling in mammary epithelial cells. The proximal signal transduction event of insulin receptor phosphorylation is not dependent on extracellular matrix, but the activation of downstream effectors requires adhesion to BM. Since phosphatidylinositol 3-kinase was required for mammary epithelial cell survival, we propose that a possible mechanism for BM-mediated suppression of apoptosis is through its facilitative effects on insulin signaling.
Inhibition of DNA methyltransferases, histone deacetylases and lysine-specific demethylase-1 suppresses the tumorigenicity of the ovarian cancer ascites cell line SKOV3 (2013)

Ovarian cancer is one of the most lethal female malignancies and epigenetic abnormalities are thought to play a vital role in the pathogenesis, development and progression of ovarian cancer. Our goal was to investigate whether the combination of trichostatin A (TSA) and 5-aza-2'-deoxycytidine (decitabine) was superior to single agent on tumorigenicity of ovarian cancer cells. We found that tumorigenicity and metastasis of SKOV3 cells were significantly suppressed by the combination of TSA and decitabine in xenograft mouse models. Migration capacity was markedly suppressed through the induction of E-cadherin and suppression of N-cadherin when treated with TSA and decitabine. Invasion was also suppressed at least partially through inhibition of MMP-2 and MMP-9 with the combined treatment. The combination drugs markedly inhibited spheroid formation and significantly impaired migration and invasion capacity of spheroid derived cells through inhibition of Twist, N-cadherin, MMP-2, MMP-9 and induction of E-cadherin. Epigenetically, the activity of DNA methyltransferases (DNMTs) and histone deacetylases (HDACs) were markedly inhibited when TSA was used in combination with decitabine, especially the expression of DNMT3A/3B and HDAC1/2. Acetylation of histone H3 and H4 were more markedly stimulated with the combination than with either agent alone. The expression level of lysine-specific demethylase-1 (LSD1) was also suppressed. The transcription activity marker dimethylated-H3K4 was induced, but the dimethylated-H3K9 was suppressed by exposure to the combined drugs. These results suggest that the combination of TSA and decitabine significantly suppresses tumorigenicity by inhibiting migration and invasion of ovarian cancer cells via regulating the expression of the cadherins and MMPs, which may be epigenetically regulated by DNA methylation and histone modification.
The Autoxidation of the Reduced Forms of EO9 (1996)

The properties of the semiquinone radical from [3-hydroxy-5-aziridmyl-1-methyl-2-(1H-indole-4,7-indi one)-prop-β-en-α-ol], EO9, have been studied using pulse-radiolysis techniques. The reduction potential of the semiquinone of EO9 at pH 7.4, E(EO9/EO9−), is -253 ± 6 mV and hence this quinone can be readily reduced by one-electron reducing enzymes such as cytochrome P450 reductase and xanthine oxidase. However, the radical is unstable in the presence of oxygen (k = 1.3 ± 0.15 × 108 M−1 s−1). The semiquinone radicals and the hydroquinone are in equilibrium, although the formation of the hydroquinone is favoured at physiologically relevant pH. The hydroquinone of EO9 is also unstable in the presence of oxygen and it is predicted that in fully aerated solutions, its half life is 1.5 ± 0.3 seconds. These results are discussed in view of the selective cytoxicity of EO9 and its ability to undergo bioreductive activation by one-electron reducing enzymes and DT-diaphorase.
Bromo-, chloro-, and amino-derivatives of 5α-androstane and 5α-oestrane (1974)

D. B. Cowell, A. K. Davis, D. W. Mathieson and P. D. Nicklin, J. Chem. Soc., Perkin Trans. 1, 1974, 1505 DOI: 10.1039/P19740001505
Tc-99m HIDA dosimetry in patients with various hepatic disorders. (1984)

The pharmacodynamics of Tc-99m dimethyliminodiacetic acid were studied for normal subjects and for patients with a variety of hepatobiliary disorders. It was determined that, in normal subjects, approximately 65% of the gallbladder agent bypassed the gallbladder and was excreted directly from the liver into the small intestine. This bypassing of the gallbladder was even higher in patients with cystic-duct or common-duct obstruction. The radiation burdens to the gallbladder wall and other critical organs were calculated using the dynamic data obtained from patients with a variety of gallbladder disease. The dose to the gallbladder wall was found to be significantly lower than previously reported. Gallbladder ejection and clearance characteristics when stimulated by food intake were studied for normal subjects. Dosimetry calculations demonstrated a fivefold reduction of absorbed dose to the gallbladder wall when the gallbladder was stimulated to contract using a fatty meal. Accordingly, a fatty meal is recommended for patients at the end of all gallbladder imaging studies.
Modeling axon membranes for functional electrical stimulation (1993)

Four models are discussed which can be used to predict the behavior of warm-blooded axons, when excited by electric fields. Up to now, most results were obtained with the Frankenhaeuser-Huxley model, but nearly all of them are wrong in time scale and the cathodic block phenomenon was not observable because the temperature dependence of the gating mechanism has been neglected. However, in the corrected form this model reacts with similar excitability as the two other myelinated nerve models which consider that the potassium current is negligible in mammalian axon membranes. Strength-duration relations for cathodic and anodic excitations, as well as for cathodic blockade, are presented. Paradoxically, the "warm" squid model of Hodgkin and Huxley is the only one which reflects phenomena known from stimulations of the (myelinated) acoustic nerve by cochlear implants.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Investigation into excimer laser radiation damage of deep ultraviolet optical phase masking films (1997)

A variety of materials based on various oxides, nitrides, fluorides, and composites have been found to be potentially suitable for use as attenuated phase masking materials for use at excimer laser wavelengths. Presented here are results from the investigation into 193 nm excimer laser radiation of zirconium–nitride-based, aluminum–nitride-based, chrome–fluoride, amorphous-carbon, and tantalum–silicon–nitride (TaN/Si3N4) attenuated phase-shift mask materials at fluence levels mask materials experience during wafer exposure. Spectroscopic photometric and ellipsometric methods were utilized to quantify damage through measurement of transmission and reflection properties and extraction of optical constants. Results show that understoichiometric zirconium– and aluminum–nitride materials are susceptible to radiation-induced modification through oxidation effects while tantalum–silicon–nitride and chrome–fluoride films are able to withstand exposure to several thousand J/cm2 without significant degradation.
Predictors of 12‐week remission in a nationwide cohort of people with depressive disorders: the CRESCEND study (2011)

Remission associated with unrestricted clinical interventions was comparable to STAR*D estimates for citalopram alone. Comorbid anxiety and previous suicide attempt were markers of worse outcome.
Multi-document Summarization by Graph Search and Matching (1997)

We describe a new method for summarizing similarities and differences in a pair of related documents using a graph representation for text. Concepts denoted by words, phrases, and proper names in the document are represented positionally as nodes in the graph along with edges corresponding to semantic relations between items. Given a perspective in terms of which the pair of documents is to be summarized, the algorithm first uses a spreading activation technique to discover, in each document, nodes semantically related to the topic. The activated graphs of each document are then matched to yield a graph corresponding to similarities and differences between the pair, which is rendered in natural language. An evaluation of these techniques has been carried out.
Laser plasma x-ray sources for microlithography (1988)

A plasma produced by laser irradiation of solid targets is a promising candidate as an efficient x-ray lithography source. In order to design a practical laser created x-ray source, it is necessary to study the factors affecting the x-ray emission. For this purpose, we investigate both theoretically and experimentally the influence of the laser target parameters on the x-ray emission in different spectral ranges for two laser wavelengths (λ=1.06 μm, λ=0.26 μm). From these results and considering mask transmission, resist sensitivities, and wafer throughput, we establish the characteristics of the laser required as an x-ray lithography source with performance acceptable for industrial applications.
WE‐E‐214‐03: Biology and Physiology of Targeted Radionuclide Therapy (TRT) (2011)

Radiolabeled agents are being developed for TRT (Targeted Radionuclide Therapy). Included in the 50 to 200 nm scale of this project are liposomes, short segments of DNA or RNA, nanoparticles and proteins. Because of possibly multiple lesion sites, these radiopharmaceuticals (RPs) are usually given by IV injection. Targeting, which requires a number of hours to days to accomplish, is effected by various means. The simplest method is to have the agent pass out of the blood and into the tumor space using the fenestrations in tumor capillaries. Liposomes are one such example whose membranes are dissolved in the lesion so as to release vesicle contents. Among the most specific localization processes is protein binding to a molecular marker on ‐ or near ‐ the tumor cell. Among such markers are Carcinoembryonic Antigen (CEA) and human epidermal growth factor receptor 2 (HER2). CEA is associated with colon, lung and some breast cancers, while HER2 is a breast cancer marker in approximately 25% of patients. These antigens are found in normal colon lumen and heart muscle respectively. A protein used in finding a molecular target may be something as simple as a mouse‐derived antibody or an engineered protein construct. One constraint is that proteins from alien species eventually generate their own human antibodies when repeatedly used in a given patient. This effect can be moderated by DNA manipulation of the alien antibody to change its structure to a more human‐like amino‐acid sequence. Use of a blood‐injection for the RP may result in sequestration by a normal tissue such as the liver or kidneys. In the renal case, small proteins (&lt;25 kDa) would be very rapidly taken out of circulation so as to prevent significant tumor targeting. Various strategies have been developed to minimize sequestration; e.g., blocking or use of polyethylene glycol covering molecules (“stealth”) to prolong protein circulation. Because of the large numbers of possible RPs, it is necessary that preselection be done on any putative clinical RP. A figure of merit (FOM) may be used to choose one of a series of agents dedicated to the same tumor type; e.g., cognate antibodies to CEA. Both imaging and therapeutic FOMs have been developed. These indicators are used to differentiate RPs using animal data. This preferential ordering process is needed since the number of agents is large while volunteers for research studies are only a small fraction (2 to 5%) of the total patient population. One is still left with the question of the relationship between animal and clinical biodistribution data. Learning Objectives: 1. Know the types of agents presently being studied for TRT. 2. Understand the reasons for tumor targeting by engineered pharmaceuticals (RPs). 3. Realize the importance of the RP blood curve for the targeting process. 4. Use of Figures of Merit to select an optimal imaging or therapy agent.
Community-associated methicillin-resistant Staphylococcus aureus infections at an Army training installation (2010)

To assess the burden of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) in a high-risk population, the monthly incidence of laboratory-confirmed MRSA in service members/trainees stationed at Fort Benning, Georgia, USA without hospitalization or surgery documented 30 days prior to infection was calculated for calendar years 2002-2007. Clinical management and antibiotic susceptibility patterns were also evaluated. By 2007, approximately 67% of S. aureus strains were MRSA, and approximately 82% of these were community-associated, primarily in trainees. In total, 3531 CA-MRSA infections were identified. Rates appeared to be seasonal, peaking at 42 cases/1000 soldiers in 2005, with rates remaining above 35/1000 soldiers thereafter. Increased prescription of effective antibiotics was documented. Susceptibility to clindamycin, ciprofloxacin, and levofloxacin decreased from 2002 to 2007 by 6%, 17%, and 14%, respectively. The sustained high prevalence of CA-MRSA observed highlights the need for more vigilant population-based counter-measures at military training installations.
IFN-gamma-inducing factor (IGIF) is a costimulatory factor on the activation of Th1 but not Th2 cells and exerts its effect independently of IL-12 (1997)

We have previously reported the cloning of a novel cytokine, IFN-gamma-inducing factor (IGIF), which shared some biologic activities with IL-12. In this study, we analyzed the effects of murine IGIF on the activation of T cells, and compared the effects with those of IL-12. IGIF alone had no effect on the activation of T cell lines or Th1 clones, while IGIF increased the IFN-gamma production by antigen-stimulated T cell lines, but had no effect on IL-4 or IL-10 production. As reported with IL-12, IGIF served as a costimulatory factor for Th1 clones stimulated with Ag on B cell APC, immobilized anti-CD3, Con A, or IL-2 to augment IFN-gamma production and to induce IL-2R alpha-chain expression and proliferation of the Th1 clones, whereas IGIF had little or no effect on the IL-4 production and proliferation of Th2 clones stimulated with anti-CD3 or Ag. However, IGIF synergized with IL-12 to further augment the IFN-gamma production of the Th1 clones. Even in the presence of saturated amounts of IL-12, IGIF still augmented the IFN-gamma production and proliferation and enhanced the IL-2R alpha-chain expression of the Th1 clones. In contrast with IL-12, IGIF induced IL-2 production by Ag- or anti-CD3-stimulated Th1 clones. These two findings indicate that IGIF and IL-12 are utilizing different signal transduction pathways. We also found that IGIF as well as IL-12 was endogenously released through interaction between Th1 cells and spleen cell APC in the presence of specific Ag, and that it regulated IFN-gamma production. These results further suggest that IGIF may act as an immunoregulatory factor in the immune response.
Enhancing the performance of model-based elastography by incorporating additionala prioriinformation in the modulus image reconstruction process (2005)

Model-based elastography is fraught with problems owing to the ill-posed nature of the inverse elasticity problem. To overcome this limitation, we have recently developed a novel inversion scheme that incorporates a priori information concerning the mechanical properties of the underlying tissue structures, and the variance incurred during displacement estimation in the modulus image reconstruction process. The information was procured by employing standard strain imaging methodology, and introduced in the reconstruction process through the generalized Tikhonov approach. In this paper, we report the results of experiments conducted on gelatin phantoms to evaluate the performance of modulus elastograms computed with the generalized Tikhonov (GTK) estimation criterion relative to those computed by employing the un-weighted least-squares estimation criterion, the weighted least-squares estimation criterion and the standard Tikhonov method (i.e., the generalized Tikhonov method with no modulus prior). The results indicate that modulus elastograms computed with the generalized Tikhonov approach had superior elastographic contrast discrimination and contrast recovery. In addition, image reconstruction was more resilient to structural decorrelation noise when additional constraints were imposed on the reconstruction process through the GTK method.
An RNA Mapping DataBase for curating RNA structure mapping experiments (2012)

Supplementary data are available at Bioinformatics Online.
Direct Binding of Integrin αvβ3 to FGF1 Plays a Role in FGF1 Signaling (2008)

Integrins play a role in fibroblast growth factor (FGF) signaling through cross-talk with FGF receptors (FGFRs), but the mechanism underlying the cross-talk is unknown. We discovered that FGF1 directly bound to soluble and cell-surface integrin alphavbeta3 (K(D) about 1 microm). Antagonists to alphavbeta3 (monoclonal antibody 7E3 and cyclic RGDfV) blocked this interaction. alphavbeta3 was the predominant, if not the only, integrin that bound to FGF1, because FGF1 bound only weakly to several beta1 integrins tested. We presented evidence that the CYDMKTTC sequence (the specificity loop) within the ligand-binding site of beta3 plays a role in FGF1 binding. We found that the integrin-binding site of FGF1 overlaps with the heparin-binding site but is distinct from the FGFR-binding site using docking simulation and mutagenesis. We identified an FGF1 mutant (R50E) that was defective in integrin binding but still bound to heparin and FGFR. R50E was defective in inducing DNA synthesis, cell proliferation, cell migration, and chemotaxis, suggesting that the direct integrin binding to FGF1 is critical for FGF signaling. Nevertheless, R50E induced phosphorylation of FGFR1 and FRS2alpha and activation of AKT and ERK1/2. These results suggest that the defect in R50E in FGF signaling is not in the initial activation of FGF signaling pathway components, but in the later steps in FGF signaling. We propose that R50E is a useful tool to identify the role of integrins in FGF signaling.