gebhart/patrepeval huggingface dataset:
14,15-Epoxyeicosa-5,8,11-trienoic Acid (14,15-EET) Surrogates Containing Epoxide Bioisosteres: Influence upon Vascular Relaxation and Soluble Epoxide Hydrolase Inhibition (2009)

All-cis-14,15-epoxyeicosa-5,8,11-trienoic acid (14,15-EET) is a labile, vasodilatory eicosanoid generated from arachidonic acid by cytochrome P450 epoxygenases. A series of robust, partially saturated analogues containing epoxide bioisosteres were synthesized and evaluated for relaxation of precontracted bovine coronary artery rings and for in vitro inhibition of soluble epoxide hydrolase (sEH). Depending upon the bioisostere and its position along the carbon chain, varying levels of vascular relaxation and/or sEH inhibition were observed. For example, oxamide 16 and N-iPr-amide 20 were comparable (ED(50) 1.7 microM) to 14,15-EET as vasorelaxants but were approximately 10-35 times less potent as sEH inhibitors (IC(50) 59 and 19 microM, respectively); unsubstituted urea 12 showed useful activity in both assays (ED(50) 3.5 microM, IC(50) 16 nM). These data reveal differential structural parameters for the two pharmacophores that could assist the development of potent and specific in vivo drug candidates.
Abstract 5130: Src and Caveolin-1 reciprocally regulate metastasis via Rho Kinase (2010)

Abstract In human bladder cancer, overexpression of Caveolin-1 (Cav-1) and downregulation of Src expression and kinase activity correlate with aggressive behavior suggesting they may have causal and perhaps interactive roles in this process. Here we show that Cav-1 and Src are reciprocally expressed in the same tumors, suggesting they act on a similar pathway. RNAi mediated Cav-1 depletion or expression of constitutively active Src in invasive human urothelial cancer cells UMUC-3 and KU-7 resulted in loss of stress fibers and reduced capacity to migrate. Cav-1 depletion was associated with loss of pY14 Cav-1 while increased p190RhoGAP was seen with Src over-expression while both led to a significant reduction in RhoA and RhoC levels and activity. Conversely, expression of Cav-1 but not the non-phosphorylatable mutant of Cav-1 or suppression of Src using PP2 or Src RNAi in noninvasive human urothelial RT4 cancer cells, increased RhoA and RhoC GTP and cell migration. Use of ROCK inhibitor Y27632 in RT4 cells completely abolished enhanced migration induced by Cav-1 expression or that associated with Src inhibition. Furthermore, metastatic lung colonization of UMUC-3 cells expressing constitutively active Src or depleted of Cav-1 was significantly reduced while having marginal effect on subcutaneous tumor growth. Moreover, ROCK inhibitor prevented bladder cancer lung metastasis in vivo. Our findings indicate Src is metastasis suppressor protein in bladder cancer and describe a novel relationship between Cav-1 and Src in regulating RhoA and RhoC providing a unifying molecular mechanism for prior descriptive studies suggesting a role for these proteins in bladder cancer progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5130.
COMPUTER CHESS AND SEARCH (1992)

Article prepared for the 2nd edition of the ENCYCLOPEDIA OF ARTIFICIAL INTELLIGENCE, S. Shapiro (editor), to be published by John Wiley, 1992.
Origin of the sharp boundary that discriminates positive and negative selection of thymocytes (2008)

T lymphocytes play a key role in adaptive immunity and are activated by interactions of their T cell receptors (TCR) with peptides (p) derived from antigenic proteins bound to MHC gene products. The repertoire of T lymphocytes available in peripheral organs is tuned in the thymus. Immature T lymphocytes (thymocytes) interact with diverse endogenous peptides bound to MHC in the thymus. TCR expressed on thymocytes must bind weakly to endogenous pMHC (positive selection) but must not bind too strongly to them (negative selection) to emerge from the thymus. Negatively selecting pMHC ligands bind TCR with a binding affinity that exceeds a sharply defined (digital) threshold. In contrast, there is no sharp threshold separating positively selecting ligands from those that bind too weakly to elicit a response. We describe results of computer simulations and experiments, which suggest that the contrast between the characters of the positive and negative selection thresholds originates in differences in the way in which Ras proteins are activated by ligands of varying potency. The molecular mechanism suggested by our studies generates hypotheses for how genetic aberrations may dampen the digital negative selection response, with concomitant escape of autoimmune T lymphocytes from the thymus.
Treatment of corneal neovascularization with argon laser (1993)

Corneal neovascularization, which is associated with complications in corneal diseases, can cause lipid deposit, decreasing vision, and graft rejection after penetrating keratoplasty (PKP). Corneal laser photocoagulation using an argon laser or yellow dye laser for ablation of corneal neovascularization has been described. We performed corneal argon laser photocoagulation (CALP) in two male patients with corneal neovascularization after herpetic keratitis. One PKP was performed after CALP and restored good vision with no rejection of the graft during an 8 month follow-up period. In the other case we observed visual improvement and no recurrence of corneal neovascularization after CALP.
Effect of dopant type on the properties of polyaniline (2009)

Abstract The comparative study on the effect of different type of dopants on the properties of polyaniline (PANI) is relative less although dopant has profound effect of the properties of PANI. So, the aim of the present work is to study the effect of different type of dopant, namely strong inorganic hydrochloric acid (HCl), organic and aromatic acids containing different aromatic substitution, namely p ‐toluene sulfonic acid (PTSA), dodecylbenzenesulfonic acid (DBSA), organic and aliphatic acids having long hydrocarbon chain, namely lauric acid (LA), on the properties of PANI. The PANI was prepared through oxidative polymerization methods and doped with HCl, PTSA, DBSA, and LA and then characterized through different methods like conductivity measurement, UV, X‐ray, DSC, TGA, and SEM. It was found that the properties of doped PANI depend on the type and molecular size of the dopant. With the increase in dopant chain length, the crystallinity is decreased, whereas the d ‐spacing, interchain separation, and solubility are increased. The bond formation of water molecules with the backbone nitrogen of the polymers is much less in presence of aromatic dopants when compared with those of inorganic or aliphatic dopants. All the doped polyanilines under investigation do not decompose up to 500°C. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
Human and Non-Human Primate Intestinal FcRn Expression and Immunoglobulin G Transcytosis (2013)

In adult primates, FcRn is expressed more highly in distal intestinal epithelial cells. However, mAb delivery to that region results in low serum levels, in part because apical surface FcRn binding does not influence mAb transcytosis. High FcRn expression in enteroendocrine cells could provide a novel means to target mAbs for metabolic diseases after systemic administration.
A Comparison of Fat‐free Mass Estimates in Men Infected With the Human Immunodeficiency Virus (1995)

In individual subjects, no alternate method gave estimates of lean-body mass that were the same as estimates from total body electrical conductivity. One prediction equation (Brozek) gave estimates that might be useful for following changes in fat-free mass over time because the bias did not change substantially for increasing values of lean-body mass. On the other hand, because there were no statistically significant differences between the mean lean-body mass estimates by total body electrical conductivity and those measured by bioelectrical impedance assessment or a prediction equation on the basis of body mass index, the latter two methods might be useful in assessing lean-body mass in groups.
<title>Computer-Controlled Electrophoresis Microscope</title> (1980)

An automated analytical electrophoresis microscope system was developed to provide instrumentation for rapid analysis of normal and altered cells in biologic and clinical studies. The system is controlled by a computer that (i) provides for the tracking of migrating cells, whose images are projected under phase contrast onto a vidicon, (ii) permits the rapid taking of multiple measurements per cell, and (iii) calculates the electrophoretic mobility. The system contains algorithms and software programs necessary to create a large data base of cell mobilities and to determine statistically valid distributions of cell mobilities.
Characterization of Unusual Escape Variants of Hepatitis B Virus Isolated from a Hepatitis B Surface Antigen-Negative Subject (1998)

ABSTRACT Hepatitis B virus DNA was extracted from serial serum samples of a hepatitis B surface antigen-negative patient with antibodies to the core protein as the only marker of an infection with hepatitis B virus. This patient showed no symptoms of hepatic injury. Sequencing of the amplified viral DNA demonstrated multiple amino acid changes clustering in surface-exposed regions of the surface protein. Synthesis and association of the middle (M) and small (S) surface proteins could be shown in vitro. The variant surface antigens were recognized neither by monoclonal antibodies to the surface antigen nor by the vaccinee’s sera. Consequences for hepatitis B surface antigen testing and vaccine development are discussed.
Nonlinear fluorescence through intermolecular energy transfer and resolution increase in fluorescence microscopy (1999)

We investigate a novel concept to efficiently generate multiphoton induced fluorescence from organic molecules. The concept is based on frustrating the energy transfer between a fluorescent donor and one or more acceptors in conjugated molecules. The nonlinearity is not based on higher order molecular susceptibilities but entirely on their linear properties. Therefore, in contrast to nonresonant multiphoton absorption, this method does not require high local intensities. Likewise, the production of visible fluorescence does not require an infrared excitation wavelength. Hence, when applied to scanning microscopy this property is predicted to increase spatial resolution. Instead of the ∼10 GW/cm2 required in non-resonant multiphoton excitation, focal intensities ∼10 MW/cm2 are expected to produce an equally strong nonlinear signal. The predicted resolution is up to 30% greater than that of an ideal confocal microscope operating at the same fluorescence wavelength. The resolution improvement over non-resonant two-photon absorption microscopes is about two-fold in all directions.
Dynamic Host Configuration Protocol (DHCPv4 and DHCPv6) Option for Civic Addresses Configuration Information (2006)

This document specifies a Dynamic Host Configuration Protocol (DHCPv4
and DHCPv6) option containing the civic location of the client or the
DHCP server. The Location Configuration Information (LCI) includes
information about the country, administrative units such as states,
provinces, and cities, as well as street addresses, postal community
names, and building information. The option allows multiple renditions
of the same address in different scripts and languages. [STANDARDS-
TRACK]
Cytotoxic activity of the selected pyridinium salts against murine leukemia L1210. (2008)

The objective of this work was to evaluate the relationship between chemical reactivity of 3-substituted pyridinium salts and their cytotoxic properties against murine leukemia L1210. Chemical reactivity of pyridinium salts towards NADH oxidation following one-step hydride transfer depends strongly on their redox properties. The investigated reaction may reflect the ability of the salts to deplete NADH level in cells and to affect their metabolic functions. On the other hand, the cytotoxic activity against murine leukemia cells, expressed as ED50 values, varied strongly depending upon the compound used. The investigated salts showed also a diverse antileukemic effect in in vivo experiments as measured by the increase in the survival time of L1210 leukemia-bearing mice. These biological effects were correlated with equilibrium constants found for the reaction of pyridinium salts with NADH.
Antagonism by haloperidol and its metabolites of mechanical hypersensitivity induced by intraplantar capsaicin in mice: role of sigma-1 receptors (2009)

These results show that haloperidol and its metabolites I and II produce antiallodynic but not antinociceptive effects against punctate mechanical stimuli and suggest that their antiallodynic effect may be due to blockade of sigma(1) receptors but not to dopamine receptor antagonism.
Is streptolysin S of group A streptococci a virulence factor? (1999)

The possible role played by streptolysin S (SLS) of group A streptococci in the pathophysiology of streptococcal infections and in post-streptococcal sequelae is discussed. The following properties of SLS justify its definition as a distinct virulence factor: 1) its presence on the streptococcus surface in a cell-bound form, 2) its continuous and prolonged synthesis by resting streptococci, 3) its non-immunogenicity, 4) its extractability by serum proteins (albumin, alpha lipoprotein), 5) its ability to become transferred directly to target cells while being protected from inhibitory agents in the milieu of inflammation, 6) its ability to bore holes in the membrane phospholipids in a large variety of mammalian cells, 7) its ability to synergize with oxidants, proteolytic enzymes, and with additional host-derived proinflammatory agonists, and 8) its absence in streptococcal mutants associated with a lower pathogenicity for animals. Because tissue damage in streptococcal and post-streptococcal sequelae might be the end result of a distinct synergism between streptococcal and host-derived proinflammatory agonists it is proposed that only cocktails of anti-inflammatory agents including distinct inhibitors of SLS (phospholipids), gamma globulin, inhibitors of reactive oxygen species, proteinases, cationic proteins cytokines etc., will be effective in inhibiting the multiple synergistic interactions which lead to fasciitis, myositis and the flesh-eating syndromes, and often develop into sepsis, septic shock and multiple organ failure. The creation of mutants deficient in SLS and in proteases will help shed light on the specific role played by SLS in the virulence of group A hemolytic streptococci.
Comparing ATM credit-based and rate-based controls for TCP sources (2002)

TCP/IP traffic is likely to be one of the most heavily carried over ATM networks. However this kind of traffic is of connectionless nature and for this reason will be carried on an available bit rate (ABR) basis. In order to prevent the ABR traffic from congesting the network, special congestion control techniques have been devised. These schemes can be categorized in two major groups: rate-based and credit-based schemes. The most important representatives of these categories are respectively the proportional rate control algorithm (PRCA) and the flow controlled virtual circuit (FCVC). Since TCP/IP traffic is also controlled by the TCP window flow control, we present a comparison between PRCA and FCVC (via simulation of an ATM LAN) under TCP traffic. In this sense the performance measure we are mostly concerned with is the goodput. We investigate the impact of the burstiness of the guaranteed sources used as background traffic and the maximum size of TCP segments, which seems to be critical for the PRCA approach.
Leukocytosis is a risk factor for thrombosis in essential thrombocythemia: interaction with treatment, standard risk factors, and Jak2 mutation status (2006)

Leukocytes contribute to the pathogenesis of thrombosis in essential thrombocythemia (ET) through recently discovered mechanisms of activation and interaction with platelets and endothelial cells. To evaluate whether an increased leukocyte count was associated with thrombosis and whether this effect can be modulated by therapy, we analyzed the clinical course of 439 patients with ET followed at the Ospedali Riuniti di Bergamo. The strength of the association was measured at diagnosis or before thrombotic events by multivariable analyses carried out using data at baseline as well as time-varying covariates. The results showed that (1) an increased leukocyte count at diagnosis was associated with thrombosis during follow-up ("baseline analysis," relative risk [RR] 2.3, 95% confidence interval [CI] 1.4-3.9, P = .001); (2) hydroxyurea (HU) lowered leukocytosis and reduced the strength of the association between leukocytosis and thrombosis ("time-dependent analysis," RR 1.6, 95% CI 0.9-2.0, not significant [NS]); (3) the association of leukocytosis and thrombosis was more evident in untreated low-risk patients (RR 2.7, 95% CI 1.2-6.4, P = .01) compared with HU-treated high-risk patients (RR 1.6, 95% CI 0.8-3.2, NS); and (4) the presence of JAK2 V617F was not identified as a risk factor for thrombosis during follow-up despite a significant association between the mutation and leukocytosis. We suggest validation of these findings in prospective clinical studies.
The Fibromyalgia Syndrome (1997)

The term fibromyalgia describes a complex syndrome characterized by pain amplification, musculoskeletal discomfort, and systemic symptoms. Although its existence has been controversial, nearly all rheumatologists now accept fibromyalgia as a distinct diagnostic entity. In fact, in the United States it is the third or fourth most common reason for rheumatology referral. Exciting new insights into the aetiology, pathogenesis, diagnosis and treatment of fibromyalgia will be reviewed.
A Region of ς <sup>K</sup> Involved in Promoter Activation by GerE in <i>Bacillus subtilis</i> (1999)

During endospore formation in Bacillus subtilis, the DNA binding protein GerE stimulates transcription from several promoters that are used by RNA polymerase containing sigmaK. GerE binds to a site on one of these promoters, cotX, that overlaps its -35 region. We tested the model that GerE interacts with sigmaK at the cotX promoter by seeking amino acid substitutions in sigmaK that interfered with GerE-dependent activation of the cotX promoter but which did not affect utilization of the sigmaK-dependent, GerE-independent promoter gerE. We identified two amino acid substitutions in sigmaK, E216K and H225Y, that decrease cotX promoter utilization but do not affect gerE promoter activity. Alanine substitutions at these positions had similar effects. We also examined the effects of the E216A and H225Y substitutions in sigmaK on transcription in vitro. We found that these substitutions specifically reduced utilization of the cotX promoter. These and other results suggest that the amino acid residues at positions 216 and 225 are required for GerE-dependent cotX promoter activity, that the histidine at position 225 of sigmaK may interact with GerE at the cotX promoter, and that this interaction may facilitate the initial binding of sigmaK RNA polymerase to the cotX promoter. We also found that the alanine substitutions at positions 216 and 225 of sigmaK had no effect on utilization of the GerE-dependent promoter cotD, which contains GerE binding sites that do not overlap with its -35 region.
Four-channel polarimeter for time-resolved ellipsometry (1987)

A new four-channel partial polarimeter was designed for use in time-resolved ellipsometry measurements. The device outputs four parallel, equispaced beams from a single input beam. By detecting and digitizing the intensities of these four beams, the intensity, as well as two of the three elements of the reduced Stokes vector can be determined. Since there are no moving parts to the polarimeter, time resolution is limited only by the response time of the photodetectors and the digitizers. The linear array of output beams is ideal for streak-camera detection, yielding a potential time resolution of ~1 psec. A beam splitter is described that separates the input beam into two beams, which are parallel to the input beam and whose polarizations are nearly the same as the input beam. In addition, the polarimeter is achromatic, operating in the wavelength region from 220 to 1100 nm.
Functional Role of P-Selectin Glycoprotein Ligand 1/P-Selectin Interaction in the Generation of Tolerogenic Dendritic Cells (2007)

Dendritic cells (DCs) have a key role in both the generation of the immune response and the induction of tolerance to self-Ags. In this work, the possible role of P-selectin glycoprotein ligand 1 (PSGL-1) on the tolerogenic activity of human DCs was explored. We found that the engagement of PSGL-1 by P-selectin on DCs induced the expression of c-Fos, IDO, IL-10, and TGF-beta genes. Remarkably, stimulation of DCs through PSGL-1 with P-selectin enhanced their capability to generate CD4(+)CD25(+)Foxp3(+) regulatory T cells, which expressed high levels of TGF-beta1 mRNA, synthesized IL-10, and suppressed the proliferation of autologous CD4(+)CD25(-) T cells. Accordingly, we found that DCs from PSGL-1(-/-) mice expressed higher levels of MHC class II molecules, and exhibited an enhanced immunogenicity compared with wild-type mice. In addition, the percentage of CD4(+)CD25(+)Foxp3(+) regulatory T cells in the thymus of PSGL-1-deficient animals was significantly reduced. Our data reveal an unexpected role of PSGL-1 on the tolerogenic function of DCs, and the regulation of the immune response.
War and Culture, a Case Study: The Enlightenment and the Conduct of the British Army in America, 1755–1781 (1990)

(1990). War and Culture, a Case Study: The Enlightenment and the Conduct of the British Army in America, 1755–1781. War & Society: Vol. 8, No. 1, pp. 1-28.
The Peroxyester Reaction (1964)

Abstract The reactions of t‐butyl peroxyesters with various classes of compounds in the presence of a catalytic amount of copper ions produce well‐defined acyloxy derivatives. This peroxyester reaction, discovered by Kharasch and Sosnovsky, can be used to effect one‐step oxidation of saturated and unsaturated hydrocarbons, alcohols, aldehydes, esters, ethers, sulfides, organosilicon compounds, etc. The reaction can be highly selective: in most cases only one specific carbon atom is attacked. However, with some ethers and, sulfides the reaction can take a more complex course, other products being formed in addition to the acyloxy derivatives. The mechanism of the reaction has been extensively investigated, and several concerted and chain mechanisms have been proposed.
Effect of Curing Conditions on Alkali-Activated Slags (1989)

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