gebhart/patrepeval huggingface dataset:
Murine NK cell cultures: effects of interleukin-2 and interferon on cell growth and cytotoxic reactivity. (1981)

Abstract Murine spleen cell populations were stimulated in vitro with 50 µg of poly l:C and 24 h later, were transferred to medium containing lnterleukin-2 (IL-2). Under these conditions, cytotoxic cells could be maintained indefinitely. Removal of mature T cells at the initiation of culture, by treatment with anti-Thy 1.2 antibody in the presence of complement, was without effect on the development of cytotoxic cells. Cells harvested from such cultures exhibited surface markers characteristic of NK cells (Thy 1 +, asialo GMI +, Lyt 2−). Concordant with the display of NK phenotypic markers, the cytotoxic cells lysed YAC-1 lymphoma cells and an NK-susceptible clone (27v) of the L5178Y lymphoma, but did not lyse clone 27av cells, an NK-insusceptible variant of L5178Y. Studies involving the addition of graded doses of mouse fibroblast interferon (IF) to mouse spleen cells, showed maximal potentiating effects of 103 U/culture, with significantly less augmentation of NK cytotoxicity at higher IF concentrations. When partially purified IL-2 was concomitantly added, IL-2 and IF were at least additive in their effects at all IF concentrations. Several observations suggested that IL-2 itself, like IF, was capable of augmenting NK cell-mediated cytotoxicity. Thus, preparations of IL-2, which lacked IF, caused a rapid increase in NK cell activity. Additionally, the ability to augment cytotoxicity was removed from IL-2 preparations not only by absorption with IL-2 receptor-bearing cells, but also by precipitation with a monoclonal antibody directed against IL-2. One explanation for the cooperation between IF and IL-2 was suggested by the finding that spleen cell population exposed to IF showed a markedly augmented ability to bind IL-2, suggesting that IF may cause an increased display and/or affinity of IL-2 receptors. Furthermore, T cell-depleted spleen cells cultured in IF and IL-2 possessed readily demonstrable Thy 1 antigen, suggesting that these agents either modulate the display of cell surface macromolecules or, perhaps, that they potentiate T cell differentiation in vitro.
Biologically active glycosides from asteroidea, XIII. Glycosphingolipids from the starfish Acanthaster planci, 2. Isolation and structure of six new cerebrosides (1988)

Abstract Six new cerebrosides (ceramide monohexosides), acanthacerebroside A ( 1 ), B ( 2 ), C ( 3 ), D ( 4 ), E ( 5 ), and F ( 6 ) were isolated from the water‐insoluble lipid fraction of the chloroform‐methanol extract of the starfish Acanthaster planci . On the basis of chemical and spectral evidences, they were characterized as 1‐ O ‐(β‐ D ‐glucopyranosyl)‐substituted (1 S ,3 S ,4 R )‐2‐[(2 R )‐2‐hydroxytetracosanoylamino]‐1,3,4‐hexadecanetriol ( 1 ), (2 S ,3 S ,4 R )‐2‐[(2 R )‐2‐hydroxyhexadecanoylamino]‐1,3,4‐docosanetriol ( 2 ), (2 S ,3 S ,4 R ,13 E )‐2‐[(2 R )‐2‐hydroxyhexadecanoylamino]‐13‐docosene‐1,3,4‐triol ( 3 ), (2 S ,3 R ,4 E ,10 E )‐2‐[(2 R )‐2‐hydroxydocosanoylamino]‐4,10‐octadecadiene‐1,3‐diol ( 4 ), (2 S ,3 R ,4 E ,10 E )‐2‐[(2 R )‐2‐hydroxydocosanoylamino]‐4,10‐octadecadiene‐1,3‐diol ( 5 ), and (2 S ,3 R ,4 E ,10 E )‐2‐[(2 R )‐2‐hydroxytetracosanoylamino]‐4,10‐octadecadiene‐1,3‐diol ( 6 ). Reversed‐phase HPLC was effective to isolate these cerebrosides revealing the very close resemblance in structure. Negative FABMS spectrometry was useful in providing information on the molecular mass of the cerebrosides.
Sphingosine-1-phosphate receptor signalling in the heart (2008)

The five known members of the sphingosine-1-phosphate (S1P) receptor family exhibit diverse tissue expression profiles and couple to distinct G-protein-mediated signalling pathways. S1P1, S1P2, and S1P3 receptors are all present in the heart, but the ratio of these subtypes differs for various cardiac cells. The goal of this review is to summarize data concerning which S1P receptor subtypes regulate cardiac physiology and pathophysiology, which G-proteins and signalling pathways they couple to, and in which cell types they are expressed. The available information is based on studies using a lamentably limited set of pharmacological agonists/antagonists, but is complemented by work with S1P receptor subtype-specific knockout mice and sphingosine kinase knockout mice. In cardiac myocytes, the S1P1 receptor subtype is the predominant subtype expressed, and the activation of this receptor inhibits cAMP formation and antagonizes adrenergic receptor-mediated contractility. The S1P3 receptor, while expressed at lower levels, mediates the bradycardic effect of S1P agonists. Studies using knockout mice indicate that S1P2 and S1P3 receptors play a major role in mediating cardioprotection from ischaemia/reperfusion injury in vivo. S1P receptors are also involved in remodelling, proliferation, and differentiation of cardiac fibroblasts, a cell type in which the S1P3 receptor predominates. Receptors for S1P are also present in endothelial and smooth muscle cells where they mediate peripheral vascular tone and endothelial responses, but the role of this regulatory system in the cardiac vasculature is unknown. Further understanding of the contributions of each cell and receptor subtype to cardiac function and pathophysiology should expedite consideration of the endogenous S1P signalling pathway as a therapeutic target for cardiovascular disease.
Service disciplines for guaranteed performance service (2002)

The choice of the packet service disciplines is an important issue in providing guaranteed performance service at switching nodes. The service disciplines at a switching node control the order in which packets are serviced and thus determine how packets from different connections interact with each other. In addition, we also need to guarantee the bounds on end-to-end performance in a networking environment, where traffic dynamics are more complex than in a single switching node. In this paper, we give an overview of these proposed service disciplines. Furthermore, we analyze the delay bounds and fairness property of the Hierarchical Packet Fair Queuing (H-PFQ) algorithm.
Endogenous Cannabinoids: Structure and Metabolism (2008)

The finding of specific binding sites for Delta(9)-tetrahydrocannabinol, the psychoactive component of Cannabis sativa, has led to the discovery of the endocannabinoid system and has emphasised the physiological and pathological relevance of endocannabidoid lipid signalling. Subsequently, an increasing number of papers have been published on the biochemistry and pharmacology of endocannabinoids. An overview of the current understanding of structure and metabolism of the best studied endocannabinoids is provided, with a focus on the mechanisms responsible for their biosynthesis and inactivation.
Diabetes Mellitus Associated with Recombinant Human Growth Hormone for HIV Wasting Syndrome (2000)

Recombinant human growth hormone (rhGH) is an important treatment option for patients with human immunodeficiency virus (HIV) wasting syndrome. Side effects of rhGH are minimal when administered at physiologic and moderately high dosages, as seen in growth hormone deficiency and Turner's syndrome, respectively. The dosage of rhGH is significantly higher to treat wasting syndrome and still is being studied to determine its long-term efficacy and safety. Individuals with HIV infection are at increased risk for adverse effects due to polypharmacy, immune system alterations, and treatment with newer agents that lack long-term safety data. In addition, rhGH's potential for side effects becomes greater when given at high dosages for wasting syndrome. Clinically significant hyperglycemia developed in an HIV-positive man who started rhGH for wasting syndrome 38 days before the diagnosis of diabetes mellitus.
Phage Display as a Tool for Protease Ligand Discovery (2002)

Proteolytic enzymes have been implicated as the pathological agent in a number of disease states. For this reason proteases are attractive therapeutic targets. Phage display of peptide libraries can be used to identify peptides that may be used either directly as inhibitors or serve as leads in the generation of prodrugs and peptidomimetics.
Anticoagulant potential of synthetic and recombinant inhibitors of factor Xa and thrombin in vitro (1993)

The anticoagulant effects of thrombin inhibitors in vitro and ex vivo are well characterized. Inhibitors of factor Xa might also be effective as anticoagulants. We studied several synthetic, low-molecular-weight inhibitors with varying affinity to thrombin and factor Xa using three in vitro clot-based assays representative of the effects of thrombin added or generated via the intrinsic or extrinsic coagulation pathways. The recombinant selective thrombin and factor Xa inhibitors, hirudin and antistasin, were studied for comparison. The thrombin time assay is a measure of the antithrombin potential of a given inhibitor, while the activated partial thromboplastin time is influenced by inhibition of thrombin and/or of factor Xa in a similar manner. The prothrombin time assay was more sensitive to inhibition of factor Xa, as evidenced by the potent and selective inhibitor antistasin as well as for less potent and less selective synthetic inhibitors of factor Xa. Direct synthetic or recombinant inhibitors of factor Xa with Ki values in the submicromolar range were potent anticoagulants, approaching or exceeding the potency of hirudin in prolonging the prothrombin time and the activated partial thromboplastin time in vitro.
Clostridium difficile-associated diarrhoea in hospitalised patients (2000)

Patients admitted from NHs are at increased risk of development of CDAD; receiving cefotaxime or cefuroxime axetil (oral form), being elderly and being female are risk factors for the development of CDAD. Treatment of CDAD with oral metronidazole or oral vancomycin gives rise to similar response times and efficacy.
Contemporary management of penile squamous cell carcinoma (2004)

Squamous cell carcinoma (SCC) is the most common tumor of the penis. The natural history and its proclivity to spread via regional lymphatics has been well defined. Laser ablation of the primary tumor has a prominent role in patients with a superficial tumor as a penis-conserving approach. Patients with deeper infiltrating tumors, should undergo (partial) penile amputation. For patients presenting with proven metastatic nodes complete (ilio-) inguinal lymphadenectomy should be performed. During the last two decades, the management of penile carcinoma patients with impalpable regional lymph nodes has improved due to better knowledge of risks for metastases, the introduction of modified lymphadenectomy, and sentinel node biopsy. Future perspectives in penile cancer comprises continuing research to reduce mutilation without jeopardizing clinical outcome.
Reassessment of autoreactivity of the broadly neutralizing HIV antibodies 4E10 and 2F5 and retrospective analysis of clinical safety data (2007)

Monoclonal antibody 4E10 but not 2F5 or 2G12 showed autoreactive binding specificities. Infusion of 4E10 resulted in transient low anticardiolipin titers. Although an increased thromboembolic risk cannot definitely be excluded, this risk appears to be low and likely depend on underlying disorders.
Optically Tunable Gelled Photonic Crystal Covering Almost the Entire Visible Light Wavelength Region (2003)

By fixing charged colloidal crystals in a poly(acrylamide) hydrogel matrix, we fabricated photonic crystals whose diffraction peak wavelengths were tunable by applying mechanical stress. The reflection spectrum for a single crystal grain was measured by applying microspectroscopy under compression. The photonic band gap wavelength shifted linearly and reversibly over almost the entire visible light wavelength region (460−810 nm).
A protease-resistant immunotoxin against CD22 with greatly increased activity against CLL and diminished animal toxicity (2008)

Immunotoxins based on Pseudomonas exotoxin A (PE) are promising anticancer agents that combine a variable fragment (Fv) from an antibody to a tumor-associated antigen with a 38-kDa fragment of PE (PE38). The intoxication pathway of PE immunotoxins involves receptor-mediated internalization and trafficking through endosomes/lysosomes, during which the immunotoxin undergoes important proteolytic processing steps but must otherwise remain intact for eventual transport to the cytosol. We have investigated the proteolytic susceptibility of PE38 immunotoxins to lysosomal proteases and found that cleavage clusters within a limited segment of PE38. We subsequently generated mutants containing deletions in this region using HA22, an anti-CD22 Fv-PE38 immunotoxin currently undergoing clinical trials for B-cell malignancies. One mutant, HA22-LR, lacks all identified cleavage sites, is resistant to lysosomal degradation, and retains excellent biologic activity. HA22-LR killed chronic lymphocytic leukemia cells more potently and uniformly than HA22, suggesting that lysosomal protease digestion may limit immunotoxin efficacy unless the susceptible domain is eliminated. Remarkably, mice tolerated doses of HA22-LR at least 10-fold higher than lethal doses of HA22, and these higher doses exhibited markedly enhanced antitumor activity. We conclude that HA22-LR advances the therapeutic efficacy of HA22 by using an approach that may be applicable to other PE-based immunotoxins.
Pulmonary surfactant proteins A and D enhance neutrophil uptake of bacteria (1998)

The collectins are a class of collagenous lectin proteins present in serum and pulmonary secretions [pulmonary surfactant protein (SP) A and SP-D] that are believed to participate in innate immune responses to various pathogens. With the use of flow cytometric and fluorescent-microscopic assays, SP-A and SP-D were shown to increase calcium-dependent neutrophil uptake of Escherichia coli, Streptococcus pneumoniae, and Staphylococcus aureus. Evidence is provided that the collectins enhanced bacterial uptake through a mechanism that involved both bacterial aggregation and direct actions on neutrophils. The degree of multimerization of SP-D preparations was a critical determinant of both aggregating activity and potency in enhancing bacterial uptake. The mechanisms of opsonizing activity of SP-D and SP-A differed in important respects from those of opsonizing antibodies. These results provide the first evidence that surfactant collectins may promote neutrophil-mediated clearance of bacteria in the lung independently of opsonizing antibody.
FH Afrikaner-3 LDL Receptor Mutation Results in Defective LDL Receptors and Causes a Mild Form of Familial Hypercholesterolemia (1995)

Three founder-related gene mutations (FH Afrikaner-1, -2, and -3) that affect the LDL receptor are responsible for 90% of the familial hypercholesterolemia (FH) in South African Afrikaners. Patients heterozygous for the FH Afrikaner-1 (FH1) mutation, which results in receptors having approximately 20% of normal receptor activity, have significantly lower plasma cholesterol levels and milder clinical symptoms than heterozygotes with the FH Afrikaner-2 mutation, which completely abolishes LDL receptor activity. In this study we re-created the FH3 mutation (Asp154-->Asn) in exon 4 by site-directed mutagenesis and analyzed the expression of the mutant receptors in Chinese hamster ovary cells. The mutation resulted in the formation of LDL receptors that are markedly defective in their ability to bind LDL, whereas binding of apoE-containing beta-VLDL is less affected. The mutant receptors are poorly expressed on the cell surface as a result of significant degradation of receptor precursors. The plasma cholesterol levels of 31 FH3 heterozygotes were similar to FH1 heterozygotes but significantly lower than FH2 heterozygotes. The FH1 and FH3 heterozygotes also tended to be less severely affected clinically (by coronary heart disease and xanthomata) than FH2 patients. This study demonstrates that mutational heterogeneity in the LDL receptor gene influences the phenotypic expression of heterozygous FH and that severity of expression correlates with the activity of the LDL receptor measured in vitro. The results further indicate that knowledge of the specific mutation underlying FH in heterozygotes is valuable in determining the potential risk of premature atherosclerosis and should influence the clinical management of FH patients.
Contactless Sleep Apnea Detection on Smartphones (2015)

We present a contactless solution for detecting sleep apnea events on smartphones. To achieve this, we introduce a novel system that monitors the minute chest and abdomen movements caused by breathing on smartphones. Our system works with the phone away from the subject and can simultaneously identify and track the fine-grained breathing movements from multiple subjects. We do this by transforming the phone into an active sonar system that emits frequency-modulated sound signals and listens to their reflections; our design monitors the minute changes to these reflections to extract the chest movements. Results from a home bedroom environment shows that our design operates efficiently at distances of up to a meter and works even with the subject under a blanket.
Tip-Shaping for HP Turbine Blade Aerothermal Performance Management (2013)

A large portion of the over-tip leakage flow is often transonic for a typical high pressure (HP) turbine blade. It has been observed that the tip heat transfer is noticeably lower in a high speed flow tip region than in a low speed region. The present study therefore investigates the feasibility of controlling blade heat transfer by tip shaping to locally accelerate the flow to a transonic regime. The results show that a significant heat load reduction can be achieved by the local flow acceleration. Such over-tip-shaping provides a great potential as an effective means to control heat load distribution (and hence thermal stress) over the blade tip surface. The feasibility of the concept and flow physics have been demonstrated in detail by CFD analyses, with and without the effect of moving casing. The experimental results obtained from a high speed linear cascade facility have also been presented. The novel tip-shaping concept proposed in this paper could provide a potential for promoting choking inside the tip gap as a new way to control the over-tip leakage mass flow.
Escherichia coli Enoyl-Acyl Carrier Protein Reductase (FabI) Supports Efficient Operation of a Functional Reversal of the β-Oxidation Cycle (2014)

We recently used a synthetic/bottom-up approach to establish the identity of the four enzymes composing an engineered functional reversal of the -oxidation cycle for fuel and chemical production in Escherichia coli (J. M. Clomburg, J. E. Vick, M. D. Blankschien, M. Rodriguez-Moya, and R. Gonzalez, ACS Synth Biol 1:541–554, 2012, http://dx.doi.org/10.1021/sb3000782).While native enzymes that catalyze the first three steps of the pathway were identified, the identity of the native enzyme(s) acting as the trans-enoyl coenzyme A (CoA) reductase(s) remained unknown, limiting the amount of product that could be synthesized (e.g., 0.34 g/liter butyrate) and requiring the overexpression of a foreign enzyme (the Euglena gracilis trans-enoyl-CoA reductase [EgTER]) to achieve high titers (e.g., 3.4 g/liter butyrate). Here, we examine several native E. coli enzymes hypothesized to catalyze the reduction of enoyl-CoAs to acyl-CoAs. Our results indicate that FabI, the native enoyl-acyl carrier protein (enoyl-ACP) reductase (ENR) from type II fatty acid biosynthesis, possesses sufficient NADH-dependent TER activity to support the efficient operation of a -oxidation reversal. Overexpression of FabI proved as effective as EgTER for the production of butyrate and longer-chain carboxylic acids. Given the essential nature of fabI, we investigated whether bacterial ENRs from other families were able to complement a fabI deletion without promiscuous reduction of crotonyl-CoA. These characteristics from Bacillus subtilis FabL enabled deltaffabI complementation experiments that conclusively established that FabI encodes a native enoyl-CoA reductase activity that supports the β-oxidation reversal in E. coli.
On the mechanism of antiaggregatory effect of myricetin. (1989)

Myricetin at a dose of 3.6 micrograms/kg iv was found to inhibit the cat blood platelet aggregation in vivo. It disaggregated platelet thrombi in vitro at a concentration of 60 nM. This flavonoid bound to platelet membranes and prevented prostacyclin synthase against oxygen free radicals owing to its antioxidant properties. Myricetin inhibited soybean lipoxygenase when linoleic acid was used as a substrate.
CC Chemokine Receptor 2 Is Required for Macrophage Infiltration and Vascular Hypertrophy in Angiotensin II–Induced Hypertension (2000)

Abstract —Recent studies have identified the presence of macrophages in the arterial wall of hypertensive animals and suggested that as is the case in atherosclerosis, macrophage products may be important mediators of the adaptive response of the arterial wall. In support of this, we have previously shown that the expression of monocyte chemoattractant protein-1 is upregulated in the arteries of hypertensive animals. We hypothesized that macrophage recruitment is a critical step in the pathogenesis of hypertension. To obtain insights into this potential mechanism, we made use of mice deficient in the CC chemokine receptor 2 (CCR2), the receptor for monocyte chemoattractant protein-1. Hypertension was induced with the subcutaneous administration of angiotensin II (0.75 mg · kg −1 · d −1 ) for 7 days. Using in situ hybridization with a probe for c- fms to identify macrophages, we found that hypertension-induced macrophage infiltration of the arterial wall was virtually eliminated in CCR2-deficient mice. In addition, vascular hypertrophy was reduced by ≈65% compared with wild-type animals. These data demonstrate that CCR2 is essential for the recruitment of macrophages into the arterial wall in the setting of hypertension. Furthermore, the decreased hypertrophic response suggests that vascular hypertrophy occurs in part as a consequence of macrophage infiltration. In angiotensin II–induced hypertension, CCR2-mediated responses are critical to the process of macrophage recruitment and vascular hypertrophy and may represent one mechanism by which at least some forms of hypertension may lead to the development of atherosclerosis.
Binding of NF-kappaB p65 subunit to the promoter elements is involved in LPS-induced transactivation of miRNA genes in human biliary epithelial cells (2010)

The majority of human miRNA genes is transcribed by polymerase II and can be classified as class II genes similar to protein-coding genes. Whereas current research on miRNAs has focused on the physiological and pathological functions, the molecular mechanisms underlying their transcriptional regulation are largely unknown. We recently reported that lipopolysaccharide (LPS) alters mature miRNA expression profile in human biliary epithelial cells. In this study, we tested the role of transcription factor NF-kappaB in LPS-induced transcription of select miRNA genes. Of the majority of LPS-up-regulated mature miRNAs in cultured human biliary epithelial cells, potential NF-kappaB binding sites were identified in the putative promoter elements of their corresponding genes. Inhibition of NF-kappaB activation by SC-514, an IKK2 inhibitor, blocked LPS-induced up-regulation of a subset of pri-miRNAs, including pri-miR-17-92, pri-miR-125b-1, pri-miR-21, pri-miR-23b-27b-24-1, pri-miR-30b, pri-miR-130a and pri-miR-29a. Moreover, direct binding of NF-kappaB p65 subunit to the promoter elements of mir-17-92, mir-125b-1, mir-21, mir-23b-27b-24-1, mir-30b and mir-130a genes was identified by chromatin immunoprecipitation analysis and confirmed by the luciferase reporter assay. Thus, a subset of miRNA genes is regulated in human biliary epithelial cells through NF-kappaB activation induced by LPS, suggesting a role of the NF-kappaB pathway in the transcriptional regulation of miRNA genes.