gebhart/patrepeval huggingface dataset:
Analysis of human immunodeficiency virus-infected tissues by amplification and in situ hybridization reveals latent and permissive infections at single-cell resolution. (1993)

Latent and productive viral infections are at the extremes of the spectrum of virus-cell interactions that are thought to play a major role in the ability of such important human pathogens as human immunodeficiency virus (HIV) to elude host defenses and cause disease. The recent development of PCR-based methods to amplify target sequences in individual cells in routinely fixed tissues affords opportunities to directly examine the subtle and covert virus-cell relationships at the latent end of the spectrum that are inaccessible to analysis by conventional in situ hybridization techniques. We have now used PCR in situ with in situ hybridization to document latent and permissive HIV infection in routinely fixed and paraffin-embedded tissue. In one of the first specimens we examined, a tumor biopsy from an HIV-infected individual, we found many of the lymphocytes and lymphocytes infiltrating the tumor had HIV DNA that was detectable only by PCR in situ. The fraction of positive cells varied regionally, but there were foci where most of the cells contained HIV DNA. Most of these lymphocytes and macrophages are latently infected, as we could detect HIV RNA in fewer than one in a thousand of these cells. We also detected HIV RNA, surprisingly, in 6% of the tumor cells, where the number of copies of viral RNA per cell was equivalent to productively infected cell lines. The alternative states of HIV-gene expression and high local concentration of latently infected lymphocytes and monocytes revealed by these studies conceptually supports models of lentiviral pathogenesis that attribute persistence to the reservoir of latently infected cells and disease to the consequences of viral-gene expression in this population. The magnitude of infection of lymphocytes documented in this report is also consistent with the emerging view that HIV infection per se could contribute substantially to depletion of immune cells in AIDS.
An Integrated Distributed Control Structure for Global Communications (1980)

The worldwide communications resources of the Defense Communications System (DCS) are controlled by a multilevel control complex, with distribution of control functions among many control facilities. The control structure is going through substantial changes, driven by considerations of reliability, survivability, crisis management capability, and of course, cost. This paper introduces the control structure, the ongoing and programmed improvements for the control capabilities, and how the Automated Technical Control (ATEC) equipments will form the basis of a distributed, processor based communications control utility. Finally, the unique features of the Real Time Adaptive Control System (RTACS) for the third generation Defense Satellite Communications System (DSCS) will be described, along with the integration of RTACS into the distributed global control structure.
New Vaccine and Treatment Excite Ebola Researchers (2003)

VIROLOGYRecent advances--including a second vaccine candidate and the first treatment shown to work in monkeys--offer hope for controlling a gruesome disease.
Characterization of the Anti-HCV Activities of the New Cyclophilin Inhibitor STG-175 (2016)

Shortened current direct-acting antiviral (DAA) therapies while less expensive, have not provided satisfactory efficacy in naïve cirrhotics, treatment experienced non-cirrhotics or even genotype-3 (GT3)-infected patients. Since DAA regimens consist of the same classes of inhibitors-NS5A (NS5Ai) and NS5B (NS5Bi) +/- NS3 (NS3i) inhibitors-it is likely that their costs will be high and will provide similar degrees of protection. Integrating drugs with distinct mechanisms of action (MoA) into DAA regimens could provide the solution for shortening the period of treatment. One such class of agents is the cyclophilin inhibitors (CypI), which has shown efficacy in patients. Resistance-associated variants persist for years post-treatment in patients exposed to NS5Ai or NS5Bi who fail to achieve a sustained virologic response, impairing their chance for cure on retreatment with existing DAA combinations. Because of their high barrier to resistance, CypI may be particularly useful as a rescue therapy for patients who have relapsed with DAA resistance-associated variants. In this study, we analyzed the anti-HCV properties of the novel cyclosporine A (CsA) derivate-STG-175. The non-immunosuppressive STG-175 possesses a high (EC50 11.5-38.9 nM) multi-genotypic (GT1a to 4a) anti-HCV activity. STG-175 clears cells from HCV since no viral replication rebound was observed after cessation of drug treatment. It presents a higher barrier to resistance than other CypI or selected DAAs. HCV variants, which emerged under STG-175 pressure, are only ~2-fold resistant to the drug. No cross-resistance was observed with DAAs STG-175 was efficacious against DAA-resistant HCV variants. Drug combination studies revealed that STG-175 provides additive and synergistic effects against GT1a to 4a. STG-175 inhibits the infection of HCV, HIV-1 and HBV in mono-, dual- and triple-infection settings. Altogether these results suggest that the new CypI STG-175 represents an attractive drug partner for IFN-free DAA regimens for the treatment of HCV and co-infections.
The effects of the phospholipase a2 inhibitor, manoalide, on cartilage degradation, stromelysin expression, and synovial fluid cell count induced by intraarticular injection of human recombinant interleukin‐1α in the rabbit (1996)

These studies demonstrate that manoalide is a potent inhibitor of inflammation and cartilage catabolism, and suggest that PLA2 is involved in the pathophysiology of rHuIL-1 alpha-induced arthritis in rabbits.
The Taccalonolides: Microtubule Stabilizers That Circumvent Clinically Relevant Taxane Resistance Mechanisms (2008)

The taccalonolides are a class of structurally and mechanistically distinct microtubule-stabilizing agents isolated from Tacca chantrieri. A crucial feature of the taxane family of microtubule stabilizers is their susceptibility to cellular resistance mechanisms including overexpression of P-glycoprotein (Pgp), multidrug resistance protein 7 (MRP7), and the betaIII isotype of tubulin. The ability of four taccalonolides, A, E, B, and N, to circumvent these multidrug resistance mechanisms was studied. Taccalonolides A, E, B, and N were effective in vitro against cell lines that overexpress Pgp and MRP7. In addition, taccalonolides A and E were highly active in vivo against a doxorubicin- and paclitaxel-resistant Pgp-expressing tumor, Mam17/ADR. An isogenic HeLa-derived cell line that expresses the betaIII isotype of tubulin was generated to evaluate the effect of betaIII-tubulin on drug sensitivity. When compared with parental HeLa cells, the betaIII-tubulin-overexpressing cell line was less sensitive to paclitaxel, docetaxel, epothilone B, and vinblastine. In striking contrast, the betaIII-tubulin-overexpressing cell line showed greater sensitivity to all four taccalonolides. These data cumulatively suggest that the taccalonolides have advantages over the taxanes in their ability to circumvent multiple drug resistance mechanisms. The ability of the taccalonolides to overcome clinically relevant mechanisms of drug resistance in vitro and in vivo confirms that the taccalonolides represent a valuable addition to the family of microtubule-stabilizing compounds with clinical potential.
Monocyte chemoattractant protein-1 expression in renal tissue is associated with monocyte recruitment and tubulo-interstitial lesions in patients with lupus nephritis. (2001)

The expression of MCP-1 in the renal tubules and vascular wall was markedly increased in patients with lupus nephritis. The overproduction of MCP-1 in renal tissue may contribute to monocyte recruitment in the interstitium and thus result in tubulo-interstitial damage in lupus nephritis.
Design and implementation of a real-time multimedia presentation system using RTP (2002)

A new class of protocols like RTP, RTSP and RSVP are tailoring today's packet networks for streaming real time multimedia data that once carried only non real time traffic. Multimedia networking is now possible with the existing network infrastructure. We describe a real time multimedia presentation system for media on demand over the Internet. It uses RTP and is capable of real time video/audio transmission. Our system consists of servers that maintain video/audio clips and clients that retrieve and present them to the users. It provides VCR like control features for user interactivity during playback. The paper describes the system architecture, and the communication protocols, along with media synchronization and dynamic QoS control mechanisms.
Current medical treatment of pulmonary arterial hypertension. (2004)

Primary pulmonary hypertension is a rare disease of the pulmonary vasculature manifested by dyspnea on exertion, syncope, and signs and symptoms of right heart failure. In the absence of adequate treatment, primary pulmonary hypertension has a grave prognosis, with a median survival of 2.8 years. Pulmonary arterial hypertension develops in association with known risk factors and predisposing clinical conditions, and shares many clinical, pathological and therapeutic characteristics with primary pulmonary hypertension. Therapeutic choices in pulmonary arterial hypertension depend on the etiology of the disease, severity of functional impairment and hemodynamic response following acute vasodilator administration during right heart catheterization. Agents currently approved for the specific treatment of pulmonary arterial hypertension are continuous intravenous epoprostenol, subcutaneous treprostinil and oral bosentan. A small group of patients who demonstrate true acute vasoreactivity at right heart catheterization may be chronically treated with oral calcium channel blockers. In addition, most patients with pulmonary hypertension receive conventional treatment, represented by anticoagulants, diuretics, inotropic medication or oxygen supplementation. Treatment of pulmonary arterial hypertension has significantly altered the natural course of the disease, with pronounced symptomatic, functional and survival benefit. Current clinical research focuses on the discovery of new targets of therapy and the use of a combination treatment approach, which will offer hope and valuable insight into the pathogenetic basis of this devastating illness.
The lymphoid cell surface receptor NTB‐A: a novel monoclonal antibody target for leukaemia and lymphoma therapeutics (2007)

NTB-A is a CD2-related cell surface protein expressed primarily on lymphoid cells including B-lymphocytes from chronic lymphocytic leukaemia (CLL) and lymphoma patients. We have generated a series of monoclonal antibodies (mAbs) against NTB-A and assessed their therapeutic potential for CLL. Selective mAbs to NTB-A were further tested in functional complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicty (ADCC) assays in cell lines and B lymphocytes freshly isolated from CLL patients. While lower levels of NTB-A were detected in T and natural killer (NK) cells, CDC activity was demonstrated primarily in B cells isolated from CLL patients and B lymphoma cell lines. Knockdown of NTB-A by small interfering RNA in target cells results in lower cytotoxicity, demonstrating the specificity of the mAbs. Furthermore, anti NTB-A mAbs demonstrated anti-tumour activity against CA46 human lymphoma xenografts in nude mice and against systemically disseminated Raji human lymphoma cells in severe combined immunodeficient mice. Taken together, these results demonstrate NTB-A as a potential new target for immunotherapy of leukaemia and lymphomas.
Mechanistic and clinical rationales for using beta-blockers in heart failure. (2000)

In the 1980s and early 1990s, evidence suggesting a pivotal role for chronic neurohormonal stimulation in the pathophysiology of heart failure began to emerge, which has now produced a dramatic change in the way heart failure is viewed and treated. Preclinical data and results from clinical trials revealed that blocking the actions or generation of norepinephrine or angiotensin II positively affected the course of left ventricular dysfunction and myocardial failure, despite the fact that this inhibition had minimal or negative effects on hemodynamics. Angiotensin-converting enzyme (ACE) inhibitors have been used for heart failure for many years, but only recently have beta-blockers been recommended as part of standard treatment for heart failure. The negative inotropic effects of beta-blockers are well known; these agents must be used with caution in patients with heart failure. However, after several months of treatment, left ventricular ejection fraction (LVEF) gradually increases, and a reversal of the pathological remodeling associated with chronic heart failure occurs: left ventricular mass decreases, chamber shape becomes more elliptical, and mitral regurgitation decreases. Data from clinical trials have shown that long-term beta-adrenergic blockade halts the progression of pump dysfunction, substantially improves left ventricular function, and reduces morbidity and mortality rates in patients with mild-to-moderate heart failure. This article provides a detailed rationale for the use of beta-blockers in patients with chronic heart failure, based on the current understanding of pathophysiology and recent clinical trial data.
Dependence of antithrombin III and thrombin binding stoichiometries and catalytic activity on the molecular weight of affinity-purified heparin. (1986)

Heparin was fractionated by affinity chromatography on immobilized antithrombin III followed by gel filtration on Sephadex G-100. Eighteen fractions were obtained ranging in molecular weight from 9,700 to 34,300 as determined by sedimentation equilibrium. The binding stoichiometries of antithrombin III and thrombin interactions with the heparin of these fractions were measured, using changes in intrinsic and extrinsic fluorescence. Catalytic activity also was measured for each of the heparin fractions. As the molecular weight of heparin varied from about 10,000 to 30,000, the average number of antithrombin and thrombin sites/heparin molecule varied from 1.0 to 2.1 and 2.4 to 6.8. In addition, the molar specific activity increased 5.7-fold, an increase which correlated directly with the product of the number of antithrombin III and thrombin molecules bound. Thus as the number of bound molecules increased with increased molecular weight, the rate of reaction/bound antithrombin III increased in proportion to the number of bound thrombin molecules and vice versa. This can be explained by assuming that heparin functions as a template for both proteins, that all bound thrombin and antithrombin III molecules are accessible to each other, and that the rate at which a bound molecule reacts is proportional to the number of molecules of its interacting counterpart bound. These observations and conclusions are similar to those of Hoylaerts et al. (Hoylaerts, M., Owen, W. G., and Collen, D. (1984) J. Biol. Chem. 259, 5670-5677), who demonstrated that the rate at which single molecules of antithrombin III, covalently attached to heparin, react increases as the thrombin binding capacity (chain length) of heparin increases.
Benzotriazole-Mediated Selective Chromium(VI) Oxidations (1985)

Abstract Complexation of chromium trioxide with benzotriazole has been found to be an effective reagent for allylic oxidation. Pyridinium chlorochromate complexed with benzotriazole was found to selectively oxidize steroidal allylic alchols in high yield.
A significant correlation between clonogenic radiosensitivity and the simultaneous assessment of micronucleus and apoptotic cell frequencies (1999)

These results suggest the usefulness of the simultaneous assessment of the MN frequency and the detection of floating cells in culture medium or apoptotic cells among attached cells to predict cellular intrinsic radiosensitivity. In order to predict cell survival after irradiation from these factors, the use of multivariate analyses is more useful than simple summation.
PicoJava: a direct execution engine for Java bytecode (1998)

Key to the central promise inherent in Java technology-"write once, run anywhere"-is the fact that Java programs run on the Java virtual machine, insulating them from any contact with the underlying hardware. Consequently, Java programs must execute indirectly through a translation layer built into the Java virtual machine. Translation essentially converts Java virtual machine instructions (called bytecodes) into corresponding machine-specific binary instructions. Bytecode is a single image of a program that will execute identically (in principle) on any system equipped with a JVM. The first step toward the development of a new class of Java processors was the creation of the bytecode execution engine itself, called the picoJava core. PicoJava directly executes Java bytecode instructions and provides hardware support for other essential functions of the JVM. Executing bytecode instructions in hardware eliminates the need for dynamic translation, thus extending the useful range of Java bytecode programs to embedded environments. By the end of 1998, Java processors like Sun's microJava 701 should be available for evaluation from several licensees of the picoJava core technology.
Tetracycline-inducible systems for Drosophila (2001)

Since their inception, tetracycline (Tet)-inducible systems have become the method of choice for transgenic research. The Tet-Off systems have a number of advantages, including robust target induction using a relatively benign effector molecule. However, use of the Tet-On system has been fraught with difficulties, including high background expression in the absence of effector molecules and inconsistent gene induction. Recently, second generation Tet-On transactivators (TAs) have been described. In HeLa cells, they are far more efficient than the original reverse TA protein, and they exhibit lower background activity in the absence of effectors. Here we examine the most promising TA in transgenic Drosophila and characterize its in vivo properties. We report that low levels of doxycycline, when added to normal fly food, efficiently and rapidly induce target transgenes in adults, larvae, and embryos. This TA is superior to all other Tet-On proteins, and its performance is comparable to that of the widely used Tet-Off TA. In addition, combining the improved Tet-On TA with the Gal4-UAS (upstream-activating sequence) system produces robust, spatially restricted, temporally controlled transgene induction. Because this Tet-On TA is significantly more efficient than previous ones used in Drosophila, it is also possible to modulate gene induction by controlling the dosage of the antibiotic in the food.
Interleukin‐8 as a mediator of sympathetic pain (1991)

1. The hyperalgesic effects of interleukin-8 (IL-8), interleukin-1 beta (IL-1 beta) and carrageenin were measured in a rat paw pressure test. 2. IL-8 evoked a dose-dependent hyperalgesia which was attenuated by a specific antiserum, the beta-adrenoceptor antagonists atenolol and propranolol, the dopamine receptor antagonist SCH 23390 and the adrenergic neurone-blocking agent guanethidine. The hyperalgesia was not attenuated by the cyclooxygenase inhibitor indomethacin or the IL-1 beta analogue Lys-D-Pro-Thr. 3. IL-1 beta-evoked hyperalgesia was attenuated by indomethacin and Lys-D-Pro-Thr but not by atenolol or SCH 23390. 4. Carrageenin-evoked hyperalgesia was attenuated by atenolol, indomethacin and anti-IL-8 serum. The effects of atenolol and anti-IL-8 serum were not additive. The effects of indomethacin and anti-IL-8 serum were additive: this combination abolished carrageenin-evoked hyperalgesia. 5. A new biological activity of IL-8 is described, namely the capacity to evoke hyperalgesia by a prostaglandin-independent mechanism. IL-8 is the first endogenous mediator to be identified as evoking hyperalgesia involving the sympathetic nervous system. Since IL-8 is released by activated macrophages and endothelial cells it may be a humoral link between tissue injury and sympathetic hyperalgesia.
Purification ofBacillus circulansF-2 Amylase and Its General Properties (1983)

Journal Article Purification of Bacillus circulans F-2 Amylase and Its General Properties Get access Hajime Taniguchi, Hajime Taniguchi Laboratory of Biochemistry, Department of Agricultural Chemistry, The University of Tokyo, Bunkyo-ku, Tokyo 113, Japan Search for other works by this author on: Oxford Academic Google Scholar Man Jae Chung, Man Jae Chung Laboratory of Biochemistry, Department of Agricultural Chemistry, The University of Tokyo, Bunkyo-ku, Tokyo 113, Japan Present Address: Department of Agricultural Chemistry, Chung-Buk National University, Cheong ju-si, Chung buk, Korea, 311 Search for other works by this author on: Oxford Academic Google Scholar Naohiro Yoshigi, Naohiro Yoshigi Laboratory of Biochemistry, Department of Agricultural Chemistry, The University of Tokyo, Bunkyo-ku, Tokyo 113, Japan Present Address: Research and Development Laboratories, Sapporo Breweries Ltd., Meguro-ku, Tokyo 153, Japan Search for other works by this author on: Oxford Academic Google Scholar Yoshiharu Maruyama Yoshiharu Maruyama Laboratory of Biochemistry, Department of Agricultural Chemistry, The University of Tokyo, Bunkyo-ku, Tokyo 113, Japan Search for other works by this author on: Oxford Academic Google Scholar Agricultural and Biological Chemistry, Volume 47, Issue 3, 1 March 1983, Pages 511–519, https://doi.org/10.1080/00021369.1983.10865675 Published: 01 March 1983 Article history Received: 09 August 1982 Published: 01 March 1983
Electrical Transport Through Individual Vanadium Pentoxide Nanowires (2000)

The controlled deposition of individual V2O5 nanowires on chemically modified SiO2 substrates is reported here. Electrical transport measurements were performed on individual fibers (see Figure) and on thin fiber networks, and the conductivity of an individual V2O5 nanowire was estimated to be ∼0.5 S/cm at room temperature. The structure of the fibers was investigated using scanning force microscopy.
A functional interaction between the histone deacetylase Rpd3 and the corepressor Groucho in Drosophila development (1999)

The Drosophila gene groucho (gro) encodes a transcriptional corepressor that has critical roles in many development processes. In an effort to illuminate the mechanism of Gro-mediated repression, we have employed Gro as an affinity reagent to purify Gro-binding proteins from embryonic nuclear extracts. One of these proteins was found to be the histone deacetylase Rpd3. Protein-protein interaction assays suggest that Gro and Rpd3 form a complex in vivo and that they interact directly via the glycine/proline rich (GP) domain in Gro. Cell culture assays demonstrate that Rpd3 potentiates repression by the GP domain. Furthermore, experiments employing a histone deacetylase inhibitor, as well as a catalytically inactive form of Rpd3, imply that histone deacetylase activity is required for efficient Gro-mediated repression. Finally, mutations in gro and rpd3 have synergistic effects on embryonic lethality and pattern formation. These findings support the view that Gro mediates repression, at least in part, by the direct recruitment of the histone deacetylase Rpd3 to the template, where it can modulate local chromatin structure. They also provide evidence for a specific role of Rpd3 in early development.
Tree structure search for matching pursuit (2005)

Matching pursuit has found many applications recently especially in very low bit rate video coding. In this paper we show how the complexity of matching pursuit can be reduced from O(N) to O(log(2N)) using tree structured dictionaries. Moreover, we show how tree structured dictionaries provide an efficient coding strategy that is more resilient to error than random coding. Our simulation results showed an improvement of about 3 dB in PSNR can be achieved using the code provided by the tree structured dictionary.