gebhart/patrepeval huggingface dataset:
Molecular Basis for Attenuation of Neurovirulence of a Yellow Fever Virus/Japanese Encephalitis Virus Chimera Vaccine (ChimeriVax-JE) (2001)

A yellow fever virus (YFV)/Japanese encephalitis virus (JEV) chimera in which the structural proteins prM and E of YFV 17D are replaced with those of the JEV SA14-14-2 vaccine strain is under evaluation as a candidate vaccine against Japanese encephalitis. The chimera (YFV/JEV SA14-14-2, or ChimeriVax-JE) is less neurovirulent than is YFV 17D vaccine in mouse and nonhuman primate models (F. Guirakhoo et al., Virology 257:363-372, 1999; T. P. Monath et al., Vaccine 17:1869-1882, 1999). Attenuation depends on the presence of the JEV SA14-14-2 E protein, as shown by the high neurovirulence of an analogous YFV/JEV Nakayama chimera derived from the wild JEV Nakayama strain (T. J. Chambers, A. Nestorowicz, P. W. Mason, and C. M. Rice, J. Virol. 73:3095-3101, 1999). Ten amino acid differences exist between the E proteins of ChimeriVax-JE and the YFV/JEV Nakayama virus, four of which are predicted to be neurovirulence determinants based on various sequence comparisons. To identify residues that are involved in attenuation, a series of intratypic YFV/JEV chimeras containing either single or multiple amino acid substitutions were engineered and tested for mouse neurovirulence. Reversions in at least three distinct clusters were required to restore the neurovirulence typical of the YFV/JEV Nakayama virus. Different combinations of cluster-specific reversions could confer neurovirulence; however, residue 138 of the E protein (E(138)) exhibited a dominant effect. No single amino acid reversion produced a phenotype significantly different from that of the ChimeriVax-JE parent. Together with the known genetic stability of the virus during prolonged cell culture and mouse brain passage, these findings support the candidacy of this experimental vaccine as a novel live-attenuated viral vaccine against Japanese encephalitis.
Crystal engineering of the composition of pharmaceutical phases. 3. Primary amide supramolecular heterosynthons and their role in the design of pharmaceutical co-crystals (2005)

Abstract A Cambridge Structural Database study of supramolecular synthons involving primary amides reveals that 84% form amide-amide dimers, whereas 14% form catemers in the absence of other competing hydrogen bond donors and/or acceptors. However in the presence of chemically different but complementary functional groups, e.g. , carboxylic acids or aromatic nitrogen moieties, primary amides tend to form supramolecular heterosynthons. Supramolecular heterosynthons represent an opportunity for design of multi-component crystals (co-crystals) in which one molecule contains a primary amide and a second molecule (the co-crystal former) contains the functional group that is complementary to the primary amide. The results of the CSD analysis facilitated the selection of components for seven new primary amide co-crystals: A . Isonicotinamide/2-hydroxybenzoic acid (1:1); B. Nicotinäamide/3-hydroxybenzoic acid (1:1); C. Pyrazinamide/2,5-dihydroxybenzoic acid (1:1); D. Carbamazepine (CBZ)/4,4′-bipyridine (2:1); E. CBZ/4-aminobenzoic acid (2:1); F. CBZ/4-aminobenzoic acid/H 2 O (2:1:1); G. CBZ/2,6-pyridinedicarboxylic acid (1:1). The molecular recognition events involving the amide moieties are discussed in the context of our experimental results and their implications for crystal engineering of pharmaceutical co-crystals.
Effects of pretreatment of serotonin synthesis inhibitorp-chlorophenylalanine on lipopolysaccharide-induced anorexia in rats (2001)

In the present study, we investigated the effect of pretreatment of p-chlorophenylalanine (PCPA), inhibitor of serotonin synthesis, on lipopolysaccharide (LPS)-induced anorexia in rats. First of all, effects of PCPA injection on food intake and body weight in rats were investigated. During 4 days of PCPA injection (300 mg/kg BW once a day), food intake was decreased by 33% and daily gain in body weight was inhibited compared with controls. Twenty-four hours after last PCPA injection, food intake and gain in body weight returned toward almost normal. Pair-feeding to PCPA (PCPAP) injection revealed that body weight of rats in PCPA group was not different from rats in PCPAP groups. To quantify the effects of LPS on food intake and body weight, we administered varying doses of LPS to rats. LPS induced a reduction of food intake and weight loss in a dose dependent manner compared with controls. To evaluate the effects of PCPA pretreatment on LPS injection, rats were treated with PCPA for 4 days (300 mg/kg BW once a day), which was followed by LPS injection for 2 days (PCPA+LPS group), while rats in LPS group had injections with normal saline instead of PCPA for 4 days, which was followed by LPS administration. Rats in control group received 0.9% NaCl for 6 days. LPS decreased food intake by 80% and inhibited gain in body weight, while PCPA pretreated rats showed normalized food intake and gain in weight during the days of LPS injections compared with controls. In conclusion, pretreatment of PCPA prevented LPS-induced anorexia.
Inhibition of Leukocyte Eicosanoid Generation and Radical Scavenging Activity by Gnaphalin, a Lipophilic Flavonol Isolated from Helichrysum picardii (1999)

The lipophilic aglycone 5,7-dihydroxy-3,8-dimethoxyflavone (gnaphalin) isolated from the aerial flowering parts of Helichrysum picardii Boiss. & Reuter (Asteraceae) was tested for interactions with the cyclo-oxygenase and 5-lipoxygenase pathways of arachidonate metabolism in stimulated rat peritoneal leukocytes, and for its effects on leukocyte granular enzyme release, cell viability and interactions with reactive oxygen species. Gnaphalin dose-dependently inhibited generation of the cyclo-oxygenase metabolite thromboxane B2 (IC50 = 39.9 +/- 3.9 microM), and of the 5-lipoxygenase metabolite leukotriene B4, although the potency was two-fold less (IC50 = 81.8 +/- 12.9 microM). At concentrations of 6 to 320 microM, gnaphalin did not affect secretion of the pro-inflammatory enzymes lysozyme, myeloperoxidase and beta-glucuronidase from the neutrophil secretory granules, and did not scavenge hydrogen peroxide or hypochlorous acid. However, gnaphalin effectively scavenged superoxide radicals generated in the hypoxanthine/xanthine oxidase system (IC50 = 40 microM) and by PMA-stimulated leukocytes (> 60% at 500 microM), directly inhibited xanthine oxidase (85% at 395 microM) and inhibited Fe(3+)-ascorbate-induced liposomal peroxidation (IC50 = 215 microM). Thus, like some other flavonoids found in medicinal herbs, gnaphalin possesses an array of potentially beneficial anti-eicosanoid and free-radical scavenging properties which may alongside other constituents contribute to the claimed medicinal properties of the plant from which it is derived.
CamDroid (1995)

In this paper, a method of encapsulation camera tasks into well defined units called “camera modules” is described. Through this encapsulation, camera modules can be programmed and sequenced, and thus can be used as the underlying framework for controlling the virtual camera in the widely disparate types of graphical environments. Two examples of the camera framework are shown: an agent which can film a conversation between two virtual actors and a visual programming language for filming a virtual football game.
PD-L1 Expression Is Associated with Tumor FOXP3+ Regulatory T-Cell Infiltration of Breast Cancer and Poor Prognosis of Patient (2016)

The results suggest that PD-L1 and FOXP3(+)Tregs may work synergistically and their up-regulated expressions promote tumor immune evasion in breast cancer. Combinatorial immunotherapeutic approaches aiming on blocking PD-L1 and depleting Tregs might improve therapeutic efficacy in breast cancer patients, especially those with basal-like carcinoma.
A Rev-inducible mutant gag gene stably transferred into T lymphocytes: an approach to gene therapy against human immunodeficiency virus type 1 infection. (1994)

One strategy for somatic gene therapy for human immunodeficiency virus type 1 (HIV-1) infection is based on the regulated expression of dominant negative mutants of the HIV-1 gag gene. To limit expression of the mutant Gag polypeptide to HIV-1-infected cells, we have constructed a replication-defective retroviral vector that contains a Rev-responsive element. By using this construct we have obviated problems that can be associated with constitutive expression of an exogenous gene, an important step toward developing a human therapy. In uncloned T lymphocytes infected (transduced) with this retroviral construct, HIV-1 replication was inhibited by 94% with a concomitant decrease in the cytopathic effects of the virus. In addition, simian immunodeficiency virus (SIV) replication was also shown to be significantly inhibited, suggesting that this mutant Gag protein may have antiviral efficacy against a broad range of primate lentiviruses and that an SIV/macaque model can be used for further in vivo studies. These results have important implications in assessing the potential of somatic gene therapy in the treatment of HIV-1 infection.
Diagnosis and treatment of severe sepsis (2007)

The burden of infection in industrialized countries has prompted considerable effort to improve the outcomes of patients with sepsis. This has been formalized through the Surviving Sepsis Campaign 'bundles', derived from the recommendations of 11 professional societies, which have promoted global improvement in those practices whose primary goal it is to reduce sepsis-related death. However, difficulties remain in implementing all of the procedures recommended by the experts, despite the apparent pragmatism of those procedures. We summarize the main proposals made by the Surviving Sepsis Campaign and focus on the difficulties associated with making a proper diagnosis and supplying adequate treatment promptly to septic patients.
Cathelicidin peptide SMAP‐29: comprehensive review of its properties and potential as a novel class of antibiotics (2009)

Abstract Sheep myeloid antimicrobial peptide of 29 amino acids (SMAP‐29) is one of the most potent antimicrobial peptides known, with a broad spectrum of activity against bacteria, fungi, and viruses. It has also been shown to prevent infections in animals. SMAP‐29 is an α‐helical cathelicidin that acts rapidly to permeabilize membranes of susceptible organisms. However, it is also cytotoxic and hemolytic to mammalian cells. In this review, all published data on inhibition constants and hemolytic activities of SMAP‐29 are brought together for the first time, including data for the peptide of 28 residues that lacks the C‐terminal glycine and that also has the new C‐terminal residue amidated. Both peptides have been called SMAP‐29 in the literature. Antimicrobial activity of SMAP‐29 variants (including ovispirins) against Gram‐positive bacteria is also comprehensively tabulated, and anomalies in the nomenclature of the ovispirins are highlighted. The secondary structure, mode of action, and structure–activity relationships of SMAP‐29 are outlined, and the properties that indicate its therapeutic potential are identified; these are its broad‐spectrum antimicrobial activity with high potency, rapid biocidal action, limited development of bacterial resistance, synthesis by recombinant technology, ability to bind lipopolysaccharide, and demonstrated protection against infection in animal models. The limitations of SMAP‐29 are its high cytotoxicity and hemolytic activity, reduced activity under physiological conditions, and limited evidence for synergistic effects in combination with conventional antibiotics. Strategies with the potential to improve the selectivity toward pathogenic microorganisms over mammalian cells have been devised by the authors and are outlined. Drug Dev Res 70: 481–498, 2009. © 2009 Commonwealth of Australia; Published 2009 Wiley‐Liss, Inc.
Dephosphorylation of Cdk2 Thr 160 by the Cyclin-Dependent Kinase-Interacting Phosphatase KAP in the Absence of Cyclin (1995)

The activation of cyclin-dependent kinases (CDKs) requires the phosphorylation of a conserved threonine (Thr160 in Cdk2) by CDK-activating kinase (CAK). Human KAP (also called Cdi1), a CDK-associated phosphatase, was shown to dephosphorylate Thr160 in human Cdk2. KAP was unable to dephosphorylate Tyr15 and only dephosphorylated Thr160 in native monomeric Cdk2. The binding of cyclin A to Cdk2 inhibited the dephosphorylation of Thr160 by KAP but did not preclude the binding of KAP to the cyclin A-Cdk2 complex. Moreover, the dephosphorylation of Thr160 by KAP prevented Cdk2 kinase activity upon subsequent association with cyclin A. These results suggest that KAP binds to Cdk2 and dephosphorylates Thr160 when the associated cyclin subunit is degraded or dissociates.
Tolerance induction in mice by conjugates of monoclonal immunoglobulins and monomethoxypolyethylene glycol. Transfer of tolerance by T cells and by T cell extracts. (1987)

The specific tolerance induced in mice by conjugates of human monoclonal IgG (HIgG) with monomethoxypolyethylene glycol (mPEG) was transferred to normal mice by spleen cells or a surface immunoglobulin negative (sIg-) Lyt-2+ subpopulation of these cells. Although transferable tolerance was demonstrable 6 to 14 days after treatment of the cell donors with tolerogen, the state of tolerance persisted in the treated mice for at least 43 days. Moreover, an extract prepared by freezing and thawing of the sIg- spleen cells obtained from mice 6 days after treatment with HIgG(mPEG)20 was capable of reducing (greater than 85%) the immune response of normal mice to heat aggregated HIgG. On the basis of these results, it is suggested that similar tolerogenic mPEG derivatives of xenogeneic monoclonal immunoglobulins (XIg) may prove to be useful therapeutic agents in man when administered before treatment with the unmodified XIg.
Reconstruction of metabolic networks using incomplete information. (1995)

This paper describes an approach that uses methods for automated sequence analysis (Gaasterland et al. August 1994) and multiple databases accessed through an object+attribute view of the data (Baehr et al. 1992), together with metabolic pathways, reaction equations, and compounds parsed into a logical representation from the Enzyme and Metabolic Pathway Database (Selkov, Yunus, & et.al. 1994), as the sources of data for automatically reconstructing a weighted partial metabolic network for a prokaryotic organism. Additional information can be provided interactively by the expert user to guide reconstruction.
Columbia TAG System - Transductive Annotation by Graph Version 1.0 (2008)

The Columbia TAG (Transductive Annotation by Graph) system is deigned to facilitate rapid retrieval and exploration of large image and video collections. It incorporates novel graph-based label propagation methods and intuitive graphic user interfaces (GUI) that allow users quickly browse and annotate a small number of images/videos, and then in real or near real time receive
Potent antitumor activity of 2-methoxyestradiol in human pancreatic cancer cell lines. (1999)

We examined the effect of 2-methoxyestradiol (2-ME) on the growth and tumorigenesis of human pancreatic cancer cells. 2-ME inhibited the growth of these cell lines (50-90%) in a dose- and time-dependent fashion, and terminal deoxynucleotidyl transferase staining showed that it induced apoptotic cell death. Flow cytometric analysis indicated that 2-ME-sensitive cells showed a prolonged S phase after 48 h of treatment. We used a mouse model for in vivo studies of lung metastasis and injected MIA PaCa-2 cells into the tail veins of nu/nu mice; lung colonies were formed. Mice given oral 2-ME showed 60% inhibition in the number of lung colonies compared with control, untreated animals. These results suggest that 2-ME may have clinical application for the treatment of pancreatic cancer.
Guinea pigs sublethally infected with aerosolized Legionella pneumophila develop humoral and cell-mediated immune responses and are protected against lethal aerosol challenge. A model for studying host defense against lung infections caused by intracellular pathogens. (1987)

We have employed the guinea pig model of L. pneumophila infection, which mimics Legionnaires' disease in humans both clinically and pathologically, to study humoral and cell-mediated immune responses to L. pneumophila and to examine protective immunity after aerosol exposure, the natural route of infection. Guinea pigs exposed to sublethal concentrations of L. pneumophila by aerosol developed strong humoral immune responses. By the indirect fluorescent antibody assay, exposed guinea pigs had a median serum antibody titer (expressed as the reciprocal of the highest positive dilution) of 32, whereas control guinea pigs had a median titer of less than 1. Sublethally infected (immunized) guinea pigs also developed strong cell-mediated immune responses. In response to L. pneumophila antigens, splenic lymphocytes from immunized but not control animals proliferated strongly in vitro, as measured by their capacity to incorporate [3H]thymidine. Moreover, immunized but not control guinea pigs developed strong cutaneous delayed-type hypersensitivity to intradermally injected L. pneumophila antigens. Sublethally infected (immunized) guinea pigs exhibited strong protective immunity to L. pneumophila. In two independent experiments, all 22 immunized guinea pigs survived aerosol challenge with one or three times the lethal dose of L. pneumophila whereas none of 16 sham-immunized control guinea pigs survived (p less than 0.0001 in each experiment). Immunized guinea pigs were not protected significantly from challenge with 10 times the lethal dose. Immunized but not control animals cleared the bacteria from their lungs. This study demonstrates that guinea pigs sublethally infected with L. pneumophila by the aerosol route develop strong humoral immune responses to this pathogen, develop strong cell-mediated immune responses and cutaneous delayed-type hypersensitivity to L. pneumophila antigens, are protected against subsequent lethal aerosol challenge, and are able to clear the bacteria from their lungs. The guinea pig model of L. pneumophila pulmonary infection is as an excellent one for studying general principles of host defense against pulmonary infections caused by intracellular pathogens.
Integration mechanisms in Cedar (1985)

The importance of integration in programming environments is well known. Perhaps the easiest way to build an integrated system is to build a closed system; the designers of the system can use whatever ad hoc techniques are available to make the pieces they provide hang together nicely. Many of the integrated editor/compiler/execution environments (like the Cornell Program Synthesizer) fall into this category [Teitelbaum81].
Control of Upper Limb Prostheses: Terminology and Proportional Myoelectric Control—A Review (2012)

The recent introduction of novel multifunction hands as well as new control paradigms increase the demand for advanced prosthetic control systems. In this context, an unambiguous terminology and a good understanding of the nature of the control problem is important for efficient research and communication concerning the subject. Thus, one purpose of this paper is to suggest an unambiguous taxonomy, applicable to control systems for upper limb prostheses and also to prostheses in general. A functionally partitioned model of the prosthesis control problem is also presented along with the taxonomy. In the second half of the paper, the suggested taxonomy has been exploited in a comprehensive literature review on proportional myoelectric control of upper limb prostheses. The review revealed that the methods for system training have not matured at the same pace as the novel multifunction prostheses and more advanced intent interpretation methods. Few publications exist regarding the choice of training method and the composition of the training data set. In this context, the notion of outcome measures is essential. By definition, system training involves optimization, and the quality of the results depends heavily on the choice of appropriate optimization criteria. In order to further promote the development of proportional myoelectric control, these topics need to be addressed.
A Phase II Open-Label Study Evaluating Hemostatic Activity, Pharmacokinetics and Safety of Recombinant Porcine Factor VIII (OBI-1) in Hemophilia A Patients with Alloantibody Inhibitors Directed Against Human FVIII. (2007)

Abstract Development of inhibitors to human FVIII (hFVIII) is a significant complication in the reversal and prevention of bleeding events in hemophilia A patients. Porcine FVIII (pFVIII) possesses low cross reactivity to anti-hFVIII antibodies. OBI-1, a recombinant B-domain deleted pFVIII, has recently been tested in a Phase II trial in patients with congenital hemophilia A and inhibitors experiencing a non-life/non-limb threatening bleed. In patients with a measurable anti-pFVIII antibody titer, dosing was initiated with a loading dose (LD) followed by up to 8 doses of 50 to 150 U/kg of OBI-1 administered at 6 hour intervals until the bleed was controlled. The PK profile of OBI-1 was assessed for the first OBI-1 infusion of each patient. FVIII levels were measured 30 minutes after each infusion. Inhibitor titers were evaluated for a minimum of 6 months after the first OBI-1 infusion. A total of 25 bleeding episodes in 9 patients were treated successfully with OBI-1. The median time from bleeding onset to treatment was 7 hours (range: 3 20 hr). OBI-1 showed a cumulative efficacy of 72% after 1 injection, 84% after 2 injections or less, 92% after 3 injections or less, and 100% after 8 or less injections. In over 40 infusions, OBI-1 was well tolerated and no drug related SAEs were observed. One case of pruritus rated as mild was easily controlled with diphenhydramine. FVIII levels measured 30 minutes after each OBI-1 infusion ranged from &lt; 0.5% to 226%. They were generally lower with higher anti-pFVIII titers although all bleeds were successfully controlled. Follow up inhibitor titers are still being monitored and final results will be presented and discussed. Other investigative parameters, including vital signs and laboratory variables did not show treatment related abnormalities. OBI-1 can be given as a short infusion. It was effective in controlling all bleeds which occurred in this study and was well tolerated. The results suggest that a LD is not needed with OBI-1 treatment, and in some instances patients may have been over treated. Given the promising results in this study, additional studies are planned to optimize dose range for OBI-1 and to confirm the long term safety and efficacy of OBI-1 in the treatment of bleeds in a larger cohort of individuals with hemophilia A complicated by the presence of hFVIII inhibitors.