gebhart/patrepeval huggingface dataset:
Identification of profound peripheral T lymphocyte immunodeficiencies in the spontaneously diabetic BB rat. (1983)

Abstract The BB rat is presently the best available animal model for human insulin dependent diabetes (IDD). Because of the extreme susceptibility of the strain to opportunistic infections and because current studies suggest that they have an autoimmune diathesis, of which IDD is but one result, aspects of the immune system of the BB rat were studied. Severe T lymphopenia was observed in all BB rats, irrespective of sex or the presence of IDD, while numbers of B cells and serum immunoglobulin levels were normal. Both the helper T lymphocyte and cytotoxic/suppressor T lymphocyte subsets, defined by reactions with monoclonal antibodies, were depressed, and an inversion of the helper T cell subset to cytotoxic/suppressor T lymphocyte subset ratio occurred in all BB rats with increasing maturity. Concomitantly, severe impairments of T cell-mediated immune responses were noted. BB rats poorly rejected allografts across both major and minor histocompatibility barriers, and BB splenic or peripheral blood lymphocytes had markedly defective proliferative responses to mitogens and to allogeneic cells in MLC. Irradiated and nonirradiated BB spleen cells did not inhibit WF mitogenic or MLC responses, which suggests that the T cell defect in BB rats is not solely due to increased suppressor activity. Because irradiated WF cells and Con A supernatants did not restore BB proliferative responses, and BB lymphocytes were able to produce IL-2 normally, a reduced ability of BB lymphocytes to respond to helper factors such as IL-2 is suggested. In contrast to T lymphocytes from spleen or peripheral blood, BB thymocytes responded as well as did WF thymocytes to Con A or Con A supernatants. Percentages of T lymphocyte subsets and histology of BB thymuses were also normal when compared to WF thymuses. However, spleens and lymph nodes from BB rats were severely depleted of T lymphocytes, and thymocytotoxic autoantibodies were detected in many BB rat sera. The above findings indicate that BB rats have T lymphocyte immunoincompetence, which appears to be a post-thymic or peripherally acquired maturational defect.
Efficacy of hydrocortisone acetate/hyaluronidase vs triamcinolone acetonide/hyaluronidase in the treatment of oral submucous fibrosis. (2010)

Treatment regimen of group B was more convenient to the patients because less number of visits required and cheap. No side effects were seen. A follow up study is required to see long term effects.
Differential sensitivity to proteolysis by brain calpain of adult human tau, fetal human tau and PHF‐tau (1995)

Reduced turn-over of tau by calpains is a possible mechanism to facilitate the incorporation into paired helical filaments (PHFs) in Alzheimer's disease. The present study shows that the differently phosphorylated fetal tau isoforms are all rapidly proteolysed to an equal extent by human brain m-calpain. This result argues against the hypothesis that this type of fetal phosphorylation is involved in reducing tau turn-over by calpain in Alzheimer's disease. Adult and fetal tau fragments in vitro generated by m-calpain, but not trypsin, cathepsin D or chymotrypsin resemble the post-mortem in situ degradation patterns, suggesting a possible role for calpains in tau metabolism in vivo. Tau incorporated into PHFs was considerably more resistant to proteolysis by calpain which can help to explain the persistence of these structures in Alzheimer's disease.
Current distribution for parallel-connected DC power sources without remote sensing (2002)

The analytical proof showing that output voltage droop characteristics of parallel-connected DC-DC power converters are only appropriate for limited applications is presented. Because power converters are very seldom identical, near-uniform current-sharing without additional control can be achieved only when paralleled power converters have similar characteristics and behave like ideal current sources. This can be achieved at the expense of poor voltage regulation. As an alternative, a current-sharing control technique, which requires no remote sensing, is proposed. This technique ensures uniform or designated current distribution throughout specified load range. A control circuit module is independently implemented without any preliminary knowledge or any circuit modification of the source power converters.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Synthesis of Schiff Bases of 2‐amino‐5‐aryl‐1,3,4‐thiadiazole and Its Analgesic, Anti‐Inflammatory and Anti‐Bacterial Activity (2011)

Schiff Bases of 2‐amino‐5‐aryl‐1,3,4‐thiadiazole derivatives have been synthesized with different aromatic aldehyde. 1,3,4‐thiadiazole derivatives were prepared by the reaction of thiosemicarbazide, sodium acetate and aromatic aldehyde. The structures of the titled Schiff bases were elucidated by IR and 1 H NMR spectral measurements. All the compounds were evaluated for their analgesic activity against swiss albino mice, anti‐inflammatory activity against Wister albino rats. The compounds showed significant antibacterial activity against Staphylococcus aureus (gram‐positive) bacteria and E. coli (gram‐negative) bacteria.
Neuroimaging and Physiological Evidence for Involvement of Glutamatergic Transmission in Regulation of the Striatal Dopaminergic System (2009)

Aberrant neurotransmissions via glutamate and dopamine receptors have been the focus of biomedical research on the molecular basis of psychiatric disorders, but the mode of their interaction is yet to be uncovered. In this study, we demonstrated the pharmacological reversal of methamphetamine-stimulated dopaminergic overflow by suppression of group I metabotropic glutamate (mGlu) receptor in living primates and rodents. In vivo positron emission tomography (PET) was conducted on cynomolgus monkeys and rats using a full agonistic tracer for dopamine D(2/3) receptor, [(11)C]MNPA [(R)-2-(11)CH(3)O-N-n-propylnorapomorphine], and fluctuation of kinetic data resulting from anesthesia was avoided by scanning awake subjects. Excessive release of dopamine induced by methamphetamine and abolishment of this alteration by treatment with an antagonist of group I mGlu receptors, 2-methyl-6-(phenylethynyl)pyridine (MPEP), were measured in both species as decreased binding potential because of increased dopamine and its recovery to baseline levels, respectively. Counteraction of MPEP to the methamphetamine-induced dopamine spillover was also supported neurochemically by microdialysis of unanesthetized rat striatum. Moreover, patch-clamp electrophysiological assays using acute brain slices prepared from rats indicated that direct targets of MPEP mechanistically involved in the effects of methamphetamine are present locally within the striatum. Because MPEP alone did not markedly alter the baseline dopaminergic neurotransmission according to our PET and electrophysiological data, the present findings collectively extend the insights on dopamine-glutamate cross talk from extrastriatal localization of responsible mGlu receptors to intrastriatal synergy and support therapeutic interventions in case of disordered striatal dopaminergic status using group I mGlu receptor antagonists assessable by in vivo imaging techniques.
Interparticle Coupling Effects on Plasmon Resonances of Nanogold Particles (2003)

The collaborative oscillation of conductive electrons in metal nanoparticles results in a surface plasmon resonance that makes them useful for various applications including biolabeling. We investigate the coupling between pairs of elliptical metal particles by simulations and experiments. The results demonstrate that the resonant wavelength peak of two interacting particles is red-shifted from that of a single particle because of near-field coupling. It is also found that the shift decays approximately exponentially with increasing particle spacing and become negligible when the gap between the two particles exceeds about 2.5 times the particle short-axis length.
Hematopoietic and lung abnormalities in mice with a null mutation of the common beta subunit of the receptors for granulocyte-macrophage colony-stimulating factor and interleukins 3 and 5. (1995)

Gene targeting was used to create mice with a null mutation of the gene encoding the common beta subunit (beta C) of the granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 3 (IL-3; multi-CSF), and interleukin 5 (IL-5) receptor complexes (beta C-/- mice). High-affinity binding of GM-CSF was abolished in beta C-/- bone marrow cells, while cells from heterozygous animals (beta C+/- mice) showed an intermediate number of high-affinity receptors. Binding of IL-3 was unaffected, confirming that the IL-3-specific beta chain remained intact. Eosinophil numbers in peripheral blood and bone marrow of beta C-/- animals were reduced, while other hematological parameters were normal. In clonal cultures of beta C-/- bone marrow cells, even high concentrations of GM-CSF and IL-5 failed to stimulate colony formation, but the cells exhibited normal quantitative responsiveness to stimulation by IL-3 and other growth factors. beta C-/- mice exhibited normal development and survived to young adult life, although they developed pulmonary peribronchovascular lymphoid infiltrates and areas resembling alveolar proteinosis. There was no detectable difference in the systemic clearance and distribution of GM-CSF between beta C-/- and wild-type littermates. The data establish that beta C is normally limiting for high-affinity binding of GM-CSF and demonstrate that systemic clearance of GM-CSF is not mediated via such high-affinity receptor complexes.
[Therapeutic effect of methyl 5-aminosalicylate on experimental ulcerative colitis in rabbits]. (1990)

Using the improved Kirsner model of ulcerative colitis in rabbits, we found that the therapeutic effect of methyl 5-amino salicylate hydrochloride (M-5-AS) was similar to that of sulfasalazine (salicylazosulfapyridine, SZ). The length of pathological damage and the range of diffuse ulcers were decreased in comparison with the control group (P less than 0.01, 0.05). Microscopically, tissue repairing at the regions of ulcers and proliferation in serolemma were noted, and the edema in muscular mesenchyme was less evident in the treated rabbits. M-5-AS completely inhibited the spontaneous contraction of rat stomach fundus strips and colon. The IC50 of the resting tone of the 2 tissues were 1.30 +/- 0.39 and 0.72 +/- 0.25 mmol/L, respectively. In addition, M-5-AS antagonized the contraction induced by human fresh semen. The results suggest that the therapeutic mechanism is related to the antagonism of prostaglandins in the inflammatory regions.
Selective induction of chemotherapy resistance of mammary tumors in a conditional mouse model for hereditary breast cancer (2007)

We have studied in vivo responses of "spontaneous" Brca1- and p53-deficient mammary tumors arising in conditional mouse mutants to treatment with doxorubicin, docetaxel, or cisplatin. Like human tumors, the response of individual mouse tumors varies, but eventually they all become resistant to the maximum tolerable dose of doxorubicin or docetaxel. The tumors also respond well to cisplatin but do not become resistant, even after multiple treatments in which tumors appear to regrow from a small fraction of surviving cells. Classical biochemical resistance mechanisms, such as up-regulated drug transporters, appear to be responsible for doxorubicin resistance, rather than alterations in drug-damage effector pathways. Our results underline the promise of these mouse tumors for the study of tumor-initiating cells and of drug therapy of human cancer.
5-Lipoxygenase Metabolite 4-HDHA Is a Mediator of the Antiangiogenic Effect of ω-3 Polyunsaturated Fatty Acids (2011)

Lipid signaling is dysregulated in many diseases with vascular pathology, including cancer, diabetic retinopathy, retinopathy of prematurity, and age-related macular degeneration. We have previously demonstrated that diets enriched in ω-3 polyunsaturated fatty acids (PUFAs) effectively reduce pathological retinal neovascularization in a mouse model of oxygen-induced retinopathy, in part through metabolic products that suppress microglial-derived tumor necrosis factor-α. To better understand the protective effects of ω-3 PUFAs, we examined the relative importance of major lipid metabolic pathways and their products in contributing to this effect. ω-3 PUFA diets were fed to four lines of mice deficient in each key lipid-processing enzyme (cyclooxygenase 1 or 2, or lipoxygenase 5 or 12/15), retinopathy was induced by oxygen exposure; only loss of 5-lipoxygenase (5-LOX) abrogated the protection against retinopathy of dietary ω-3 PUFAs. This protective effect was due to 5-LOX oxidation of the ω-3 PUFA lipid docosahexaenoic acid to 4-hydroxy-docosahexaenoic acid (4-HDHA). 4-HDHA directly inhibited endothelial cell proliferation and sprouting angiogenesis via peroxisome proliferator-activated receptor γ (PPARγ), independent of 4-HDHA's anti-inflammatory effects. Our study suggests that ω-3 PUFAs may be profitably used as an alternative or supplement to current anti-vascular endothelial growth factor (VEGF) treatment for proliferative retinopathy and points to the therapeutic potential of ω-3 PUFAs and metabolites in other diseases of vasoproliferation. It also suggests that cyclooxygenase inhibitors such as aspirin and ibuprofen (but not lipoxygenase inhibitors such as zileuton) might be used without losing the beneficial effect of dietary ω-3 PUFA.
Design and bioinformatics analysis of genome-wide CLIP experiments (2015)

The past decades have witnessed a surge of discoveries revealing RNA regulation as a central player in cellular processes. RNAs are regulated by RNA-binding proteins (RBPs) at all post-transcriptional stages, including splicing, transportation, stabilization and translation. Defects in the functions of these RBPs underlie a broad spectrum of human pathologies. Systematic identification of RBP functional targets is among the key biomedical research questions and provides a new direction for drug discovery. The advent of cross-linking immunoprecipitation coupled with high-throughput sequencing (genome-wide CLIP) technology has recently enabled the investigation of genome-wide RBP-RNA binding at single base-pair resolution. This technology has evolved through the development of three distinct versions: HITS-CLIP, PAR-CLIP and iCLIP. Meanwhile, numerous bioinformatics pipelines for handling the genome-wide CLIP data have also been developed. In this review, we discuss the genome-wide CLIP technology and focus on bioinformatics analysis. Specifically, we compare the strengths and weaknesses, as well as the scopes, of various bioinformatics tools. To assist readers in choosing optimal procedures for their analysis, we also review experimental design and procedures that affect bioinformatics analyses.
Nanoparticle‐based approaches to immune tolerance for the treatment of autoimmune diseases (2018)

Autoimmune diseases are caused by antigenically complex immune responses of the adaptive and innate immune system against specific cells, tissues or organs. Antigen-specific approaches for induction of immune tolerance in autoimmunity, based on the use of antigenic peptides or proteins, have failed to deliver the desired therapeutic results in clinical trials. These approaches, which are largely relying on triggering clonal anergy and/or deletion of defined autoreactive specificities, do not address the overwhelming antigenic, molecular, and cellular complexity of most autoimmune diseases, which involve various immune cells and ever-growing repertoires of antigenic epitopes on numerous self-antigens. Advances in the field of regulatory T-cell (Treg) biology have suggested that Treg cells might be able to afford dominant tolerance provided they are properly activated and expanded in vivo. More recently, nanotechnology has introduced novel technical advances capable of modulating immune responses. Here, we review nanoparticle-based approaches designed to induce immune tolerance, ranging from approaches that primarily trigger clonal T-cell anergy or deletion to approaches that trigger Treg cell formation and expansion from autoreactive T-cell effectors. We will also highlight the therapeutic potential and positive outcomes in numerous experimental models of autoimmunity.
Kinetically controlled catalytic synthesis of highly dispersed metal-in-carbon composite and its electrochemical behavior (2009)

We report here a facile and generic synthesis method involving low-temperature, kinetically controlled catalysis followed by in situ carbothermal reduction to fabricate highly dispersed metal-in-carbon composites. The method achieves the homogeneous dispersion of metal particles with retention of the crystal structure of the carbon matrix. As a proof of concept, we fabricated tin-in-graphite composites in which the tin particles (200–500 nm) are highly dispersed within the compliant and conductive matrix of graphite, without destroying the crystal structure of the graphite. Electrochemical performance measurements indicate that the composite with Sn content of ∼15 wt% has a reversible capacity of ∼450 mAh g−1 with stable cyclability, a superior initial Coulombic efficiency, and a flat voltage profile, when evaluated as anode material for lithium ion batteries.
Further Studies on the Site-Specific Protein Modification by Microbial Transglutaminase (2001)

A guinea pig liver transglutaminase (G-TGase)-mediated procedure for the site-specific modification of chimeric proteins was recently reported. Here, an alternative method with advantages over the recent approach is described. This protocol utilizes a microbial transglutaminase (M-TGase) instead of the G-TGase as the catalyst. M-TGase, which has rather broad structural requirements as compared to the G-TGase, tends to catalyze an acyl transfer reaction between the gamma-carboxamide group of a intact protein-bound glutamine residue and various primary amines. To demonstrate the applicability of the M-TGase-catalyzed protein modification in a drug delivery system, we have utilized recombinant human interleukin 2 (rhIL-2) as the target protein and two synthetic alkylamine derivatives of poly(ethyleneglycol) (PEG12; MW 12 kDa) and galactose-terminated triantennary glycosides ((Gal)(3))) as the modifiers. For the M-TGase-catalyzed reaction with PEG12 and (Gal)(3), 1 mol of alkylamine was incorporated per mole of rhIL-2, respectively. Peptide mapping of (Gal)(3)-modified rhIL-2 ((Gal)(3)-rhIL-2) by liquid chromatography-electrospray ionization mass spectrometry (LC-ESI/MS) suggested that the Gln74 residue in rhIL-2 was site specifically modified with (Gal)(3). The PEG12-rhIL-2 and (Gal)(3)-rhIL-2 conjugates retained full bioactivity relative to the unmodified rhIL-2. In pharmacokinetic studies, PEG12-rhIL-2 was eliminated more slowly from the circulation than rhIL-2, whereas (Gal)(3)-rhIL-2 accumulated in the liver via hepatic asialoglycoprotein receptor binding. The results of this study expand the applicability of the TGase-catalyzed methodology for the preparation of protein conjugates for clinical use.
Improved rhizosphere competence in a protoplast fusion progeny of Trichoderma harzianum (1991)

The level and pattern of rhizosphere competence of a strain of Trichoderma harzianum (1295-22) derived from fusing protoplasts of auxotrophic mutants of the prototrophic strains T12 and T95 were studied and compared with those of the original strains. Colonization of the rhizosphere by the three strains was tested after treating seeds of cotton and maize with conidia and planting them in soil at a constant moisture content. Propagules of the fungi were removed by a washing technique, Trichoderma spp. were isolated by plating serial dilutions on a selective medium, and individual strains were identified by their characteristic growth on differential media. Both strains T12 and T95 colonized the entire length of maize roots, but strain 1295-22 was more effective in colonizing the middle sections of the roots than either parental strain. All strains colonized cotton roots more poorly than maize roots; strains T12 and T95 were not detected on some root segments of this crop. Strain T95 was, however, found on the root tip, while T12 was absent from this root portion. Conversely, strain 1295-22 colonized all root sections of this crop, and its population levels were higher in the middle root portions than those of either parental strain.
Cotreatment with 17-Allylamino-Demethoxygeldanamycin and FLT-3 Kinase Inhibitor PKC412 Is Highly Effective against Human Acute Myelogenous Leukemia Cells with Mutant FLT-3 (2004)

Presence of the activating length mutation (LM) in the juxtamembrane domain or point mutation in the kinase domain of FMS-like tyrosine kinase-3 (FLT-3) mediates ligand-independent progrowth and prosurvival signaling in approximately one-third of acute myelogenous leukemia (AML). PKC412, an inhibitor of FLT-3 kinase activity, is being clinically evaluated in AML. Present studies demonstrate that treatment of human acute leukemia MV4-11 cells (containing a FLT-3 LM) with the heat shock protein 90 inhibitor 17-allylamino-demethoxy geldanamycin (17-AAG) attenuated the levels of FLT-3 by inhibiting its chaperone association with heat shock protein 90, which induced the poly-ubiquitylation and proteasomal degradation of FLT-3. Treatment with 17-AAG induced cell cycle G(1) phase accumulation and apoptosis of MV4-11 cells. 17-AAG-mediated attenuation of FLT-3 and p-FLT-3 in MV4-11 cells was associated with decrease in the levels of p-AKT, p-ERK1/2, and p-STAT5, as well as attenuation of the DNA binding activity of STAT-5. Treatment with 17-AAG, downstream of STAT5, reduced the levels of c-Myc and oncostatin M, which are transactivated by STAT5. Cotreatment with 17-AAG and PKC412 markedly down-regulated the levels of FLT-3, p-FLT-3, p-AKT, p-ERK1/2, and p-STAT5, as well as induced more apoptosis of MV4-11 cells than either agent alone. Furthermore, the combination of 17-AAG and PKC412 exerted synergistic cytotoxic effects against MV4-11 cells. Importantly, 17-AAG and PKC412 induced more loss of cell viability of primary AML blasts containing FLT-3 LM, as compared with those that contained wild-type FLT-3. Collectively, these in vitro findings indicate that the combination of 17-AAG and PKC412 has high level of activity against AML cells with FLT-3 mutations.