gebhart/patrepeval huggingface dataset:
PD-L1 is required for optimal protective immunity to Salmonella infection (40.8) (2010)

Abstract Robust antibody and CD4 T cell responses are required for protective immunity against Salmonella infection. Here we examined the role of programmed death ligand 1 (PD-L1) in resolution of primary Salmonella infection. Infected PD-L1-deficient mice had higher bacterial burdens in the spleen and liver at day 21 and day 35 compared to wild-type mice indicating that PD-L1 is required for optimal protective immunity to Salmonella. Although Salmonella specific IgM and IgG2a Ab responses were similar between PD-L1-deificent and wild-type mice, PD-L1-deficient mice displayed a deficiency in CD4 T cells. Specifically, infected PD-L1-deficient mice had a significantly lower percentage of IFNγ-, and TNF-producing CD4 T cells and expressed lower levels of T-bet than wild-type CD4 T cells. These data demonstrate that PD-L1 expression is required for the generation of effective Th1 responses to Salmonella and optimal protective immunity.
The Anti-HIV Pentameric Pseudopeptide HB-19 Binds the C-terminal End of Nucleolin and Prevents Anchorage of Virus Particles in the Plasma Membrane of Target Cells (2002)

The multivalent pseudopeptide HB-19 that binds the cell-surface-expressed nucleolin is a potent inhibitor of human immunodeficiency virus (HIV) infection by blocking virus particle attachment and thus anchorage in the plasma membrane. We show that cross-linking of surface-bound HB-19A (like HB-19 but with a modified template) results in aggregation of HB-19A with surface nucleolin. Consistent with its specific action, HB-19A binding to different types of cells reaches saturation at concentrations that have been reported to result in inhibition of HIV infection. By using Chinese hamster ovary mutant cell lines, we confirm that the binding of HB-19A to surface nucleolin is independent of heparan and chondroitin sulfate proteoglycans. In vitro generated full-length nucleolin was found to bind HB-19A, whereas the N-terminal part containing the acidic amino acid stretches of nucleolin did not. The use of various deletion constructs of the C-terminal part of nucleolin then permitted the identification of the extreme C-terminal end of nucleolin, containing repeats of the amino acid motif, RGG, as the domain that binds HB-19A. Finally, a synthetic peptide corresponding to the last C-terminal 63 amino acids was able to inhibit HIV infection at the stage of HIV attachment to cells, thus suggesting that this domain could be functional in the HIV anchorage process.
Technical Approach for Reanimation of the Chronically Denervated Larynx by Means of Functional Electrical Stimulation (1994)

Functional electrical stimulation (FES) of the posterior cricoarytenoid (PCA) muscle to produce vocal fold abduction offers an alternative approach to current surgical therapies for bilateral vocal fold paralysis. The purpose of this study was to characterize the application of FES to chronically denervated PCA muscles. Specific goals were to develop a stimulus delivery system for the PCA muscle, determine a practical means of implantation, and identify stimulus parameters effective in activating chronically denervated muscle. Seventeen dogs were implanted with planar electrode arrays 3 months after unilateral recurrent laryngeal nerve resection. A nail-bed electrode array allowed discrete activation of the PCA muscle and gave the greatest abductions, with minimal charge dissipation. Muscle mapping revealed hot-spot regions on the PCA muscle surface, in which stimulation produced maximum abduction. A conservative stimulus paradigm effective in activating chronically denervated muscle was a 1-second pulse train of 2-millisecond-duration pulses, delivered at a tetanizing frequency of 30 Hz and an amplitude of 4 to 14 mA.
Analysis and functional classification of transcripts from the nematode Meloidogyne incognita (2003)

With sequencing from plant parasitic nematodes accelerating, the approaches to transcript characterization described here can be applied to more extensive datasets and also provide a foundation for more complex genome analyses.
Elastin‐like polypeptides as models of intrinsically disordered proteins (2015)

Elastin-like polypeptides (ELPs) are a class of stimuli-responsive biopolymers inspired by the intrinsically disordered domains of tropoelastin that are composed of repeats of the VPGXG pentapeptide motif, where X is a "guest residue". They undergo a reversible, thermally triggered lower critical solution temperature (LCST) phase transition, which has been utilized for a variety of applications including protein purification, affinity capture, immunoassays, and drug delivery. ELPs have been extensively studied as protein polymers and as biomaterials, but their relationship to other disordered proteins has heretofore not been established. The biophysical properties of ELPs that lend them their unique material behavior are similar to the properties of many intrinsically disordered proteins (IDP). Their low sequence complexity, phase behavior, and elastic properties make them an interesting "minimal" artificial IDP, and the study of ELPs can hence provide insights into the behavior of other more complex IDPs. Motivated by this emerging realization of the similarities between ELPs and IDPs, this review discusses the biophysical properties of ELPs, their biomedical utility, and their relationship to other disordered polypeptide sequences.
Fundamental Escherichia coli biochemical pathways for biomass and energy production: creation of overall flux states (2004)

We have previously shown that the metabolism for most efficient cell growth can be realized by a combination of two types of elementary modes. One mode produces biomass while the second mode generates only energy. The identity of the four most efficient biomass and energy pathway pairs changes, depending on the degree of oxygen limitation. The identification of such pathway pairs for different growth conditions offers a pathway-based explanation of maintenance energy generation. For a given growth rate, experimental aerobic glucose consumption rates can be used to estimate the contribution of each pathway type to the overall metabolic flux pattern. All metabolic fluxes are then completely determined by the stoichiometries of involved pathways defining all nutrient consumption and metabolite secretion rates. We present here equations that permit computation of network fluxes on the basis of unique pathways for the case of optimal, glucose-limited Escherichia coli growth under varying levels of oxygen stress. Predicted glucose and oxygen uptake rates and some metabolite secretion rates are in remarkable agreement with experimental observations supporting the validity of the presented approach. The entire most efficient, steady-state, metabolic rate structure is explicitly defined by the developed equations without need for additional computer simulations. The approach should be generally useful for analyzing and interpreting genomic data by predicting concise, pathway-based metabolic rate structures.
Reinforcement learning in case-based systems (2004)

Case-based reasoning (CBR) systems compare a new problem to a library of cases and adapt a similar library case to the problem, producing a preliminary solution. Since CBR systems require only a record of library cases with successful solutions, they are often used in areas lacking a strong theoretical domain model, such as medicine, economics and law. The problem is that many CBR systems use expert knowledge to determine how to build indexes for the case library so that cases that match the current situation can be identified. Human experts - whose time is valuable and scarce - often find it difficult to explain precisely their reasoning. Thus, a knowledge elicitation bottleneck occurs for many knowledge-based applications. Reinforcement-trained case-based reasoning (RETCBR) uses feedback from the user or some external process to learn how to match cases. RETCBR expands the domains in which CBR techniques can be applied, because it requires knowledge only for case recognition, not for determining indexing strategies. We are currently applying these techniques to human-computer interaction problems, such as user modeling and collaborative filtering.
IL-15R -IgG1-Fc Enhances IL-2 and IL-15 Anti-tumor Action through NK and CD8+ T Cells Proliferation and Activation (2010)

Natural killer (NK) cells-based immunotherapy is one of the most promising treatments for incurable malignant tumors. NK cells in combination with monoclonal antibodies to surface antigens of the tumor cell have been proved to be effective in a number of clinical trials. A limiting step in the development of successful cellular immunotherapy lies in developing an efficient and economic method to expand appropriate amount of NK cells and CD8(+) T cells. In this study, we constructed a humanized IL-15Ralpha-IgG1-Fc, which mimicked IL-15 trans-presentation. The feasibility of expanding populations of the human NK and CD8(+) T cells by IL-15Ralpha-IgG1-Fc complexes was tested. We then measured the cytotoxicity of expanded NK and CD8(+) T cells against tumor cell lines and primary tumor cells. When tested ex vivo, IL-2/IL-15Ralpha-IgG1-Fc complexes significantly enhanced NK and CD8(+) T cells expansion, isolated or non-isolated from PBMCs. The effect of IL-15Ralpha-IgG1-Fc was dependent on the presence of IL-2 or IL-15. IL-15Ralpha-IgG1-Fc complexes increased NK, CD8(+) T and NKT cells ratio in PBMC and BMMC after 14 days incubation. High level of granzyme B expression was observed in the supernatant of the complexes-treated NK cells. Expanded NK and CD8(+) T cell populations had cytotoxic function against the PC3, LNCaP, K562 and chronic lymphocytic leukemia (CLL) patient primary B cell lymphoma. We concluded that IL-2/IL-15Ralpha-IgG1-Fc significantly enhanced NK, CD8(+) T and NKT cells expansion, which possess strong anti-tumor activity. These data support clinical testing IL-2/IL-15Ralpha-IgG1-Fc expanded NK cells in patients with prostate cancer and CLL.
A functional microcircuit for cat visual cortex. (1991)

1. We have studied in vivo the intracellular responses of neurones in cat visual cortex to electrical pulse stimulation of the cortical afferents and have developed a microcircuit that simulates much of the experimental data. 2. Inhibition and excitation are not separable events, because individual neurones are embedded in microcircuits that contribute strong population effects. Synchronous electrical activation of the cortex inevitably set in motion a sequence of excitation and inhibition in every neurone we recorded. The temporal form of this response depends on the cortical layer in which the neurone is located. Superficial layer (layers 2+3) pyramidal neurones show a more marked polysynaptic excitatory phase than the pyramids of the deep layers (layers 5+6). 3. Excitatory effects on pyramidal neurones, particularly the superficial layer pyramids, are in general not due to monosynaptic input from thalamus, but polysynaptic input from cortical pyramids. Since the thalamic input is transient it does not provide the major, sustained excitation arriving at any cortical neurone. Instead the intracortical excitatory connections provide the major component of the excitation. 4. The polysynaptic excitatory response would be sustained well after the stimulus, were it not for the suppressive effect of intracortical inhibition induced by the pulse stimulation. 5. Intracellular recording combined with ionophoresis of gamma-aminobutyric acid (GABA) agonists and antagonists showed that intracortical inhibition is mediated by GABAA and GABAB receptors. The GABAA component occurs in the early phase of the impulse response. It is reflected in the strong hyperpolarization that follows the excitatory response and lasts about 50 ms. The GABAB component occurs in the late phase of the response, and is reflected in a sustained hyperpolarization that lasts some 200-300 ms. Both components are seen in all cortical pyramidal neurones. However, the GABAA component appears more powerful in deep layer pyramids than superficial layer pyramids. 6. The microcircuit simulates with good fidelity the above data from experiments in vivo and provides a novel explantation for the apparent lack of significant inhibition during visual stimulation. The basic circuit may be common to all cortical areas studied and thus the microcircuit may be a 'canonical' microcircuit for neocortex.
Infrared spectroscopic analysis of tumor pathology. (2007)

Infrared spectra of normal and malignant breast tissues were measured in the 600 cm(-1) to 4000 cm(-1) region. The measured spectroscopic features which are the spectroscopic fingerprints of the tissues contain the vital information about the malignant and normal tissues. Fourier Transform Infrared (FTIR) data on 25 cases of infiterating ductal carcinoma of breast with different grades of malignancy from patients of different age groups were analyzed. The samples were taken from the tumor sections of the tissue removed during surgery. Infrared spectra demonstrate significant spectral differences between the normal and the cancerous breast tissues. In particular changes in frequency and intensity in the spectra of protein, nucleic acid and glycogen vibrational modes as well as the band intensity ratios for lipid/proteins, protein/nucleic acids, protein/glycogen were observed. This allows to make a qualitative and semi quantitative evaluation of the changes in proliferation activity from normal to diseased tissue. It was evident that the sample to sample or patient to patient variations were small and the spectral differences between normal and diseased tissues were reproducible. The findings establish a framework for additional studies, which may enable us to establish a relation of the diseased state with its infrared spectra.
Analysis of the c-src gene product structure, abundance, and protein kinase activity in human neuroblastoma and glioblastoma cells. (1987)

We have compared in different human neuroblastoma cell lines and human glioblastoma cells the expression level, structure, and tyrosine-specific protein kinase activity of pp60c-src. Our results show that not all human neuroblastoma cell lines express pp60c-src molecules with amino-terminal structural alterations. In neuroblastoma cells which possess pp60c-src with altered gel migration, the diminished polyacrylamide gel mobility of pp60c-src was found not to be dependent upon amino-terminal phosphorylations since extensive treatment of these molecules with phosphatase did not significantly change their gel migration properties. Similar differences in gel migration were observed when RNA from the various neuroblastoma and glioblastoma cells was translated in vitro using either rabbit reticulocyte or wheat germ lysates. White the level of c-src mRNA in the different cells analyzed was found to be similar, the abundance of pp60c-src in these same cells was found to vary by as much as 12-fold. This suggests that the abundance of pp60c-src in human neuroendocrine tumors is regulated through post-transcriptional and/or post-translational events which may be related to the stage of neuronal differentiation of the cells. Based upon determination of pp60c-src abundance by immunoblot analysis, we demonstrate that pp60c-src molecules derived from human neuroblastoma and glioblastoma cells have very similar in vitro protein kinase activities.
Comparison of the Collagen Meniscus Implant with Partial Meniscectomy (2008)

New biomechanically competent meniscus-like tissue forms after placement of a collagen meniscus implant, and use of the implant appears safe. The collagen meniscus implant supports new tissue ingrowth that appears to be adequate to enhance meniscal function as evidenced by improved clinical outcomes in patients with a chronic meniscal injury. The collagen meniscus implant has the utility to be used to replace irreparable or lost meniscal tissue in patients with a chronic meniscal injury. The implant was not found to have any benefit for patients with an acute injury.
Protofibrillar intermediates of amyloid beta-protein induce acute electrophysiological changes and progressive neurotoxicity in cortical neurons. (1999)

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is thought to be caused in part by the age-related accumulation of amyloid beta-protein (Abeta). The presence of neuritic plaques containing abundant Abeta-derived amyloid fibrils in AD brain tissue supports the concept that fibril accumulation per se underlies neuronal dysfunction in AD. Recent observations have begun to challenge this assumption by suggesting that earlier Abeta assemblies formed during the process of fibrillogenesis may also play a role in AD pathogenesis. Here, we present the novel finding that protofibrils (PF), metastable intermediates in amyloid fibril formation, can alter the electrical activity of neurons and cause neuronal loss. Both low molecular weight Abeta (LMW Abeta) and PF reproducibly induced toxicity in mixed brain cultures in a time- and concentration-dependent manner. No increase in fibril formation during the course of the experiments was observed by either Congo red binding or electron microscopy, suggesting that the neurotoxicity of LMW Abeta and PF cannot be explained by conversion to fibrils. Importantly, protofibrils, but not LMW Abeta, produced a rapid increase in EPSPs, action potentials, and membrane depolarizations. These data suggest that PF have inherent biological activity similar to that of mature fibrils. Our results raise the possibility that the preclinical and early clinical progression of AD is driven in part by the accumulation of specific Abeta assembly intermediates formed during the process of fibrillogenesis.
Glitch-free implementation of masking in modern FPGAs (2012)

Due to the propagation of the glitches in combinational circuits side-channel leakage of the masked S-boxes realized in hardware is a known issue. Our contribution in this paper is to adopt a masked AES S-box circuit according to the FPGA resources in order to avoid the glitches. Our design is suitable for the 5, 6, and 7 FPGA series of Xilinx although our practical investigations are performed using a Virtex-5 chip. In short, compared to the original design synthesized by automatic tools while requiring the same area (slice count) our design reduces power consumption, critical path delay, and more importantly the side-channel leakage. In our practical investigations we could not recover any first-order leakage of our design using up to 50 million traces. However, since the targeted S-box realizes a first-order boolean masking, the second-order leakage could be revealed using around 25 million measurements.
Nitric Oxide Reversibly Inhibits the Migration of Cultured Vascular Smooth Muscle Cells (1996)

Augmentation of nitric oxide (NO) production in vivo decreases lesions in a variety of models of arterial injury, and inhibition of NO synthase exacerbates experimental intimal lesions. Both vascular smooth muscle cell (VSMC) proliferation and migration contribute to lesion formation. Although NO inhibits VSMC proliferation, its effects on VSMC migration are unknown. To test the hypothesis that NO inhibits VSMC migration independent of inhibition of proliferation, we examined migration of rat aortic VSMCs after wounding of a confluent culture in the presence of chemical donors of NO. Hydroxyurea was used to eliminate any confounding effect of NO on proliferation. Three NO donors, diethylamine NONOate, spermine NONOate, and S-nitrosoglutathione, exhibited concentration-dependent inhibition of both number of migrating VSMCs and maximal distance migrated. Inhibition of migration was also seen with 8-Br-cGMP, suggesting that activation of guanylate cyclase may play a role in mediating the antimigratory effects of NO. Migration resumed after removal of NO donors, as evidenced by an increase in distance migrated. Measurement of VSMC protein synthesis and mitochondrial respiration indicated that inhibition of migration by NO donors was not due to metabolic cytostasis. These findings indicate that NO reversibly inhibits VSMC migration independent of proliferation or cytotoxicity, a novel mechanism by which both endogenous and pharmacological NO may alter vascular pathology.
Akinesia in Parkinson's disease. I. Shortening of simple reaction time with focal, single‐pulse transcranial magnetic stimulation (1994)

We studied the effects of transcranial magnetic stimulation (TMS) of the motor cortex on simple reaction time (RT) in 10 patients with Parkinson's disease compared with 10 age-matched normal controls. The subjects flexed their right elbow rapidly in response to a visual go-signal. In random trials, TMS was applied to the left motor cortex at varying delays after the go-signal. In trials without TMS, RT was longer in the patients. However, in the trials with subthreshold TMS, RT in the patients became as fast as RT in trials without TMS in the controls. This shortening was associated with normalization of the voluntary triphasic EMG pattern and the pre-movement cortical excitability increase.
NDUFA4L2 expression predicts poor prognosis in clear cell renal cell carcinoma patients (2016)

Our study has provided the significant clinical relevance of NDUFA4L2 in ccRCC and suggested that ccRCC patients with NDUFA4L2 overexpression may be suitable as a potential therapeutic target for ccRCC patients.
Expression and function of galectin-3, a beta-galactoside-binding lectin, in human monocytes and macrophages. (1995)

A family of beta-galactoside-binding animal lectins has recently been designated as galectins. One member of this family, galectin-3, has been known as epsilon BP for its IgE-binding activity and as Mac-2, a macrophage surface antigen, CBP35, CBP30, L-29, and L-34. Although much information has accumulated on the expression of this lectin in murine macrophages and human monocytic cell lines, little is known about the expression and function of this protein in normal human monocytes/macrophages. We now report that galectin-3 is expressed in normal human peripheral blood monocytes and its level increases dramatically as human monocytes differentiate into macrophages upon culturing in vitro. Immunoblot analysis showed that there was a 5-fold increase in the level of galectin-3 after 1 day of culture and greater than a 12-fold increase after 5 days. Immunocytochemical analysis confirmed this progressive increase of galectin-3 expression in cultured monocytes. Immunogold cytochemistry/electron microscopy analysis revealed that galectin-3 was expressed on the surface of human monocytes and that the level of cell surface galectin-3 increased progressively as these cells differentiated into macrophages. The level of galectin-3 in human monocytes/macrophages was modulated by stimuli such as lipopolysaccharide and interferon-gamma, and galectin-3 was secreted when monocytes were stimulated by calcium ionophore A23187 Soluble galectin-3 caused superoxide release from human monocytes; this activity was dependent on the lectin property of galectin-3, as it was inhibitable by lactose. Thus, galectin-3 may modulate the function of this cell type in an autocrine or paracrine fashion through binding to cell surface glycoconjugates.