gebhart/patrepeval huggingface dataset:
Exhaustive Characterization of TCR–pMHC Binding Energy Estimated by the String Model and Miyazawa-Jernigan Matrix (2014)

Accurate calculations of protein-protein binding free energies based on rigorous models, which consider the binding complex structure in atomic detail, are computationally expensive and impracticable to apply to T cell repertoire formation that occurs in the thymus because this process involves the interactions among numerous combinations of T cell receptors (TCRs) and presented peptides. By comparison, an evaluation of binding free-energy using a combination of the string model and Miyazawa-Jernigan matrix is very efficient and was therefore applied to estimate interaction energies between T cell receptor-peptide-MHC (TCR-pMHC) complexes, which appeared to successfully explain the effects of binding capacity of MHC on repertoire-formation and the reason for the presence of elite-controllers of some viral infections. However, this evaluation method is overly simplified and requires more detailed considerations when applied to evaluating TCR-pMHC interactions. In this study, we examined this method exhaustively and revealed the limitations of the method. Following features necessitate cautious attitude when interpreting the calculation results: first, the apparent increase in the number of hot spots in accordance with an increase of educational epitope pool size does not mean an increased TCR specificity of surviving clones; second, strong binders to any TCR converge to some limited sequences that are determined by the physical nature of the Miyazawa-Jernigan matrix.
Bacterial Invasion: The Paradigms of Enteroinvasive Pathogens (2004)

Invasive bacteria actively induce their own uptake by phagocytosis in normally nonphagocytic cells and then either establish a protected niche within which they survive and replicate, or disseminate from cell to cell by means of an actin-based motility process. The mechanisms underlying bacterial entry, phagosome maturation, and dissemination reveal common strategies as well as unique tactics evolved by individual species to establish infection.
Potential Therapeutic Drugs and Methods for the Treatment of Amyotrophic Lateral Sclerosis (2014)

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disorder caused by damage of motoneurons leading to paralysis state and long term disability. Riluzole is currently the only FDA-approved drug for the treatment of ALS. The proposed mechanisms of ALS include glutamate excitotoxicity, oxidative stress, mitochondrial dysfunction, protein aggregation, SOD1 accumulations, and neuronal death. In this review, we discuss potential biomarkers for the identification of patients with ALS. We further emphasize potential therapy involving the uses of neurotrophic factors such as IGFI, GDNF, VEGF, ADNF-9, colivelin and angiogenin in the treatment of ALS. Moreover, we described several existing drugs such as talampanel, ceftriaxone, pramipexole, dexpramipexole and arimoclomol potential compounds for the treatment of ALS. Interestingly, the uses of stem cell therapy and immunotherapy are promising for the treatment of ALS.
Telepresence: An opportunity to develop real-world experimentation in education (1997)

A would-be autodidact can nowadays find educational material in the form of printed documents or digital supports, or it can access it via the Internet. In the field of automatic control, these media only carry virtual information, i.e., they do not provide real-world equipment. This drawback is the last obstacle to a possible "virtual campus". The aim of this paper is to present an approach for remote experimentation and to stress its educational and economic benefits. Remote PID control of an electrical drive illustrates the applicability of the approach.
A General Review of Linear Varying Parameter and Nonlinear Circuit Analysis (1950)

Variable and nonlinear systems are classified from the standpoint of their significance in communication problems. Methods of solution are reviewed and appropriate references are cited. The paper is a synopsis of a talk given at the Symposium on Network Theory of the 1949 National IRE Convention.
Construction and characterization of infectious intragenotypic and intergenotypic hepatitis C virus chimeras (2006)

Chronic liver disease caused by infection with hepatitis C virus (HCV) is an important global health problem that currently affects 170 million people. A major impediment in HCV research and drug development has been the lack of culture systems supporting virus production. This obstacle was recently overcome by using JFH1-based full-length genomes that allow production of viruses infectious both in vitro and in vivo. Although this improvement was important, because of the restriction to the JFH1 isolate and a single chimera consisting of J6CF and JFH1-derived sequences, broadly based comparative studies between different HCV strains were not possible. Therefore, in this study we created a series of further chimeric genomes allowing production of infectious genotype (GT) 1a, 1b, 2a, and 3a particles. With the exception of the GT3a/JFH1 chimera, efficient virus production was obtained when the genome fragments were fused via a site located right after the first transmembrane domain of NS2. The most efficient construct is a GT2a/2a chimera consisting of J6CF- and JFH1-derived sequences connected via this junction. This hybrid, designated Jc1, yielded infectious titers 100- to 1,000-fold higher than the parental isolate and all other chimeras, suggesting that determinants within the structural proteins govern kinetic and efficiency of virus assembly and release. Finally, we describe an E1-specific antiserum capable of neutralizing infectivity of all HCV chimeras.
Robust Automatic Speech Recognition system based on using adaptive time-frequency masking (2016)

The Automatic Speech Recognition (ASR) systems suffer from many types of noises in different environments. Nowadays, developing robust ASR system is an attractive research topic due to the high demands in many commercial applications. In this paper, the Mel-Frequency Cepstral Coefficients (MFCC) is modified to robust the noise, where the spectrogram is used as time-frequency analysis tool. The proposed system is designed to remove the energy, which is affected by the noise. It uses an adaptive filtering technique to robust the noise without loss of performance in case of undistorted speech data. The proposed system is evaluated in a noisy environment. The experimental results demonstrated that the proposed MFCC method provides significant improvements in recognition accuracy at low Signal to Noise Ratio (SNR). The average recognition accuracy is improved by 11% and 12.56% compared to standard MFCC and RASTA-PLP, respectively.
Modeling early retinal development with human embryonic and induced pluripotent stem cells (2009)

Human pluripotent stem cells have the potential to provide comprehensive model systems for the earliest stages of human ontogenesis. To serve in this capacity, these cells must undergo a targeted, stepwise differentiation process that follows a normal developmental timeline. Here we demonstrate the ability of both human embryonic stem cells (hESCs) and induced pluripotent stem (iPS) cells to meet these requirements for human retinogenesis. Upon differentiation, hESCs initially yielded a highly enriched population of early eye field cells. Thereafter, a subset of cells acquired features of advancing retinal differentiation in a sequence and time course that mimicked in vivo human retinal development. Application of this culture method to a human iPS cell line also generated retina-specific cell types at comparable times in vitro. Lastly, altering endogenous signaling during differentiation affected lineage-specific gene expression in a manner consistent with established mechanisms of early neural and retinal cell fate determination. These findings should aid in the investigation of the molecular events governing retinal specification from human pluripotent stem cells.
Isolation of myelin basic protein–specific T cells predominantly from the memory T‐cell compartment in multiple sclerosis (1999)

Myelin antigen–reactive T cells have been implicated in the pathogenesis of multiple sclerosis (MS). Myelin-reactive T cells can be isolated from control subjects as well as individuals who have MS. Experimental models of MS indicate that recently stimulated, myelin-reactive T cells have greater encephalitogenic potential than resting T cells. Activation induces changes in T-cell surface antigens that may distinguish previously stimulated, memory T cells from naive T cells. Therefore, we examined 108 myelin basic protein (MBP)-reactive T-cell lines from 7 MS and 8 control subjects to determine whether MBP-reactive T cells originated in the memory T-cell subset or in the naive subset. Isotypes of CD45 were used that designate memory or naive T cells. In subjects having MS, 84% of the MBP-reactive T cells resided in the memory T-cell subset. However, in control subjects, only 13% of MBP-specific T cells originated from the memory T-cell subset. This result suggests that a substantial proportion of MBP-reactive T cells from some individuals with MS have been previously activated in vivo. This difference provides additional support for the hypothesis that myelin antigen–specific T cells are involved in the pathogenesis of MS. Ann Neurol 1999;45:33–39
High-level goal recognition in a wireless LAN (2004)

Plan recognition has traditionally been developed for logically encoded application domains with a focus on logical reasoning. In this paper, we present an integrated plan-recognition model that combines low-level sensory readings with high-level goal inference. A two-level architecture is proposed to infer a user's goals in a complex indoor environment using an RF-based wireless network. The novelty of our work derives from our ability to infer a user's goals from sequences of signal trajectory, and the ability for us to make a trade-off between model accuracy and inference efficiency. The model relies on a dynamic Bayesian network to infer a user's actions from raw signals, and an N-gram model to infer the users' goals from actions. We present a method for constructing the model from the past data and demonstrate the effectiveness of our proposed solution through empirical studies using some real data that we have collected.
Dietary Fish Oil Supplementation Alters Leukocyte Function and Cytokine Production in Healthy Women (1995)

The effect of low-dose fish oil supplementation on cytokines and white cell function in women was investigated. Thirty-three healthy, nonsmoking women entered the double-blind study. For 4 weeks, 2.4 g of either fish oil (n = 16) or fish oil with vitamin E (n = 17) was added daily to the subjects' otherwise unchanged diets. Venous blood samples were taken at the onset of the trial, after the supplementation period, and again after a 9-week washout period. Plasma levels of platelet-derived growth factor and myeloperoxidase were measured using immunoassays. The intracellular peroxidase content of white blood cells was measured using a staining technique. Platelet-derived growth factor levels were significantly lowered after supplementation (P < or = .05). Intracellular peroxidase was increased (P < or = .01), and extracellular myeloperoxidase levels were lowered (P < or = .05). Taken together, these results suggest that the anti-inflammatory effect of fish oil may be due at least partly to alterations in white cell function and growth factor levels.
Effects of Interleukin-1β Inhibition With Canakinumab on Hemoglobin A1c, Lipids, C-Reactive Protein, Interleukin-6, and Fibrinogen (2012)

Canakinumab, a human monoclonal antibody that neutralizes interleukin-1β, significantly reduces inflammation without major effect on low-density lipoprotein cholesterol or high-density lipoprotein cholesterol. These phase II trial data support the use of canakinumab as a potential therapeutic method to test directly the inflammatory hypothesis of atherosclerosis.
Warfarin-Drug Interactions Among Older Adults (2007)

Warfarin-drug interactions are often encountered in the care of older adults. Interactions may be classified as pharmacokinetic, resulting in changes in serum warfarin concentrations, or pharmacodynamic, resulting in changes in hemostasis or platelet function. Knowledge of these mechanisms of warfarin-drug interactions may help identify warfarin interactions, facilitate prescribing decisions, and assist with appropriate monitoring.
Cyclostationary noise modeling in narrowband powerline communication for Smart Grid applications (2012)

A Smart Grid intelligently monitors and controls energy flows in an electric grid. Having up-to-date distributed readings of grid conditions helps utilities efficiently scale generation up or down to meet demand. Narrowband powerline communication (PLC) systems can provide these up-to-date readings from subscribers to the local utility over existing power lines. A key challenge in PLC systems is overcoming additive non-Gaussian noise. In this paper, we propose to use a cyclostationary model for the dominant component of additive non-Gaussian noise. The key contributions are (1) fitting measured data from outdoor narrowband PLC system field trials to a cyclostationary model, and (2) developing a cyclostationary noise generation model that fits measured data. We found that the period in the cyclostationary model matched half of the period of the main powerline frequency, which is consistent with previous work in indoor PLC additive noise modeling.
TCP Slow Start, Congestion Avoidance, Fast Retransmit, and Fast Recovery Algorithms (1997)

Modern implementations of TCP contain four intertwined algorithms that have never been fully documented as Internet standards: slow start, congestion avoidance, fast retransmit, and fast recovery. [2] and [3] provide some details on these algorithms, [4] provides examples of the algorithms in action, and [5] provides the source code for the 4.4BSD implementation. RFC 1122 requires that a TCP must implement slow start and congestion avoidance (Section 4.2.2.15 of [1]), citing [2] as the reference, but fast retransmit and fast recovery were implemented after RFC 1122. The purpose of this document is to document these four algorithms for the Internet.
Nucleotide sequence and functional map of pC194, a plasmid that specifies inducible chloramphenicol resistance (1982)

The nucleotide sequence of pC194, a small plasmid from Staphylococcus aureus which is capable of replication in Bacillus subtilis, has been determined. The genetic determinant of chloramphenicol (CAM) resistance, which includes the chloramphenicol acetyl transferase (CAT) structural gene, the putative promoter and controlling element of this determinant, have been mapped functionally by subcloning a 1,035-nucleotide fragment which specifies the resistance phenotype using plasmid pBR322 as vector. Expression of CAM resistance is autogenously regulated since the 1,035-nucleotide fragment containing the CAT gene sequence and its promoter cloned into pBR322 expresses resistance inducibly in the Escherichia coli host. A presumed controlling element of CAT expression consists of a 37-nucleotide inverted complementary repeat sequence that is located between the -10 and ribosome-loading sequences of the CAT structural gene. Whereas the composite plasmid containing the minimal CAT determinant cloned in pBR322 could not replicate in B. subtilis, ability to replicate in B. subtilis was seen if the fragment cloned included an extension consisting of an additional 300 nucleotides beyond the 5' end of the single pC194 MspI site associated with replication. This 5' extension contained a 120-nucleotide inverted complementary repeat sequence similar to that found in pE194 TaqI fragment B which contains replication sequences of that plasmid. pC194 was found to contain four opening reading frames theoretically capable of coding for proteins with maximum molecular masses, as follows: A, 27,800 daltons; B, 26,200 daltons; C, 15,000 daltons; and D, 9,600 daltons. Interruption or deletion of either frame A or D does not entail loss of ability to replicate or to express CAM resistance, whereas frame B contains the CAT structural gene and frame C contains sequences associated with plasmid replication.
Impact of molecular profiling on overall survival of patients with advanced ovarian cancer (2016)

This report demonstrates the ability of multi-platform molecular profiling to identify EOC patients at risk of inferior survival. It also suggests a potential beneficial role of avoidance of lack-of-benefit therapies which, when administered, resulted in decreased survival relative to patients who received only therapies predicted to be of benefit.
Ketamine as a Fast Acting Antidepressant: Current Knowledge and Open Questions (2013)

Several recent studies have shown that a single intravenous subanesthetic dose of ketamine, a NMDA receptor antagonist, exerts rapid antidepressant effects in patients with treatment refractory mood disorders and reduces suicidal ideation. Those insights have fueled tremendous excitement in the efforts to elucidate the mechanism underlying ketamine's antidepressant properties in animal models of depression, as well as in humans through the use of brain imaging as well as peripheral blood measurements. For example, there is emerging evidence that ketamine's antidepressant properties rely on increasing AMPA signaling and rapidly inducing synaptogenesis. While pilot clinical studies are promising, a number of critical questions still remain unanswered. They relate to the safe and effective use of ketamine in patients with mood disorders regarding the optimal dose range, modality and method of administration for acute and long-term maintenance of effect, and the biomarkers associated with response/nonresponse. In this review article, we first summarize the clinical evidence about the use of ketamine in mood disorders, as well as preclinical and humans studies which investigated the mechanisms of action of ketamine, and predictors of antidepressant response in clinical populations. We then provide a critical overview of the knowledge gaps about the use of ketamine in depression and suggest some future research directions for the investigation of ketamine as a promising tool to develop novel more effective and fast acting antidepressants.
Enhancement of Angiogenic Efficacy of Human Cord Blood Cell Transplantation (2006)

We tested the hypotheses that angiogenic efficacy of cord blood mononuclear cell (CBMNC) transplantation would be enhanced by using matrix and that combined therapy of CBMNC transplantation using matrix and sustained delivery of basic fibroblast growth factor (bFGF) would be synergistic in angiogenesis induction in ischemic limbs. One day after surgical induction of hindlimb ischemia, C57BL/6J mice were randomized to receive either medium injection, CBMNC transplantation using medium, CBMNC transplantation using fibrin matrix, sustained delivery of bFGF, or a combination of sustained delivery of bFGF and CBMNC transplantation using fibrin matrix. Four weeks after treatment, the angiogenic efficacy of the treatments was evaluated by immunohistochemical examinations and microvessel density determination in the ischemic sites. Transplanted CBMNCs survived, proliferated, and participated in capillary formation in ischemic limbs. CBMNC transplantation using fibrin matrix significantly increased the densities of capillaries and arterioles compared with CBMNC transplantation using medium. Importantly, combined therapy of sustained delivery of bFGF and CBMNC transplantation using fibrin matrix further increased the densities of capillaries and arterioles compared with either therapy alone. The angiogenic efficacy of angiogenic cell transplantation is enhanced by cell transplantation using matrix. Combined therapy of sustained release of angiogenic protein and angiogenic cell transplantation synergistically enhances angiogenesis in ischemic limbs compared to each therapy separately.
Infection of Neonatal Mice with Sindbis Virus Results in a Systemic Inflammatory Response Syndrome (1999)

Laboratory strains of viruses may contain cell culture-adaptive mutations which result in significant quantitative and qualitative alterations in pathogenesis compared to natural virus isolates. This report suggests that this is the case with Sindbis virus strain AR339. A cDNA clone comprising a consensus sequence of Sindbis virus strain AR339 has been constructed (W. B. Klimstra, K. D. Ryman, and R. E. Johnston, J. Virol. 72:7357-7366, 1998). This clone (pTR339) regenerates a sequence predicted to be very close to that of the original AR339 isolate by eliminating several cell culture-adaptive mutations present in individual laboratory strains of the virus (K. L. McKnight et al., J. Virol. 70:1981-1989, 1996). It thus provides a unique reagent for study of the pathogenesis of Sindbis virus strain AR339 in mice. Neonatal mouse pathogenesis of virus (TR339) generated from the pTR339 clone was compared with that of virus from a cDNA clone of the cell culture-passaged laboratory AR339 strain, TRSB, and virus from a clone of a more highly cell culture-adapted strain, HR(sp) (Toto 50). The sequence of TRSB differs from the consensus at three coding positions, while Toto 50 differs at eight codons and one nucleotide in the 5' nontranslated region. Both cell culture-adapted strains contain mutations associated with heparan sulfate (HS)-dependent attachment to cells (W.B. Klimstra, K. D. Ryman, and R. E. Johnston, J. Virol. 72:7357-7366, 1998). TR339 caused 100% mortality with an average survival time (AST) of 1.7 +/- 0.25 days. While TRSB also caused 100% mortality, the AST was extended to 2.9 +/- 0.52 days. The more extensively cell culture-adapted virus Toto 50 caused only 30% mortality with an AST extended to 11.0 +/- 4.8 days. TRSB and TR339 induced high serum levels of alpha/beta interferon, gamma interferon, tumor necrosis factor alpha, interleukin-6, and corticosterone and induced pathology reminiscent of lipopolysaccharide-induced endotoxic shock, a type of systemic inflammatory response syndrome. However, the reduced intensity of this response in TRSB-infected mice correlated with the increased AST. Toto 50 failed to induce the shock-like cytokine cascade. In situ hybridization studies indicated that TR339 and TRSB replicated in identical tissues, but the TRSB signal was less widespread at early times postinfection. While Toto 50 also replicated in similar tissues, the extent of replication was severely restricted and mice developed lesions characteristic of encephalitis. A single mutation in TRSB at E2 position 1 (Arg) conferred HS-dependent attachment to cells and was associated with reduced cytokine induction and extended AST in vivo.
Pathways to a Protein Folding Intermediate Observed in a 1-Microsecond Simulation in Aqueous Solution (1998)

An implementation of classical molecular dynamics on parallel computers of increased efficiency has enabled a simulation of protein folding with explicit representation of water for 1 microsecond, about two orders of magnitude longer than the longest simulation of a protein in water reported to date. Starting with an unfolded state of villin headpiece subdomain, hydrophobic collapse and helix formation occur in an initial phase, followed by conformational readjustments. A marginally stable state, which has a lifetime of about 150 nanoseconds, a favorable solvation free energy, and shows significant resemblance to the native structure, is observed; two pathways to this state have been found.