gebhart/patrepeval huggingface dataset:
Automatic Differentiationin Machine Learning: a Survey (2018)

Derivatives, mostly in the form of gradients and Hessians, are ubiquitous in machine learning. Automatic differentiation (AD), also called algorithmic differentiation or simply “auto-diff”, is a family of techniques similar to but more general than backpropagation for efficiently and accurately evaluating derivatives of numeric functions expressed as computer programs. AD is a small but established field with applications in areas including computational fluid dynamics, atmospheric sciences, and engineering design optimization. Until
very recently, the fields of machine learning and AD have largely been unaware of each other and, in some cases, have independently discovered each other’s results. Despite its
relevance, general-purpose AD has been missing from the machine learning toolbox, a situation slowly changing with its ongoing adoption under the names “dynamic computational
graphs” and “differentiable programming”. We survey the intersection of AD and machine learning, cover applications where AD has direct relevance, and address the main imple-
mentation techniques. By precisely defining the main differentiation techniques and their interrelationships, we aim to bring clarity to the usage of the terms “autodiff”, “automatic differentiation”, and “symbolic differentiation” as these are encountered more and more in machine learning settings.
Prevention of Hypotension by a Single 5-mg Dose of Ephedrine During Small-Dose Spinal Anesthesia in Prehydrated Cesarean Delivery Patients (2000)

To evaluate the effectiveness of prophylactic ephedrine for the prevention of hypotension associated with spinal anesthesia, 50 parturients undergoing cesarean delivery received either ephedrine 5 mg or saline IV in a double-blinded fashion immediately after the induction of spinal anesthesia. Spinal anesthesia was performed with hyperbaric bupivacaine 6.6 mg combined with sufentanil 3.3 μg as part of a combined spinal-epidural technique. All patients received 1000 mL of lactated Ringer’s solution and 500 mL of hydroxyethylstarch 6% before the spinal injection. Additional ephedrine boluses (5 mg) were administered IV when the systolic blood pressure or heart rate decreased by more than 30% from baseline values, when systolic blood pressure became <100 mm Hg, or when patients complained of nausea or feeling faint. The height of the block was equal in the groups; however, more patients in the placebo group were found to develop hypotension (58% vs 25%, P < 0.05). Only 2 (8%) patients in the ephedrine group developed hypotension with systolic blood pressure values <90 mm Hg, whereas 10 patients (42%) in the saline group experienced hypotension of this severity (P < 0.05). In addition, there was a higher incidence of nausea in the placebo-treated patients. The total amount of ephedrine administered did not differ between groups. These findings suggest that the incidence and severity of hypotension are significantly reduced by the IV administration of a prophylactic dose of 5 mg ephedrine in patients receiving small-dose spinal anesthesia for cesarean delivery. Implications Ephedrine is the drug most often used to correct hypotension during spinal anesthesia for cesarean delivery in healthy patients. A single IV dose of 5 mg decreases the occurrence and limits the severity of hypotension in prehydrated subjects receiving a small-dose spinal local anesthetic-opioid combination.
INTERNAL COLOR OF SPANISH PEANUT HULLS AS AN INDEX OF KERNEL MATURITY (1971)

SUMMARY A nonsacrificial index of peanut kernel maturity was developed, based upon objective color measurement of the internal hull color which was then related to other indices of maturity and quality. Kernel density and light transmittance of the oil at 480 mμ were confirmed as good indices of quality. Internal hull color, kernel density and light transmittance of peanut oil were found to be significantly related. With appropriate instrumentation, objective evaluation of the internal hull surface color of peanuts is feasible as a good index of quality and maturity.
Epithelial growth factor receptor (EGFR)-inhibition for relief of neuropathic pain–A case series (2013)

Background Neuropathic pain remains a significant challenge with unsatisfactory therapeutic options. Its pathogenesis may involve the neuropathic triad of neuronal, glial and immune cells. Communication between these cells is possibly perpetuated by mitogen-activated protein kinase (MAPK)-signaling. For several years, we successfully treated a rectal cancer patient with the epithelial growth factor receptor (EGFR)-inhibitor cetuximab, for debilitating neuropathic pain due to progressive malignant invasion of the sacral plexus. Here, we report the effect of treatment with various EGFR-inhibitors in five additional patients with severe and long-standing, therapy-resistant neuropathic pain. Methods All patients had well-documented neuropathic pain syndromes with the following etiologies: inflammatory polyneuropathy, complex regional pain syndrome type 1, radiculopathy after failed back surgery, malignant invasion of the sacral plexus by bladder cancer, and phantom limb pain. All patients were given intravenous (extracellular) EGFR-inhibitors (cetuximab, panitumumab) initially, and switched to oral (intracellular) agents (gefitinib, erlotinib) after an analgesic effect was obtained. Results Four of the five patients responded, all within 24h of intravenous administration, with a mean decrease in worst pain from 9 to 1 on a 10-point scale. All four EGFR-inhibitors were effective. The clinical courses, including patient-reported pain relief, are prospectively documented with 78-219 days follow-up for those who responded to treatment. Toxicities were transient and manageable. Conclusions/implications EGFR-inhibition resulted in dramatic relief of neuropathic pain. A plausible biological explanation involves the interruption of MAPK-signaling. The role of EGFR-inhibition as a target for the treatment of neuropathic pain appears promising and warrants investigation.
Transgenic mice expressing the human high-affinity immunoglobulin (Ig) E receptor alpha chain respond to human IgE in mast cell degranulation and in allergic reactions. (1996)

The high-affinity receptor for immunoglobulin (Ig) E (Fc epsilon RI) on mast cells and basophils plays a key role in IgE-mediated allergies. Fc epsilon RI is composed of one alpha, one beta, and two gamma chains, which are all required for cell surface expression of Fc epsilon RI, but only the alpha chain is involved in the binding to IgE. Fc epsilon RI-IgE interaction is highly species specific, and rodent Fc epsilon RI does not bind human IgE. To obtain a "humanized" animal model that responds to human IgE in allergic reactions, transgenic mice expressing the human Fc epsilon RI alpha chain were generated. The human Fc epsilon RI alpha chain gene with a 1.3-kb promoter region as a transgene was found to be sufficient for mast cell-specific transcription. Cell surface expression of the human Fc epsilon RI alpha chain was indicated by the specific binding of human IgE to mast cells from transgenic mice in flow cytometric analyses. Expression of the transgenic Fc epsilon RI on bone marrow-derived mast cells was 4.7 x 10(4)/cell, and the human IgE-binding affinity was Kd = 6.4 nM in receptor-binding studies using 125I-IgE. The transgenic human Fc epsilon RI alpha chain was complexed with the mouse beta and gamma chains in immunoprecipitation studies. Cross-linking of the transgenic Fc epsilon RI with human IgE and antigens led to mast cell activation as indicated by enhanced tyrosine phosphorylation of the Fc epsilon RI beta and gamma chains and other cellular proteins. Mast cell degranulation in transgenic mice could be triggered by human IgE and antigens, as demonstrated by beta-hexosaminidase release in vitro and passive cutaneous anaphylaxis in vivo. The results demonstrate that the human Fc epsilon RI alpha chain alone not only confers the specificity in human IgE binding, but also can reconstitute a functional receptor by coupling with the mouse beta and gamma chains to trigger mast cell activation and degranulation in a whole animal system. These transgenic mice "humanized" in IgE-mediated allergies may be valuable for development of therapeutic agents that target the binding of IgE to its receptor.
Enhancing practical security of quantum key distribution with a few decoy states (2005)

Quantum key distribution establishes a secret string of bits between two distant parties. Of concern in weak laser pulse schemes is the especially strong photon number splitting attack by an eavesdropper, but the decoy state method can detect this attack with current technology, yielding a high rate of secret bits. In this Letter, we develop rigorous security statements in the case of finite statistics with only a few decoy states, and we present the results of simulations of an experimental setup of a decoy state protocol that can be simply realized with current technology.
Single factors direct the differentiation of stem cells from the fetal and adult central nervous system. (1996)

Identifying the signals that regulate stem cell differentiation is fundamental to understanding cellular diversity in the brain. In this paper we identify factors that act in an instructive fashion to direct the differentiation of multipotential stem cells derived from the embryonic central nervous system (CNS). CNS stem cell clones differentiate to multiple fates: neurons, astrocytes, and oligodendrocytes. The differentiation of cells in a clone is influenced by extracellular signals: Platelet-derived growth factor (PDGF-AA, -AB, and -BB) supports neuronal differentiation. In contrast, ciliary neurotrophic factor and thyroid hormone T3 act instructively on stem cells to generate clones of astrocytes and oligodendrocytes, respectively. Adult stem cells had remarkably similar responses to these growth factors. These results support a simple model in which transient exposure to extrinsic factors acting through known pathways initiates fate decisions by multipotential CNS stem cells.
Effects of Length and Location on the Cellular Response to Double-Stranded RNA (2004)

Since double-stranded RNA (dsRNA) has not until recently generally been thought to be deliberately expressed in cells, it has commonly been assumed that the major source of cellular dsRNA is viral infections. In this view, the cellular responses to dsRNA would be natural and perhaps ancient antiviral responses. While the cell may certainly react to some dsRNAs as an antiviral response, this does not represent the only response or even, perhaps, the major one. A number of recent observations have pointed to the possibility that dsRNA molecules are not seen only as evidence of viral infection or recognized for degradation because they cannot be translated. In some instances they may also play important roles in normal cell growth and function. The purpose of this review is to outline our current understanding of the fate of dsRNA in cells, with a focus on the apparent fact that their fates and functions appear to depend critically not only on where in the cell dsRNA molecules are found, but also on how long they are and perhaps on how abundant they are.
Human Herpesviruses: Biology, Therapy, and Immunoprophylaxis (2007)

Part I. Introduction Part II. Basic Virology and Viral Gene Effects on Host Cell Functions Part II. Basic Virology and Viral Gene Effects on Host Cell Functions Part II. Basic Virology and Viral Gene Effects on Host Cell Functions Part III. Pathogenesis, Clinical Disease, Host Response, and Epidemiology Part III. Pathogenesis, Clinical Disease, Host Response, and Epidemiology Part III. Pathogenesis, Clinical Disease, Host Response, and Epidemiology Part III. HHV- 6a, 6b and 7 Ann Arvin and Richard Whitley Part III. Pathogenesis, Clinical Disease, Host Response, and Epidemiology Part IV. Non-Human Primate Herpesviruses Ann Arvin, Patrick Moore and Richard Whitley Part V. Subversion of Adaptive Immunity Richard Whitley and Ann Arvin Part VI. Antiviral Therapy Richard Whitley Part VII. Vaccines and Immunotherapy Ann Arvin and Koichi Yamanishi Part VIII. Herpes as Therapeutic Agents Richard Whitley and Bernard Roizman.
CD2/LFA-3 ligation induces phospholipase-C gamma 1 tyrosine phosphorylation and regulates CD3 signaling (1992)

Activation of T cells through the TCR/CD3 receptor complex with either specific Ag or antibody results in tyrosine phosphorylation of intracellular protein substrates and phosphatidylinositol-phospholipase C (PLC) signaling, leading to the generation of PI breakdown products and the mobilization of intracellular calcium. Stimulation of the T cell surface receptor CD2 similarly propagates early signals through phosphatidylinositol-PLC activation. Previous reports have shown that CD3 activation leads to tyrosine phosphorylation of the PLC isozyme PLC gamma 1. In this report, we investigated the potential similarity between CD3-induced signaling through PLC gamma 1 and that induced by CD2. We show that stimulation of CD2 receptors on T cells caused tyrosine phosphorylation of PLC gamma 1. Cross-linking of CD2 with CD3 receptors augmented the phosphorylation of PLC gamma 1 on tyrosine, whereas ligation of the CD45 tyrosine phosphatase with CD2 receptors prevented PLC gamma 1 tyrosine phosphorylation. T cells stimulated by ligation of CD2 with its counter-receptor in the form of a soluble LFA-3/Ig fusion protein cross-linked on the cell surface, resulted in a low, but detectable level of PLC gamma 1 phosphorylation with prolonged kinetics, whereas that induced by cross-linking with anti-CD2 was stronger but transient. Co-ligation of LFA-3/Ig with suboptimal concentrations of anti-CD3 resulted in profound augmentation of PLC gamma 1 tyrosine phosphorylation, mobilization of intracellular calcium and T cell proliferation. To explore the relationship between CD3- and CD2-stimulated signaling, T cells were desensitized through 1 h incubation with anti-CD3. CD3 receptor modulation potently down-regulated CD2-induced PLC gamma 1 tyrosine phosphorylation and calcium mobilization. In contrast, PMA or ionomycin treatment did not alter CD2-stimulated tyrosine phosphorylation of PLC gamma 1, suggesting that tyrosine kinase inhibition by CD3 receptor modulation was not caused by signaling events downstream of PLC gamma 1. Taken together, these results support the hypothesis that CD2 provides a potent co-stimulatory signal for CD3-induced T cell activation that is associated with tyrosine kinase(s) and PLC gamma 1.
Rough vaccines in animal brucellosis: Structural and genetic basis and present status (2004)

Brucellosis control and eradication requires serological tests and vaccines. Effective classical vaccines (S19 in cattle and Rev 1 in small ruminants), however, induce antibodies to the O-polysaccharide of the lipopolysaccharide which may be difficult to distinguish from those resulting from infection and may thus complicate diagnosis. Rough attenuated mutants lack the O-polysaccharide and would solve this problem if eliciting protective immunity; the empirically obtained rough mutants 45/20 and RB51 have been used as vaccines. Strain 45/20 is reportedly unstable and it is not presently used. RB51 is increasingly used instead of S19 in some countries but it is rifampicin resistant and its effectiveness is controversial. Some controlled experiments have found good or absolute protection in adult cattle vaccinated orally (full dose) or subcutaneously (reduced dose) and in one field experiment, RB51 was reported to afford absolute protection to calves and to perform better than S19. Controlled experiments in calves, however, have shown reduced doses of RB51 to be ineffective, full doses only partially effective, and RB51 less effective than S19 against severe challenges. Moreover, other observations suggest that RB51 is ineffective when prevalence is high. RB51 is not useful in sheep and evidence in goats is preliminary and contradictory. Rough mutants obtained by molecular biology methods on the knowledge of the genetics and structure of Brucella lipopolysaccharide may offer alternatives. The B. abortus manBcore (rfbK) mutant seems promising in cattle, and analyses in mice suggest that mutations affecting only the O-polysaccharide result in better vaccines than those affecting both core and O-polysaccharide. Possible uses of rough vaccines also include boosting immunity by revaccination but solid evidence on its effectiveness, safety and practicality is not available.
Demand-based document dissemination to reduce traffic and balance load in distributed information systems (2002)

Research on replication techniques to reduce traffic and minimize the latency of information retrieval in a distributed system has concentrated on client-based caching, whereby recently/frequently accessed information is cached at a client (or at a proxy thereof) in anticipation of future accesses. We believe that such myopic solutions-focussing exclusively on a particular client or set of clients-are likely to have a limited impact. Instead, we offer a solution that allows the replication of information to be done on a global supply/demand basis. We propose a hierarchical demand-based replication strategy that optimally disseminates information from its producer to servers that are closer to its consumers. The level of dissemination depends on the relative popularity of documents, and on the expected reduction in traffic that results from such dissemination. We used extensive HTTP logs to validate an analytical model of server popularity and file access profiles. Using that model we show that by disseminating the most popular documents on servers closer to clients, network traffic could be reduced considerably, while servers are load-balanced. We argue that this process could be generalized to provide for an automated server-based information dissemination protocol that will be more effective in reducing both network bandwidth and document retrieval times than client-based caching protocols.
Mimicking a conformational B cell epitope of the heat shock protein PfHsp70‐1 antigen of Plasmodium falciparum using a multiple antigenic peptide (2000)

The Pf72/Hsp70‐1 antigen is a major target in the naturally acquired immunity against Plasmodium falciparum malaria. We carried out an extensive analysis of the responses to several epitopes on the least conserved C ‐terminal domain, according to the mode of sensitization: malaria infection or immunization with different immunogens. We found significant differences in the panel of B‐cell epitopes recognized by animal models including primates, and by humans sensitized by natural infection. We focused the analysis on one epitope that is unique to Plasmodium species. It is specifically recognized by a monoclonal antibody that mediates the killing of infected hepatocytes in vitro . We produced a polymeric multiple antigenic peptide (MAP) form of this sequence, which enabled us to identify a new B‐cell epitope not detected by ELISA with linear peptides. The polymer was strongly recognized by sera from monkeys or humans sensitized by natural infection, whereas the monomer was not. We modelled the three‐dimensional structure of the Pf72/Hsp70‐1 sequence, using known Escherischia coli DnaK structures as a template. This predicted that the corresponding region would form a loop in the native antigen. The results presented here suggest that the MAP strategy is also particularly useful as a means of obtaining suitable synthetic models for conformation‐dependent epitopes .
Antisense oligonucleotide therapy for neurodegenerative disease (2006)

Neurotoxicity from accumulation of misfolded/mutant proteins is thought to drive pathogenesis in neurodegenerative diseases. Since decreasing levels of proteins responsible for such accumulations is likely to ameliorate disease, a therapeutic strategy has been developed to downregulate almost any gene in the CNS. Modified antisense oligonucleotides, continuously infused intraventricularly, have been demonstrated to distribute widely throughout the CNS of rodents and primates, including the regions affected in the major neurodegenerative diseases. Using this route of administration, we found that antisense oligonucleotides to superoxide dismutase 1 (SOD1), one of the most abundant brain proteins, reduced both SOD1 protein and mRNA levels throughout the brain and spinal cord. Treatment initiated near onset significantly slowed disease progression in a model of amyotrophic lateral sclerosis (ALS) caused by a mutation in SOD1. This suggests that direct delivery of antisense oligonucleotides could be an effective, dosage-regulatable means of treating neurodegenerative diseases, including ALS, where appropriate target proteins are known.
Expression of functional B7 and CTLA4 on rheumatoid synovial T cells. (1994)

To assess the role of B7, CTLA4, and CD28 in the pathogenesis of chronic synovitis we analyzed the expression and function of these cell surface molecules in patients with rheumatoid arthritis, osteoarthritis, and psoriatic arthritis, and in normal controls. Immunoperoxidase staining of rheumatoid synovial membranes showed reactivity of 30% of T cells with anti-B7 mAb, in contrast to osteoarthritic and normal synovial membranes, in which no such staining was seen. In addition, rheumatoid synovial fluid T cells were positive by flow cytometric analysis for B7 (mean 20%, range 0 to 96%), as measured by staining with anti-B7 mAb or the CTLA4 Ig fusion protein, whereas no B7 expression was detected on peripheral blood T cells (mean 1%). To analyze the functional importance of B7 expressed on synovial fluid T cells, we used these cells as stimulator cells in primary allogeneic MLC. Purified synovial fluid T cells were far stronger stimulator cells compared with paired peripheral blood T cells and resulted in a fivefold greater increase in allogeneic T cell proliferation. Furthermore, the proliferation induced by purified synovial T cells was markedly inhibited by addition of the CTLA4 Ig fusion protein (77%). Moreover, anti-B7 mAb (37%), anti-CTLA4 mAb (33%), and Fab fragments of anti-CD28 mAb (52%) partially inhibited the primary MLC. The expression of functional B7, together with the increased expression of MHC class II molecules, indicates that synovial T cells may serve as functional APCs and may be capable of autocrine stimulation via the CD28 activation pathway.
Requirements for T cell activation by OKT3 monoclonal antibody: role of modulation of T3 molecules and interleukin 1. (1985)

The requirements for activation of human peripheral blood T cells by the mitogenic monoclonal antibody OKT3 were examined. OKT3 binds to a T cell molecule, T3, associated with the T cell antigen receptor and involved in T cell activation. Activation of T cells by OKT3 requires signals provided by accessory cells and is IL 2 dependent. In the presence of accessory cells, OKT3 induces loss of T3 molecules from the cell surface, production of IL 2, expression of IL 2 receptors, and proliferation. Modulation of T3 molecules by OKT3 can be induced in the absence of accessory cells with anti-mouse IgG. These T cells, however, are not induced to express IL 2 receptors or secrete IL 2. The addition of IL 1 induces expression of IL 2 receptors, but does not induce IL 2 secretion or proliferation. Thus, peripheral blood T cells appear to have different requirements for activation compared with antigen-specific T cell clones that can be induced to produce IL 2 when stimulated with OKT3 and IL 1. Expression of IL 2 receptors does not require modulation of T3 molecules, because the binding of OKT3 to T cells in the presence of IL 1 alone is sufficient to induce IL 2 receptor expression. The results suggest that IL 2 secretion depends on cross-linking and modulation of T3 molecules, and additional, as yet undefined, accessory cell signals. The expression of IL 2 receptors and proliferation of T cells can be induced in the absence of these signals when exogenous IL 2 is provided.