gebhart/patrepeval huggingface dataset:
Fracture Strength of Single-Crystal Silicon Carbide Microspecimens at 24 $^{\circ}\hbox{C}$ and 1000 $^{\circ}\hbox{C}$ (2008)

Three shapes of silicon carbide tensile specimens were tested - curved with a low stress-concentration factor and straight with a circular hole or an elliptical hole. The nominal thickness was 125 mum with a net section that is 100-mum wide; the overall length of these microspecimens was 3.1 mm. They were fabricated by an improved version of deep reactive ion etching, which produced specimens with smooth sidewalls and cross sections having a slightly trapezoidal shape that was exaggerated inside the holes. The novel test setup used a vertical load train extending into a resistance furnace. The specimens had wedge-shaped ends which fit into ceramic grips. The fixed grip was mounted on a ceramic post, and the movable grip was connected to a load cell and actuator outside the furnace with a ceramic-encased nichrome wire. The same arrangement was used for tests at 24degC and at 1000degC. The strengths of the curved specimens for two batches of material (made with slightly different processes) were 0.66plusmn0.12 and 0.45plusmn0.20 GPa, respectively, at 24degC with identical values at 1000degC. The fracture strengths of the circular-hole and elliptical-hole specimens (computed from the stress-concentration factors and measured loads at failure) were approximately 1.2 GPa with slight decreases at the higher temperature. Fractographic examinations showed failures initiating on the surface - primarily at corners. Weibull predictions of fracture strengths for the hole specimens based on the properties of the curved specimens were reasonably effective for the circular holes but not for the elliptical holes.
Proteasomal dysfunction in sporadic Parkinson's disease (2006)

The cause and mechanism of neuronal death in sporadic Parkinson's disease (PD) continue to elude investigators. Recently, alterations in proteasomal function have been detected in the brain of patients with the illness. The biochemical basis of the defect and its relevance to the disease process are now being studied. The available results suggest that proteasomal dysfunction could underlie protein accumulation, Lewy body formation, and neuron death in PD. The cause of proteasomal dysfunction is unknown at present, but this could relate to gene mutations, oxidative damage, ATP depletion, or the actions of environmental toxins. It remains to be established if proteasomal dysfunction plays a primary or a secondary role in the initiation or progression of the neurodegenerative process in PD.
A systematic review on the <i>Rosa canina</i> effect and efficacy profiles (2008)

Rose hip, rose hip and seed and rose hip seed, all were negatively monographed by the German Commission E due to insufficient evidence of effects and effectiveness. Therefore a comprehensive review of the literature was conducted to summarize the pharmacological and clinical effects of Rosa canina L. to reevaluate its usefulness in traditional medicine. For various preparations of rose hip and rose hip and seed, antioxidative and antiinflammatory effects have been demonstrated. Lipophilic constituents are involved in those mechanisms of action. The proprietary rose hip and seed powder Litozin has been employed successfully in a number of exploratory studies in patients suffering from osteoarthritis, rheumatoid arthritis and low back pain. However, the sizes of the clinical effects for the different indications need to be determined to assure clinical significance. There is also a rationale behind the use of Litozin as part of a hypocaloric diet based on the rose hip probiotic, stool regulating and smooth muscle-relaxing actions, as well as the rose hip seed lipid-lowering, antiobese and antiulcerogenic effects. Further research is needed to clarify the importance of the reported promising experimental effects in clinical use and to characterize the optimum rose hip seed oil preparation for topical use in the treatment of skin diseases.
Iron supplementation in the non-dialysis chronic kidney disease (ND-CKD) patient: oral or intravenous? (2009)

Intravenous iron offers an effective, feasible route towards reducing the heavy burden of iron-deficiency anaemia in the non-dialysis CKD patient, even in the absence of ESA therapy.
Alternative splicing and endoproteolytic processing generate tissue-specific forms of pituitary peptidylglycine alpha-amidating monooxygenase (PAM). (1992)

The pituitary is a rich source of peptidylglycine alpha-amidating monooxygenase (PAM). This bifunctional protein contains peptidylglycine alpha-hydroxylating monooxygenase (PHM) and peptidyl-alpha-hydroxyglycine alpha-amidating lyase (PAL) catalytic domains necessary for the two-step formation of alpha-amidated peptides from their peptidylglycine precursors. In addition to the four forms of PAM mRNA identified previously, three novel forms of PAM mRNA were identified by examining anterior and neurointermediate pituitary cDNA libraries. None of the PAM cDNAs found in pituitary cDNA libraries contained exon A, the 315-nucleotide (nt) segment situated between the PHM and PAL domains and present in rPAM-1 but absent from rPAM-2. Although mRNAs of the rPAM-3a and -3b type encode bifunctional PAM precursors, the proteins differ significantly. rPAM-3b lacks a 54-nt segment encoding an 18-amino acid peptide predicted to occur in the cytoplasmic domain of this integral membrane protein; rPAM-3a lacks a 204-nt segment including the transmembrane domain and encodes a soluble protein. rPAM-5 is identical to rPAM-1 through nt 1217 in the PHM domain; alternative splicing generates a novel 3'-region encoding a COOH-terminal pentapeptide followed by 1.1 kb of 3'-untranslated region. The soluble rPAM-5 protein lacks PAL, transmembrane, and cytoplasmic domains. These three forms of PAM mRNA can be generated by alternative splicing. The major forms of PAM mRNA in both lobes of the pituitary are rPAM-3b and rPAM-2. Despite the fact that anterior and neurointermediate pituitary contain a similar distribution of forms of PAM mRNA, the distribution of PAM proteins in the two lobes of the pituitary is quite different. Although integral membrane proteins similar to rPAM-2 and rPAM-3b are major components of anterior pituitary granules, the PAM proteins in the neurointermediate lobe have undergone more extensive endoproteolytic processing, and a 75-kDa protein containing both PHM and PAL domains predominates. The bifunctional PAM precursor undergoes tissue-specific endoproteolytic cleavage reminiscent of the processing of prohormones.
A 31-mutation assay for cystic fibrosis testing in the clinical molecular diagnostics laboratory (1995)

We devised a set of allele-specific probes to detect simultaneously 31 known cystic fibrosis mutations using PCR and the reverse dot blot detection format. The assay has been implemented in a clinical setting to the screening of over 750 individuals. Of these 102 Caucasians, 20 Hispanics and 1 Indian patient were affected with cystic fibrosis. The mutation detection rate in the 204 Caucasian and 40 Hispanic CF chromosomes was respectively, 88% and 85%. The availability of the probe sequences to CF screening laboratories should allow implementation of this assay in a clinical setting and comparison of its mutation typing rate among different centers.
Currents to Conductors Induced by a Moving Point Charge (1938)

General expressions are derived for the currents which flow in the external circuit connecting a system of conductors when a point charge is moving among the conductors. The results are applied to obtain explicit expressions for several cases of practical interest.
Isolation and Characterization of a Chromoplast-Specific Carotenoid-Associated Protein from Cucumis sativus Corollas (1993)

The differentiation of chloroplasts to chromoplasts in corollas of cucumber (Cucumis sativus) is subject to developmental control. To study factors involved in the chloroplast-chromoplast conversion, a chromoplast-specific protein of 35 kD was isolated, and polyclonal antibodies were prepared against it. This protein was found to be a principal component of the carotenoid-protein complex resolved from chromoplast membranes by nondenaturing gel electrophoresis. Immunological studies revealed that expression of this protein is regulated in a temporal and tissue-specific manner. Its steady-state level increased in parallel with flower development and carotenoid accumulation, peaking in mature flowers and then rapidly decreasing to very low levels. The protein was not detectable in cucumber leaves or fruits. To ascertain whether an organ-specific system regulates the chloroplast-chromoplast conversion and to enable future molecular studies of factors involved in this regulation, an in vitro bud culture system was established. Patterns of expression of the 35-kD protein and carotenoids in corollas of detached buds were similar to those in intact buds.
Metabolic and Regulatory Changes Associated with Growth of Saccharomyces cerevisiae in 1.4 M NaCl (1997)

The salt-instigated protein expression of Saccharomyces cerevisiae during growth in either 0.7 or 1.4 M NaCl was studied by two-dimensional polyacrylamide gel electrophoresis. The 73 protein spots that were identified as more than 3-fold responsive in 1.4 M NaCl were further grouped by response class (halometric, low-salt, and high-salt regulation). Roughly 40% of these responsive proteins were found to decrease in expression, while at higher magnitudes of change (>8-fold) only induction was recorded. Enolase 1 (Eno1p) was the most increasing protein by absolute numbers per cell, but not by -fold change, and the enzymes involved in glycerol synthesis, Gpd1p and Gpp2p, were also induced to a similar degree as Eno1p. We furthermore present evidence for salt induction of glycerol dissimilation via dihydroxyacetone and also identify genes putatively encoding the two enzymes involved; dihydroxyacetone kinase (DAK1 and DAK2) and glycerol dehydrogenase (YPR1 and GCY1). The GPD1, GPP2, GCY1, DAK1, and ENO1 genes all displayed a halometric increase in the amount of transcript. This increase was closely linked to the salt-induced rate of protein synthesis of the corresponding proteins, indicating mainly transcriptional regulation of expression for these genes. A consensus element with homology to the URS sequence of the ENO1 promoter was found in the promoters of the GPD1, GPP2, GCY1, and DAK1 genes.
On the Relationship Between the OpenAI Evolution Strategy and Stochastic Gradient Descent (2017)

Because stochastic gradient descent (SGD) has shown promise optimizing neural networks with millions of parameters and few if any alternatives are known to exist, it has moved to the heart of leading approaches to reinforcement learning (RL). For that reason, the recent result from OpenAI showing that a particular kind of evolution strategy (ES) can rival the performance of SGD-based deep RL methods with large neural networks provoked surprise. This result is difficult to interpret in part because of the lingering ambiguity on how ES actually relates to SGD. The aim of this paper is to significantly reduce this ambiguity through a series of MNIST-based experiments designed to uncover their relationship. As a simple supervised problem without domain noise (unlike in most RL), MNIST makes it possible (1) to measure the correlation between gradients computed by ES and SGD and (2) then to develop an SGD-based proxy that accurately predicts the performance of different ES population sizes. These innovations give a new level of insight into the real capabilities of ES, and lead also to some unconventional means for applying ES to supervised problems that shed further light on its differences from SGD. Incorporating these lessons, the paper concludes by demonstrating that ES can achieve 99% accuracy on MNIST, a number higher than any previously published result for any evolutionary method. While not by any means suggesting that ES should substitute for SGD in supervised learning, the suite of experiments herein enables more informed decisions on the application of ES within RL and other paradigms.
Physiological roles for amyloid β peptides (2006)

Alzheimer's disease is recognized post mortem by the presence of extracellular senile plaques, made primarily of aggregation of amyloid beta peptide (Abeta). This peptide has consequently been regarded as the principal toxic factor in the neurodegeneration of Alzheimer's disease. As such, intense research effort has been directed at determining its source, activity and fate, primarily with a view to preventing its formation or its biological activity, or promoting its degradation. Clearly, much progress has been made concerning its formation by proteolytic processing of the amyloid precursor protein, and its degradation by enzymes such as neprilysin and insulin degrading enzyme. The activities of Abeta, however, are numerous and yet to be fully elucidated. What is currently emerging from such studies is a diffuse but steadily growing body of data that suggests Abeta has important physiological functions and, further, that it should only be regarded as toxic when its production and degradation are imbalanced. Here, we review these data and suggest that physiological levels of Abeta have important physiological roles, and may even be crucial for neuronal cell survival. Thus, the view of Abeta being a purely toxic peptide requires re-evaluation.
Increased levels of plasma total tau in adult Down syndrome (2017)

Down syndrome (DS) is the most prevalent chromosomal abnormality. Early-onset dementia with the pathology of Alzheimer's disease (AD) frequently develops in DS. Reliable blood biomarkers are needed to support the diagnosis for dementia in DS, since positron emission tomography or cerebrospinal fluid sampling is burdensome, particularly for patients with DS. Plasma t-tau is one of the established biomarkers for the diagnosis of AD, suggesting the potential value of t-tau as a biomarker for dementia in DS. The aim of this study was to assess and compare plasma levels of t-tau in adults with DS and in an age-matched control population. In this study, plasma levels of t-tau in 21 patients with DS and 22 control participants were measured by an ultrasensitive immunoassay technology, the single-molecule immunoarray (Simoa) method. We observed significantly increased plasma t-tau levels in the DS group (mean ± standard deviation (SD) = 0.643±0.493) compared to those in the control group (mean ± SD = 0.470±0.232): P = 0.0050. Moreover, age dependent correlation of plasma t-tau was only found in the DS group, and not in the control group. These findings suggest that elevated plasma t-tau levels reflect AD pathology and therefore have potential as an objective biomarker to detect dementia in adult DS.
Phase 1 clinical results with tandutinib (MLN518), a novel FLT3 antagonist, in patients with acute myelogenous leukemia or high-risk myelodysplastic syndrome: safety, pharmacokinetics, and pharmacodynamics (2006)

Tandutinib (MLN518/CT53518) is a novel quinazoline-based inhibitor of the type III receptor tyrosine kinases: FMS-like tyrosine kinase 3 (FLT3), platelet-derived growth factor receptor (PDGFR), and KIT. Because of the correlation between FLT3 internal tandem duplication (ITD) mutations and poor prognosis in acute myelogenous leukemia (AML), we conducted a phase 1 trial of tandutinib in 40 patients with either AML or high-risk myelodysplastic syndrome (MDS). Tandutinib was given orally in doses ranging from 50 mg to 700 mg twice daily The principal dose-limiting toxicity (DLT) of tandutinib was reversible generalized muscular weakness, fatigue, or both, occurring at doses of 525 mg and 700 mg twice daily. Tandutinib's pharmacokinetics were characterized by slow elimination, with achievement of steady-state plasma concentrations requiring greater than 1 week of dosing. Western blotting showed that tandutinib inhibited phosphorylation of FLT3 in circulating leukemic blasts. Eight patients had FLT3-ITD mutations; 5 of these were evaluable for assessment of tandutinib's antileukemic effect. Two of the 5 patients, treated at 525 mg and 700 mg twice daily, showed evidence of antileukemic activity, with decreases in both peripheral and bone marrow blasts. Tandutinib at the MTD (525 mg twice daily) should be evaluated more extensively in patients with AML with FLT3-ITD mutations to better define its antileukemic activity.
[Repair of rabbit articular surfaces with allografts of chondrocytes embedded in collagen gels]. (1989)

In an attempt to restore articular cartilage, allogeneic articular chondrocytes embedded in collagen gels were transplanted onto full-thickness defects in rabbit articular cartilage. Within 24 weeks after the transplantation, the defects were filled with hyaline cartilage, specifically synthesizing type II collagen. These chondrocytes were autoradiographically proven to be originated from the originally transplanted chondrocytes. As histologically assessed, success rate was about 80%, a marked improvement over the results (40% success rate) in previous studies reporting chondrocyte transplantation without collagen gels. On the other hand, the defects without chondrocyte transplantation healed with fibrocartilaginous tissue more than 24 weeks after treatment. Immunological enhancement induced by transplanted allogeneic chondrocytes or collagen was not significant for eight weeks after treatment, so far as shown by both direct and indirect blastformation reactions. Thus, allogeneic transplantation of isolated chondrocytes embedded in collagen gels appears to be one of the most promising methods for the restoration of articular cartilage.
The automated in-vitro assesment of β-lactamase inhibitors (1991)

Journal Article The automated in-vitro assesment of β-lactamase inhibitors Get access DAVID J. PAYNE, DAVID J. PAYNE SmithKline Beecham PharmaceuticalsBrockham Park. Betchworth, Surrey, RH3 7AJ, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar KENNETH COLEMAN, KENNETH COLEMAN SmithKline Beecham PharmaceuticalsBrockham Park. Betchworth, Surrey, RH3 7AJ, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar REBECCA CRAMP REBECCA CRAMP SmithKline Beecham PharmaceuticalsBrockham Park. Betchworth, Surrey, RH3 7AJ, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar Journal of Antimicrobial Chemotherapy, Volume 28, Issue 5, November 1991, Pages 775–776, https://doi.org/10.1093/jac/28.5.775 Published: 01 November 1991
Intracellular Neutralization of Shiga Toxin 2 by an A Subunit-Specific Human Monoclonal Antibody (2008)

Infection of children with Shiga toxin (Stx)-producing Escherichia coli (STEC) is the leading cause of hemolytic-uremic syndrome (HUS). Stx2, one of two toxins liberated by the bacteria, is directly linked with HUS. We have previously shown that Stx2-specific human monoclonal antibodies (HuMAbs) protect mice and piglets from fatal systemic complications of Stx2. The present study investigates the mechanisms by which our most efficacious A- and B-subunit-specific HuMAbs neutralize the cytotoxic effects of Stx2 in vitro. Whereas the B-subunit-specific HuMAb 5H8 blocked binding of Stx2 to its receptor on the cell surface, the A-subunit-specific HuMAb 5C12 did not interfere with the toxin-receptor binding. Further investigations revealed that 5C12 did not block endocytosis of Stx2 by HeLa cells as both Stx2 and 5C12 colocalized with early endosomes. However, 5C12 blocked the retrograde transport of the toxin into the Golgi and the endoplasmic reticulum, preventing the toxin from entering the cytosol where the toxin exerts its cytotoxic effect. The endocytosed 5C12/Stx2 complexes appear to be rapidly transported to the plasma membrane and/or to the slow recycling perinuclear compartments, followed by their slow recycling to the plasma membrane, and release into the extracellular environment.
A tunable zinc finger-based framework for Boolean logic computation in mammalian cells (2012)

The ability to perform molecular-level computation in mammalian cells has the potential to enable a new wave of sophisticated cell-based therapies and diagnostics. To this end, we developed a Boolean logic framework utilizing artificial Cys(2)-His(2) zinc finger transcription factors (ZF-TFs) as computing elements. Artificial ZFs can be designed to specifically bind different DNA sequences and thus comprise a diverse set of components ideal for the construction of scalable networks. We generate ZF-TF activators and repressors and demonstrate a novel, general method to tune ZF-TF response by fusing ZF-TFs to leucine zipper homodimerization domains. We describe 15 transcriptional activators that display 2- to 463-fold induction and 15 transcriptional repressors that show 1.3- to 16-fold repression. Using these ZF-TFs, we compute OR, NOR, AND and NAND logic, employing hybrid promoters and split intein-mediated protein splicing to integrate signals. The split intein strategy is able to fully reconstitute the ZF-TFs, maintaining them as a uniform set of computing elements. Together, these components comprise a robust platform for building mammalian synthetic gene circuits capable of precisely modulating cellular behavior.
The Problem with Cationic Liposome / Micelle-Based Non-Viral Vector Systems for Gene Therapy (2003)

Gene therapy research is in crisis owing to the lack of acceptable vector systems to deliver nucleic acids to patients for therapy. Viral vectors are efficient but currently appear to be too dangerous for routine clinical use. Synthetic non-viral vectors are inherently much safer but are currently not efficient enough to be clinically viable. The solution for gene therapy lies with improved synthetic non-viral vectors based upon well-found platform technologies and a thorough understanding of the barriers to efficient gene delivery and expression (transfection) relevant to clinical applications of interest. In this review, the current status and prospects for cationic liposome/micelle-based synthetic non-viral vector systems are discussed including a description of the barriers to efficient transfection, a summary of the main structure/activity studies and mention of ternary cationic liposome/micelle-nucleic acid (LD) systems. The review culminates with a description of two promising cationic liposome/micelle-based non-viral vector platform systems known as liposome:mu:DNA (LMD) and stabilised plasmid-lipid particles (SPLP) that should create a real opportunity for the development of clinically viable synthetic vector systems within the next few years.
Sender-initiated multicast for small group communications (2003)

Sender-Initiated Multicast for small
Substance P antagonist improves both obesity and asthma in a mouse model (2012)

In an experimental model of obesity and asthma in mice, NK1-R blockade improved metabolic and systemic biomarkers, as well as allergen sensitization and bronchial inflammation. These positive effects support a common pathway in the obese-asthma phenotype and highlight SP as a target with potential clinical interest in the obese-asthma epidemics.
Direct Observation of Streptavidin Specifically Adsorbed on Biotin‐Functionalized Self‐Assembled Monolayers with the Scanning Tunneling Microscope (1991)

Surface recognition of biotin‐functionalized, chemisorbed thiol monolayers by streptavadin results in the formation of protein‐covered surfaces with no longrange order. This is due to the low lateral and vertical mobility of the solidbound thiols. On the other hand, protein surfaces transferred from a water surface reveal a good crystal structure under the scanning electron microscope, but the adhesion of these applied layers to the solid is unsatisfactory.