gebhart/patrepeval huggingface dataset:
Quantitative targeted absolute proteomics of human blood–brain barrier transporters and receptors (2011)

We have obtained, for the first time, a quantitative protein expression profile of membrane transporters and receptors in human brain microvessels, that is, the blood-brain barrier (BBB). Brain microvessels were isolated from brain cortexes of seven males (16-77 years old) and protein expression of 114 membrane proteins was determined by means of a liquid chromatography-tandem mass spectrometric quantification method using recently established in-silico peptide selection criteria. Among drug transporters, breast cancer resistance protein showed the most abundant protein expression (8.14 fmol/μg protein), and its expression level was 1.85-fold greater in humans than in mice. By contrast, the expression level of P-glycoprotein in humans (6.06 fmol/μg protein) was 2.33-fold smaller than that of mdr1a in mice. The organic anion transporters reported in rodent BBB, that is, multidrug resistance-associated protein, organic anion transporter and organic anion-transporting polypeptide family members, were under limit of quantification in humans, except multidrug resistance-associated protein 4 (0.195 fmol/μg protein). Among detected transporters and receptors for endogenous substances, the glucose transporter 1 level was similar to that of mouse, while the L-type amino acid transporter 1 level was fivefold smaller than that of mouse. These findings should be useful for understanding human BBB function and its differences from that in mouse.
Leukocyte chemotactic activity of cyclophilin. (1992)

During the purification of eosinophil chemotactic factors synthesized by the uterus in response to estrogen we isolated a protein having an N-terminal (15 amino acids) sequence identical to that of rat cyclophilin. Our data demonstrate that cyclophilin, a cytosolic protein isolated from bovine thymocytes, which specifically binds the immunosuppressive drug cyclosporin A, as well as recombinant human cyclophilin, displays eosinophil chemotactic activity. In addition to its chemotactic activity, cyclophilin stimulated the release of peroxidase activity from eosinophils. Maximal chemotactic activity of cyclophilin was achieved at a concentration of approximately 10 nM. At similar concentrations cyclophilin was also able to stimulate the migration of neutrophils. This chemotactic activity could be prevented by the addition of cyclosporin A, but not by a nonimmunosuppressive analog (1-fur-furyl-cyclosporin A) at similar concentrations. This chemotactic activity may represent an additional mechanism by which immunosuppressive drugs function to prevent tissue rejection.
Multichannel Generalization of Kitaev’s Majorana End States and a Practical Route to Realize Them in Thin Films (2010)

The ends of one-dimensional p+ip superconductors have long been predicted to possess localized Majorana fermion modes [A. Kitaev, arXiv:cond-mat/0010440]. We show that Majorana end states are robust beyond the strict 1D single-channel limit, so long as the sample width is not much larger than the superconducting coherence length, and they exist when an odd number of transverse quantization channels are occupied. Consequently, the system undergoes a sequence of topological phase transitions driven by changing the chemical potential. These observations make it feasible to implement quasi-1D p+ip superconductors in metallic thin-film microstructures, which offer 3-4 orders of magnitude larger energy scales than semiconductor-based schemes. Some promising candidate materials are described.
Policy Gradient Methods for Reinforcement Learning with Function Approximation (1999)

Function approximation is essential to reinforcement learning, but the standard approach of approximating a value function and determining a policy from it has so far proven theoretically intractable. In this paper we explore an alternative approach in which the policy is explicitly represented by its own function approximator, independent of the value function, and is updated according to the gradient of expected reward with respect to the policy parameters. Williams&amp;apos;s REINFORCE method and actor--critic methods are examples of this approach. Our main new result is to show that the gradient can be written in a form suitable for estimation from experience aided by an approximate action-value or advantage function. Using this result, we prove for the first time that a version of policy iteration with arbitrary di#erentiable function approximation is convergent to a locally optimal policy. Large applications of reinforcement learning (RL) require the use of generalizing function approxima...
Synthesis and Antiviral Activity of Three Pyrazole Analogues of Distamycin A. (1994)

The synthesis of three new monopyrazole analogues of the antiviral compound distamycin A is reported. Suitably protected 4-amino-1-methylpyrrole-2-carboxylic acid and 3-amino-1-methylpyrazole-5-carboxylic acid derivatives were chosen as starting materials. The construction of the trimeric polyamide framework was accomplished by assembly of the monomeric precursors under condensing conditions by analogy with our previous methodology, although with significant improvements in some pivotal steps. After chromatographic purification and spectroscopic characterisation, the analogues were assayed for antiviral activity. Compounds 7a-c inhibited vaccinia virus at a concentration similar to or lower than distamycin A and the related antibiotic netropsin. Analogues 7b and 7c exhibited an antiviral effect comparable to those of distamycin A and netropsin against HSV-1 and HSV-2, whereas their antiviral activity against several other viruses including HIV-1 and HIV-2 was somewhat lower. The cellular toxicity of 7a-c toward different host cell types proved to be of similar magnitude or lower than those of distamycin A and netropsin.
Biological Control of Damping-Off of Alfalfa Seedlings with Bacillus cereus UW85 (1990)

We explored the potential of biological control of alfalfa (Medicago sativa L.) seedling damping-off caused by Phytophthora megasperma f. sp. medicaginis by screening root-associated bacteria for disease suppression activity in a laboratory bioassay. A total of 700 bacterial strains were isolated from the roots of field-grown alfalfa plants by using Trypticase soy agar. A simple, rapid assay was developed to screen the bacteria for the ability to reduce the mortality of Iroquois alfalfa seedlings that were inoculated with P. megasperma f. sp. medicaginis zoospores. Two-day-old seedlings were planted in culture tubes containing moist vermiculite, and each tube was inoculated with a different bacterial culture. Sufficient P. megasperma f. sp. medicaginis zoospores were added to each tube to result in 100% mortality of control seedlings. Of the 700 bacterial isolates tested, only 1, which was identified as Bacillus cereus and designated UW85, reduced seedling mortality to 0% in the initial screen and in two secondary screens. Both fully sporulated cultures containing predominantly released spores and sterile filtrates of these cultures of UW85 were effective in protecting seedlings from damping-off; filtrates of cultures containing predominantly vegetative cells or endospores inside the parent cell had low biocontrol activity. Cultures grown in two semidefined media had significantly greater biocontrol activities than cultures grown in the complex tryptic soy medium. In a small-scale trial in a field infested with P. megasperma f. sp. medicaginis, coating seeds with UW85 significantly increased the emergence of alfalfa. The results suggest that UW85 may have potential as a biocontrol agent for alfalfa damping-off, thus providing an alternative to current disease control strategies.
Treatment of Ulcerative Colitis with a Humanized Antibody to the α 4 β 7 Integrin (2005)

In this short-term study, MLN02 was more effective than placebo for the induction of clinical and endoscopic remission in patients with active ulcerative colitis.
Evaluation and Validation of a Crohn's Disease Inflammatory Activity Index Reflecting Pattern of Endoscopic Severity (1998)

On a qualitative level focusing on clinical relevance, the endoscopic and biologic findings of Crohn's disease are highly associated. In addition to clinical assessment, usage of the developed index as a rationale contributing to therapeutic decisions in the short- and long-term management might be reasonable.
A methodology for creating fast wait-free data structures (2012)

Lock-freedom is a progress guarantee that ensures overall program progress. Wait-freedom is a stronger progress guarantee that ensures the progress of each thread in the program. While many practical lock-free algorithms exist, wait-free algorithms are typically inefficient and hardly used in practice. In this paper, we propose a methodology called fast-path-slow-path for creating efficient wait-free algorithms. The idea is to execute the efficient lock-free version most of the time and revert to the wait-free version only when things go wrong. The generality and effectiveness of this methodology is demonstrated by two examples. In this paper, we apply this idea to a recent construction of a wait-free queue, bringing the wait-free implementation to perform in practice as efficient as the lock-free implementation. In another work, the fast-path-slow-path methodology has been used for (dramatically) improving the performance of a wait-free linked-list.
Use of cholinesterase inhibitors for treatment of Alzheimer disease. (2001)

The four cholinesterase inhibitors now available for treatment of Alzheimer disease (AD) may be most beneficial, especially in the long run, if started early in the course of the disease. This paper reviews the efficacy, pharmacokinetics, metabolism, side effects, dosage, and precautions for the use of these agents, which may produce modest improvements in cognition, behavior, and the ability to perform activities of daily living.
Time course of sympathovagal imbalance and left ventricular dysfunction in conscious dogs with heart failure (1998)

To elucidate the time course of sympathovagal balance and its relationship to left ventricular function in heart failure, we serially evaluated left ventricular contractility and relaxation and autonomic tone in 11 conscious dogs with tachycardia-induced heart failure. We determined a dynamic map of sympathetic and parasympathetic modulation by power spectral analysis of heart rate variability. The left ventricular peak +dP/dt substantially fell from 3,364 +/- 338 to 1,959 +/- 318 mmHg/s (P < 0.05) on the third day and declined gradually to 1,783 +/- 312 mmHg/s at 2 wk of rapid ventricular pacing. In contrast, the time constant of left ventricular pressure decay and end-diastolic pressure increased gradually from 25 +/- 4 to 47 +/- 5 ms (P < 0.05) and from 10 +/- 2 to 21 +/- 3 mmHg (P < 0.05), respectively, at 2 wk of pacing. The high-frequency component (0.15-1.0 Hz), a marker of parasympathetic modulation, decreased from 1,928 +/- 1,914 to 62 +/- 68 x 10(3) ms2 (P < 0.05) on the third day and further to 9 +/- 12 x 10(3) ms2 (P < 0.05) at 2 wk. Similar to the time course of left ventricular diastolic dysfunction, plasma norepinephrine levels and the ratio of low (0.05- to 0.15-Hz)- to high-frequency component increased progressively from 135 +/- 50 to 532 +/- 186 pg/ml (P < 0.05) and from 0.06 +/- 0.06 to 1.12 +/- 1.01 (P < 0.05), respectively, at 2 wk of pacing. These cardiac and autonomic dysfunctions recovered gradually toward the normal values at 2 wk after cessation of pacing. Thus a parallel decline in left ventricular contractility with parasympathetic influence and a parallel progression in left ventricular diastolic dysfunction with sympathoexcitation suggest a close relationship between cardiac dysfunction and autonomic dysregulation during development of heart failure.
Statistical properties of high quality stereo signals in the time domain (2003)

Bit-rate reduction algorithms are examined for compact disks, containing high-quality stereo signals sampled at 44.1 kHz and 16 bits/sample. Reducing the bit rate for the stereo signals requires knowledge of the statistics. Probability densities and joint probability densities provide parameters for individual samples. Short-time energies and correlation coefficients express similarities and linear relationships of blocks of samples. It is shown that by replacing the original signals in the left and the right channel by half of the sum and half of the difference, a small reduction of the amplitudes takes place. Linear relationships in the channels could not be found. The similarities of the short time energies together with the retaining of the energy after a transform indicate possible correlations in the frequency domain.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Expression patterns of genes encoding elastase and controlling mucoidy: co‐ordinate regulation of two virulence factors in Pseudomonas aeruginosa isolates from cystic fibrosis (1990)

Transcriptional patterns of lasB and algD were compared in isogenic mucoid and non-mucoid Pseudomonas aeruginosa isolates from cystic fibrosis patients. The lasB gene encodes elastase, a major proteolytic enzyme secreted by P. aeruginosa, while algD is required for the synthesis of alginate, an exopolysaccharide frequently overproduced by strains infecting cystic fibrosis patients. A possible coregulation at the transcriptional level of these major virulence determinants was analysed. The lasB and algD genes showed inverse levels of promoter activity. The lasB promoter was active in non-mucoid cells and inactive in mucoid cells (in four out of five tested pairs), while the algD promoter was active in mucoid cells and silent in non-mucoid cells in all cases. When PAO568, a model strain for the analysis of control of the alginate system, was grown under conditions promoting mucoidy, the algD promoter was activated, whereas lasB mRNA could not be detected. This effect was reversed when the cells were grown in a medium suppressing mucoidy. Insertional inactivation of algR, a member of the signal-transduction systems regulating algD transcription, although abolishing algD expression and rendering cells non-mucoid, did not alter the nature of the induction and repression patterns of lasB seen in the parental strain PAO568. These results suggest that the lasB gene and the alginate system are co-ordinately regulated at a level parallel to or above the algR gene.
Indole Alkaloids fromAntirhea lucida (1995)

A new indole alkaloid, N,N-methyl-3'-indolylmethyl-5-methoxytryptamine, as well as the known gramine, N,N-dimethyltryptamine and 6-methoxy-2-methyl-1,2,3,4-tetrahydro-beta-carboline were isolated from the roots of Antirhea lucida (Sw.) Hook (Rubiaceae). Their structures were established by spectroscopic methods.
EVALUATING STRUCTURAL CRACK REPAIRS (1995)

Structural crack repairs are often inappropriately specified by using descriptive or proprietary specifications. Performance specifications are the most desirable; however, an adequate quality assurance test and acceptance criterion must be established for performance specifications to be effective. Using the splitting tensile test as a potential quality assurance test and proposing an acceptance criterion based on the results of 146 such strength tests on cores drilled from repaired cracked concrete should be given some consideration.
Role of copper in mitochondrial iron metabolism (1976)

Heme synthesis by copper-deficient cells was investigated to elucidate the nature of the defect in intracellular iron metabolism. Iron uptake from transferrin by copper-deficient reticulocytes was 52% of normal, and the rate of heme synthesis was 33% of normal. Hepatic mitochondria isolated from copper-deficient animals were deficient in cytochrome oxidase activity and failed to synthesize heme from ferric iron (Fe III) and protoporphyrin at the normal rate. The rate of heme synthesis correlated with the cytochrome oxidase activity. Heme synthesis from Fe(III) and protoporphyrin by normal mitochondria was enhanced by succinate and inhibited by malonate, antimycin A, azide, and cyanide. It is proposed that an intact electron transport system is required for the reduction of Fe(III), thereby providing a pool of ferrous iron (Fe II) for protoheme and heme a synthesis.
Multiple enlargements in the right inverted terminal repeat of the DNA of canine adenovirus type 2. (1992)

The Manhattan strain of canine adenovirus type 2 (CAV 2) was examined. Restriction endonuclease analysis and blot hybridization experiments revealed the heterogeneity of the viral DNA. At least 9 unequally expanded species of the viral genome have been recognized. This diversity is caused by different enlargements in the right inverted terminal repeat (ITR) of the virus. The differences between the individual enlargements were shown to be the different multiples of 150 base pairs. Relatedness of CAV 2 DNA to the DNA of bovine adenovirus type 2 (BAV 2) and human adenovirus type 2 (HAV 2) has also been observed during DNA hybridization experiments.
Synergism among Ternary Mixtures of Fourteen Sweeteners (2000)

The purpose of the present study was to determine the degree of synergism of sweet taste among ternary mixtures of 14 sweeteners. A trained panel evaluated ternary mixtures of 14 sweeteners varying in chemical structure and type. The ternary mixtures that were tested were limited to those in which the compounds comprising the mixture were synergistic in binary combinations, according to an earlier study. All sweeteners in the ternary mixtures were isointense with 2% sucrose, according to a previously developed formulae. Each self-mixture was also tested (e.g. 2% sucrose + 2% sucrose + 2% sucrose). The triad with the highest mean sweetness intensity rating was alitame-neohesperidin dihydrochalcone-rebaudioside-A (10.8). This represents an increase of 99.4% when compared with the average of the self-mixtures. While this is greater than the maximum of 74% increase found for binary mixtures, more dyadic combinations of sweeteners tested previously exhibited synergism than ternary combinations tested here. However, most ternary mixtures were synergistic (significantly greater than the average of the three self-mixtures) to some degree.
Analysis of Optical Absorption in Silicon Nanowire Arrays for Photovoltaic Applications (2007)

This paper presents analysis of the optical absorption in silicon nanowire arrays that have potential applications in solar cells. The effects of wire diameter, length, and filling ratio on the absorptance of nanowire arrays are simulated. The study reveals that nanowire arrays with moderate filling ratio have much lower reflectance compared to thin films. In a high-frequency regime, nanowire arrays have higher absorptance than their thin film counterparts. In low-frequency regime, nanowire arrays absorb less but can be designed to approach that of the film by changing the filling ratio.
Supporting the evolution of design artifacts with representations of context and intent (1995)

The design of complex artifacts is essentially an evolu-tionary process that requires collaboration among stakeholders. Domain-oriented design environments (DODEs) support the evolution of artifacts both by in-dividual designers and by designers participating in long-term, indirect collaboration. DODEs provide represen-tations for generic and specific levels of context. This con-text supports individual designers by making the infor-mation space relevant to the current design intent, and long-term collaboration among designers by allowing them to ground their communication around design artifacts. We demonstrate our approach using the KID (Knowing-in-Design) system, articulate principles for representations of context and intent, and discuss various approaches to represent intent and context in design environments.
Design and Fabrication of Low-Loss Toroidal Air-Core Inductors (2007)

The design and fabrication of high-Q air-core toroidal inductors are described. Designs are optimized for maximum Q for a given size and inductance, independent any particular fabrication process. A fabrication process using a combination of thin-film processes and conventional machining has been used to make prototypes. Measurements performed on the first prototypes confirm the predicted Q of 115 at 50 MHz.
The C3 domain ofPasteurella multocidatoxin is the minimal domain responsible for activation of Gq‐dependent calcium and mitogenic signaling (2008)

The large 1285-amino-acid protein toxin from Pasteurella multocida (PMT) is a multifunctional single-chain polypeptide that binds to and enters eukaryotic cells and acts intracellularly to promote G(q) and G(12/13) protein-dependent calcium and mitogenic signal transduction. Previous studies indicated that the intracellular activity domain responsible for PMT action was located within the C-terminal 600-700 amino acids. In this study, we have exogenously expressed a series of N- and C-terminal PMT fragments directly in mammalian cells and have used the dual luciferase reporter system to assay for toxin-mediated activation of calcium-calcineurin-NFAT signaling (NFAT-luciferase) and mitogenic serum response signaling (SRE-luciferase). Using this approach, we have defined the last 180 amino acids, which encompass the C3 domain in the crystal structure, as the minimum domain sufficient to activate both NFAT and SRE signaling pathways.
Automated analysis of mammographic densities (1996)

Information derived from mammographic parenchymal patterns provides one of the strongest indicators of the risk of developing breast cancer. To address several limitations of subjective classification of mammographic parenchyma into coarse density categories, we have been investigating more quantitative, objective methods of analysing the film-screen mammogram. These include measures of the skewness of the image brightness histogram, and of image texture characterized by the fractal dimension. Both measures were found to be strongly correlated with radiologists' subjective classifications of mammographic parenchyma (Spearman correlation coefficients, Rs = -0.88 and -0.76 for skewness and fractal dimension measurements, respectively). Further, neither measure was strongly dependent on simulated changes in mammographic technique. Correlation with subjective classification of mammographic density was better when both the skewness and fractal measures were used in combination than when either was used alone. This suggests that each feature provides some independent information.
Homer 1b Regulates the Trafficking of Group I Metabotropic Glutamate Receptors (1999)

The molecular basis for glutamate receptor trafficking to the plasma membrane is not understood. In the present study, we demonstrate that Homer 1b (H1b), a constitutively expressed splice form of the immediate early gene product Homer (now termed Homer 1a) regulates the trafficking and surface expression of group I metabotropic glutamate receptors. H1b inhibits surface expression of the metabotropic glutamate receptor mGluR5 in heterologous cells, causing mGluR5 to be retained in the endoplasmic reticulum (ER). In contrast, mGluR5 alone or mGluR5 coexpressed with Homer 1a successfully travels through the secretory pathway to the plasma membrane. In addition, point mutations that disrupt mGluR5 binding to H1b eliminate ER retention of mGluR5, demonstrating that H1b affects metabotropic receptor localization via a direct protein-protein interaction. Electron microscopic analysis reveals that the group I metabotropic receptor mGluR1alpha is significantly enriched in the ER of Purkinje cells, suggesting that a similar mechanism may exist in vivo. Because H1b is found in dendritic spines of neurons, local retention of metabotropic receptors within dendritic ER provides a potential mechanism for regulating synapse-specific expression of group I metabotropic glutamate receptors.