gebhart/patrepeval huggingface dataset:
Up‐Regulation of Neurosteroid Biosynthesis as a Pharmacological Strategy to Improve Behavioural Deficits in a Putative Mouse Model of Post‐Traumatic Stress Disorder (2011)

Benzodiazepines remain the most frequently used psychotropic drugs for the treatment of anxiety spectrum disorders; however, their use is associated with the development of tolerance and dependence. Another major hindrance is represented by their lack of efficacy in many patients, including patients with post-traumatic stress disorder (PTSD). For these nonresponders, the use of selective serotonin reuptake inhibitors (SSRIs) has been the therapy of choice. In the past decade, clinical studies have suggested that the pharmacological action of SSRIs may include the ability of these drugs to normalise decreased brain levels of neurosteroids in patients with depression and PTSD; in particular, the progesterone derivative allopregnanolone, which potently, positively and allosterically modulates the action of GABA at GABA(A) receptors. Preclinical studies using the socially-isolated mouse as an animal model of PTSD have demonstrated that fluoxetine and congeners ameliorate anxiety-like behaviour, fear responses and aggressive behaviour expressed by such mice by increasing corticolimbic levels of allopregnanolone. This is a novel and more selective mechanism than serotonin reuptake inhibition, which, for half a century, has been considered to be the main molecular mechanism for the therapeutic action of SSRIs. Importantly, this finding may shed light on the high rates of SSRI resistance among patients with PTSD and depression, comprising disorders in which there appears to be a block in allopregnanolone synthesis. There are several different mechanisms by which such a block may occur, and SSRIs may only be corrective under some conditions. Thus, the up-regulation of allopregnanolone biosynthesis in corticolimbic neurones may offer a novel nontraditional pharmacological target for a new generation of potent nonsedating, anxiolytic medications for the treatment of anxiety, depression, and PTSD: selective brain steroidogenic stimulants.
Glucocorticoid receptor is activated by heparin and deactivated by plasmin. (1985)

Chick thymus glucocorticoid receptor activation was followed in the presence of heparin and/or plasmin. Heparin, at a concentration of 9 microM, accelerated the rate of activation at 25 degrees C without influencing significantly the maximum activated fraction of the 3H-triamcinolone acetonide-receptor complex. On the contrary, 0.7 microM plasmin added prior to incubation at 25 degrees C (activation) of the complex blocked DNA cellulose binding. Thrombin did not influence receptor activation. Added to the activated complex, plasmin resulted in a rapid deactivation, i.e. an irreversible loss of DNA binding capacity. Plasmin and heparin appeared to exert their effects independent of each other in spite of the fact that they are known to interact in the concentration range in question.
Downloader-Initiated Random Linear Network Coding for Peer-to-Peer File Sharing (2010)

Network coding has recently drawn tremendous attention. Applying network coding to Peer-to-Peer (P2P) file sharing is still a relatively new area of study. Adopting network coding in a P2P file sharing network can make data distribution more effective and relieve the burden of the original seeder. In this paper, we first provide the mathematical analysis modeled from contemporary P2P file sharing protocols to analyze the efficiency of network coding in P2P file sharing networks. Then, we further investigate the “unlucky combination” problem encountered by the traditional random linear network coding algorithm when applied to a P2P file sharing network. Hence, we propose a “Downloader-Initiated Random Linear Network Coding” algorithm, which lets the downloader determine the random linear coding to eliminate the “unlucky combination” problem, and therefore further improves the performance of P2P file sharing networks.
A structural homologue of the N-formyl peptide receptor. Characterization and chromosome mapping of a peptide chemoattractant receptor family. (1992)

Phagocytic cells of many higher species express calcium mobilizing G protein-coupled receptors for bacterial N-formyl peptides which mediate chemotaxis, degranulation, and the respiratory burst. cDNA encoding an N-formyl peptide receptor (FPR) has been reported. We now report the isolation of a closely related cDNA, 2.6 kilobase pairs in length, which we have designated as the FPRL1 receptor cDNA (FPRL1 = formyl peptide receptor like-1). FPR and the FPRL1 receptor derive from small, single-copy genes, both of which are located on human chromosome 19. The gene loci are designated FPR1 and FPRL1, respectively. Both FPR and FPRL1 cDNA cross-hybridize under high stringency conditions with a third gene, designated as FPRL2, which does not appear to be expressed in neutrophils. In contrast, transcripts for both the FPRL1 receptor and FPR are detected only in differentiated myeloid cells; the distribution of N-formyl peptide binding sites is also restricted to mature myeloid cells. FPRL1 cDNA encodes a 351-amino acid polypeptide whose sequence is 69% identical to that of FPR. G protein-coupled receptors that exhibit this degree of structural similarity typically possess a conserved ligand specificity. However, the FPRL1 receptor does not bind prototype N-formyl peptide ligands when expressed in heterologous cell types. These results suggest that FPR1 may be the only gene that is expressed by neutrophils that encodes a receptor capable of binding prototype N-formyl peptides. Moreover, discovery of the FPRL1 receptor indicates the existence of another as yet unidentified peptide that may recruit neutrophils to sites of inflammation.
A robust method for the amplification of RNA in the sense orientation (2005)

The protocol we describe here is readily adaptable for the production of sense or antisense, labeled or unlabeled RNA from intact or partially-degraded prokaryotic or eukaryotic total RNA. The method outperforms several commercial RNA amplification kits and can be used in conjunction with a variety of microarray platforms, such as cDNA arrays, oligonucleotide arrays, and Affymetrix GeneChip arrays.
ZnII–Salphen Complexes as Versatile Building Blocks for the Construction of Supramolecular Box Assemblies (2005)

Zn(II)-salphen complexes are readily accessible and interesting supramolecular building blocks with a large structural diversity. Higher-order supramolecular assemblies, such as molecular boxes based on a bis-Zn(II)-salphen building block and various ditopic bipyridine ligands, have been constructed by means of supramolecular, coordinative Zn(II)-N(pyr) interactions. The use of bipyridine ligands of differing sizes enables the construction of structures with predefined box diameters. The features of the 2:2 box assemblies were investigated in detail by (variable temperature) NMR spectroscopy, UV-visible spectroscopy, NMR titrations, and X-ray crystallographic studies. The spectroscopic studies reveal a high association constant for the Zn(II)-salphen-pyridyl motif, which lies in the range 10(5)-10(6) M(-1). The strong interaction between the Zn(II) center and pyridine donors was supported by PM3 calculations that showed a relatively high Lewis acid character of the metal center in the salphen complex. Titration curves monitored by UV-visible show a cooperative effect between the two bipyridine ligands upon complexation to the bis-Zn(II) template, suggesting the formation of 2:2 complexes. The crystal structures of two supramolecular boxes have been determined. In both examples such a 2:2 assembly is present in the solid state, and the box size is different because they consist of different building blocks. Interestingly, the box assemblies line up in the solid state to form porous channels that are potentially useful in a number of applications.
Modelling of the homogeneous barrier discharge in helium at atmospheric pressure (2002)

Numerical calculations of spatio-temporal characteristics of the homogeneous barrier discharge in helium are performed by means of a one-dimensional fluid model. The influence of the elementary processes on the discharge behaviour is studied by variation of the corresponding rate constants. The simulation and the analytical interpretation are carried out for two basic modes of the homogeneous barrier discharge, i.e. the Townsend and glow modes. The Townsend discharge is characterized by the absence of quasineutral plasma; several current peaks may occur during the half-cycle. The oscillations of the current are caused by a lag between the ion production nearby the anode and the subsequent ion–electron emission on the cathode. The specificity of the glow discharge is the development of a cathode region and a positive column during the breakdown, as well as the presence of quasineutral plasma in subsequent phases. The positive column occurs because the shielding of the external field by the plasma is not instantaneous. The dependence of the discharge behaviour on the external parameters, such as the amplitude and frequency of the applied voltage, discharge gap width, and thickness of dielectric barriers, is analysed. The mode of the discharge is governed mostly by the gap width and barrier thickness and depends weakly on the amplitude and frequency of the applied voltage. As the barriers are thin and the discharge gap is sufficiently wide, the glow mode occurs; otherwise, the discharge is Townsend.
Detection and Tracking of Point Features (1991)

The factorization method described in this series of reports requires an algorithm to track the motion of features in an image stream. Given the small inter-frame displacement made possible by the factorization approach, the best tracking method turns out to be the one proposed by Lucas and Kanade in 1981. The method defines the measure of match between fixed-size feature windows in the past and current frame as the sum of squared intensity differences over the windows. The displacement is then defined as the one that minimizes this sum. For small motions, a linearization of the image intensities leads to a Newton-Raphson style minimization. In this report, after rederiving the method in a physically intuitive way, we answer the crucial question of how to choose the feature windows that are best suited for tracking. Our selection criterion is based directly on the definition of the tracking algorithm, and expresses how well a feature can be tracked. As a result, the criterion is opti...
Molecular determinants of bioactivity of the Saccharomyces cerevisiae lipopeptide mating pheromone. (1994)

The a-factor of Saccharomyces cerevisiae (YIIKGVF-WDPAC(Farnesyl)-OCH3) is a peptide pheromone in which post-translational modification with a farnesyl isoprenoid and carboxyl methyl group is required for export and bioactivity. Truncated and carboxyl-terminal modified analogs of the a-factor were synthesized in order to determine the effect of such modifications on bioactivity. Bioactivity studies on carboxyl-terminal analogs in which the chirality, the cysteine thioether, and the carboxyl ester were varied in an attempt to study the influence of topology on a-factor activity indicate that the hydrophobicity conferred by the farnesyl moiety and not its specific spatial orientation is a key determinant of a-factor potency. Analyses on truncated a-factors suggest that sequential removal of NH2-terminal residues leads to a gradient of potency loss, with some amino acids exhibiting a slightly greater contribution to bioactivity than others. Random oligonucleotide-targeted mutagenesis of the gene encoding a-factor was coupled to a biological screen to identify altered a-factor peptides which are secreted yet exhibit a loss of a-factor bioactivity. Transformants exhibiting this phenotype were examined to identify codon changes presumably responsible for the altered phenotype, thus indicating residues that may contribute significantly to a-factor bioactivity.
Combination of Ciprofloxacin and Metronidazole in Severe Perianal Crohn’s Disease (1993)

perianal involvement in Crohn's disease often is refractory to both medical and surgical treatment. The object of this study was to review retrospectively the response of patients with severe perianal Crohn's disease to a combination of ciprofloxacin and metronidazole. Fourteen patients (seven males, seven females, mean age 34.8 years) were treated consecutively with a combination of ciprofloxacin (1000 to 1500 mg/day) and metronidazole (500 to 1500 mg/day). All had 4uiescent bowel disease. Perianal disease had been present for a mean of 28.4 months. Six patients were on metronidazole at presentation and seven had had previous perianal surgery (mean of three operations per patient). All patients were symptomatic. Nine patients had complex fistula, six had anal canal ulceration, one had a rectovaginal fistula and five had discharging abscesses. Seven patients had multiple perianal lesions. Physician assessment at a mean of 12 weeks after commencing therapy revealed three patients healed, nine improved, one unchanged and one worsened, requiring a defunctioning stoma. Thus, 12 of 14 (85%) showed benefit from combination therapy. Patients have been followed a mean of 6.4 months since commencing therapy. Five patients had therapy stopped at 12 weeks and have not required further treatment, six patients required continuo us low dose therapy (ciprofloxacin 500 to 1000 mg/day plus metronidazole 500 to 750 mg/day), three patients stopped therapy at 12 weeks hut subsequently restarted therapy because of relapse. Thus, nine of 14 patients (64%) required continuous or repeat therapy. At present, seven patients have quiescent, six have mild, and one has moderate perianal disease. These results suggest that ctprofloxacin plus metronidazole may be effective in severe pcrianal Crohn's disease. (Pour resume , voir page
Nanoporous membranes generated from self‐assembled block polymer precursors: Quo Vadis? (2014)

ABSTRACT Nanoporous membranes based on self‐assembled block polymer precursors are an emerging class of promising separation, purification, and sensing devices due to the ability of researchers to control the nanostructure and chemistry of these multifunctional materials and devices. In fact, modern polymer chemistry provides techniques for the facile, controlled synthesis of the block polymers that constitute these devices. These designer macromolecules, in turn, can then self‐assemble into functional nanostructures depending upon the chemical identity of the synthesized block polymers and the thin film fabrication methods employed. After fabrication, these nanoporous membranes offer a highly tunable platform for applications that require high throughput, high surface area, homogeneous pore size, and varying material properties. And, with these readily tunable chemical and structural properties, block polymer membranes will allow for significant improvements in myriad applications. In this Review, we summarize the key advances, with a specific emphasis on the previous 5 years of work, that have allowed block polymer‐based membranes to reach their current level of technology. Furthermore, we project how these state‐of‐art, self‐assembled block polymer membrane technologies can be utilized in present‐day and future application arenas. In this way, we aim to demonstrate that the rigorous work performed on block polymer‐based membranes has laid a strong foundation that will allow these macromolecular systems to: (1) be major avenues of fundamental scientific research and (2) be parlayed into transferable technologies for the betterment of society in the imminent future. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132 , 41683.
Ontogeny of blood-brain barrier function in ovine fetuses, lambs, and adults (1996)

The ontogeny of regional blood-brain barrier function was quantified with the rate constant for influx (Ki) across the blood-brain barrier with the small molecular weight synthetic, inert hydrophilic amino acid alpha-aminoisobutyric acid (AIB) in chronically instrumented early (87 days of gestation, 60% of gestation) and late (137 days of gestation, 90% of gestation) gestation fetal, newborn (3 days of age), older (24 days of age), and adult (3 years of age) sheep. The Ki was significantly (P < 0.05) lower in the brain regions of the adult sheep and in most brain regions of newborn and older lambs compared with fetuses at 60 and 90% of gestation. The Ki exhibited regional brain heterogeneity (P < 0.05) in the five groups. The patterns of regional heterogeneity were accentuated (P < 0.05) in the younger groups. We conclude that ontogenic decreases in blood-brain barrier permeability are observed in ovine fetuses from 60% of gestation to maturity in the adult.
Techniques of model-based control (2002)

Preface. Acknowledgements. 1. Introduction. 2. Continuous-Time Models. 3. One-Degree of Freedom Internal Model Control. 4. Two-Degree of Freedom Internal Model Control. 5. Model State Feedback Implementations of IMC. 6. PI and PID Parameters From IMC Designs. 7. Tuning and Synthesis of 1DF IMC for Uncertain Processes. 8 Tuning and Synthesis of 2DF IMC for Uncertain Processes. 9. Feedforward Control. 10. Cascade Control. 11. Output Constraint Control (Override Control). 12. Single Variable Inferential Control (IC). 13. Inferential Estimation Using Multiple Measurements. 14. Discrete-Time Models. 15. Identification: Basic Concepts. 16. Identification: Advanced Concepts. 17. Basic Model-Predictive Control. 18. Advanced Model-Predictive Control. 19. Inferential Model-Predictive Control. Appendix A. Review of Basic Concepts. Appendix B. Review of Frequency Response Analysis. Appendix C: Review of Linear Least-Squares Regression. Appendix D: Review of Random Variables and Random Processes. Appendix E: MATLAB and Control Toolbox Tutorial. Appendix F: SIMULINK Tutorial. Appendix G: Tutorial on IMCTUNE Software. Appendix H: Identification Software. Appendix I: SIMULINK Models for Projects. Index.
Manufacturing implementation of corona oxide silicon (COS) systems for diffusion furnace contamination monitoring (2002)

Maximizing production utilization of manufacturing tools is of vital importance to the economic health of a wafer fabrication facility; however, preventative maintenance and qualification is important to maintain the highest quality product from these tools. This imposes contradictory constraints on the time allocated to preventative maintenance qualification activities. For diffusion furnaces, the standard procedure is to utilize high-frequency capacitance-voltage (CV) measurements to assess the overall cleanliness of the quartzware. This requires an oxide to be grown in the furnace on test wafers usually without the presence of product. Following this, additional processing of these wafers is necessary to generate a structure which can be probed (electrode deposition, doping, pattern, and etch) and some type of furnace cleaning cycle is run for each boat in the system. Depending upon the type of furnace, the total time that product cannot be run can amount to one day and, depending on the qualification cycle, this hit in manufacturing time can occur each week, every two weeks, or every month. Once the furnace returns to manufacturing for running production, an additional delay is encountered prior to learning the outcome of the CV results potentially resulting in material being run through the furnace out of specification. By utilizing a state-of-the-art Corona Oxide Semiconductor (COS) system for furnace qualifications, we have been able to cut our qualification time from 26.5 hours to 2.5 hours per week and have effectively increased our furnace capacity.
Advances in Molecular Design and Synthesis of Regioregular Polythiophenes (2008)

Regioregular poly(3-alkylthiophene)s (rrP3ATs) are an important class of pi-conjugated polymers that can be used in plastic electronic devices such as solar cells and field-effect transistors. rrP3ATs can be ordered in three dimensions: conformational ordering along the backbone, pi-stacking of flat polymer chains, and lamellar stacking between chains. All of these features lead to the excellent electrical properties of these materials. Creative molecular design and advanced synthesis are critical in controlling the properties of the materials as well as their device performance. This Account reports the advances in molecular design of new functional polythiophenes as well as the associated polymerization methods. Many functionalized regioregular polythiophenes have been designed and synthesized and show fascinating properties such as high conductivity, mobility, chemosensitivity, liquid crystallinity, or chirality. The methods for the synthesis of rrP3ATs are also applicable to other functional side chains. Di- and triblock copolymers consisting of rrP3AT and polyacrylate or polystyrene have also been successfully synthesized, which can facilitate the assembly of the polythiophene segments. The synthesis of rrP3ATs has evolved into a simple and economical system in which the synthesis can be carried out quickly at room temperature and is thus suitable for large-scale manufacturing. Intensive study has revealed that the regioregular polymerization of 3-alkylthiophenes proceeds by a chain-growth mechanism and can be made into a living system. This feature enables precise control of the molecular weight and facile end-group functionalization of the polymer chains, leading to tailor-made regioregular polythiophenes for specific applications. In addition, researchers have recently designed and synthesized regiosymmetric polythiophenesthese are regioregular but not coupled in a head-to-tail fashionby various methods. These reports indicate that these regiosymmetric polymers show very high mobilities when used in field-effect transistors due to their highly ordered structure. The remarkable performance of regioregular polythiophenes in recent years has allowed for the rapid development in printable electronics and seems destined to lead to further advances in this field.
Approximately optimal assignment for unequal loss protection (2002)

This paper describes an algorithm that achieves an approximately optimal assignment of forward error correction to progressive data within the unequal loss protection framework. It first finds the optimal assignment under convex hull and fractional bit allocation assumptions. It then relaxes those constraints to find an assignment that approximates the global optimum. The algorithm has a running time of O(hNlogN) where h is the number of points on the convex hull of the source's utility-cost curve and N is the number of packets transmitted.
From Imidazoles to Pyrimidines:  New Inhibitors of Cytokine Release (2002)

On the basis of model imidazole inhibitors of cytokine release, a series of novel pyridinyl pyrimidine derivatives was prepared and tested on their ability to inhibit the release of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) from peripheral blood mononuclear cells (PBMC) and human whole blood. In the pyrimidine series, structure-activity relationships (SARs) similar to those of the imidazole series were found, although generally pyrimidine compounds were less potent. Modification of the substituent at the 2 position of the pyrimidine led to the most active compound 14 which inhibited release of TNF-alpha (IC(50) = 3.2 microM) and IL-1beta (IC(50) = 2.3 microM) from PBMC as effectively as the model imidazole inhibitor ML 3163 (TNF-alpha, IC(50) = 3.7 microM; IL-1beta, IC(50) = 0.9 microM). Screening in an isolated enzyme assay revealed both imidazole and pyrimidine compounds as inhibitors of p38 MAP (mitogen-activated protein) kinase.