gebhart/patrepeval huggingface dataset:
Hepatitis C Virus NS5A Replication Complex Inhibitors: The Discovery of Daclatasvir (2014)

The biphenyl derivatives 2 and 3 are prototypes of a novel class of NS5A replication complex inhibitors that demonstrate high inhibitory potency toward a panel of clinically relevant HCV strains encompassing genotypes 1-6. However, these compounds exhibit poor systemic exposure in rat pharmacokinetic studies after oral dosing. The structure-activity relationship investigations that improved the exposure properties of the parent bis-phenylimidazole chemotype, culminating in the identification of the highly potent NS5A replication complex inhibitor daclatasvir (33) are described. An element critical to success was the realization that the arylglycine cap of 2 could be replaced with an alkylglycine derivative and still maintain the high inhibitory potency of the series if accompanied with a stereoinversion, a finding that enabled a rapid optimization of exposure properties. Compound 33 had EC50 values of 50 and 9 pM toward genotype-1a and -1b replicons, respectively, and oral bioavailabilities of 38-108% in preclinical species. Compound 33 provided clinical proof-of-concept for the NS5A replication complex inhibitor class, and regulatory approval to market it with the NS3/4A protease inhibitor asunaprevir for the treatment of HCV genotype-1b infection has recently been sought in Japan.
Plant Population and Yields in<i>Tagetes patula</i>and<i>Tagetes erecta</i> (2000)

ABSTRACT In a field experiment with Tagetes patula and Tagetes erecta during the winter-spring season of 1996–1997 at Lucknow, India, four cultivars were evaluated for flower production and helenien yields under a series of plant populations (56,000, 71,000, and 111,000 plants/ ha). At the highest plant population tested, a local Tagetes patula cultivar and a hybrid Tagetes erecta cullivar had 56.3 and 68.2 percent higher flower yields, respectively, than the lowest plant population tested. At the same population density, these same cultivars also produced higher yields of helenien (a dipalmitate ester of xanthophyll) than other tested cultivars.
Design of a dynamic memory access scheduler (2007)

Computer systems are becoming increasingly limited by memory performance. A dynamic SDRAM access scheduler (DSAS) according to modern SDRAM technology and memory access scheduling algorithms is proposed in this paper. Based on SDR-SDRAM technology and new version AMBA AXI bus, DSAS dynamically schedules the accesses to SDRAM and reduces precharge time. A modularized configurable automatic verification platform is established to verify basic functions of DSAS. We analyze the results and conclude that the memory controller using DSAS is capable of predicting future operations, thus greatly hide the precharge time, which takes much time in SDRAM operations; AXI bus throughput rate has improved by 19%~52% during frequent SDRAM accesses.
Seasonal variations in endotoxin sensitivity. (1967)

In the autumn season in rabbits of the same strain we have seen a spontaneous (natural) resistance to either Escherichia coli or Serratia marcescens endotoxin revealed by the Shwartzman reaction model. This `spontaneous' resistance could easily be increased by two small doses of endotoxin, in contrast to January and June. Apart from the difference of the season, the experiments were carried out under identical conditions. The animals, however, were not air-conditioned and the seasonal variation in endotoxin sensitivity could be explained by the stress of the previous hot summer which might have enhanced the function of the non-specific defence mechanism of the organism. Dietary factors may also have a role in the variation of sensitivity, but this is not definitely proven in this experiment. The chance eliciting the Shwartzman reaction could be enhanced by increasing the provoking dose in the above experiments. The Shwartzman reaction could be elicited by homologous and also heterologous endotoxin. However, the reaction was more marked at the skin site of the heterologous endotoxin preparation. This confirms the immunological specificity in the skin preparation of the Shwartzman reaction.
Supercharged Homogeneous Charge Compression Ignition (1998)

<div class="htmlview paragraph">The Homogeneous Charge Compression Ignition (HCCI) is the third alternative for combustion in the reciprocating engine. Here, a homogeneous charge is used as in a spark ignited engine, but the charge is compressed to auto-ignition as in a diesel. The main difference compared with the Spark Ignition (SI) engine is the lack of flame propagation and hence the independence from turbulence. Compared with the diesel engine, HCCI has a homogeneous charge and hence no problems associated with soot and NO<sub>X</sub> formation. Earlier research on HCCI showed high efficiency and very low amounts of NO<sub>X</sub>, but HC and CO were higher than in SI mode. It was not possible to achieve high IMEP values with HCCI, the limit being 5 bar. Supercharging is one way to dramatically increase IMEP. The influence of supercharging on HCCI was therefore experimentally investigated. Three different fuels were used during the experiments: <i>iso</i>-octane, ethanol and natural gas. Two different compression ratios were used, 17:1 and 19:1. The inlet pressure conditions were set to give 0, 1 or 2 bar of boost pressure. The highest attainable IMEP was 14 bar using natural gas as fuel at the lower compression ratio. The limit in achieving even higher IMEP was set by the high rate of combustion and a high peak pressure.</div> <div class="htmlview paragraph">Numerical calculations of the HCCI process have been performed for natural gas as fuel. The calculated ignition timings agreed well with the experimental findings. The numerical solution, is however, very sensitive to the composition of the natural gas.</div>
High-Throughput Classical Chiral Resolution Screening of Synthetic Intermediates: Effects of Resolving Agents, Crystallization Solvents, and Other Factors (2020)

Using a statistical Z-score methodology, enantiomeric excess (ee) data from our historical high-throughput classical chiral resolution screens were analyzed. In total, 19 of the screens used chiral acids as resolving agents, and 20 used chiral bases. The results show clear trends in terms of the selection of chiral acids/bases in conjunction with a crystallization solvent. We rank ordered resolving agents, solvents, and resolving agent/solvent combinations by applying the Z-score method on the ee of isolated solids, and provided recommendations on executing more efficient classical chiral resolution screening for synthetic intermediates.
The integral membrane FtsW protein and peptidoglycan synthase PBP3 form a subcomplex in Escherichia coli (2010)

During the cell cycle of rod-shaped bacteria, two morphogenetic processes can be discriminated: length growth of the cylindrical part of the cell and cell division by formation of two new cell poles. The morphogenetic protein complex responsible for the septation during cell division (the divisome) includes class A and class B penicillin-binding proteins (PBPs). In Escherichia coli, the class B PBP3 is specific for septal peptidoglycan synthesis. It requires the putative lipid II flippase FtsW for its localization at the division site and is necessary for the midcell localization of the class A PBP1B. In this work we show direct interactions between FtsW and PBP3 in vivo and in vitro by FRET (Förster resonance energy transfer) and co-immunoprecipitation experiments. These proteins are able to form a discrete complex independently of the other cell-division proteins. The K2-V42 peptide of PBP3 containing the membrane-spanning sequence is a structural determinant sufficient for interaction with FtsW and for PBP3 dimerization. By using a two-hybrid assay, the class A PBP1B was shown to interact with FtsW. However, it could not be detected in the immunoprecipitated FtsW-PBP3 complex. The periplasmic loop 9/10 of FtsW appeared to be involved in the interaction with both PBP1B and PBP3. It might play an important role in the positioning of these proteins within the divisome.
Syntheses of (<i>R</i>)- and (<i>S</i>)-2- and 6-Fluoronorepinephrine and (<i>R</i>)- and (<i>S</i>)-2- and 6-Fluoroepinephrine:  Effect of Stereochemistry on Fluorine-Induced Adrenergic Selectivities (2000)

Several routes to the enantiomers of fluoronorepinephrines (1) and fluoroepinephrines (2) were explored. A catalytic enantioselective oxazaborolidine reduction and a chiral (salen)Ti(IV) catalyzed asymmetric synthesis of silyl cyanohydrins proved efficacious in the key stereo-defining steps of two respective routes. Binding studies of the catecholamines with alpha(1)-, alpha(2)-, beta(1)-, and beta(2)-adrenergic receptors were examined. The assays confirmed that fluorine substitution had marked effects on the affinity of (R)-norepinephrine and (R)-epinephrine for adrenergic receptors, depending on the position of substitution. Thus, a fluoro substituent at the 2-position of (R)-norepinephrine and (R)-epinephrine reduced activity at both alpha(1)- and alpha(2)-receptors and enhanced activity at beta(1)- and beta(2)-receptors, while fluorination at the 6-position reduced activity at the beta(1)- and beta(2)-receptors. The effects of fluorine substitution on the S-isomers were less predictable.
Relevance of hyperglycemia to early mechanical hyperalgesia in streptozotocin‐induced diabetes (2004)

A modified von Frey filament test and an algesiometer paw pressure test were used to measure mechanical nociceptive withdrawal thresholds of the hind limb of control rats and rats injected with streptozotocin (STZ, 50 mg/kg). STZ treatment induced hyperglycemia (HG rats) in about 40% of treated animals. The rest of the STZ-treated and control rats remained normoglycemic (NG rats) throughout the entire experiment. No indications of mechanical hyperalgesia were observed in control groups of animals injected with physiological buffer only. However, both the behavioral tests used detected a 15-30% decrease in the mechanical nociceptive threshold of rats treated with STZ. Furthermore, mechanical nociceptive threshold changes were statistically indistinguishable between NG and HG rats. Glucose tolerance test did not reveal abnormalities of glucose metabolism in NG rats (compared to control animals). However, 1 week after STZ injection, the serum insulin level of NG rats was significantly lower than that of age-matched control rats (0.81 +/- 0.16 vs. 3.5 +/- 0.4 ng/mL; p < 0.01). These data strongly argue that systemic hyperglycemia is not the only factor triggering the development of mechanical hyperalgesia in the STZ rat model of diabetes. Other than hyperglycemia, consequences of insulinemia or insulinemia itself may play an important role in early impairment of mechanical nociception in this animal model.
The mechanism of shear thickening fluid with nanoparticles applied to liquid armor (2007)

Shear thickening fluid (STF) has been reported that it can be applied in defensive and protective equipment, however, to meet the protection requirements for typical ballistic threats, approximately 20-50 layers of fabric are required. The resulting bulk and stiffness of the armor limits its comfort, and has restricted its application primarily to torso protection. Utilization of this shear thickening characteristic, the ballistic protection capability afforded by fabricated, flexible body armor can be enhanced tremendously. The ballistic protection properties of this complex system can be predicted or controlled only if the mechanism is fully understood. But the mechanism of shear thickening is still a matter of debate. It has been ascribed either to an order-disorder transition or to the formation of hydroclusters, however, our research verifies that the hydrogen bond might play an important role on the forming of STF. From our results, it is possible to interpret the occurrence of shear thickening behavior in terms of the shear-induced structure of the suspension once the critical shear strain is reached. The shear -induced structure can only be obtained for the suspension system with intensive hydrogen bonding within the system. The degree of shear thickening also depends on the concentration and temperature of the system.
Concurrent statistical evaluation during patient monitoring (1970)

The Shock Research Unit, a specialized clinical research facility, has been developed by the University of Southern California's School of Medicine for the purpose of rendering intensive care to seriously ill patients. Included is a medium-sized digital computer with a real-time system which monitors the critically ill patient. In addition, the system is being used to study the underlying mechanisms of the disease process and for developing new techniques of evaluating and treating seriously ill patients.
EPIDEMIOLOGICAL STUDIES ON MATERNAL AND CHILD HEALTH IN GUNMA PREFECTURE, JAPAN (1975)

The present paper discussed the perinatal emergency care system for further improvement of child and maternal health in Gunma prefecture, Japan.The possibilities for the prevention of perinatal deaths were estimated from the data about the causes and local distribution of hebdomadal deaths which were main concern of emergency care system.The deaths from obstetrical causes, which were mostly preventable, were less than one third of the total cases. The rest of above were caused by environmental factors and most of them were difficult to prevent. Introduction of high risk care unit for pregnant women as developed in advanced nations was needed to reduce the number of deaths from environmental factors.The frequency of toxaemia and bleeding in the rural under-doctored region and part of town area (previously published data) also urged the need of careful perinatal control in these area.The definite plan for these emergency care system are under investigation analyzing the data from questionnaire.
Microwave exposure induces Hsp70 and confers protection against hypoxia in chick embryos (2002)

To determine if microwave exposure could elicit a biological effect in the absence of thermal stress, studies were designed in which chick embryos were exposed to athermal microwave radiation (915 MHz) to look for induction of Hsp70, a protein produced during times of cellular stress that aids in the protection of cellular components. Levels of Hsp70 were found to increase within 2 h, with maximum expression ( approximately 30% higher than controls) typically occurring by 3 h from the start of exposure. Other embryos were exposed to microwave radiation prior to being subjected to hypoxic stress, and were found to have significantly higher survival (P < 0.05) following re-oxygenation than non-exposed controls. The results of these studies indicate that not only can athermal microwave exposures activate the stress protein response pathway; they can also enhance survivability following exposure to a subsequent, potentially lethal stress. From a public health standpoint, it is important that more studies be performed to determine if repeated exposures, a condition likely to be found in cell phone use, are still beneficial.
Post-compaction register assignment in a retargetable compiler (1990)

The authors discuss graph-coloring register assignment in a retargetable compiler for long-instruction-word architectures. Of specific concern is when, during the compilation process, should register assignment be performed. The authors conclude that, for best results, register assignment should follow compaction. They discuss methods of circumventing the implementation problems inherent in such late register assignment. >
Aromatherapy Massage on the Abdomen for Alleviating Menstrual Pain in High School Girls: A Preliminary Controlled Clinical Study (2011)

This study investigated the alleviating effects of aromatherapy massage and acetaminophen on menstrual pain in Korean high school girls. Subjects were divided into two groups: the aromatherapy massage (treatment) group (n = 32) and the acetaminophen (control) group (n = 23). Aromatherapy massage was performed on subjects in the treatment group. The abdomen was massaged once using clary sage, marjoram, cinnamon, ginger, and geranium in a base of almond oil. The level of menstrual pain was assessed using a visual analogue scale at baseline and twenty-four hours afterward. The reduction of menstrual pain was significantly higher in the aromatherapy group than in the acetaminophen group. Using multiple regression, aromatherapy massage was found to be more highly associated with reduction in the level of menstrual pain than acetaminophen. These finding suggest that aromatherapy massage may be an effective treatment for menstrual pain in high school girls. However, it could not be verified whether the positive effects derived from the aromatherapy, the massage, or both. Further rigorous studies should be conducted using more objective measures.
Neurological events related to influenza <scp>A</scp> (<scp>H</scp>1<scp>N</scp>1) pdm09 (2014)

Fatal cases and severe, permanent, neurological sequelae were observed in the infection group only. Clinical outcome was more favorable in the post-vaccination group. In this context, the relevance of an accurate neurological evaluation is demonstrated for all suspicious cases, as well as the need of an appropriate long-term clinical and imaging follow-up of infection and post-vaccination events related to influenza A (H1N1) pdm09, to clearly estimate the magnitude of neurological complications leading to permanent disability.
Ultra-fast Microwave Synthesis of ZnO Nanowires and their Dynamic Response Toward Hydrogen Gas (2009)

Ultra-fast and large-quantity (grams) synthesis of one-dimensional ZnO nanowires has been carried out by a novel microwave-assisted method. High purity Zinc (Zn) metal was used as source material and placed on microwave absorber. The evaporation/oxidation process occurs under exposure to microwave in less than 100 s. Field effect scanning electron microscopy analysis reveals the formation of high aspect-ratio and high density ZnO nanowires with diameter ranging from 70 to 80 nm. Comprehensive structural analysis showed that these ZnO nanowires are single crystal in nature with excellent crystal quality. The gas sensor made of these ZnO nanowires exhibited excellent sensitivity, fast response, and good reproducibility. Furthermore, the method can be extended for the synthesis of other oxide nanowires that will be the building block of future nanoscale devices.
Instant Medical Pill Recognition on Mobile Phones (2011)

Smartphones have attracted a lot of interest recently as they are becoming more and more computationally powerful platforms for all kinds of tasks in mobile environments. Due to the availability of high quality mobile phone cameras, the use of these platforms even for critical applications leveraging Computer Vision techniques is justified. In this paper we present an application of Computer Vision techniques for instant and interactive medical pill detection and recognition on mobile phones. Our approach is designed to help trained or untrained personnel outside of medical facilities to perform the task of identifying tablets interactively with or without the help of online resources. By describing our application in detail and giving results on the recognition task we are proofing the plausibility of our approach.
Zinc-cyclen coordination to UTP, TTP or pyrophosphate induces pyrene excimer emission (2010)

Pyrene labelled Zn(2+)-cyclen 1 and bis-Zn(2+)-bis-cyclen 2 complexes were synthesized. The reversible coordination at physiological pH of Zn(2+)-cyclens to phosphate anions and to imide moieties, as present in thymine and uracil nucleotides, is well known. In the presence of analytes bearing a phosphate and an imide or two phosphate groups the formation of a ternary complex consisting of two pyrene-labelled metal complexes and the analyte molecule, is observed. The close proximity of the pyrene labels in the complex induces pyrene excimer emission, which is observable by the unarmed eye. By this, the presence of UMP, UDP, UTP and TTP in buffered aqueous solution is signalled, while other nucleotides are not able to induce excimer emission. In the same way, Zn(2+)-cyclen-pyrene acts as luminescent chemosensor for PP(i) and fructose-1,6-bisphosphate in aqueous buffer.
Organizing engineering designs and design techniques (2002)

The authors present an approach to organizing engineering designs and design techniques in a database system. This database system stores existing designs and provides a mechanism for capturing the design process in the database. The authors develop the notions of assembly objects and component objects, define the idea of design dependencies among objects and explain dependencies in terms of constraints. They also develop a representation of design techniques, show a representation of design objects, techniques, and dependencies, and present a scenario for performing designs. Dependencies between objects are recognized and treated uniformly as objects in a database. It is pointed out how this environment may be used for conducting the design process by selection of components.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Polyamine-induced hydrolysis of apurinic sites in DNA and nucleosomes (1982)

The ability of different polyamines to catalyze hydrolysis of phosphodiester linkages in apurinic and apyrimidinic (AP) sites has been investigated in supercoiled, relaxed and denatured DNA, and also in core and chromatosome particles. The rate constants for the hydrolysis in the DNAs have been determined. In general the order of effectiveness of the polyamines were: spermine greater than spermidine greater than putrescine greater than cadaverine. A 9 fold difference in rate constants was found between spermine and cadaverine. No difference in the rate of hydrolysis was seen between AP-sites in supercoiled and relaxed DNAs, whereas the rate for the single-stranded DNA and DNA in core and chromatosome particles was only half of that in the double-stranded DNA. All AP-sites in both free DNA and DNA-histone particles were hydrolyzed in the presence of polyamines. For all polyamines, with the exception of spermine, increasing concentration of both Mg++ and salts such as KCl both led to a large decrease in the rate of polyamine-induced hydrolysis of AP-sites. The rate of hydrolysis increased markedly with increasing pH in the pH range pH 6 - pH 11.
Genomic Instability, Defective Spermatogenesis, Immunodeficiency, and Cancer in a Mouse Model of the RIDDLE Syndrome (2011)

Eukaryotic cells have evolved to use complex pathways for DNA damage signaling and repair to maintain genomic integrity. RNF168 is a novel E3 ligase that functions downstream of ATM,γ-H2A.X, MDC1, and RNF8. It has been shown to ubiquitylate histone H2A and to facilitate the recruitment of other DNA damage response proteins, including 53BP1, to sites of DNA break. In addition, RNF168 mutations have been causally linked to the human RIDDLE syndrome. In this study, we report that Rnf168(-/-) mice are immunodeficient and exhibit increased radiosensitivity. Rnf168(-/-) males suffer from impaired spermatogenesis in an age-dependent manner. Interestingly, in contrast to H2a.x(-/-), Mdc1(-/-), and Rnf8(-/-) cells, transient recruitment of 53bp1 to DNA double-strand breaks was abolished in Rnf168(-/-) cells. Remarkably, similar to 53bp1 inactivation, but different from H2a.x deficiency, inactivation of Rnf168 impairs long-range V(D)J recombination in thymocytes and results in long insertions at the class-switch junctions of B-cells. Loss of Rnf168 increases genomic instability and synergizes with p53 inactivation in promoting tumorigenesis. Our data reveal the important physiological functions of Rnf168 and support its role in both γ-H2a.x-Mdc1-Rnf8-dependent and -independent signaling pathways of DNA double-strand breaks. These results highlight a central role for RNF168 in the hierarchical network of DNA break signaling that maintains genomic integrity and suppresses cancer development in mammals.