gebhart/patrepeval huggingface dataset:
Effective suppression of luteinizing hormone and testosterone by single doses of the new gonadotropin-releasing hormone antagonist cetrorelix (SB-75) in normal men. (1992)

In rats and nonhuman primates the new GnRH antagonist cetrorelix (SB-75; [Ac-D-Nal(2)1,D-Phe(4Cl)2,D-Pal(3)3,D-Cit6,D-Ala10]GnR H) has been shown to suppress testosterone secretion effectively and persistently. A clinical phase I study was performed to assess the hormonal effects of this highly potent antagonist in normal men. After 2 control examinations 30 young male volunteers were randomly assigned to 6 treatment groups (n = 5/group), and single doses of 0 (placebo), 0.25, 0.5, 1.0, 2.0, and 5.0 mg cetrorelix were administered sc. Blood samples were obtained over the course of 7 days postinjection. After maximal cetrorelix serum levels were achieved 1 h postinjection, the GnRH antagonist serum levels decreased with a terminal t1/2 of 29.8 +/- 4.2 h (mean +/- SE). LH secretion was suppressed dose- and time-dependently; maximal suppression occurred 4-6 h postinjection. Suppression of FSH did not reach statistical significance. Doses of 1.0, 2.0, and 5.0 mg cetrorelix significantly suppressed testosterone secretion compared to that in the placebo group. After the administration of 1.0 mg cetrorelix, maximal suppression was seen 8 h after injection, with testosterone levels of 7.5 +/- 1.1 nmol/L compared to 15.8 +/- 2.2 nmol/L in the placebo group. Maximal testosterone suppression by 2.0 and 5.0 mg cetrorelix occurred 12 h after injection, with testosterone concentrations of 4.9 +/- 0.5 and 2.2 +/- 0.4 nmol/L, respectively, compared to 16.5 +/- 1.7 nmol/L in the placebo group. Twenty-four hours after the injection of 1.0 and 2.0 mg cetrorelix, testosterone values were no longer significantly different from those in the placebo group, whereas in the 5.0-mg dose group testosterone concentrations increased slightly and reached serum concentrations in the lower normal range after 48 h. The only side-effect observed after the administration of cetrorelix was a transient local erythema at the injection site that disappeared within 30 min. No local induration or pruritus, or any adverse systemic side-effect occurred in any volunteer. In conclusion, the new GnRH antagonist cetrorelix effectively decreases serum LH and testosterone concentrations in a dose- and time-dependent manner and, therefore, has potential for treatment of sex hormone-dependent diseases and male contraception.
A mosaic hemagglutinin-based influenza virus vaccine candidate protects mice from challenge with divergent H3N2 strains (2019)

Current seasonal influenza virus vaccines only provide limited, short-lived protection, and antigenic drift in the hemagglutinin surface glycoprotein necessitates their annual re-formulation and re-administration. To overcome these limitations, universal vaccine strategies that aim at eliciting broadly protective antibodies to conserved epitopes of the hemagglutinin show promise for protecting against diverse and drifted influenza viruses. Here a vaccination strategy that focuses antibody responses to conserved epitopes of the H3 hemagglutinin is described. The approach is based on antigenic silencing of the immunodominant major antigenic sites of an H3 protein from 2014 by replacing them with corresponding sequences of exotic avian hemagglutinins, yielding "mosaic" hemagglutinins. In mice, vaccination with inactivated viruses expressing mosaic hemagglutinins induced highly cross-reactive antibodies against the H3 stalk domain that elicited Fc-mediated effector functions in vitro. In addition, the mosaic viruses elicited head-specific antibodies with neutralizing and hemagglutination-inhibiting activity against recent H3N2 viruses in vitro. Immune sera protected mice from heterologous challenge with viruses carrying H3 proteins from 1968 and 1982, whereas immune sera generated with a seasonal vaccine did not protect. Consequently, the mosaic vaccination approach provides a promising avenue toward a universal influenza virus vaccine.
Stability effects associated with the introduction of a partial and a complete Ca<sup>2+</sup>-binding site into human lysozyme (1993)

Two mutants of human lysozyme were synthesized. Mutant A92D, in which Ala92 was substituted by Asp, contains a partial Ca(2+)-binding site and mutant M4, in which Ala83, Gln86, Asn88 and Ala92 were replaced by Lys, Asp, Asp and Asp respectively, contains the complete Ca(2+)-binding site of bovine alpha-lactalbumin. The Ca(2+)-binding constants of wild type human lysozyme and of mutants A92D and M4, measured at 25 degrees C and pH 7.5, were 2(+/- 1) x 10(2) M-1, 8(+/- 2) x 10(3) M-1 and 9(+/- 0.5) x 10(6) M-1 respectively. Information gathered from microcalorimetric and CD spectroscopic measurements indicates that the conformational changes of the M4 mutant lysozyme, induced by Ca2+ binding, are smaller than those observed for bovine alpha-lactalbumin and for the Ca(2+)-binding equine lysozyme. At pH 4.5, the thermostability of both the apo and Ca2+ forms of the A92D human was decreased in comparison with that of native human lysozyme. In particular, within the apo form of this mutant an alpha-helix-containing sequence was destabilized. In contrast, at the same pH the thermostability of the apo and Ca2+ forms of the M4 mutant lysozyme was increased. The epsilon-ammonium group of the Lys83 side chain is assumed to be responsible for the stabilization of the apo form of this mutant.
Resistance to ddI and Sensitivity to AZT Induced by a Mutation in HIV-1 Reverse Transcriptase (1991)

Serial human immunodeficiency virus type-1 (HIV-1) isolates were obtained from five individuals with acquired immunodeficiency syndrome (AIDS) who changed therapy to 2',3'-dideoxyinosine (ddI) after at least 12 months of treatment with 3'-azido-3'-deoxythymidine (zidovudine, AZT). The in vitro sensitivity to ddI decreased during the 12 months following ddI initiation, whereas AZT sensitivity increased. Analysis of the reverse transcriptase coding region revealed a mutation associated with reduced sensitivity to ddI. When this mutation was present in the same genome as a mutation known to confer AZT resistance, the isolates showed increased sensitivity to AZT. Analysis of HIV-1 variants confirmed that the ddI resistance mutation alone conferred ddI and 2',3'-dideoxycytidine resistance, and suppressed the effect of the AZT resistance mutation. The use of combination therapy for HIV-1 disease may prevent drug-resistant isolates from emerging.
New laboratory model for neurosurgical training that simulates live surgery (2002)

This model mimics the normal human anatomy and dynamic vascular filling found in real surgery and presents it from the training perspective, allowing a wide range of skill development and repeated practice. It provides an alternative model to laboratory animals. It is inexpensive and readily available, and has great value for the acquisition and refinement of surgical skills that are not only specific to neurosurgery, but are applicable to other surgical disciplines.
Suppression of anti-glomerular basement membrane nephritis by administration of anti-monocyte chemoattractant protein-1 antibody in WKY rats. (1997)

Anti-glomerular basement membrane (GBM) nephritis in WKY rats is characterized by an accumulation of CD8-positive lymphocytes (CD8+ lym) and monocytes/macrophages (Mo/M psi) in the glomeruli and crescent formation. In the study presented here, the involvement of a chemokine for Mo/M psi, monocyte chemoattractant protein-1 (MCP-1), was examined in this model. An intense induction of mRNA for MCP-1 in the glomeruli and a suppressive effect of anti-MCP-1 antibody administration on the glomerular Mo/M psi accumulation and proteinuria were found. MCP-1 mRNA was expressed intensely in the glomeruli 4 d after the anti-GBM antibody injection. When MCP-1 was neutralized with anti-MCP-1 antibody administration, the number of Mo/M psi infiltrating in the glomeruli decreased by 34.7% (19.6 +/- 7.1 versus 30.0 +/- 6.0 per glomerular cross-section, P < 0.01) and proteinuria by 66.2% (15.6 +/- 9.3 versus 46.1 +/- 15.1 mg/d, P < 0.01) at day 4. In contrast, the number of CD8+ lym accumulating in the glomeruli was not affected significantly (6.6 +/- 2.7 versus 6.0 +/- 3.0 per glomerular cross-section, P > 0.05). However, the treatment with the anti-MCP-1 antibody did not reduce Mo/M psi infiltration, urinary protein excretion, and crescent formation at day 8. These data suggest that MCP-1 plays a role in the glomerular accumulation of Mo/M psi, and that the infiltrating Mo/M psi cause glomerular injury and increased excretion of protein in the urine.
Role of the Immune Modulator Programmed Cell Death-1 during Development and Apoptosis of Mouse Retinal Ganglion Cells (2009)

These findings collectively support a novel role for a PD-1-mediated signaling pathway in developmental PCD during postnatal RGC maturation.
Aqueous and nonaqueous lithium-air batteries enabled by water-stable lithium metal electrodes (2014)

The extremely high theoretical energy density of the lithium-oxygen couple makes it very attractive for next-generation battery development. However, there are a number of challenging technical hurdles that must be addressed for Li-Air batteries to become a commercial reality. In this article, we demonstrate how the invention of water-stable, solid electrolyte-protected lithium electrodes solves many of these issues and paves the way for the development of aqueous and nonaqueous Li-Air batteries with unprecedented energy densities. We also show data for fully packaged Li-Air cells that achieve more than 800 Wh/kg.
A Practical Kernel Criterion for Feature Extraction and Recognition of MSTAR SAR Images (2006)

Complete kernel fisher discriminant analysis (CKFDA) is essentially a practical nonlinear feature extraction criterion based on kernel trick. The process is divided into two phases, i.e., kernel principal component analysis (KPCA) and linear discriminant analysis (LDA). This work uses two different kinds of CKFDA methods to extract the features of MSTAR SAR images: one only obtains the regular information in "single discriminant space", the other gains regular and irregular information in "double discriminant subspaces". The inspiring recognition results verify that the features not only overcome aspect sensitivity existent in SAR images, but also are robust to variants within the target classes which have small configuration differences
Identification of a New Family of Higher Eukaryotic Histone Deacetylases (1999)

The histone deacetylase domain of almost all members of higher eukaryotic histone deacetylases already identified (HDAC family) is highly homologous to that of yeast RPD3. In this paper we report the cloning of two cDNAs encoding members of a new family of histone deacetylase in mouse that show a better homology to yeast HDA1 histone deacetylase. These cDNAs encode relatively large proteins, presenting an in vitro trichostatin A-sensitive histone deacetylase activity. Interestingly, one, mHDA2, encodes a protein with two putative deacetylase domains, and the other, mHDA1, contains only one deacetylase homology domain, located at the C-terminal half of the protein. Our data showed that these newly identified genes could belong to a network of genes coordinately regulated and involved in the remodeling of chromatin during cell differentiation. Indeed, the expression of mHDA1 and mHDA2 is tightly linked to the state of cell differentiation, behaving therefore like the histone H1 degrees-encoding gene. Moreover, like histone H1(0) gene, mHDA1 and mHDA2 gene expression is induced upon deacetylase inhibitor treatment. We postulate the existence of a regulatory mechanism, commanding a coordinate expression of a group of genes involved in the remodeling of chromatin not only during cell differentiation but also after abnormal histone acetylation.
Neutralization of Antimicrobial Substances in New BacT/Alert FA and FN Plus Blood Culture Bottles (2013)

Time to detection (TTD) in automated blood culture systems is delayed for sensitive microorganisms in the presence of antimicrobial substances and has been associated with worse outcomes for sepsis patients on inadequate empirical therapy. While resin addition removes antimicrobial substances to various degrees from blood culture media, media formulations and the blend of resins may influence performance. The BacT/Alert 3D system (bioMérieux) was investigated using the new resin-containing medium types FA Plus (aerobic) and FN Plus (anaerobic). TTD was compared between control and test bottles containing relevant bacteria or Candida albicans, with and without defined concentrations of antimicrobials. Failure of neutralization was defined as a negative blood culture on day 3. In general, growth delay was nonlinear, concentration dependent, bottle type specific, and reciprocally associated with MICs. Substance-specific serum drug concentrations corresponding to a predefined, clinically relevant 3-h delay of TTD were calculated. Where appropriate, a time interval allowing for drug elimination below this critical level was obtained by pharmacokinetic modeling. Clarithromycin, clindamycin, gentamicin, linezolid, tigecycline, vancomycin, and fluconazole were neutralized. For ciprofloxacin and piperacillin-tazobactam, which were only incompletely neutralized in combination with the most sensitive test strains, a maximum waiting time for blood draw of 1 h was determined based on pharmacokinetics. One or more test strains did not grow in bottles containing either amoxicillin-clavulanate, cefepime, cefotaxime, meropenem, or metronidazole, and we thus recommend particular caution in timing of blood draws if patients have been pretreated with these agents.
The crucial role of extracellular polymeric substances in biofilms (2003)

A review on the compn., properties and functions of extracellular polymeric substances (EPS), esp. their role in microbial aggregation, with 130 refs. The EPS-mediated mech. stability of biofilms and other microbial aggregates is of importance for the performance of tech. biofilm processes as in wastewater treatment, but also in the control or removal of unwanted biofilms in other industrial systems. From an ecol. point of view, the EPS matrix provides the possibility that the microorganisms can form stable aggregates of mixed populations, leading to the synergistic microconsortia. This facilitates the sequential degrdn. of substances that are not readily biodegradable.
Efficient Tempo and Beat Tracking in Audio Recordings (2003)

Automatic beat tracking consists of estimating the number of beats per minutes at which a music track is played and identifying exactly when these beats occur. Applications range from music analysis, sound-effect synchronization, and audio editing to automatic playlist generation and deejaying. An off-line beat-tracking technique for estimating a time-varying tempo in an audio track is presented. The algorithm uses an MMSE estimation of local tempo and beat location candidates, followed by a dynamic programming stage used to determine the optimum choice of candidate in each analysis frame. The algorithm is efficient in its use of computation resource, yet provides very good results on a wide range of audio tracks. The algorithm details are presented, followed by a discussion of the performance and suggestions for further improvements.
Accumulation of PiZ alpha 1-antitrypsin causes liver damage in transgenic mice. (1989)

Circulating alpha 1-antitrypsin is synthesized primarily in the liver and secreted into the bloodstream, where it serves as the major protease inhibitor. The PiZ variant of alpha 1-antitrypsin is associated with decreased levels of the protein in sera as a result of its retention within hepatocytes. Homozygosity for the variant allele predisposes individuals to the development of pulmonary emphysema and an increased risk for liver disease. We and others have previously demonstrated that the normal PiM human alpha 1-antitrypsin gene can be properly expressed in the livers of transgenic mice. The PiZ variant of the human alpha 1-antitrypsin gene was introduced into the germline of mice to determine whether the mutant protein would accumulate in mouse hepatocytes and if such accumulation would result in the development of liver damage in an animal model. As expected, the mutant human protein was abundantly synthesized in the livers of the transgenic animals and accumulated within the rough endoplasmic reticulum of hepatocytes as it does in human patients. PiZ mice developed significantly more liver necrosis and inflammation than PiM transgenic mice or control littermates. The degree of liver damage was correlated with the amount of PiZ alpha 1-antitrypsin accumulated in the liver of the different pedigrees of mice. Although 40% of PiZ mice tested were seropositive for mouse hepatitis virus (MHV), the degree of liver damage was not influenced by the MHV seropositivity; rather, it was related only to the presence of accumulated PiZ protein.
Tonic vibration reflex and muscle afferent block in writer's cramp (1995)

Patients with focal dystonia take advantage of certain cutaneous or proprioceptive sensory inputs to alleviate their symptoms ("sensory trick"). We examined the effects of increasing muscle spindle activity by the tonic vibration reflex maneuver and decreasing it by intramuscular injection of lidocaine. The vibration was applied to the palm or the tendon of forearm muscles in 15 patients with writer's cramp and 15 age-matched normal subjects. In 11 patients, the vibration induced dystonic postures or movements typical of those seen during writing. Normal subjects showed either no response to the vibration or a gradually developing tonic vibration reflex only in the wrist and finger flexors, which produced visible movements with a significantly longer latency (12.5 +/- 6.7 seconds [mean +/- standard deviation]) than what was observed in the patients (2.7 +/- 2.5 seconds, p < 0.0001). Local injection of lidocaine (0.5%, 5-40 ml/muscle) attenuated the tendon reflex with relatively little effect on the M response. Injection into muscles with increased activity produced marked reduction of dystonic movements and significant clinical improvement in 13 patients, whereas injection into the other muscles had no effect. The clinical benefit lasted for 1 to 24 hours after injection. In 13 patients who had additional injections of 10% ethanol, which blocks sodium channels for a longer period than does lidocaine, the duration of action was prolonged to 5 to 21 days. These findings suggest that muscles causing dystonic movements have abnormal sensitivities to vibration at rest and that muscle afferents may play a pivotal role in producing dystonic movements.(ABSTRACT TRUNCATED AT 250 WORDS)
Low cost trace-driven memory simulation using SimPoint (2005)

Trace-driven memory simulation tools such as MetaSim Tracer [1] capture the address stream of an application during an instrumented program run. Various statistics can be measured using the in-flight address stream including anticipated cache hit rates. This paper reports on performance improvements of MetaSim Tracer gained by using techniques developed in SimPoint [2]. Concurrent research [3] addresses techniques that can be used to reduce the instrumentation overhead involved in memory tracing, and this work addresses a technique that can be used to decrease the amount of cache simulation that is required on top of this. The result is a tool for trace driven cache simulation that is practical to use for memory performance studies of full sized scientific applications.
Membrane-associated phosphatidylglycerophosphate synthetase from Escherichia coli: purification by substrate affinity chromatography on cytidine 5'-diphospho-1,2-diacyl-sn-glycerol sepharose (1976)

The membrane-associated cytidine 5'-diphospho-1,2-diacyl-sn-glycerol (CDP-diglyceride):sn-glycerol-3-phosphate phosphatidyltransferase (EC 2.7.8.5) from Escherichia coli has been solubilized wiTriton X-100 and purified 6000-fold to 85% of homogeneity. The major purification was attained using several modifications of the the CDP-diglyceride Sepharose affinity chromatography system described by Larson et al. (Larson, T.J., Hirabayashi, T., and Dowhan, W. (1976), Biochemistry 15, 974). The native enzyme in Triton X-100 had an apparent molecular weight of over 200 000, as judged by Sepharose 6B gel filtration. The apparent size of the native enzyme appeared to be due to its association with Triton X-100, as judged by sucrose gradient centrifugation, polyacrylamide gel electrophoresis, and the lack of affinity for ion-exchange resins. The minimum subunit molecular weight of the enzyme, determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis, was 24 000. This low molecular weight is consistent with the stability of enzyme to heat, urea, or sodium dodecyl sulfate denaturation. The purified enzyme had an absolute requirement for magnesium ion (KM = 50 mM) and Triton X-100 (0.5-6%) for activity when either CDP-diglyceride or dCDP-diglyceride was used as substrate. Kinetic analysis of the enzymatic reaction indicated an ordered sequential Bi-Bi reaction with the liponucleotide forming a dead-end complex at high concentration, which inhibited both the forward and reverse reactions. The enzyme would not hydrolyze the pyrophosphate bond of its lipid substrate or the phosphate esters of its lipid product but would catalyze a cytidine 5'-monophosphate dependent exchange reaction between glycero-3-phosphate and phosphatidylglycerophosphate.
Unified monitoring and analytics in the cloud (2015)

Modern cloud applications are distributed across a wide range of instances of multiple types, including virtual machines, containers, and baremetal servers. Traditional approaches to monitoring and analytics fail in these complex, distributed and diverse environments. They are too intrusive and heavy-handed for short-lived, lightweight cloud instances, and cannot keep up with rapid the pace of change in the cloud with continuous dynamic scheduling, provisioning and auto-scaling. We introduce a unified monitoring and analytics architecture designed for the cloud. Our approach leverages virtualization and containerization to decouple monitoring from instance execution and health. Moreover, it provides a uniform view of systems regardless of instance type, and operates without intervening with the end-user context. We describe an implementation of our approach in an actual deployment, and discuss our experiences and observed results.
Preliminary communication: The synthesis of new mesogenic 1,3,4‐thiadiazole‐2‐carboxylate esters via a novel ring‐closure (2005)

Two new 5‐substituted 1,3,4‐thiadiazole‐2‐carboxylate esters have been synthesized via ring closure of appropriate tricarbonyl precursors using Lawesson's reagent. The chemistry described is the first report of such methodology in the organic literature. The new materials display broad smectic C phases and show considerable potential for use in electrooptic display devices.
Atrial fibrillation after cardiac surgery: where are we now? (2008)

POAF occurs in 25-60% of patients depending on the type of cardiac surgery performed. POAF generally occurs on postoperative day 2 or 3. POAF is associated with an increased risk of morbidity and mortality, and longer hospital stay. Prophylactic treatments reduce the likelihood of POAF. In patients who experience POAF, rhythm strategies should be used in those who are symptomatic and hemodynamically unstable. All other patients should be managed with rate strategies.
Lenalidomide in the treatment of multiple myeloma (2007)

Lenalidomide, a thalidomide analogue, has produced good results when used with dexamethasone in patients with relapsed or refractory MM. Lenalidomide is associated with hematologic toxicities, and participation in a restricted-distribution program is required of prescribers, pharmacies, and patients because of the drug's teratogenic potential.