gebhart/patrepeval huggingface dataset:
Pharmacophore/Receptor Models for GABA<sub>A</sub>/BzR Subtypes (α1β3γ2, α5β3γ2, and α6β3γ2) via a Comprehensive Ligand-Mapping Approach (1999)

Pharmacophore/receptor models for three recombinant GABA(A)/BzR subtypes (alpha1beta3gamma2, alpha5beta3gamma2, and alpha6beta3gamma2) have been established via an SAR ligand-mapping approach. This study was based on the affinities of 151 BzR ligands at five distinct (alpha1-3,5,6beta3gamma2) recombinant GABA(A)/BzR receptor subtypes from at least nine different structural families. Examination of the included volumes of the alpha1-, alpha5-, and alpha6-containing subtypes indicated that region L(2) for the alpha5-containing subtype appeared to be larger in size than the analogous region of the other receptor subtypes. Region L(Di), in contrast, appeared to be larger in the alpha1 subtype than in the other two subtypes. Moreover, region L(3) in the alpha6 subtype is either very small or nonexistent in this diazepam-insensitive subtype (see Figure 16 for details) as compared to the other subtypes. Use of the pharmacophore/receptor models for these subtypes has resulted in the design of novel BzR ligands (see 27) selective for the alpha5beta3gamma2 receptor subtype. alpha5-Selective ligand 27 when injected directly into the hippocampus did enhance memory in one paradigm (Bailey et al., unpublished observations); however, systemic administration of either 9 or 27 into animals did not provide an observable enhancement. This result is in complete agreement with the observation of Liu (1996). It has been shown (Liu, 1996; Wisden et al., 1992) that in the central nervous system of the rat (as well as monkeys and pigeons) there are several native subtypes of the GABA(A) receptor which exhibit different functions, regional distributions, and neuronal locations. Although 27 binds more potently at alpha5beta3gamma2 receptor subtypes and is clearly an inverse agonist (Liu et al., 1996; Liu, 1996), it is possible that this ligand acts as an agonist at one or more subtypes. Liu (1996) clearly showed that a number of imidazobenzodiazepines were negative modulators at one subtype and agonists at another. Therefore, selectivity for a particular subtype at this point is not sufficient to rule out some physiological effect at other GABA(A)/BzR subtypes. The inability of 27 to potentiate memory when given systemically is again in support of this hypothesis, especially since alpha1beta2gamma2 subtypes are distributed throughout the brain (Wisden et al., 1992). A drug delivered systemically is far more likely to interact with all subtypes than one delivered to a specific brain region. This observation (systemic vs intrahippocampal) provides further support for the design of more subtype-specific ligands at the BzR to accurately define their pharmacology, one key to the design of new drugs with fewer side effects.
A Implementation of Object Oriented Database Security (2007)

This paper is to address high-level authorization specifications and its efficient implementation in object oriented database scenario. Premchand Ambhore is with higher and technical education, maharashtra state, india, e-mail: pbambhore@yahoo.com . The rest of the paper is organized as follows. Section 2 specifies object oriented database system; section 3 incorporates authorization rules into database and section 4 maps the specification into a logic programming language and implements the language. Section 5 concludes the paper. The integration of object-oriented programming concepts with databases is one of the most significant advances in the evolution of database system, therefore the problems involved in providing data security for object oriented databases have been receiving very great attention from researchers. As a matter of fact, data are the most sensitive part of any system and its loss or compromise can have disastrous consequences. We discuss three different types of access: discretionary access control (DAC), mandatory access control (MAC) and role based access control (RBAC) in relational DBMS and object oriented data bases. We have identified some of the issues and current proposals; current security models in object oriented database systems and outline possible direction issues for future research.
Data transmission at 19.2 kbit/s over telephone circuits (1983)

The paper describes a theoretical study of two different 19200 bit/s q.a.m. data-transmission systems suitable for use over voice-band telephone circuits. One of the systems employs a 64-point q.a.m. signal with an element rate of 3200 bauds, and the other employs a 256-point q.a.m. signal with an element rate of 2400 bauds. A near-maximum-likelihood detection process, derived from a reduced-state Viterbi-algorithm detector, is used at the receiver in each case. Results of computer-simulation tests are presented, comparing the tolerances of the two systems to additive white Gaussian noise, where the data are transmitted over models of four different telephone circuits. The effects, on the tolerance to noise, of inaccuracies in the estimates of the level and carrier phase of the received signal are also studied.
Delivering MBA Programs in Emerging Markets (2013)

Increasingly, Western-style MBA programs are being delivered in emerging markets, as the developed countries become more and more saturated with MBAs and related offerings. This article, based on the global experience of the author in teaching and assessing MBA modules including thesis and dissertation research and writing, suggests approaches to coping with the special challenges faced in new markets for MBA delivery worldwide. The differences with typical experiences in the West are cultural, linguistic, behavioral and relate to learning styles, economic backgrounds, use of technology, and relationships with administrators, teachers and fellow-students. This article is based on the author’s experiences of MBA course delivery in China, the Arab World, Africa, Iran, Malaysia and Indonesia, Vietnam, Eastern Europe, former Russian states such as Kazakhstan, and South America, such as Peru and Suriname. Examples of specific MBA teaching and assessment challenges are provided, with possible solutions and approaches for coping.
Thioredoxin 1 as a serum marker for breast cancer and its use in combination with CEA or CA15-3 for improving the sensitivity of breast cancer diagnoses (2014)

Taken together, we conclude that serum Trx1 is useful for the early diagnosis of breast cancer or the early prediction prognosis of breast cancer, and therefore has a valuable use as a diagnostic marker and companion marker to CEA and CA15-3 for breast cancer.
Soldering technology for optoelectronic packaging (2002)

Soldering technology for optoelectronic packaging is reviewed by studying modules in four categories: solder assembly with no precision self-alignments, and self-aligned solder assembly with no, one or two mechanical stops. There have been at least 60 papers and 8 U.S. patents published between 1990 and 1995. In addition to die-attachments, soldering technology has been successfully demonstrated for precision alignments. However, some packaging issues may hamper the progress of its manufacturing insertion for wide applications. Four of the issues to be discussed are solder materials, fluxless reflow, design, and reliability. More studies on these issues are needed to support the advancement of optoelectronic packaging for low-cost, high-performance and high-reliability modules.
Extraction of glycerol from biodiesel into a eutectic based ionic liquid (2007)

A Lewis basic mixture of quaternary ammonium salts with glycerol has been used to extract excess glycerol from biodiesel formed from the reaction of triglycerides with ethanol in the presence of KOH. The effect of the cation on the partition coefficient of glycerol was determined, together with the time taken for the systems to reach equilibrium. Protocols were also investigated for the separation of glycerol from the quaternary ammonium salt mixtures.
A Meta-Analysis of Randomized Controlled Trials Comparing Endoscopic and Open Carpal Tunnel Decompression (2004)

Controversy exists regarding the benefit of endoscopic carpal tunnel release versus open carpal tunnel release in terms of grip/pinch strength, scar tenderness, pain, return to work, reversible/irreversible nerve damage, and adverse effects. Although a number of randomized controlled trials and systematic reviews have been published on the subject, to date, no large definitive randomized controlled trial or meta-analysis has been performed comparing endoscopic to open carpal tunnel release. This meta-analysis was undertaken to address the effectiveness of endoscopic carpal tunnel release relative to open carpal tunnel release. Key outcome measures from 13 randomized controlled trials were extracted and statistically combined. Heterogeneity was observed in three of the outcomes (i.e., grip strength, pain, and return to work), but the causes of heterogeneity could not be explained because of insufficient detail in the reported studies. Using the Jadad et al. scale, nine of 13 studies were of low methodologic quality. The effect sizes were compared between the studies that were rated as high quality and the studies that were rated as low quality on the Jadad et al. scale. Similarly, the studies that were rated as high quality on the Gerritsen et al. scale were compared with those that were rated as low quality. No clinically significant difference in effect sizes was apparent between studies of high and low methodologic quality. This meta-analysis supports the conclusion that endoscopic carpal tunnel release is favored over the open carpal tunnel release in terms of a reduction in scar tenderness and increase in grip and pinch strength at a 12-week follow-up. With regard to symptom relief and return to work, the data are inconclusive. Irreversible nerve damage is uncommon in either technique; however, there is an increased susceptibility to reversible nerve injury that is three times as likely to occur with endoscopic carpal tunnel release than with open carpal tunnel release.
Münsteraner Wiedertäufer Revivals, Teil 2. Eine Antwort auf Armin Scholl (2000)

Medien & Kommunikationswissenschaft provides a forum for discussion of media and communications related issues as well as for analyses of current media developments from various perspectives that are directed to all kinds of media. The journal reflects the latest trends in research and public discussion of media. Medien & Kommunikationswissenschaft primarily addresses scholars, journalists, media organisations, the press, radio and tv broadcaster, film, tv, and video production companies, organisations, and teachers. Website: www.m-und-k.nomos.de
Secondary Metabolites Produced by the Marine Bacterium <i>Halobacillus salinus</i> That Inhibit Quorum Sensing-Controlled Phenotypes in Gram-Negative Bacteria (2008)

Certain bacteria use cell-to-cell chemical communication to coordinate community-wide phenotypic expression, including swarming motility, antibiotic biosynthesis, and biofilm production. Here we present a marine gram-positive bacterium that secretes secondary metabolites capable of quenching quorum sensing-controlled behaviors in several gram-negative reporter strains. Isolate C42, a Halobacillus salinus strain obtained from a sea grass sample, inhibits bioluminescence production by Vibrio harveyi in cocultivation experiments. With the use of bioassay-guided fractionation, two phenethylamide metabolites were identified as the active agents. The compounds additionally inhibit quorum sensing-regulated violacein biosynthesis by Chromobacterium violaceum CV026 and green fluorescent protein production by Escherichia coli JB525. Bacterial growth was unaffected at concentrations below 200 microg/ml. Evidence is presented that these nontoxic metabolites may act as antagonists of bacterial quorum sensing by competing with N-acyl homoserine lactones for receptor binding.
Cultural perspectives on romantic love (1996)

Abstract Culture‐related dimensions contribute to a more complete understanding of romantic love. In particular, we suggest that the dimensions of individualism and collectivism, at both societal and psychological levels, offer insights into the nature of romantic love and its perceived importance for marriage. Changes In values pertaining to romantic love and its role In choosing a spouse are evident In several traditionally collectivistic societies and among persons from these societies emigrating to countries such as Canada, Australia, and the United States. Given these trends, we discuss the need to study individualism and collectivism at the psychological level and present findings from our own program of research.
Eight forces shaping legal innovation in the Australian market (2019)

In their research paper, entitled State of Legal Innovation in the Australian market, authors Eric Chin, Graeme Grovum and Matthew Grace, from the Alpha Creates legal industry consulting firm, explain how the Australian legal sector is changing. They also reveal gaps in the market that are creating opportunities for innovative legal services providers.
Antisense suppression of the rice transporter gene, <i>OsSUT1</i> , leads to impaired grain filling and germination but does not affect photosynthesis (2002)

OsSUT1 encodes a rice sucrose transport protein that is highly expressed in developing grain, leaf sheath and stem after heading, and in germinating seedlings, but only at very low levels in source leaves. In this study, we have used antisense gene suppression to elucidate the in vivo function of OsSUT1. Rice was transformed with an antisense construct containing a portion of the 3'-coding and non-coding regions of OsSUT1 driven by the maize ubiquitin-1 promoter. Twenty-six independent stably transformed lines were obtained. T0 and selfed T1 progeny were analysed for suppression of OsSUT1 expression and function. Many of the plants showed a significant reduction in their ability to produce filled grain, and final grain weight was reduced. Severe phenotypes correlated with a reduction in OsSUT1 transcript level in filling grain. Unlike SUT1 antisense suppression in dicots, source supply of photosynthate was unaffected in these transformants. This provides the first direct evidence for the requirement of a sucrose transporter for grain filling in a cereal species. Furthermore, seed from some of the T0 population showed a reduction in the rate of germination and growth, supporting the hypothesis that OsSUT1 may also play a role in transporting sucrose remobilized from starch reserves in germinating seeds.
In vitro formation of a lariat structure containing a G2'-5'G linkage. (1987)

We have examined the effects of base changes at the lariat branch site of a modified adenovirus major late precursor mRNA (pre-mRNA). Replacement of the A residue at the lariat attachment site with a G residue was studied. Incubation of this altered pre-mRNA with nuclear extracts of HeLa cells yielded less spliced mRNA (10-fold) than similar reactions with the wild type pre-mRNA. The intron lariat formed during the reaction with the mutant transcript contained the predominant branch (2'-5' phosphodiester linkage) to an upstream A residue. In contrast, the intron/exon 2 lariat contained the predominant branch to the substituted G residue. These results indicated that detectable spliced RNA was formed when the lariat was attached at the A residue but not when the lariat was attached to the substituted G residue. A second mutation was introduced into the transcript by substituting an additional G residue at the alternative A branch site. When transcript derived from this plasmid was incubated with nuclear extract, cleavage occurred at the 5' splice site, and an intron/exon 2 lariat was produced, but spliced RNA was not detected. T1 RNase digestion and primer extension analyses of this intron/exon 2 lariat revealed that all of the lariat formed on the G residue at the normal attachment site.
Myosin IIA-related Actomyosin Contractility Mediates Oxidative Stress-induced Neuronal Apoptosis (2017)

Oxidative stress-induced neuronal apoptosis plays an important role in the progression of central nervous system (CNS) diseases. In our study, when neuronal cells were exposed to hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>), an exogenous oxidant, cell apoptosis was observed with typical morphological changes including membrane blebbing, neurite retraction and cell contraction. The actomyosin system is considered to be responsible for the morphological changes, but how exactly it regulates oxidative stress-induced neuronal apoptosis and the distinctive functions of different myosin II isoforms remain unclear. We demonstrate that myosin IIA was required for neuronal contraction, while myosin IIB was required for neuronal outgrowth in normal conditions. During H<sub>2</sub>O<sub>2</sub>-induced neuronal apoptosis, myosin IIA, rather than IIB, interacted with actin filaments to generate contractile forces that lead to morphological changes. Moreover, myosin IIA knockout using clustered regularly interspaced short palindromic repeats/CRISPR-associated protein-9 nuclease (CRISPR/Cas9) reduced H<sub>2</sub>O<sub>2</sub>-induced neuronal apoptosis and the associated morphological changes. We further demonstrate that caspase-3/Rho-associated kinase 1 (ROCK1) dependent phosphorylation of myosin light chain (MLC) was required for the formation of the myosin IIA-actin complex. Meanwhile, either inhibition of myosin II ATPase with blebbistatin or knockdown of myosin IIA with siRNA reversely attenuated caspase-3 activation, suggesting a positive feedback loop during oxidative stress-induced apoptosis. Based on our observation, myosin IIA-actin complex contributes to actomyosin contractility and is associated with the positive feedback loop of caspase-3/ROCK1/MLC pathway. This study unravels the biochemical and mechanistic mechanisms during oxidative stress-induced neuronal apoptosis and may be applicable for the development of therapies for CNS diseases.
Cyclobutane pyrimidine dimers are predominant DNA lesions in whole human skin exposed to UVA radiation (2006)

Solar UV radiation is the most important environmental factor involved in the pathogenesis of skin cancers. The well known genotoxic properties of UVB radiation (290-320 nm) mostly involve bipyrimidine DNA photoproducts. In contrast, the contribution of more-abundant UVA radiation (320-400 nm) that are not directly absorbed by DNA remains poorly understood in skin. Using a highly accurate and quantitative assay based on HPLC coupled with tandem mass spectrometry, we determined the type and the yield of formation of DNA damage in whole human skin exposed to UVB or UVA. Cyclobutane pyrimidine dimers, a typical UVB-induced DNA damage, were found to be produced in significant yield also in whole human skin exposed to UVA through a mechanism different from that triggered by UVB. Moreover, the latter class of photoproducts is produced in a larger amount than 8-oxo-7,8-dihydro-2'-deoxyguanosine, the most common oxidatively generated lesion, in human skin. Strikingly, the rate of removal of UVA-generated cyclobutane pyrimidine dimers was lower than those produced by UVB irradiation of skin. Finally, we compared the formation yields of DNA damage in whole skin with those determined in primary cultures of keratinocytes isolated from the same donors. We thus showed that human skin efficiently protects against UVB-induced DNA lesions, whereas very weak protection is afforded against UVA. These observations emphasize the likely role played by the UVA-induced DNA damage in skin carcinogenesis and should have consequences for photoprotection strategies.
The peroxisome proliferator‐activated receptor‐γ agonist 1,1‐bis(3′‐indolyl)‐1‐(p‐trifluoromethylphenyl)methane suppresses manganese‐induced production of nitric oxide in astrocytes and inhibits apoptosis in cocultured PC12 cells (2007)

Reactive astrogliosis is a prominent neuropathologic feature of manganism, a neurodegenerative disorder caused by excessive accumulation of manganese (Mn) in the basal ganglia. Activation of astrocytes has been linked to neuronal injury in manganism resulting from overproduction of inflammatory mediators, including tumor necrosis factor-alpha (TNFalpha), interferon-gamma (IFNgamma), interleukin-1beta (IL-1beta), and nitric oxide (NO), but the signaling mechanisms by which Mn regulates these factors remain poorly understood. We previously reported that Mn enhances production of NO in activated astrocytes that promotes apoptosis in cocultured neuronal cells by a mechanism involving the transcription factor nuclear factor-kappaB (NF-kappaB) (Liu et al., 2005). Because NF-kappaB-dependent expression of inducible nitric oxide synthase (NOS2) can be antagonized by the nuclear orphan receptor peroxisome proliferator-activated receptor-gamma (PPARgamma), we postulated that a novel agonist of this receptor, 1,1-bis(3'-indolyl)-1-(p-trifluoromethylphenyl)methane (cDIM1), would suppress expression of NOS2 in astrocytes and protect cocultured neuronal cells from apoptosis. Submicromolar concentrations of cDIM1 potently suppressed production of NO and expression of NOS2 in cultured astrocytes exposed to Mn and IFNgamma/TNFalpha and prevented apoptosis in cocultures of differentiated PC12 cells, but this neuroprotective effect was lost in the absence of astrocytes. By using fluorescence reporter and chromatin immunoprecipitation (ChIP) assays, we found that cDIM1 prevented activation of NF-kappaB in astrocytes by a mechanism involving stabilization of the nuclear corepressor 2 (NCoR2) on the proximal NF-kappaB binding site of the NOS2 promoter. These data suggest that PPARgamma may be an effective target for limiting inflammatory activation of astrocytes during neurologic injury.
Impact of Impaired Receptor Internalization on Calcium Homeostasis in Knock-In Mice Expressing a Phosphorylation-Deficient Parathyroid Hormone (PTH)/PTH-Related Peptide Receptor (2006)

Internalization of G protein-coupled receptors (GPCRs) and desensitization of the hormonal responses are well characterized in vitro for several hormonal systems. The physiological role of internalization for a GPCR receptor involved in homeostatic functions has not been established, although it has been assumed based on in vitro data. We have previously shown that phosphorylation of the PTH/PTHrP receptor is required for its internalization and for the desensitization of the responsiveness to PTH and PTHrP in vitro; the internalization and desensitization response is impaired in a PTH/PTHrP receptor mutant bearing serine to alanine mutations in the phosphate acceptor sites. To understand the physiological role of receptor internalization on calcium homeostasis, we have knocked-in the internalization-impaired PTH/PTHrP receptor mutant using homologous recombination technology. The genetically modified animals exhibited calcium levels no different from control animals, but PTH levels were one third of those in control animals indicating that homeostasis could be maintained only by 3-fold suppression of PTH secretion. We also analyzed the calcemic response to PTH in vivo. Here we show that mice expressing the internalization-impaired PTH/PTHrP receptor mutant have dramatically exaggerated cAMP and calcemic responses to sc PTH administration when compared with control animals given the same dose. These data show for the first time the role of G protein receptor phosphorylation and internalization per se in the regulatory function of an endocrine system controlled by a GPCR.