gebhart/patrepeval huggingface dataset:
Principals’ Behavior and Job Satisfaction of Secondary School Teachers (2011)

Without question, the concept and practice of shared governance is critical to the health and vitality ofany institution of higher education. Perhaps no other characteristic distinguishes American highereducation more than this system of participatory governance and oversight. Democratic involvement ininstitutional decision-making, both operational and strategic, and at the institutional, school, and evenacademic department level, is necessary for institutional effectiveness and efficiency (Eckel, 2000).However, the issue is not without controversy, as shared governance is second only to tenure as mostdebated topic in academe (Tierney &amp; Holley, 2005).
Bone Microenvironment Modulates Expression and Activity of Cathepsin B in Prostate Cancer (2005)

Prostate cancers metastasize to bone leading to osteolysis. Here we assessed proteolysis of DQ-collagen I (a bone matrix protein) and, for comparison, DQ-collagen IV, by living human prostate carcinoma cells in vitro. Both collagens were degraded, and this degradation was reduced by inhibitors of matrix metallo, serine, and cysteine proteases. Because secretion of the cysteine protease cathepsin B is increased in human breast fibroblasts grown on collagen I gels, we analyzed cathepsin B levels and secretion in prostate cells grown on collagen I gels. Levels and secretion were increased only in DU145 cells--cells that expressed the highest baseline levels of cathepsin B. Secretion of cathepsin B was also elevated in DU145 cells grown in vitro on human bone fragments. We further investigated the effect of the bone microenvironment on cathepsin B expression and activity in vivo in a SCID-human model of prostate bone metastasis. High levels of cathepsin B protein and activity were found in DU145, PC3, and LNCaP bone tumors, although the PC3 and LNCaP cells had exhibited low cathepsin B expression in vitro. Our results suggest that tumor-stromal interactions in the context of the bone microenvironment can modulate the expression of the cysteine protease cathepsin B.
Design of 2,5-Dimethyl-3-(6-dimethyl-4-methylpyridin-3-yl)-7-dipropylaminopyrazolo[1,5-a]pyrimidine (NBI 30775/R121919) and Structure−Activity Relationships of a Series of Potent and Orally Active Corticotropin-Releasing Factor Receptor Antagonists (2004)

We have previously shown that 3-phenylpyrazolo[1,5-a]pyrimidines exemplified by 8 were potent antagonists of the human corticotropin-releasing factor-1 receptor. A series of 3-pyridylpyrazolo[1,5-a]pyrimidines 15, 25-30, 34, and 35 containing a weakly basic pyridine ring at the 3-position of the bicyclic nucleus was designed to reduce lipophilicity from the initial leads such as 7. Here, we showed that these 3-pyridyl compounds exhibited potent antagonists at the human CRF(1) receptor. Moreover, the hydrophilic and weakly basic pyridine moiety increased the water solubility of some analogues. Compound 26 h exhibited good binding affinity at the human CRF(1) receptor with a K(i) value of 3.5 nM. As a functional antagonist, it dose-dependently inhibited CRF-stimulated cAMP production in cells expressing the CRF(1) receptor (IC(50) = 50 nM), and CRF-stimulated ACTH release from cultured rat pituitary cells (IC(50) = 20 nM). 26 h had a log P value of 4.9 and water solubility of greater than 10 mg/mL. Pharmacokinetic studies in rats showed that 26 h was orally bioavailable and able to penetrate into the brain. 26 h has been demonstrated in vivo efficacy in animal behavioral models that measure anxiolytic activity. These results suggest that analogues from this series were potent CRF(1) receptor antagonists with proper physicochemical properties and good pharmacokinetic profiles. 26 h was developed into a clinical compound and exhibited efficacy in patients with major depression.
Disrupted Amygdalar Subregion Functional Connectivity and Evidence of a Compensatory Network in Generalized Anxiety Disorder (2009)

Our findings provide new insights into the functional neuroanatomy of the human amygdala and converge with connectivity studies in experimental animals. In GAD, we find evidence of an intra-amygdalar abnormality and engagement of a compensatory frontoparietal executive control network, consistent with cognitive theories of GAD.
Power Electronics forFutureUtility Applications (2007)

Medium-voltage converters, originally developed for industrial drives (e.g. insteel andpapermills), havenowadays entered utility applications. Forseveral years, thegrowing need forpowerquality indistribution systems inconjunction withthe large scale integration ofrenewable energysources hasboosted thedemandfornewtechnologies. Together withcommunication systems, powerelectronics arethekeyenabling technology to meetthese challenges. Thispaperaddresses several utility appli- cations forpowerelectronics, someofwhichareinusealready todaythoughmarketpenetration isstill low.Inthefield ofhigh powerinverters, conventional 3-level hard-switching converters as presently usede.g. inwindturbines arepresented alongside with soft-switching converters andtheir possible applications suchas STATCOMsormini-turbines. Thepossibility ofusing DC instead ofACtransmission anddistribution systems will bediscussed. DC systems havealready beenusedforseveral decades totransmit bulkpower. Newopportunities fortheuseofmodernVSC-HVDC willbeshown,suchasDC distribution systems. Forthisnovel application, newtechnologies areneeded, suchasmulti-megawatt DC-DCconverters andDC circuit breakers; possible concepts for thesetechnologies willbeaddressed. Cycloconverters, a rather conventional technology, havebeenapplied recently ininnovative waystoincrease theefficiencies ofveryhigh-power pumped- hydrostorage systems. Duetothefactthatthedevelopment ofnew converter systemsisalwaysstrongly related tothe available device technology, future high-power devices will finally bediscussed.
Interleukin‐10 Promoter Polymorphisms Influence HIV‐1 Susceptibility and Primary HIV‐1 Pathogenesis (2009)

Interleukin (IL)-10 directly inhibits human immunodeficiency virus type 1 (HIV-1) replication, but it may also promote viral persistence by inactivation of effector immune mechanisms. Here, we show in an African cohort that individuals with genotypes associated with high IL-10 production at 2 promoter single-nucleotide polymorphisms (-1082 and -592) were less likely to become HIV-1 infected but had significantly higher median plasma viral loads during the acute phase (<or=3 months after infection). However, as the infection progressed, the association between genotype and median viral load was reversed. Thus, IL-10 may influence HIV-1 susceptibility and pathogenesis, but effects on the latter may differ according to the infection phase.
Protein composition of cornified cell envelopes of epidermal keratinocytes (1994)

Terminally differentiated mammalian epidermal cells are lined with a 15 nm thick layer of proteins cross-linked by isodipeptide and disulfide bonds, called the cornified cell envelope (CE). A number of proteins, including involucrin, loricrin, cystatin A, filaggrin, a cysteine-rich protein (CRP) and the 'small proline-rich' proteins (SPRRs) have been reported to be components of this complex, but little information has been obtained as to their relative abundances because the acute insolubility of the CEs has precluded direct methods of analysis. To address this question, we have determined the amino acid compositions of isolated CEs, and then modelled them in terms of linear combinations of the candidate proteins. The results show that stratum corneum CEs have a loricrin content of 65-70% (w/w) in human, and 80-85% in mouse. In human epidermal CEs, the secondary contributors are filaggrin and CRP (each approximately 10%), with smaller amounts of involucrin, SPRR and cystatin A (2-5% each) also present. Mouse epidermal CEs have about the same amount of filaggrin and somewhat more SPRR, but only trace amounts of the other proteins. In marked contrast, the major constituents of the CEs of cultured keratinocytes induced to terminal differentiation in vitro are cystatin A, involucrin and CRP (each approximately 30%). No significant amount of loricrin was detected except in sloughed mouse cells, which represent a more advanced state of terminal differentiation than attached cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Mechanism of leakage of phospholipid vesicle contents induced by the peptide GALA (1990)

The synthetic, amphipathic peptide GALA undergoes a pH-dependent conformational change and induces leakage of contents from large unilamellar phosphatidylcholine vesicles when in a helical conformation. The kinetics of this process have been investigated over a wide range of pH and lipid and peptide concentrations. Leakage from lipid vesicles is rapidly initiated (within 2 s) when the pH is lowered below 6 and is rapidly terminated when the pH is raised to 7.5. The leakage shows a selectivity to the size of the entrapped molecules and occurs by an all or none mechanism; vesicles either leak or retain all of their contents. Using this experimental data, we have developed a mathematical description of the kinetics of leakage induced by GALA. This model assumes that GALA becomes incorporated into the vesicle bilayer and aggregates to form a pore. Leakage occurs when a critical number of peptides assemble into a supramolecular aggregate in the bilayer. Leakage curves generated at lipid/peptide ratios ranging from 500/1 to 30000/1 can be well described by this formalism. On the basis of the results and the model, we suggest that GALA forms a transbilayer channel composed of 8-12 monomers. The channel diameter ranges from 5 to 10 A. To the best of our knowledge, this is the first model that can predict the leakage kinetics of solutes entrapped in lipid vesicles induced by a pore-forming peptide. The analysis may be of general use in defining the kinetics and state of aggregation of similarly acting peptides and proteins which form multimeric assemblies in membranes.
Identification and Functional Analysis of the Gene Cluster for l -Arabinose Utilization in Corynebacterium glutamicum (2009)

Corynebacterium glutamicum ATCC 31831 grew on l-arabinose as the sole carbon source at a specific growth rate that was twice that on d-glucose. The gene cluster responsible for l-arabinose utilization comprised a six-cistron transcriptional unit with a total length of 7.8 kb. Three l-arabinose-catabolizing genes, araA (encoding l-arabinose isomerase), araB (l-ribulokinase), and araD (l-ribulose-5-phosphate 4-epimerase), comprised the araBDA operon, upstream of which three other genes, araR (LacI-type transcriptional regulator), araE (l-arabinose transporter), and galM (putative aldose 1-epimerase), were present in the opposite direction. Inactivation of the araA, araB, or araD gene eliminated growth on l-arabinose, and each of the gene products was functionally homologous to its Escherichia coli counterpart. Moreover, compared to the wild-type strain, an araE disruptant exhibited a >80% decrease in the growth rate at a lower concentration of l-arabinose (3.6 g liter(-1)) but not at a higher concentration of l-arabinose (40 g liter(-1)). The expression of the araBDA operon and the araE gene was l-arabinose inducible and negatively regulated by the transcriptional regulator AraR. Disruption of araR eliminated the repression in the absence of l-arabinose. Expression of the regulon was not repressed by d-glucose, and simultaneous utilization of l-arabinose and d-glucose was observed in aerobically growing wild-type and araR deletion mutant cells. The regulatory mechanism of the l-arabinose regulon is, therefore, distinct from the carbon catabolite repression mechanism in other bacteria.
Reprogramming mediated by stem cell fusion (2005)

Advances in mammalian cloning prove that somatic nuclei can be reprogrammed to a state of totipotency by transfer into oocytes. An alternative approach to reprogram the somatic genome involves the creation of hybrids between somatic cells and other cells that contain reprogramming activities. Potential fusion partners with reprogramming activities include embryonic stem cells, embryonic germ cells, embryonal carcinoma cells, and even differentiated cells. Recent advances in fusion-mediated reprogramming are discussed from the standpoints of the developmental potency of hybrid cells, genetic and epigenetic correlates of reprogramming, and other aspects involved in the reprogramming process. In addition, the utility of fusion-mediated reprogramming for future cell-based therapies is discussed.
Cloning Vectors Derived from Animal Viruses (1983)

Microbiology Society journals contain high-quality research papers and topical review articles. We are a not-for-profit publisher and we support and invest in the microbiology community, to the benefit of everyone. This supports our principal goal to develop, expand and strengthen the networks available to our members so that they can generate new knowledge about microbes and ensure that it is shared with other communities.
The Xenopus Chk1 Protein Kinase Mediates a Caffeine-sensitive Pathway of Checkpoint Control in Cell-free Extracts (1998)

We have analyzed the role of the protein kinase Chk1 in checkpoint control by using cell-free extracts from Xenopus eggs. Recombinant Xenopus Chk1 (Xchk1) phosphorylates the mitotic inducer Cdc25 in vitro on multiple sites including Ser-287. The Xchk1-catalyzed phosphorylation of Cdc25 on Ser-287 is sufficient to confer the binding of 14-3-3 proteins. Egg extracts from which Xchk1 has been removed by immunodepletion are strongly but not totally compromised in their ability to undergo a cell cycle delay in response to the presence of unreplicated DNA. Cdc25 in Xchk1-depleted extracts remains bound to 14-3-3 due to the action of a distinct Ser-287-specific kinase in addition to Xchk1. Xchk1 is highly phosphorylated in the presence of unreplicated or damaged DNA, and this phosphorylation is abolished by caffeine, an agent which attenuates checkpoint control. The checkpoint response to unreplicated DNA in this system involves both caffeine-sensitive and caffeine-insensitive steps. Our results indicate that caffeine disrupts the checkpoint pathway containing Xchk1.
Development and Field Demonstration of DSRC Based V2V-Assisted V2I Traffic Information System for the Work Zone (2012)

This report describes the architecture, functionality and the field demonstration results of a newly developed DSRC&#13;\nbased V2I work zone traffic information system with V2V assistance. The developed system can automatically&#13;\nacquire important work zone travel information, e.g., the travel time (TT) and the starting location of congestion&#13;\n(SLoC), and relay them back to the drivers approaching the congestion site. Such information can help drivers in&#13;\nmaking informed decisions on route choice and/or preparing for upcoming congestion. Previously, we designed&#13;\nsuch a system using DSRC based V2I-only communication, which could not handle longer congestion lengths and&#13;\nthe message broadcast range was also very limited. Our current system, on the other hand, can achieve much longer&#13;\nbroadcast range (up to a few tens of kms), and can handle much longer congestion coverage length (up to a few&#13;\nkms) by incorporating DSRC based V2I communication with V2V assistance. The new system is also portable and&#13;\nuses only one RSU, which can acquire traffic data by engaging the vehicles traveling on the roadside whether&#13;\nwithin or outside of its direct wireless access range. From the traffic data, it estimates important traffic parameters,&#13;\ni.e., TT and SLoC, and periodically broadcasts them back to the vehicles approaching the congestion well before&#13;\nthey enter the congested area. The results from the field demonstration have indicated that new system can adapt to&#13;\ndynamically changing work zone traffic environments and can handle much longer congestion lengths as compared&#13;\nto the previous system using V2I-only communication without V2V assistance.
Oxidative Stress in Chronic Obstructive Pulmonary Disease (1997)

Contains fulltext : 123872.pdf (Publisher’s version ) (Open Access)
Wildlife Fertility Control (2002)

Huge flights of Canada geese turn off local park visitors with their messy, smelly "business cards." The superabundant white-tailed deer we love to watch also can do a number on your car at night and host the ticks that carry Lyme Disease. Blackbirds and gulls and coyotes and other critters bring their own problems when their numbers get out of hand. Most such problems reach their highest profile in urban/suburban areas where traditional animal-control techniques such as hunting and trapping are frowned upon or illegal. More and more people are calling for wildlife managers to use "fertility control"–-but is that concept really feasible on populations of free-ranging wildlife? The definitive answers–in the form of the latest science–are contained in a new Technical Review titled Wildlife Fertility Control. The 29-page Review notes that in the past, fertility control has been far less successful than observers had hoped, but thanks to new findings about animal reproductive systems, the technology is advancing rapidly and is being tested on several species on a small scale. Hurdles include the need to develop and commercialize effective vaccines or baits, cost-effective delivery systems, and public-agency acceptance of the technique. The new publication states that "birth control" will undoubtedly play a role in the science of wildlife management in the future. Managers face two major challenges: integrating contraceptive tactics with more conventional ways of managing critter numbers, and giving the public accurate information about the feasibility of using fertility control vs. lethal methods to reduce populations of deer and other long-lived species.
Granulocytes, macrophages, and dendritic cells arise from a common major histocompatibility complex class II-negative progenitor in mouse bone marrow. (1993)

The developmental origin of dendritic cells, a specialized system of major histocompatibility complex (MHC) class II-rich antigen-presenting cells for T-cell immunity and tolerance, is not well characterized. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is known to stimulate dendritic cells, including growth and development from MHC class II-negative precursors in suspension cultures of mouse bone marrow. Here we studied colony formation in semi-solid methylcellulose cultures, a classical bioassay system in which GM-CSF induces the formation of mixed granulocyte-macrophage colonies. When colonies were induced from MHC class II-negative precursors, a small subset (1-2%) of typical dendritic cells developed alongside macrophages and granulocytes. The dendritic cells were distinguished by their cytologic features, high levels of MHC class II products, and distinct intracellular granule antigens. By using differential adherence to plastic, enriched populations of the various myeloid cell types were isolated from colonies. Only the dendritic cells stimulated a primary T-cell immune response, the mixed leukocyte reaction, and the potency was comparable to typical dendritic cells isolated from spleen. Macrophages from mixed or pure colonies were inactive as stimulator cells. Therefore, three distinct pathways of myeloid development--granulocytes, macrophages, and dendritic cells--can develop from a common MHC class II-negative progenitor under the aegis of GM-CSF.
Binding of the Hepatitis C Virus E2 Glycoprotein to CD81 Is Strain Specific and Is Modulated by a Complex Interplay between Hypervariable Regions 1 and 2 (2003)

The envelope glycoprotein E2 of hepatitis C virus (HCV) is the target of neutralizing antibodies and is presently being evaluated as an HCV vaccine candidate. HCV binds to human cells through the interaction of E2 with the tetraspanin CD81, a putative viral receptor component. We have analyzed four different E2 proteins from 1a and 1b viral isolates for their ability to bind to recombinant CD81 in vitro and to the native receptor displayed on the surface of Molt-4 cells. A substantial difference in binding efficiency between these E2 variants was observed, with proteins derived from 1b subtypes showing significantly lower binding than the 1a protein. To elucidate the mechanism of E2-CD81 interaction and to identify critical regions responsible for the different binding efficiencies of the E2 variants, several mutants were generated in E2 protein regions predicted by computer modeling to be exposed on the protein surface. Functional analysis of these E2 derivatives revealed that at least two distinct domains are responsible for interaction with CD81. A first segment centered around amino acid residues 613 to 618 is essential for recognition, while a second element including the two hypervariable regions (HVRs) modulates E2 receptor binding. Binding inhibition experiments with anti-HVR monoclonal antibodies confirmed this mapping and supported the hypothesis that a complex interplay between the two HVRs of E2 is responsible for modulating receptor binding, possibly through intramolecular interactions. Finally, E2 proteins from different isolates displayed a profile of binding to human hepatic cells different from that observed on Molt-4 cells or isolated recombinant CD81, indicating that additional factors are involved in viral recognition by target liver cells.
Model Studies Related to the Cofactor of the Oxomolybdoenzymes; Part 6:1An Improved Synthesis of 6-Substituted Pterins from 2,4,5-Triamino-6-hydroxypyrimidine and D-Glucose (1992)

6-Alkenylpterin 10 {2-acetylamino-6-[(3,4-isopropylidenedioxy)-1-butenyl]pyrimido [4,5-b]pyrazin-4(3H)-one} was prepared from 2,4,5-triamino-6-hydroxypyrimidine (3) and D-glucose via the Isay condensation product 2.
Circulating Tumor Cells: Clinically Relevant Molecular Access Based on a Novel CTC Flow Cell (2014)

The LiquidBiopsy platform is an automated validated platform that provides high throughput molecular access to the CTC population. It can be validated and integrated into the lab flow enabling CTC enumeration as well as recovery of consistently high purity samples for molecular analysis such as quantitative PCR and Next Generation Sequencing. This tool opens the way for clinically relevant genetic profiling of CTCs.
Structure-Function Relationships in the Vitamin D Endocrine System* (1995)

RESEARCH directed at defining the molecular mode of action of vitamin D is currently at its apex. There is now evidence implicating the essential involvement of vitamin D metabolites in a host of cellular processes, including calcium homeostasis, immunology, cell differentiation, and regulation of gene transcription. Further, there is evidence that the hormonally active form of vitamin D, 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3], may generate biological responses via both regulation of gene transcription as well as via nongenomic pathways, some of which involve opening of voltage-gated Ca2+ channels. In addition, there are many examples of pathological disruption of the normal state in which a drug form of a vitamin D metabolite is proposed to be a (potentially) useful form of treatment, e.g. renal osteodystrophy, psoriasis, leukemia, breast cancer, and osteoporosis. The importance of the molecule vitamin D in the biological systems of higher animals has been recognized since its discovery by Mellanby in 1920 (1). It was in the interval of 1920–1930 that vitamin D officially became classified as a “vitamin” that was essential for the normal development of the skeleton and maintenance of Ca2+ homeostasis. The chemical structure of vitamin D was not determined until 1932 (2), and it was only then that it was apparent that this important nutritional substance was in reality a steroid, more specifically, a secosteroid, indicating that one of the rings of the cyclopentanoperhydrophenanthrene ring structure (the 9–10 carbon-carbon bond of ring B) was broken (see Section II).