gebhart/patrepeval huggingface dataset:
Identification and characterization of an enzyme involved in the elongation of n-6 and n-3 polyunsaturated fatty acids (2000)

The enzymes that are involved in the elongation of fatty acids differ in terms of the substrates on which they act. To date, the enzymes specifically involved in the biosynthesis of polyunsaturated fatty acids have not yet been identified. In an attempt to identify a gene(s) encoding an enzyme(s) specific for the elongation of gamma-linolenic acid (GLA) (18:3n-6), a cDNA expression library was made from the fungus Mortierella alpina. The cDNA library constructed in a yeast expression vector was screened by measuring the expressed elongase activity [conversion of GLA to dihomo-GLA (20:3n-6)] from an individual yeast clone. In this report, we demonstrate the isolation of a cDNA (GLELO) whose encoded protein (GLELOp) was involved in the conversion of GLA to dihomo-GLA in an efficient manner (60% conversion). This cDNA contains a 957-nucleotide ORF that encodes a protein of 318 amino acids. Substrate specificity analysis revealed that this fungal enzyme acted also on stearidonic acid (18:4n-3). This report identifies and characterizes an elongase subunit that acts specifically on the two Delta6-desaturation products, 18:3n-6 and 18:4n-3. When this GLELO cDNA was coexpressed with M. alpina Delta5-desaturase cDNA in yeast, it resulted in the conversion of GLA to arachidonic acid (20:4n-6) as well as the conversion of stearidonic acid to eicosopentaenoic acid (20:5n-3). Thus, this GLELO gene may play an critical role in the bio-production of both n-6 and n-3 polyunsaturated fatty acids.
Melatonin in Human Preovulatory Follicular Fluid* (1987)

Melatonin, the major hormone of the pineal gland, has antigonadotrophic activity in many mammals and may also be involved in human reproduction. Melatonin suppresses steroidogenesis by ovarian granulosa and luteal cells in vitro. To determine if melatonin is present in the human ovary, preovulatory follicular fluids (n = 32) from 15 women were assayed for melatonin by RIA after solvent extraction. The fluids were obtained by laparoscopy or sonographically controlled follicular puncture from infertile women undergoing in vitro fertilization and embryo transfer. All patients had received clomiphene citrate, human menopausal gonadotropin, and hCH to stimulate follicle formation. Blood samples were obtained by venipuncture 30 min or less after follicular aspiration. All of the follicular fluids contained melatonin, in concentrations [36.5 +/- 4.8 (+/- SEM) pg/mL] substantially higher than those in the corresponding serum (10.0 +/- 1.4 pg/mL). A positive correlation was found between follicular fluid and serum melatonin levels in each woman (r = 0.770; P less than 0.001). These observations indicate that preovulatory follicles contain substantial amounts of melatonin that may affect ovarian steroidogenesis.
The Effect of Excess PbO on Dielectric and Pyroelectric Properties of Lead Scandium Tantalate Ceramics (2010)

Lead scandium tantalate (PbSc 0.5 Ta 0.5 O 3 , or PST) ceramics with the addition of 0.5–10 wt% excess PbO were fabricated by the hot‐pressing method. The percent of perovskite PST and the long‐range order parameter S were quantitatively characterized by X‐ray diffraction analysis. The grain size was measured by scanning electron microscopy. The dielectric and pyroelectric behavior under dc bias were investigated from −20° to –50°C. The relationships among dielectric constant, Curie temperature, and dc bias were analyzed by fitting to the Gibbs free energy formulas. Based on these data, the pyroelectric figures of merit F d as a function of field and temperature were calculated, and the highest F d of 15 × 10 −5 Pa −1/2 was obtained under 700 V/mm in the sample with 5 wt% excess PbO.
Application of guidelines for designing user interface software (1986)

Abstract A survey was conducted of people who had received a report on guidelines for designing user interface software. Analysis of questionnaire responses indicates that respondents considered guidelines useful, that they have used guidelines in various stages of design, and that they plan to use guidelines again. However, respondents also reported significant problems in the practical application of guidelines. Respondents had difficulty locating relevant guidelines within the report, choosing which guidelines would actually be used, establishing priorities among the selected guidelines, and translating generally worded guidelines into specific design rules.
Crystal Structures of GII.10 and GII.12 Norovirus Protruding Domains in Complex with Histo-Blood Group Antigens Reveal Details for a Potential Site of Vulnerability (2011)

Noroviruses are the dominant cause of outbreaks of gastroenteritis worldwide, and interactions with human histo-blood group antigens (HBGAs) are thought to play a critical role in their entry mechanism. Structures of noroviruses from genogroups GI and GII in complex with HBGAs, however, reveal different modes of interaction. To gain insight into norovirus recognition of HBGAs, we determined crystal structures of norovirus protruding domains from two rarely detected GII genotypes, GII.10 and GII.12, alone and in complex with a panel of HBGAs, and analyzed structure-function implications related to conservation of the HBGA binding pocket. The GII.10- and GII.12-apo structures as well as the previously solved GII.4-apo structure resembled each other more closely than the GI.1-derived structure, and all three GII structures showed similar modes of HBGA recognition. The primary GII norovirus-HBGA interaction involved six hydrogen bonds between a terminal αfucose1-2 of the HBGAs and a dimeric capsid interface, which was composed of elements from two protruding subdomains. Norovirus interactions with other saccharide units of the HBGAs were variable and involved fewer hydrogen bonds. Sequence analysis revealed a site of GII norovirus sequence conservation to reside under the critical αfucose1-2 and to be one of the few patches of conserved residues on the outer virion-capsid surface. The site was smaller than that involved in full HBGA recognition, a consequence of variable recognition of peripheral saccharides. Despite this evasion tactic, the HBGA site of viral vulnerability may provide a viable target for small molecule- and antibody-mediated neutralization of GII norovirus.
High throughput whole rumen metagenome profiling using untargeted massively parallel sequencing (2012)

We have presented a simple and high throughput method of metagenome profiling to assess the similarity of whole metagenomes, and illustrated its use on two novel datasets. This method utilises widely used freeware. The method should be useful in the exploration and comparison of metagenomes.
CYLD mutations in familial skin appendage tumours (2008)

This study provides further evidence on the role of CYLD in the pathogenesis of skin appendage tumours characterised by cylindromas, trichoepitheliomas and/or spiradenomas, but the molecular mechanisms of CYLD in skin tumorigenesis and the reasons for phenotypic variability remain to be explored.
A Standard Heparin Nomogram for the Management of Heparin Therapy (1991)

A nomogram for the adjustment of heparin dosage was developed to standardize heparin therapy and to reduce delays in achieving and maintaining a therapeutic activated partial thromboplastin time (APTT) result. Fifty consecutive patients with acute venous thromboembolism had their continuous intravenous heparin therapy adjusted according to this heparin nomogram. The effect of the nomogram on heparin therapy in these patients was compared with data from 53 historical control patients. The proportion of patients in the nomogram group who reached a therapeutic APTT at 24 hours after the start of heparin therapy was 66%, which increased to 81% at 48 hours. In contrast, 37% and 58% of the control patients reached a therapeutic APTT at 24 and 48 hours, respectively. The percentage of therapeutic APTT results of the total number of APTT determinations was greater in the nomogram patients than controls. The use of this heparin nomogram resulted in (1) achieving a therapeutic APTT at 24 and 48 hours in a large proportion of patients and (2) reduced periods of inadequate anticoagulation and overanticoagulation during heparin therapy.
Exploring Antibody Recognition of Sequence Space through Random-Sequence Peptide Microarrays (2010)

A universal platform for efficiently mapping antibody epitopes would be of great use for many applications, ranging from antibody therapeutic development to vaccine design. Here we tested the feasibility of using a random peptide microarray to map antibody epitopes. Although peptide microarrays are physically constrained to ∼10(4) peptides per array, compared with 10(8) permitted in library panning approaches such as phage display, they enable a much more high though put and direct measure of binding. Long (20 mer) random sequence peptides were chosen for this study to look at an unbiased sampling of sequence space. This sampling of sequence space is sparse, as an exact epitope sequence is unlikely to appear. Commercial monoclonal antibodies with known linear epitopes or polyclonal antibodies raised against engineered 20-mer peptides were used to evaluate this array as an epitope mapping platform. Remarkably, peptides with the most sequence similarity to known epitopes were only slightly more likely to be recognized by the antibody than other random peptides. We explored the ability of two methods singly and in combination to predict the actual epitope from the random sequence peptides bound. Though the epitopes were not directly evident, subtle motifs were found among the top binding peptides for each antibody. These motifs did have some predictive ability in searching for the known epitopes among a set of decoy sequences. The second approach using a windowing alignment strategy, was able to score known epitopes of monoclonal antibodies well within the test dataset, but did not perform as well on polyclonals. Random peptide microarrays of even limited diversity may serve as a useful tool to prioritize candidates for epitope mapping or antigen identification.
Discovery of a Potent, CNS‐Penetrant Orexin Receptor Antagonist Based on an N,N‐Disubstituted‐1,4‐diazepane Scaffold that Promotes Sleep in Rats (2009)

Silent Night: Antagonism of the orexin (or hypocretin) system has recently been identified as a novel mechanism for the treatment of insomnia. Herein, we describe discovery of a dual (OX(1)R/OX(2)R) orexin receptor antagonist featuring a 1,4-diazepane central constraint that blocks orexin signaling in vivo. In telemetry-implanted rats, oral administration of this antagonist produced a decrease in wakefulness, while increasing REM and non-REM sleep.
Role of dendritic cells in the induction of regulatory T cells (2011)

Dendritic cells (DCs) play a key role in initiating immune responses and maintaining immune tolerance. In addition to playing a role in thymic selection, DCs play an active role in tolerance under steady state conditions through several mechanisms which are dependent on IL-10, TGF-β, retinoic acid, indoleamine-2,3,-dioxygenase along with vitamin D. Several of these mechanisms are employed by DCs in induction of regulatory T cells which are comprised of Tr1 regulatory T cells, natural and inducible foxp3+ regulatory T cells, Th3 regulatory T cells and double negative regulatory T cells. It appears that certain DC subsets are highly specialized in inducing regulatory T cell differentiation and in some tissues the local microenvironment plays a role in driving DCs towards a tolerogenic response. In this review we discuss the recent advances in our understanding of the mechanisms underlying DC driven regulatory T cell induction.
Associate Systems: A Framework for Human-Machine Cooperation. (1997)

Function allocation has been an important concept and practice in the design of human-machine systems. While function allocation had lead to improvements in system design, it also has the potential to introduce undesirable properties into human-machine systems. This paper proposes the concept and practice of function integration in place of function allocation as a means for designing effective systems. Function integration is based on cooperation and collaboration between active agents and components of the system. An example of a functionally integrated system architecture, the associate system, is provided as a brief illustration of the concept.
Chromosomal breakpoints and structural alterations of the c-myc locus differ in endemic and sporadic forms of Burkitt lymphoma. (1986)

We have examined the position of the chromosomal breakpoint relative to the human c-myc gene (MYC) and the presence of other structural alterations of the same locus in 19 fresh samples of Burkitt lymphoma (BL) and 13 BL-derived cell lines. This panel includes the two pathogenetic forms of BL: the endemic (African-type) BL (eBL) and sporadic (American-type) BL (sBL). In all cases tested, including fresh samples and cell lines, structural alterations of the 5' portion of the gene were detected, suggesting that they may be necessary for c-myc activation. However, the site of chromosomal breakpoint and the type of structural alterations differ in eBL and sBL. In 16 of 18 sBL cases, chromosomal translocation truncates the gene within a 5' region that includes the first intron, the first exon, and 5' flanking sequences. Conversely, in 14 of 14 eBL samples, the chromosomal breakpoint is located outside the c-myc locus, yet the same 5' sequences are affected by several mutations identifiable by restriction enzyme polymorphisms. Different genetic mechanisms may therefore be involved in chromosomal translocation/c-myc activation, and these differences may be a function of differences in the stage of differentiation of eBL versus sBL.
Surviving the Politics of Judging: National Association of Adminsitrative Law Judges Luncheon Address, September 13, 1999 (2000)

This afternoon I am desirous of trying for a
Movement of Female's Rights in the World (2015)

This paper argues the latest needs articulating females women's rights as human rights is usually effective just by simply misrecognition with the geopolitical circumstance of human rights internationalism plus the nationalisms that are permanent because of it. Disagreeing it is just about the level of universalized buildings of ‘women’ to be a group plus the generalized invocations of oppression by simply ‘global feminism's’ ‘American’ professionals which this kind of discourses of rights become to be effective, this specific document argues which plan along with steps call for handling localised along with transnational specificities which developed gendered inequalities.
Arabidopsis RelA/SpoT homologs implicate (p)ppGpp in plant signaling (2000)

Arabidopsis RPP5 is a member of a large class of pathogen resistance genes encoding nucleotide-binding sites and leucine-rich repeat domains. Yeast two-hybrid analysis showed that RPP5 specifically interacts with At-RSH1, an Arabidopsis RelA/SpoT homolog. In Escherichia coli, RelA and SpoT determine the level of guanosine tetraphosphate (ppGpp) and guanosine pentaphosphate (pppGpp), which are the effector nucleotides of the bacterial stringent response. Functional analysis in E. coli and in Streptomyces coelicolor A3 (2) showed that At-RSH1 confers phenotypes associated with (p)ppGpp synthesis. We characterized two additional Arabidopsis RelA/SpoT homologs, At-RSH2 and At-RSH3. At-RSH genes may regulate a rapid plant (p)ppGpp-mediated response to pathogens and other stresses.
Design and analysis of a compliant bimanual rehabilitation device (2013)

Bimanual rehabilitation allows an individual with hemiparesis to use their sound arm to help rehabilitate their impaired arm and shows promise as a means of low cost home use rehabilitation. However, few studies have attempted to determine the best combination of bimanual symmetry modes and coupling stiffnesses. To examine the effects of stiffness and symmetry type, we have developed a compliant bimanual rehabilitation device (CBRD) that allows the two hands to be coupled in a variety of symmetry modes and coupling stiffnesses so that their efficacy may be tested. Preliminary analysis has shown that the CBRD can couple the motions of two healthy individuals, which we are using to simulate an individual with a hemiparesis, and improves bimanual task performance of a single individual. The results also show that a higher coupling stiffness reduces the coupling error and that some tasks were easier to complete in visual symmetry.
Federalismo y prácticas consocionales: el Gobierno Lula, un año después (2004)

El Gobierno de Lula en Brasil se entendio como la apuesta por una nueva manera de abordar la politica, tanto en relacion a las cuestiones internas como a las del ambito internacional. Brasil es la referencia del ?espiritu de Porto Alegre?, una concepcion y movimiento alternativos de la globalizacion, asi como de las politicas de combate a la pobreza, las desigualdades extremas y a favor de un mundo mas integrado y solidario. Como ejemplos concretos de las propuestas de una nueva politica, se analizan en este articulo las siguientes dos cuestiones: en primer lugar, la redefinicion del federalismo fiscal brasileno que, tras un ano de Gobierno, no ha avanzado hacia una descentralizacion federal y municipal que corresponsabilize a los diversos niveles de manera efectiva y equitativa, tanto en materia de ingresos como en materia de gastos. En segundo lugar, el Partido de los Trabajadores ha tenido que implicar en su proyecto politico a sectores del capital productivo y financiero, asi como a determinadas clases medias, en el proceso para establecer las bases para una politica de caracter consocional. Asi pues, en los ambitos social y federal, el Gobierno Lula sigue estando ubicado en el terreno de las expectativas.
Oxidative stress after human exercise: effect of N-acetylcysteine supplementation (1994)

The association between exercise intensity and related oxidative stress was investigated in nine men who exercised for 30 min at their aerobic (AeT) and anaerobic (AnaeT) thresholds. We also tested the effect of oral N-acetylcysteine (NAC) on exercise-associated rapid blood glutathione (GSH) oxidation in subjects performing two identical maximal bicycle ergometer exercise (Max) tests. Before the second test (Max with NAC supplementation [Max(NAC)]), the men took 200 x 4 mg/day of NAC tablets for 2 days and an additional 800 mg on the test morning. Blood samples were drawn before, immediately after, and 24 h after the tests. Total and oxidized GSH levels in blood were determined. Plasma thiobarbituric acid-reactive substances and net peroxyl radical scavenging capacity (PSC) were assayed. Exercise-associated damage in leukocyte DNA was estimated by fluorometric analysis of DNA unwinding. A single bout of exercise at Max, AeT, and AnaeT resulted in a significant increase in blood GSH oxidation but did not influence net PSC of plasma. Although an association between a single bout of exercise and leukocyte DNA damage was apparent, this study suggests that the parameter may not serve as a sensitive index to assess the role of exercise intensity in the extent of exercise-associated oxidative stress. Plasma thiobarbituric acid-reactive substances did not change after either Max or Max(NAC) tests. NAC supplementation resulted in an increase in preexercise PSC, indicating a higher net antioxidant capacity of the plasma, but did not affect blood GSH.(ABSTRACT TRUNCATED AT 250 WORDS)
Rational design of a compact CRISPR-Cas9 activator for AAV-mediated delivery (2018)

Abstract Akin to Zinc Finger and Transcription Activator Like Effector based transcriptional modulators, nuclease-null CRISPR-Cas9 provides a groundbreaking programmable DNA binding platform, begetting an arsenal of targetable regulators for transcriptional and epigenetic perturbation, by either directly tethering, or recruiting, transcription enhancing effectors to either component of the Cas9/guide RNA complex. Application of these programmable regulators is now gaining traction for the modulation of disease-causing genes or activation of therapeutic genes, in vivo . Adeno-Associated Virus (AAV) is an optimal delivery vehicle for in vivo delivery of such regulators to adult somatic tissue, due to the efficacy of viral delivery with minimal concerns about immunogenicity or integration. However, present Cas9 activator systems are notably beyond the packaging capacity of a single AAV delivery vector capsid. Here, we engineer a compact CRISPR-Cas9 activator for convenient AAV-mediated delivery. We validate efficacy of the CRISPR-Cas9 transcriptional activation using AAV delivery in several cell lines.
Bilateral transcutaneous tibial nerve stimulation for chronic constipation (2015)

Bilateral transcutaneous tibial nerve stimulation appears to be effective in a quarter of patients with chronic constipation. Carefully selected patients with less severe disease may benefit more. This requires further study.
The p38 Mitogen-Activated Protein Kinase Mediates Cytoskeletal Remodeling in Pulmonary Microvascular Endothelial Cells Upon Intracellular Adhesion Molecule-1 Ligation (2001)

Changes in the cytoskeleton of endothelial cells (ECs) play important roles in mediating neutrophil migration during inflammation. Previous studies demonstrated that neutrophil adherence to TNF-alpha-treated pulmonary microvascular ECs induced cytoskeletal remodeling in ECs that required ICAM-1 ligation and oxidant production and was mimicked by cross-linking ICAM-1. In this study, we examined the role of ICAM-1-induced signaling pathways in mediating actin cytoskeletal remodeling. Cross-linking ICAM-1 induced alterations in ICAM-1 distribution, as well as the filamentous actin rearrangements and stiffening of ECs shown previously. ICAM-1 cross-linking induced phosphorylation of the p38 mitogen-activated protein kinase (MAPK) that was inhibited by allopurinol and also induced an increase in the activity of the p38 MAPK that was inhibited by SB203580. However, SB203580 had no effect on oxidant production in ECs or ICAM-1 clustering. ICAM-1 cross-linking also induced phosphorylation of heat shock protein 27, an actin-binding protein that may be involved in filamentous actin polymerization. The time course of heat shock protein 27 phosphorylation paralleled that of p38 MAPK phosphorylation and was completely inhibited by SB203580. In addition, SB203580 blocked the EC stiffening response induced by either neutrophil adherence or ICAM-1 cross-linking. Moreover, pretreatment of ECs with SB203580 reduced neutrophil migration toward EC junctions. Taken together, these data demonstrate that activation of p38 MAPK, mediated by xanthine oxidase-generated oxidant production, is required for cytoskeletal remodeling in ECs induced by ICAM-1 cross-linking or neutrophil adherence. These cytoskeletal changes in ECs may in turn modulate neutrophil migration toward EC junctions.