gebhart/patrepeval huggingface dataset:
A novel functional VKORC1 promoter polymorphism is associated with inter-individual and inter-ethnic differences in warfarin sensitivity (2005)

Warfarin, a commonly prescribed anticoagulant, exhibited large inter-individual and inter-ethnic differences in the dose required for its anticoagulation effect. Asian populations, including Chinese, require a much lower maintenance dose than Caucasians, for which the mechanisms still remain unknown. We determined DNA sequence variants in CYP2C9 and VKORC1 in 16 Chinese patients having warfarin sensitivity (≤1.5 mg/day, n=11) or resistance (≥6.0 mg/day, n=5), 104 randomly selected Chinese patients receiving warfarin, 95 normal Chinese controls and 92 normal Caucasians. We identified three CYP2C9 variants, CYP2C9*3, T299A and P382L, in four warfarin-sensitive patients. A novel VKORC1 promoter polymorphism (−1639 G>A) presented in the homozygous form (genotype AA) was found in all warfarin-sensitive patients. The resistant patients were either AG or GG. Among the 104 randomly selected Chinese patients receiving warfarin, AA genotype also had lower dose than the AG/GG genotype (P<0.0001). Frequencies of AA, AG and GG genotypes were comparable in Chinese patients receiving warfarin (79.7, 17.6 and 2.7%) and normal Chinese controls (82, 18 and 0%), but differed significantly from Caucasians (14, 47 and 39%) (P<0.0001). The promoter polymorphism abolished the E-box consensus sequences and dual luciferase assay revealed that VOKRC1 promoter with the G allele had a 44% increase of activity when compared with the A allele. The differences in allele frequencies of A/G allele and its levels of VKORC1 promoter activity may underscore the inter-individual differences in warfarin dosage as well as inter-ethnic differences between Chinese and Caucasians.
Impaired febrile responses of aging mice are mediated by endogenous lipocortin-1 (annexin-1) (1993)

The mechanisms underlying age-related impairments in febrile responses were investigated in female C57Bl/lcrf-a(t) mice. Injection of norepinephrine, to assess total thermogenic capacity, significantly increased oxygen consumption (VO2) in all age groups, although the responses of the aged mice were significantly reduced. Injection of lipopolysaccharide or murine interleukin-1 beta (mIL-1 beta) significantly increased body temperature and VO2 in the young and adult mice but not in the aged mice. The impaired responses to mIL-1 beta in the aged mice were normalized by either injection of the glucocorticoid receptor antagonist RU-38486 or by injection of an antiserum to lipocortin-1 or its purified immunoglobulin G fraction. Injection of prostaglandin E2 significantly increased VO2 and body temperature in all age groups. Resting plasma corticosterone concentrations were significantly elevated in the aged and adult mice, whereas injection of mIL-1 beta significantly raised plasma corticosterone concentrations in all animals. These findings indicate that the impaired febrile response of aged female C57Bl/lcrf-a(t) mice may be caused by increased concentrations and/or sensitivity to endogenous glucocorticoids. The impaired febrile responses of aged mice appear to be mediated by endogenous lipocortin-1.
Antigen and Antibody Testing for the Diagnosis of Blastomycosis in Dogs (2008)

Antigen detection is a more sensitive test for diagnosis of blastomycosis than antibody testing by AGID, the only commercially available method. Antigen concentrations decreased with treatment.
Nucleic acid sequence of an internal image-bearing monoclonal anti-idiotype and its comparison to the sequence of the external antigen. (1986)

The monoclonal anti-idiotypic antibody (mAb2) 87.92.6 directed against the 9B.G5 antibody specific for the virus neutralizing epitope on the mammalian reovirus type 3 hemagglutinin was previously demonstrated to express an internal image of the receptor binding epitope of the reovirus type 3. Furthermore, this mAb2 has autoimmune reactivity to the cell surface receptor of the reovirus. The nucleotide and deduced amino acid sequences of the 87.92.6 mAb2 heavy and light chains are described in this report. The sequence analysis reveals that the same heavy chain variable and joining (VH and JH) gene segments are used by the 87.92.6 anti-idiotypic mAb2 and by the dominant idiotypes of the BALB/c anti-GAT (cGAT) and anti-NP (NPa) responses. [GAT; random polymer that is 60% glutamic acid, 30% alanine, and 10% tyrosine. NP; (4-hydroxy-3-nitrophenyl)-acetyl.] Despite extensive homology at the level of the heavy chain variable regions, the NPa positive BALB/c anti-NP monoclonal antibody 17.2.25 binds neither 9B.G5 nor the cellular receptor for the hemagglutinin. Amino acid sequence comparison between the viral hemagglutinin and the 87.92.6 mAb2 light chain "internal image," reveals an area of significant homology indicating that antigen mimicry by antibodies may be achieved by sharing primary structure.
Neurosteroids and GABAergic signaling in health and disease (2012)

Endogenous neurosteroids such as allopregnanolone, allotetrahydrodeoxycorticosterone, and androstanediol are synthesized either de novo in the brain from cholesterol or are generated from the local metabolism of peripherally derived progesterone or corticosterone. Fluctuations in neurosteroid concentrations are important in the regulation of a number of physiological responses including anxiety and stress, reproductive, and sexual behaviors. These effects are mediated in part by the direct binding of neurosteroids to γ-aminobutyric acid type-A receptors (GABAARs), resulting in the potentiation of GABAAR-mediated currents. Extrasynaptic GABAARs containing the δ subunit, which contribute to the tonic conductance, are particularly sensitive to low nanomolar concentrations of neurosteroids and are likely their preferential target. Considering the large charge transfer generated by these persistently open channels, even subtle changes in neurosteroid concentrations can have a major impact on neuronal excitability. Consequently, aberrant levels of neurosteroids have been implicated in numerous disorders, including, but not limited to, anxiety, neurodegenerative diseases, alcohol abuse, epilepsy, and depression. Here we review the modulation of GABAAR by neurosteroids and the consequences for health and disease.
Upstream sequences other than AAUAAA are required for efficient messenger RNA 3'-end formation in plants. (1990)

We have characterized the upstream nucleotide sequences involved in mRNA 3'-end formation in the 3' regions of the cauliflower mosaic virus (CaMV) 19S/35S transcription unit and a pea gene encoding ribulose-1,5-bisphosphate carboxylase small subunit (rbcS). Sequences between 57 bases and 181 bases upstream from the CaMV polyadenylation site were required for efficient polyadenylation at this site. In addition, an AAUAAA sequence located 13 bases to 18 bases upstream from this site was also important for efficient mRNA 3'-end formation. An element located between 60 bases and 137 bases upstream from the poly(A) addition sites in a pea rbcS gene was needed for functioning of these sites. The CaMV -181/-57 and rbcS -137/-60 elements were different in location and sequence composition from upstream sequences needed for polyadenylation in mammalian genes, but resembled the signals that direct mRNA 3'-end formation in yeast. However, the role of the AAUAAA motif in 3'-end formation in the CaMV 3' region was reminiscent of mRNA polyadenylation in animals. We suggest that multiple elements are involved in mRNA 3'-end formation in plants, and that interactions of different components of the plant polyadenylation apparatus with their respective sequence elements and with each other are needed for efficient mRNA 3'-end formation.
MODULATION OF ENDOTOXIN-INDUCED NEUTROPHIL TRANSENDOTHELIAL MIGRATION BY ALVEOLAR EPITHELIUM IN A DEFINED BILAYER MODEL (2006)

Within the alveolus, epithelial cells, due to their close association with endothelial cells, can potentially influence endothelial cell responsiveness during inflammation and their interaction with leukocytes. To investigate this, three lung epithelial cell lines (A549, Calu-3, or NCI-H441) were grown with endothelium on opposing surfaces of Transwell filters and the formation and stability of bilayers was rigorously evaluated. All epithelial lines disrupted endothelial monolayer formation on filters with 3- or 5-microm pores by breaching the filter, and this occurred regardless of seeding density, matrix composition, or duration of culture. Endothelial disruption was not detectable by electrical resistance or permeability measurements but required cell-specific staining with immunofluorescence and microscopy. Distinct bilayers formed only on filters with 0.4-microm pores and only with A549 cells and human umbilical vein endothelial cells. Endotoxin (lipopolysaccharide [LPS]) stimulation of bilayers (4 hours) enhanced neutrophil transendothelial migration, but this was significantly decreased compared with the response of endothelium grown alone, irrespective of whether LPS exposure was via the epithelial or endothelial side of the bilayer. Down-modulation required epithelial-endothelial approximation and was not seen when these cells were separated by 0.5 to 1 mm. This study defines optimal conditions required for generation of intact bilayers of lung epithelial cells with endothelium for the study of leukocyte-transendothelial migration. Furthermore, it was demonstrated that lung epithelial cells can modulate endothelial cell responsiveness to an environmental inflammatory stimulus such as LPS and thus may have an important role in minimizing excessive and deleterious neutrophilic inflammation in the lung alveolus.
2‘-Deoxy-7-(hydroxymethyl)-7-deazaadenosine:  A New Analogue to Model Structural Water in the Major Groove of DNA (1996)

A novel deoxynucleoside, 2‘-deoxy-7-(hydroxymethyl)-7-deazaadenosine, was synthesized with the intent of using the analogue to mimic the role of “structural” waters in the major groove of DNA. The target compound was synthesized in four steps starting from 2-((ethoxymethylene)amino)-5-bromo-1-(2‘-deoxy-3‘,5‘-di-O-p-toluoyl-β-d-erythro-pentofuranosyl)pyrrole-3,4-dicarbonitrile. The structure was characterized by X-ray diffraction and proton NMR spectroscopic analyses. The crystal structure shows an intramolecular hydrogen bond between an amino proton on N6 and the oxygen of the hydroxymethyl group. When superimposed onto particular adenines in the structure of the tryptophan (trp) repressor/operator complex, the analogue places the oxygen of the hydroxymethyl group very near the oxygen contributed by the water in the protein/DNA complex. This analogue may be useful for probing the role of structural waters in other specific protein/DNA complexes and in DNA bending.
Specific Interactions Improve the Loading Capacity of Block Copolymer Micelles in Aqueous Media (2007)

Block copolymer micelles find application in many fields as nanocarriers, especially in drug delivery. We report herein that specific interactions between hydrophobic guest molecules and core-forming segments can significantly improve the loading capacity of polymeric micelles. High loading capacities (>100% weight/weight of polymer (w/wp)) were systematically observed for the encapsulation of probes containing weak carboxylic acid groups by micellar nanoparticles having poly[2-(dialkylamino)ethyl methacrylate] cores (i.e., particles whose cargo space exhibits antagonist weak base functions), as demonstrated by the incorporation of indomethacin (IND), ibuprofen (IBPF), and trans-3,5-bis(trifluoromethyl)cinnamic acid (F-CIN) into either poly(ethylene oxide)-b-poly[2-(diisopropylamino)ethyl methacrylate] (PEO-b-PDPA) or poly(glycerol monomethacrylate)-b-PDPA (PG2MA-b-PDPA) micelles. The esterification of IND yielding to a nonionizable IND ethyl ester derivative (IND-Et) caused an abrupt decrease in the micellar loading capacity down to 10-15% w/wp. Similar results were also obtained when IND was combined with nonionizable block copolymers such as PEO-b-polycaprolactone (PEO-b-PCL) and PEO-b-poly(glycidyl methacrylate) (PEO-b-PGMA). The existence of acid-base interactions between the solubilizate and the weak polybase block forming the micelle core was confirmed by 1H NMR measurements. However, the incorporation of high numbers of hydrophobic guest molecules inside polymeric micelles can provoke not only an increase in the hydrodynamic size (2RH) of the objects but also a substantial change in the morphology (transition from spheres to cylinders). The application of the Higuchi model showed that the probe release followed a diffusion-controlled mechanism, and diffusion coefficients (D) on the order of 10-18-10-17 cm2/s were determined for IND release from 1.0 mg/mL PEO113-b-PDPA50 + 100% w/wp IND. Probe release from micelles with weak polybase-based cores can also be triggered by changes in the solution pH.
Assembly of Thin and Thick Fibrils of Collagen II from Recombinant Procollagen II (1996)

Human type II procollagen was prepared in a recombinant system and cleaved to pC-collagen II by procollagen N-proteinase. The pC-collagen II was then used as a substrate to generate collagen II fibrils by cleavage with procollagen C-proteinase at 37 degrees C. Electron microscopy of the fibrils demonstrated that, at the early stages of fibril assembly, very thin fibrils were formed. As the system approached equilibrium over 7-12 h, however, the thin fibrils were largely but not completely replaced by thick fibrils that had diameters of about 240 nm and a distinct D-period banding pattern. One typical fibril was photographed and analyzed in its entirety. The fibril was 776 D-periods (52 microM) long. It had a central shaft with a uniform diameter that was about 516 D-periods long and two tips of about 100 D-periods each. Most of the central shaft had a symmetrical banding pattern flanked by two transition regions of about 30 D-periods each. Measurements by scanning transmission electron microscopy demonstrated that the mass per unit length from the tips to the shafts increased linearly over approximately 100 D-periods from the fibril end. The linear increase in mass per unit length was consistent with previous observations for collagen I fibrils and established that the tips of collagen II also had a near paraboloidal shape. However, the orientation of monomers in the tips differed from the tips of collagen I fibrils in that the C termini instead of the N termini were directed toward the tips. The thin fibrils that were present at early stages of assembly and at equilibrium were comparable to the collagen II fibrils seen in embryonic tissues and probably represented intermediates on the pathway of thick fibrils formation. The results indicated that the molecular events in the self-assembly of collagen II fibrils are apparently similar to those in self-assembly of collagen I fibrils, but that there are also important differences in the structural information contained in collagen I and collagen II monomers.
Protein Function Assignment through Mining Cross-Species Protein-Protein Interactions (2008)

It can be shown through experimental results that the CSIDOP method is reliable and practical in use. The method will continue to improve as more high quality interaction data becomes available and is readily scalable to a genome-wide application.
Peptide nucleic acids containing adenine or guanine recognize thymine and cytosine in complementary DNA sequences (1993)

Peptide nucleic acid (PNA) monomer building blocks for the introduction of G and A are prepared and used to synthesise H-T4XT5-Lys-NH2(X = G or A), which are shown by Tm measurements to recognize their complementary DNA sequences in both the parallel (N-terminal PNA/5′-DNA) and the anti-parallel mode; the stoichiometry in each case is (PNA)2/DNA.
Ontologies for Modeling and Simulation: Issues and Approaches (2005)

Ontologies represent the next important phase of the World Wide Web, creating a semantic Web which links together disparate pieces of information and knowledge. Creating ontologies within computer simulation can be seen as a logical next phase of the Web-based modeling and simulation thrust, where the emphasis is on knowledge and its representation rather than on run-time network characteristics. We introduce the concept of an ontology and then survey two groups performing research in this area at the Universities of Florida and Georgia, respectively.
Vanilloid receptors: new insights enhance potential as a therapeutic target (1996)

Compounds related to capsaicin and its ultrapotent analog, resiniferatoxin (RTX), collectively referred to as vanilloids, interact at a specific membrane recognition site (vanilloid receptor), expressed almost exclusively by primary sensory neurons involved in nociception and neurogenic inflammation. Desensitization to vanilloids is a promising therapeutic approach to mitigate neuropathic pain and pathological conditions (e.g. vasomotor rhinitis) in which neuropeptides released from primary sensory neurons play a major role. Capsaicin-containing preparations are already commercially available for these purposes. The use of capsaicin, however, is severely limited by its irritancy, and the synthesis of novel vanilloids with an improved pungency/desensitization ratio is an on-going objective. This review highlights the emerging evidence that the vanilloid receptor is not a single receptor but a family of receptors, and that these receptors recognize not simply RTX and capsaicin structural analogs but are broader in their ligand-binding selectivity. We further focus on ligand-induced messenger plasticity, a recently discovered mechanism underlying the analgesic actions of vanilloids. Lastly, we give a brief overview of the current clinical uses of vanilloids and their future therapeutic potential. The possibility is raised that vanilloid receptor subtype-specific drugs may be synthesized, devoid of the undesirable side-effects of capsaicin.
Controlling the Phase Evolution of Few-Cycle Light Pulses (2000)

Using a coherent nonlinear optical technique, slipping of the carrier through the envelope of 6-fs light wave packets emitted from a mode-locked-oscillator/pulse-compressor system has been measured, permitting the generation of intense, few-cycle light with precisely reproducible electric and magnetic fields. These pulses open the way to controlling the evolution of strong-field interactions on the time scale of the light oscillation cycle and are indispensable to reproducible attosecond x-ray pulse generation.
Total solid-phase synthesis of porcine gut gastrin releasing peptide (GRP), a mammalian bombesin (1981)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTotal solid-phase synthesis of porcine gut gastrin releasing peptide (GRP), a mammalian bombesinW. Maerki, J. Spiess, Y. Tache, M. Brown, and J. E. RivierCite this: J. Am. Chem. Soc. 1981, 103, 11, 3178–3185Publication Date (Print):June 1, 1981Publication History Published online1 May 2002Published inissue 1 June 1981https://pubs.acs.org/doi/10.1021/ja00401a040https://doi.org/10.1021/ja00401a040research-articleACS PublicationsRequest reuse permissionsArticle Views184Altmetric-Citations60LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Review and status of wavelength-division-multiplexing technology and its application (1984)

Wavelength-division-multiplexing (WDM) technology is now recognized as one of the key technologies in optical communications systems. This is because it has great potential to enhance system design and flexibility. This paper reviews state-of-the-art optical multi/demultiplexers (MUX/DEMUX) and WDM system design. Various system applications are also summarized.
Biochemically based design of cyclooxygenase-2 (COX-2) inhibitors: Facile conversion of nonsteroidal antiinflammatory drugs to potent and highly selective COX-2 inhibitors (2000)

All nonsteroidal antiinflammatory drugs (NSAIDs) inhibit the cyclooxygenase (COX) isozymes to different extents, which accounts for their anti-inflammatory and analgesic activities and their gastrointestinal side effects. We have exploited biochemical differences between the two COX enzymes to identify a strategy for converting carboxylate-containing NSAIDs into selective COX-2 inhibitors. Derivatization of the carboxylate moiety in moderately selective COX-1 inhibitors, such as 5,8,11,14-eicosatetraynoic acid (ETYA) and arylacetic and fenamic acid NSAIDs, exemplified by indomethacin and meclofenamic acid, respectively, generated potent and selective COX-2 inhibitors. In the indomethacin series, esters and primary and secondary amides are superior to tertiary amides as selective inhibitors. Only the amide derivatives of ETYA and meclofenamic acid inhibit COX-2; the esters are either inactive or nonselective. Inhibition kinetics reveal that indomethacin amides behave as slow, tight-binding inhibitors of COX-2 and that selectivity is a function of the time-dependent step. Site-directed mutagenesis of murine COX-2 indicates that the molecular basis for selectivity differs from the parent NSAIDs and from diarylheterocycles. Selectivity arises from novel interactions at the opening and at the apex of the substrate-binding site. Lead compounds in the present study are potent inhibitors of COX-2 activity in cultured inflammatory cells. Furthermore, indomethacin amides are orally active, nonulcerogenic, anti-inflammatory agents in an in vivo model of acute inflammation. Expansion of this approach can be envisioned for the modification of all carboxylic acid-containing NSAIDs into selective COX-2 inhibitors.
Sooting Tendencies in an Air-Forced Direct Injection Spark-Ignition (DISI) Engine (2000)

&lt;div class="htmlview paragraph"&gt;Particulate emissions are reported for a 0.31 L single cylinder engine fitted with an air forced direct injection system. Trends in number, size, and mass of engine out particle emissions are examined as a function of injection timing, spark timing, and EGR. Injection timing determines to a large degree the nature of the combustion, with early injection leading to homogeneous like combustion and late injection producing stratified charge combustion. As fuel injection is retarded, at a fixed lean air to fuel ratio, PM emissions decline to a minimum at an injection time well within the compression stroke, after which they rapidly increase. In the heavily stratified regime, the PM increase can be attributed to a growing number of rich zones that occur in the progressively more inhomogeneous fuel mixture. At fixed injection timing, advancing the spark causes a general increase in particle emissions. This trend is opposite that of hydrocarbons, which decrease significantly as spark timing is advanced. A limited examination of the effect of EGR shows it to reduce NOx. However, PM, CO, and hydrocarbon emissions all increase with added EGR, which is linked to a loss in combustion stability. The PM emissions trends for the air assisted direct injection presented here are compared to those previously reported for a production fuel only DISI gasoline engine.&lt;/div&gt;