gebhart/patrepeval huggingface dataset:
iNOS and Nitrotyrosine Expression After Spinal Cord Injury (2001)

Secondary tissue damage after spinal cord injury (SCI) may be due to inflammatory mediators. After SCI, the nuclear factor-kappaB (NF-kappaB) transcription factor can activate many pro-inflammatory genes, one of which is inducible nitric oxide synthase (iNOS). iNOS catalyzes the synthesis of nitric oxide (NO), a key inflammatory mediator, which in turn reacts with superoxide to generate peroxynitrite. Peroxynitrite is a strong oxidant that can damage cellular enzymes, membranes, and subcellular organelles through the nitration of tyrosine residues on proteins. The presence of nitrotyrosine (NT) is an indirect chemical indicator of toxic NO and peroxynitrite-induced cellular damage. Using a New York University (NYU) impactor to induce SCI in adult rats, we examined the temporal and cellular expression of iNOS and NT. We observed a progressive increase in iNOS expression in the injured cord starting at day 1 with maximal expression occurring at day 7, as determined by Western blot analysis. iNOS expression corresponded temporally to an increase in iNOS enzyme activity after SCI. In parallel with the progressive increase in iNOS activity, NT expression also increased with time after SCI. The iNOS and NT immunoreactivity was localized in neurons, astrocytes, endothelial cells and ependymal cells at the epicenter and adjacent to the region of spinal cord impact and injury. Results from the present study suggest that increased iNOS and peroxynitrite anion, as reflected by the progressive accumulation of NT in the injured impacted spinal cord, may contribute to the secondary injury process after SCI.
Multiplexed Real-Time PCR Using Universal Reporters (2004)

Real-time quantitative PCR is a sensitive and accurate method for gene expression studies (1). The detection chemistries of all real-time PCR procedures are based on one of two principles for monitoring amplification products: binding to double-stranded DNA or hybridization to single-stranded DNA. Small molecules bind to double-stranded DNA either as intercalators or as minor groove binders, e.g., ethidium bromide (2), Hoechst 33258 (3), or SYBR® Green I (4). Several approaches using target-specific hybridization to single-stranded DNA have been introduced, including Molecular Beacons (5), Scorpions (6)(7), the TaqMan or hydrolysis/5′-nuclease assay (8)(9), the AEGIS probe system (10), labeled primers (11)(12), and light-up probes (13). In contrast to binding of dyes to double-stranded DNA, these methods are suitable for multiplexing approaches because they use differentially labeled fluorescent dyes. However, as they require a unique probe or modified primer for each target, currently used hybridization-based methods for real-time quantitative PCR have high reagent costs and require large developmental efforts.

Here we present a real-time PCR assay that uses universal hybridization-based probe sets suitable for any target. Because the assay uses tailed locus-specific nonmodified amplification primers, PCR products can be monitored via common reporters (cr) hybridizing to the common tails. The general principle of combining tailed PCR primers with universal probes has been introduced for other genetic applications, such as single-nucleotide polymorphism genotyping (14)(15) and in situ amplification (16), but these methods have not been applied to quantitative gene expression studies. Our system, which is similar to the method developed by Whitcombe et al. (15), leads to a more flexible and low-cost setup than conventional hybridization-based approaches. Using differentially labeled universal reporting reagents, we have developed a multiplex setup for simultaneous analysis of target gene and internal control (housekeeping gene), which is an accepted method for …
Virtual combinatorial libraries: Dynamic generation of molecular and supramolecular diversity by self-assembly (1997)

Molecular and supramolecular diversity may be generated, respectively, by reversible, covalent or noncovalent self-assembly of basic components whose various potential combinations in number and nature represent a virtual combinatorial library. This concept is applied to the induction of inhibitors of carbonic anhydrase (CA) by reversible recombination of aldehyde and amine components. It is found that the presence of CA favors the formation of those condensation compounds that may be expected to present the strongest binding to the CA active site. The virtual combinatorial library approach may represent a powerful methodology for the discovery of substrates, inhibitors, receptors, catalysts, and carriers for a variety of processes.
Chemoenzymatic acylation of aminoglycoside antibiotics (2008)

The chemoenzymatic installation of the clinically valuable (S)-4-amino-2-hydroxybutyryl side chain onto a number of 2-deoxystreptamine-containing aminoglycosides is described using the purified Bacillus circulans biosynthetic enzymes BtrH and BtrG in combination with a synthetic acyl-SNAC surrogate substrate.
A wide‐field‐of‐view catadioptrical head‐mounted display (2006)

Abstract The head‐mounted display (HMD) has been used widely as a visual presentation device in virtual reality, composite reality, and telepresence. However, the HMDs which are on the market have only a very narrow angular field of view, which is less than 60 ° in the horizontal direction. This is very narrow compared to the human field of view and is far from generating a feeling of presence. The poor feeling of presence is considered to be a factor that degrades the sense of realism for the user and the operating efficiency in the virtual space. In this paper, we propose an HMD with a wide field of view based on a catadioptrical system composed of hyperboloidal and ellipsoidal mirrors. The proposed HMD achieves a horizontal view angle of 180 ° , which covers the human peripheral field of vision. This wide field of view gives the user a stronger feeling of reality and ambience. The proposed HMD has a binocular overlap area of 60 ° from the center, which helps to achieve stereoscopic vision by presenting parallax images. © 2006 Wiley Periodicals, Inc. Electron Comm Jpn Pt 2, 89(9): 33–43, 2006; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/ecjb.20304
Normal Human CD4+ Memory T Cells Display Broad Heterogeneity in Their Activation Threshold for Cytokine Synthesis (1998)

CD4+ memory T cells coordinate immune responses against viruses and other pathogens via the Ag-induced secretion of potent effector cytokines. The efficacy of these responses depends on both the overall number of pathogen-specific memory T cells and the particular array of cytokines that these cells are programmed to secrete. Here, we provide evidence that heterogeneity in Ag triggering thresholds constitutes an additional critical determinant of memory T cell function. Using a novel assay that allows single-cell detection of Ag-specific T cell cytokine production, we demonstrate that CMV-specific CD4+ memory cells from human peripheral blood display pronounced differences in their costimulatory requirements for Ag-induced triggering of IFN-gamma and IL-2 secretion, ranging from cells that trigger with little costimulation (e.g., resting APC alone) to cells requiring potent costimulation through multiple pathways (resting APC plus multiple costimulatory mAbs, or activated APC). These differences in costimulatory requirements are independent of clonal differences in TCR signaling intensity, consistent with an intrinsic activation-threshold heterogeneity that is "downstream" from the TCR. Thus, "effective" frequencies of Ag-specific CD4+ memory T cells appear to depend on the activation status of available APC, a dependence that would allow the immune system to rapidly adjust the number of functional Ag-specific memory T cells in a particular effector site according to local conditions.
Thin-film CuInSe2/CdS heterojunction solar cells (1976)

The fabrication procedures and characteristics of several thin-film p-CuInSe2/n-CdS heterojunction solar cells are presented. Two modes of operation (illumination through CuInSe2 or through CdS) are discussed. Efficiencies in the range of 4–5% are reported, under 100 mW/cm2 tungsten-halogen illumination for 1.2-cm2 devices. Included are the spectral response and J-V characteristics for these photovoltaic junctions.
Analysis of the role of N-cadherin, MCAM, and β3 integrin in the proliferation, migration, and invasion of advanced-stage melanomas (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

2516 

The cell adhesion molecules N-cadherin, MCAM, and β3 integrin have been postulated to represent melanoma progression markers, and phase I clinical trials currently assess the efficacy of ανβ3 integrin as a therapeutic target for unresectable, locally advanced, or stage IV melanoma. Using whole-genome expression profiling and tissue microarray analysis, we demonstrate expression of the three molecules in the melanoma progression pathway. Since it is presently not known whether targeted inhibition of each adhesion molecule alone suffices to block tumor growth and/or metastasis, or whether expression of all three genes needs to be inhibited simultaneously to block melanoma proliferation, invasion, and metastasis formation, we performed studies, both in vitro and in vivo, to answer this question. We provide evidence that blocking N-cadherin, MCAM, or β3 integrin expression decreases melanoma cell proliferation, yet, blocking their expression in parallel does not augment the anti-proliferative effect. However, blocking N-cadherin, MCAM, andβ3 integrin in concert, inhibits melanoma cell migration and invasion to a significantly greater extent than targeting each gene alone. We further demonstrate that abrogating expression of the three adhesion molecules does not lead to upregulation of other adhesion molecules such as E-cadherin or substantial accumulation of the αv integrin subunit. Taken together, the results of our studies suggest that targeting all three genes at the same time may represent a valuable therapeutic approach for melanoma in its advanced stages.
Impaired endochondral ossification and angiogenesis in mice deficient in membrane-type matrix metalloproteinase I (2000)

Membrane-type matrix metalloproteinase I (MT1-MMP)-deficient mice were found to have severe defects in skeletal development and angiogenesis. The craniofacial, axial, and appendicular skeletons were severely affected, leading to a short and domed skull, marked deceleration of postnatal growth, and death by 3 wk of age. Shortening of bones is a consequence of decreased chondrocyte proliferation in the proliferative zone of the growth plates. Defective vascular invasion of cartilage leads to enlargement of hypertrophic zones of growth plates and delayed formation of secondary ossification centers in long bones. In an in vivo corneal angiogenesis assay, null mice did not have angiogenic response to implanted FGF-2, suggesting that the defect in angiogenesis is not restricted to cartilage alone. In tissues from null mice, activation of latent matrix metalloproteinase 2 was deficient, suggesting that MT1-MMP is essential for its activation in vivo.
Mechanisms of human autoimmunity (2015)

Autoimmune reactions reflect an imbalance between effector and regulatory immune responses, typically develop through stages of initiation and propagation, and often show phases of resolution (indicated by clinical remissions) and exacerbations (indicated by symptomatic flares). The fundamental underlying mechanism of autoimmunity is defective elimination and/or control of self-reactive lymphocytes. Studies in humans and experimental animal models are revealing the genetic and environmental factors that contribute to autoimmunity. A major goal of research in this area is to exploit this knowledge to better understand the pathogenesis of autoimmune diseases and to develop strategies for reestablishing the normal balance between effector and regulatory immune responses.
Blockade of the sympathetic nervous system degrades ligament in a rat MCL model (2004)

We hypothesize that blockade of the sympathetic nervous system degrades ligament. We tested this hypothesis in a rat medial collateral ligament (MCL) model. Fifteen animals were treated for 10 days with the sympathetic chemotoxin guanethidine using osmotic pumps, whereas 15 control rats received pumps containing saline. A reduction in plasma concentrations of norepinephrine in the guanethidine rats indicated a significant decrease in sympathetic nerve activity. Vasoactive intestinal peptide and neuropeptide Y were decreased in MCLs from guanethidine animals, as quantified by radioimmunoassays. Tissue vascularity was substantially increased in guanethidine MCLs, whereas mechanical properties were significantly decreased. Proteases, such as matrix metalloproteinases (MMP) and cysteine proteases, play a major role in ligament degradation. The proteases MMP-13, cathepsin K, and tartrate-resistant acid phosphatase (TRAP) have collagenolytic activity and have been shown in rat ligament tissues. To determine whether the degradation seen in this study was due to protease activity, we determined the expression of these enzymes in control and treated MCLs. Real-time quantitative PCR revealed that guanethidine treatment increased expression of MMP-13 and cathepsin K mRNAs, although overall expression levels of MMP-13 and TRAP were relatively low. Histology also identified increases in TRAP and cathepsin K, but not MMP-13, in guanethidine-treated tissues. Results support our hypothesis that blockade of the sympathetic nervous system substantially degrades ligament.
PAR1-Type Thrombin Receptor Stimulates Migration and Matrix Adhesion of Human Colon Carcinoma Cells by a PKCɛ-Dependent Mechanism (2004)

The proteinase-activated receptor1 (PAR1) was characterized as a functional receptor for thrombin in cells from different tumor entities. In colon carcinoma, its function has to be defined. In this study we demonstrate that the PAR1-selective agonist peptide TFLLRN induced activation of protein kinase C isoenzymes alpha and epsilon in human HT-29 colon carcinoma cells expressing PAR1 endogeneously. On the cellular level, TFLLRN and thrombin prompted HT-29 cell migration and matrix adhesion by a PKCepsilon-dependent mechanism as concluded because of the inhibition of PAR1-mediated effects by the PKC inhibitor bisindolylmaleimide I and the PKCepsilon translocation inhibitory peptide EAVSLKPT but not by the PKC inhibitor Gö 6976. In addition, blockade of PAR1 by RWJ 56110, a selective PAR1 antagonist, fully abolished the effect of thrombin on HT-29 cell migration and adhesion. Therefore, PAR1 seems to be the responsible receptor for thrombin-induced migration and adhesion of human colon carcinoma cells including PKCepsilon as an essential signal transducer.
Neuronal death in the spinal ganglia of the chick embryo and its reduction by nerve growth factor (1981)

In the spinal ganglia of the chick embryo, two neuronal populations can be distinguished: large, early differentiating ventrolateral (VL) cells and small, late differentiating dorsomedial (DM) cells. It was found that, beginning with stage 25, the DM cells originate from a narrow band of small, immature cells at the medial border of the ganglion, extending to the dorsolateral border. We have designated this band as the inner and outer marginal zone.
The nonredundant roles of two 4′-phosphopantetheinyl transferases in vital processes of Mycobacteria (2006)

Mycobacterium tuberculosis contains >20 enzymes that require activation by transfer of the 4'-phosphopantetheine moiety of CoA onto a conserved serine residue, a posttranslational modification catalyzed by 4'-phosphopantetheinyl transferases (PPTases). The modified proteins are involved in key metabolic processes such as cell envelope biogenesis and the production of virulence factors. We show that two PPTases conserved in all Mycobacterium spp. and in related genera activate two different subsets of proteins and are not functionally redundant. One enzyme, AcpS, activates the two fatty acid synthase systems of mycobacteria, whereas the other PPTase, PptT, acts on type-I polyketide synthases and nonribosomal peptide synthases, both of which are involved in the biosynthesis of virulence factors. We demonstrate that both PPTases are essential for Mycobacterium smegmatis viability and that PptT is required for the survival of Mycobacterium bovis bacillus Calmette-Guérin. These enzymes are thus central to the biology of mycobacteria and for mycobacterial pathogenesis and represent promising targets for new antituberculosis drugs.
Potential-Dependent Wetting of Aqueous Solutions on Self-Assembled Monolayers Formed from 15-(Ferrocenylcarbonyl)pentadecanethiol on Gold (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPotential-Dependent Wetting of Aqueous Solutions on Self-Assembled Monolayers Formed from 15-(Ferrocenylcarbonyl)pentadecanethiol on GoldNicholas L. Abbott and George M. WhitesidesCite this: Langmuir 1994, 10, 5, 1493–1497Publication Date (Print):May 1, 1994Publication History Published online1 May 2002Published inissue 1 May 1994https://pubs.acs.org/doi/10.1021/la00017a029https://doi.org/10.1021/la00017a029research-articleACS PublicationsRequest reuse permissionsArticle Views670Altmetric-Citations104LEARN 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
Molecular architecture of a light-harvesting antenna. Isolation and characterization of phycobilisome subassembly particles. (1982)

Synechococcus 6301 mutant, strain AN112, produces phycobilisomes containing two major biliproteins, phycocyanin and allophycocyanin, and two major linker polypeptides of 27 and 75 kilodaltons (27K and 75K). These phycobilisomes have a molecular weight of approximately 2.5 X 10(6) and are the smallest of these particles known to date. Sucrose density gradient centrifugation of AN112 phycobilisomes partially dissociated in 50 mM N-[tris(hydroxymethyl)methyl]glycine, 5 mM CaCl2, 10% (w/v) glycerol, pH 7.8, separated three distinct fractions: (1) free trimeric biliproteins, (2) hexameric complexes of phycocyanin with 27K (11 S particles), and (3) phycobilisome subassemblies equivalent in mass to approximately 25% of the intact phycobilisome (18 S particles). The 18 S particles contained equimolar amounts of phycocyanin and allophycocyanin, which represented approximately 30 and 50%, respectively, of the content of these biliproteins in the AN112 phycobilisome. The 18 S particles also contained 75% and 100%, respectively, of 27K and 75K polypeptides; i.e. 75K was present in a 2-fold higher amount than in the intact phycobilisome. The absorption spectrum (lambda max 648 nm) of the 18 S particles was similar to that of allophycocyanin. Upon excitation at 580 nm, these particles exhibited a fluorescence emission spectrum consisting of 680 and 660 nm components, identical with that of intact phycobilisomes. The circular dichroism spectra of AN112 phycobilisomes and of the 18 S particles, in the region between 650 and 700 nm, were also very similar. Allophycocyanin B, which fluoresces at 680 nm, was found in fraction 1, and was totally absent from the 18 S particle. Thus, the long wavelength emission of the 18 S particle must have arisen from another terminal energy acceptor. The most probable candidate is the 75K polypeptide, which has been shown to carry a bilin chromophore and emit near 680 nm (Lundell, D. J., Yamanaka, G., and Glazer, A. N. (1980) J. Cell Biol. 91, 315-319). The 27K polypeptide, present in both fractions 2 and 3, was a component of different complexes in the two fractions. Fraction 2 displayed the physical and spectroscopic properties characteristic of the phycocyanin-linker complex, (alpha beta)6.27K. However, in the 18 S particle, 27K functioned in the assembly and attachment of phycocyanin trimers to a core domain. Based on the analysis of the components in fractions 1-3, a model is proposed which describes the structure of the AN112 phycobilisome, with emphasis on the roles of the linker polypeptides in the assembly of the core.
A NOVEL INHIBITORY PEPTIDE OF TOLL-LIKE RECEPTOR SIGNALING LIMITS LIPOPOLYSACCHARIDE-INDUCED PRODUCTION OF INFLAMMATORY MEDIATORS AND ENHANCES SURVIVAL IN MICE (2007)

Sepsis resulting from gram-negative bacterial infections is characterized by an excessive inflammatory immune response initiated by exposure of the host innate immune system to either bacteria or bacterial products, primarily lipopolysaccharide (LPS). Engagement of the Toll-like receptor (TLR) 4 on immune cells by LPS induces production of inflammatory mediators, leading to tissue damage. We recently identified a peptide, termed P13, which was previously shown to be a potent inhibitor of in vitro TLR signaling. In this study, we demonstrate that the use of this novel peptide significantly reduces the in vitro production of inflammatory mediators seen after exposure of hepatocytes/nonparenchymal cell cocultures and endothelial cells to LPS. In addition, in vivo treatment of mice with this peptide was effective at inhibiting LPS-induced production of inflammatory mediators and significantly limited liver damage. Peptide treatment significantly increased survival of LPS-/D-galactosamine-treated mice and mice treated with high-dose LPS. These results demonstrated the therapeutic potential of peptide P13 to limit an LPS-induced inflammatory response and enhance survival in murine models of inflammation.
Intramuscularly Administered Dexmedetomidine Attenuates Hemodynamic and Stress Hormone Responses to Gynecologic Laparoscopy (1992)

The hemodynamic and endocrine effects of three different doses of dexmedetomidine (0.6, 1.2, and 2.4 micrograms/kg), oxycodone (0.13 mg/kg), and saline solution, injected intramuscularly 45-60 min before induction of general anesthesia, were compared in a double-blind, randomized study involving 100 women undergoing gynecologic diagnostic laparoscopy. Anesthesia was induced with thiopental (4.5 mg/kg) and maintained with 0.3% end-tidal isoflurane and 70% nitrous oxide in oxygen. Arterial blood pressure and heart rate increased after endotracheal intubation and during laparoscopy in all groups, but the maximal mean arterial pressure after tracheal intubation was lower in the dexmedetomidine 2.4-micrograms/kg group (104 mm Hg [SD 19]) than in the saline solution group (130 mm Hg [SD 12]). Dexmedetomidine (2.4 and 1.2 micrograms/kg) attenuated the maximal heart rate after intubation (84 [SD 11] and 101 beats/min [SD 15], respectively) compared with saline solution (116 beats/min [SD 19]). On the other hand, 40% of the patients in the dexmedetomidine 2.4-micrograms/kg group received atropine in the postanesthesia care unit for bradycardia (heart rate < or = 40 beats/min). Preoperative anxiety and sedation before and after preanesthetic medication were evaluated by the patients with the aid of a profile of mood-state questionnaire; only dexmedetomidine 2.4 micrograms/kg produced significant anxiolysis and sedation. Plasma concentrations of norepinephrine, epinephrine, 3,4-dihydroxyphenylglycol, cortisol, and beta-endorphin increased less in the dexmedetomidine 2.4-micrograms/kg group in response to tracheal intubation and surgery than in the saline solution group.