gebhart/patrepeval huggingface dataset:
The role of IL-12 in inflammatory activity of patients with rheumatoid arthritis (RA) (2000)

The aim of this study was to investigate the role of IL-12 in patients with RA. IL-12 (p70) and its associated cytokines were measured in sera and synovial fluid (SF) using an enzyme-linked immunosorbent method. Seven American College of Rheumatology (ACR) core set measures as well as IL-12 levels were sequentially monitored at the commencement and 4 months after treatment with a low-dose steroid and disease-modifying anti-rheumatic drugs (DMARDs). In sera, 64 (42.2%) of 152 RA patients had detectable concentrations of IL-12 (p70), whereas one (1.4%) of 69 osteoarthritis (OA) patients and five (10%) of 50 healthy controls had detectable IL-12 (P < 0.001). The median level of circulating IL-12 was also higher in RA patients (P < 0.001). In SF, the number of patients with detectable IL-12 and the median IL-12 levels were significantly higher in RA patients (n = 53) than in OA patients (n = 22). In paired samples (n = 53) of sera and SF from RA patients, IL-12 levels were higher in the SF than in sera (P < 0.001). Patients with detectable IL-12 (n = 51) in sera had higher tender joint scores (P = 0.003), swollen joint scores (P < 0.001) and C-reactive protein (CRP; P = 0.036), than those without (n = 55). Four months after treatment with DMARDs, the improved group showed a larger IL-12 decrease than the non-improved group (P = 0.017). The levels of IL-12 correlated positively with those of IL-2, interferon-gamma, IL-6, and tumour necrosis factor-alpha, but were correlated inversely with those of IL-10. Our results demonstrate that IL-12 levels reflect RA disease activity and that IL-12 is involved in the production of proinflammatory cytokines. An IL-12 blockade could be useful for the treatment of RA.
Spinal Inhibitory Effects of Cardiopulmonary Afferent Inputs in Monkeys: Neuronal Processing in High Cervical Segments (2002)

Noxious stimulation of spinal afferents inhibits primate spinothalamic tract (STT) neurons in segments distant from the region of afferent entry. Inhibitory effects of cardiopulmonary sympathetic afferent (CPSA) stimulation remain after C(1) transection but disappear with spinal transection between C(3) and C(7). We hypothesized that spinal inhibitory effects produced by CPSA stimulation are processed by neurons in C(1)-C(3) segments. One purpose of this study in anesthetized monkeys was to determine whether chemical activation of high cervical neurons reduced sacral STT cell responses to colorectal distension (CRD) and urinary bladder distension (UBD). First, effects and interactions of pelvic and cardiopulmonary visceral afferent inputs were determined in 10 monkeys on extracellular activity of sacral STT neurons recorded in deep dorsal horn. CRD and UBD increased activity in 95 and 91% of sacral STT neurons, respectively. CPSA and cardiopulmonary vagal stimulation decreased activity in 84 and 56% of STT neurons, respectively. CPSA stimulation decreased CRD-evoked activity in six of eight sacral STT neurons and decreased UBD-evoked activity in five of eight STT neurons tested. Excitatory amino acid application at C2 segment decreased CRD-evoked responses in 7 of 10 sacral STT neurons and decreased UBD-evoked responses in 9 of 12 STT neurons. The second purpose of this study was to examine responses of C(1)-C(3) descending propriospinal neurons to stimulation of cardiopulmonary afferent fibers. If C(1)-C(3) neurons process CPSA input to suppress STT transmission, then CPSA stimulation should excite C(1)-C(3) neurons with descending projections. Effects of thoracic vagus nerve stimulation also were examined. Vagal stimulation inhibits STT neurons in segments below C(3) but excites C(1)-C(3) STT neurons; we theorized that vagal inhibition of sensory transmission might relay in high cervical segments and, therefore, excite C(1)-C(3) descending propriospinal neurons. Extracellular discharge rate was recorded for C(1)-C(3) neurons antidromically activated from thoracic or lumbar spinal cord in 24 monkeys. CPSA stimulation increased activity of 16 of 45 neurons and inhibited one cell. Thoracic vagus stimulation increased activity of 20 of 43 neurons and inhibited one cell; stimulation of abdominal vagus fibers did not affect activity of six of six cells that were excited by thoracic vagal input. Mechanical stimulation of somatic fields excited 30 of 41 neurons tested. All neurons activated by visceral input received convergent somatic input from noxious pinch of somatic receptive fields that generally included the neck and upper body; 11 C(1)-C(3) propriospinal neurons did not respond to any afferent input examined. Results of these studies were consistent with the idea that modulation of spinal nociceptive transmission might involve neuronal connections in high cervical segments.
Kinetic Separation of Faradaic Currents: Binary Monolayers as Model Systems (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTKinetic Separation of Faradaic Currents: Binary Monolayers as Model SystemsRobert J. Forster and Larry R. FaulknerCite this: Anal. Chem. 1995, 67, 7, 1232–1239Publication Date (Print):April 1, 1995Publication History Published online1 May 2002Published inissue 1 April 1995https://pubs.acs.org/doi/10.1021/ac00103a014https://doi.org/10.1021/ac00103a014research-articleACS PublicationsRequest reuse permissionsArticle Views245Altmetric-Citations32LEARN 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
The Intermediacy of Sulfate Esters in Sulfuric Acid Catalyzed Acetylation of Carbohydrates (1993)

The acetylation of 1,2,3,4-tetra-0-acetylbeta-pglucopyranose in excess acetic anhydride/acetic acid/sulfuric acid was shown by kinetic studies and observation of intermediates to proceed y j & a rapid formation of the corresponding 6-sulfate ester, followed by rate-controlling acetolysis of the sulfate to give glucose pentaacetate product.The same mechanism is proposed, based on kinetic data, for acetylation of the secondary alcohol 1,2,3,6-tetra-0-acetyl-beta-p- glucopyranose.
Determination of the three‐dimensional solution structure of the histidine‐containing phosphocarrier protein HPr from Escherichia coli using multidimensional NMR spectroscopy (1992)

We recorded several types of heteronuclear three-dimensional (3D) NMR spectra on 15N-enriched and 13C/15N-enriched histidine-containing phosphocarrier protein, HPr, to extend the backbone assignments [van Nuland, N. A. J., van Dijk, A. A., Dijkstra, K., van Hoesel, F. H. J., Scheek, R. M. & Robillard, G. T. (1992) Eur. J. Biochem, 203, 483-491] to the side-chain 1H,15N and 13C resonances. From both 3D heteronuclear 1H-NOE 1H-13C and 1H-NOE 1H-15N multiple-quantum coherence (3D-NOESY-HMQC) and two-dimensional (2D) homonuclear NOE spectra, more than 1200 NOE were identified and used in a step-wise structure refinement process using distance geometry and restrained molecular dynamics involving a number of new features. A cluster of nine structures, each satisfying the set of NOE restraints, resulted from this procedure. The average root-mean-square positional difference for the C alpha atoms is less than 0.12 nm. The secondary structure topology of the molecule is that of an open-face beta sandwich formed by four antiparallel beta strands packed against three alpha helices, resembling the recently published structure of Bacillus subtilis HPr, determined by X-ray crystallography [Herzberg, O., Reddy, P., Sutrina, S., Saier, M. H., Reizer, J. & Kapafia, G. (1992) Proc. Natl, Acad. Sci. USA 89, 2499-2503).
Heteronuclear 2D NMR studies of an engineered insulin monomer: assignment and characterization of the receptor-binding surface by selective deuterium and carbon-13 labeling with application to protein design (1991)

Insulin provides an important model for the application of genetic engineering to rational protein design and has been well characterized in the crystal state. However, self-association of insulin in solution has precluded complementary 2D NMR study under physiological conditions. We demonstrate here that such limitations may be circumvented by the use of a monomeric analogue that contains three amino acid substitutions on the protein surface (HisB10----Asp, ProB28----Lys, and LysB29----Pro); this analogue (designated DKP-insulin) retains native receptor-binding potency. Comparative 1H NMR studies of native human insulin and a series of three related analogues--(i) the singly substituted analogue [HisB10----Asp], (ii) the doubly substituted analogue [ProB28----Lys; LysB29----Pro], and (iii) DKP-insulin--demonstrate progressive reduction in concentration-dependent line-broadening in accord with the results of analytical ultracentrifugation. Extensive nonlocal interactions are observed in the NOESY spectrum of DKP-insulin, indicating that this analogue adopts a compact and stably folded structure as a monomer in overall accord with crystal models. Site-specific 2H and 13C isotopic labels are introduced by semisynthesis as probes for the structure and dynamics of the receptor-binding surface. These studies confirm and extend under physiological conditions the results of a previous 2D NMR analysis of native insulin in 20% acetic acid [Hua, Q. X., & Weiss, M. A. (1991) Biochemistry 30, 5505-5515]. Implications for the role of protein flexibility in receptor recognition are discussed with application to the design of novel insulin analogues.
New Miniaturized Hollow-Fiber Bioreactor for in Vivo Like Cell Culture, Cell Expansion, and Production of Cell-Derived Products (2001)

We have developed a miniaturized hollow-fiber bioreactor system for mammalian cell culture with a volume of 1 mL. Cell and medium compartments of the bioreactor are separated by a semipermeable membrane, and oxygenation of the cell compartment is accomplished using an oxygenation membrane. As a result of the geometry of the transparent housing, cells can be observed by microscopy during culture. The leukemic cell lines CCRF-CEM, HL-60, and REH were cultivated up to densities of 3.5 x 10(7)/mL without medium change or manipulation of the cells. As shown using CCRF-CEM cells, growth in the bioreactor was strongly influenced and could be controlled by the medium flow rate. As a consequence, consumption of glucose and generation of lactate varied with flow rate. Depending on the molecular size cutoff of the membranes used, added growth factors such as GM-CSF, as well as factors secreted from the cells, are retained in the cell compartment for up to 1 week. This new miniaturized hollow-fiber bioreactor offers advantages in tissue engineering by continuous nutrient supply for cells in high density, retention of added or autocrine produced factors, and undisturbed long-term culture in a closed system.
Repurposing CRISPR-Cas12b for mammalian genome engineering (2018)

The prokaryotic CRISPR-Cas adaptive immune systems provide valuable resources to develop genome editing tools, such as CRISPR-Cas9 and CRISPR-Cas12a/Cpf1. Recently, CRISPR-Cas12b/C2c1, a distinct type V-B system, has been characterized as a dual-RNA-guided DNA endonuclease system. Though being active in vitro, its cleavage activity at endogenous genome remains to be explored. Furthermore, the optimal cleavage temperature of the reported Cas12b orthologs is higher than 40 °C, which is unsuitable for mammalian applications. Here, we report the identification of a Cas12b system from the <i>Alicyclobacillus acidiphilus</i> (AaCas12b), which maintains optimal nuclease activity over a wide temperature range (31 °C-59 °C). AaCas12b can be repurposed to engineer mammalian genomes for versatile applications, including single and multiplex genome editing, gene activation, and generation of gene mutant mouse models. Moreover, whole-genome sequencing reveals high specificity and minimal off-target effects of AaCas12b-meditated genome editing. Our findings establish CRISPR-Cas12b as a versatile tool for mammalian genome engineering.
Abdominal Trauma (1976)

THE INCREASING frequency in urban areas of penetrating abdominal wounds and in suburban and rural areas of blunt abdominal injuries makes trauma one of the leading causes of the acute abdomen in current surgical practice. Trauma represents an accelerated form of general surgery, and the usual criteria of peritoneal irritation and visceral damage should constitute the indications for celiotomy. <h3>To Operate or Not?</h3> Until the end of World War II, suspicion of peritoneal penetration was considered an adequate indication for abdominal exploration. The high incidence of normal findings in these circumstances suggested that approximately one third of patients could avoid operation by selective evaluation of individual cases. Although selective celiotomy requires a larger staff for observation, greater clinical acumen than routine exploration, and modification for local circumstances, the principle is valid. Peritoneal penetration under more controlled circumstances (ie, paracentesis, peritoneal dialysis, closed liver biopsy) is considered routine and safe on
Examination of DSM-IV Criteria for Attention Deficit/Hyperactivity Disorder in a County-Wide Sample (1998)

This study replicated, in the subsequent academic year, teacher-reported prevalence rates for attention deficit/hyperactivity disorder (ADHD) based on DSM-IV. Teachers in grades K-5 in a Tennessee county (10 schools, 214 teachers, and 4323 children) completed questionnaires on all their students consisting of the DSM-IV symptoms for disruptive behavior disorders, except for eight conduct disorders symptoms, seven symptoms screening for anxiety or depression, ratings of performance, and questions about the presence of ADHD, stimulant medication treatment, and behavioral or academic problems. The prevalence rates were 16.1% for ADHD-all types, 8.8% for ADHD-inattentive type (AD), 2.6% for ADHD-hyperactive/impulsive type (HI), and 4.7% for ADHD-combined type and 6.8, 3.2, 0.6, and 2.9%, respectively, when impairment was taken into consideration. The rates of problems differed mostly between ADHD-AD AND ADHD-HI (30% vs. 68%) for behavior and (56% vs. 16%) for academics. Few (11-33%) had an ADHD diagnosis or were treated with stimulant treatment (8-26%). DSM-IV criteria are likely to increase the prevalence but may better characterize the heterogeneity of this disorder.
Electrophysiological differences between nociceptive and non‐nociceptive dorsal root ganglion neurones in the rat in vivo (2005)

Intracellular recordings were made from 1022 somatic lumbar dorsal root ganglion (DRG) neurones in anaesthetized adult rats, classified from dorsal root conduction velocities (CVs) as C, Adelta or Aalpha/beta, and according to their responses to mechanical and thermal stimuli as nociceptive (including high-threshold mechanoreceptive (HTM) units), and non-nociceptive (including low-threshold mechanoreceptive (LTM) and cooling units). Of these, 463 met electrophysiological criteria for analysis of action potentials (APs) evoked by dorsal root stimulation. These included 47 C-, 71 Adelta- and 102 Aalpha/beta-nociceptive, 10 C-, 8 Adelta- and 178 Aalpha/beta-LTM, 18 C- and 19 Adelta- unresponsive, and 4 C-cooling units. Medians of AP and afterhyperpolarization (AHP) durations and AP overshoots were significantly greater for nociceptive than LTM units in all CV groups. AP overshoots and AHP durations were similar in nociceptors of all CV groups whereas AP durations were greater in slowly conducting, especially C-fibre, nociceptors. C-cooling units had faster CVs, smaller AP overshoots and shorter AP durations than C-HTM units. A subgroup of Aalpha/beta-HTM, moderate pressure units, had faster CVs and AP kinetics than other Aalpha/beta-HTM units. Of the Aalpha/beta-LTM units, muscle spindle afferents had the fastest CV and AP kinetics, while rapidly adapting cutaneous units had the slowest AP kinetics. AP variables in unresponsive and nociceptive units were similar in both C- and Adelta-fibre CV groups. The ability of fibres to follow rapid stimulus trains (fibre maximum following frequency) was correlated with CV but not sensory modality. These findings indicate both the usefulness and limitations of using electrophysiological criteria for identifying neurones acutely in vitro as nociceptive.
Increased catecholamine secretion contributes to hypertension in TRPM4-deficient mice (2010)

Hypertension is an underlying risk factor for cardiovascular disease. Despite this, its pathogenesis remains unknown in most cases. Recently, the transient receptor potential (TRP) channel family was associated with the development of several cardiovascular diseases linked to hypertension. The melastatin TRP channels TRPM4 and TRPM5 have distinct properties within the TRP channel family: they form nonselective cation channels activated by intracellular calcium ions. Here we report the identification of TRPM4 proteins in endothelial cells, heart, kidney, and chromaffin cells from the adrenal gland, suggesting that they have a role in the cardiovascular system. Consistent with this hypothesis, Trpm4 gene deletion in mice altered long-term regulation of blood pressure toward hypertensive levels. No changes in locomotor activity, renin-angiotensin system function, electrolyte and fluid balance, vascular contractility, and cardiac contractility under basal conditions were observed. By contrast, inhibition of ganglionic transmission with either hexamethonium or prazosin abolished the difference in blood pressure between Trpm4-/- and wild-type mice. Strikingly, plasma epinephrine concentration as well as urinary excretion of catecholamine metabolites were substantially elevated in Trpm4-/- mice. In freshly isolated chromaffin cells, lack of TRPM4 was shown to cause markedly more acetylcholine-induced exocytotic release events, while neither cytosolic calcium concentration, size, nor density of vesicles were different. We therefore conclude that TRPM4 proteins limit catecholamine release from chromaffin cells and that this contributes to increased sympathetic tone and hypertension.
Functional siRNA expression from transfected PCR products (2002)

RNA interference (RNAi) is a process in which double-stranded RNA (dsRNA) induces the postranscriptional degradation of homologous transcripts. RNAi can be initiated by exposing cells to dsRNA either via transfection or endogenous expression. In mammalian systems, the sequence-specific RNAi effect has been observed by expression of 21-23 base transcripts capable of forming duplexes, or via expression of short hairpin RNAs. We describe here a facile PCR based strategy for rapid synthesis of siRNA expression units and their testing in mammalian cells. The siRNA expression constructs are constructed by PCR, and the PCR products are directly transfected into mammalian cells resulting in functional expression of siRNAs. This approach should prove useful for identification of optimal siRNA-target combinations and for multiplexing siRNA expression in mammalian cells.
Combining Multi-scale Character Recognition and Linguistic Knowledge for Natural Scene Text OCR (2012)

Understanding text captured in real-world scenes is a challenging problem in the field of visual pattern recognition and continues to generate a significant interest in the OCR (Optical Character Recognition) community. This paper proposes a novel method to recognize scene texts avoiding the conventional character segmentation step. The idea is to scan the text image with multi-scale windows and apply a robust recognition model, relying on a neural classification approach, to every window in order to recognize valid characters and identify non valid ones. Recognition results are represented as a graph model in order to determine the best sequence of characters. Some linguistic knowledge is also incorporated to remove errors due to recognition confusions. The designed method is evaluated on the ICDAR 2003 database of scene text images and outperforms state-of-the-art approaches.
Immunogenicity of Recombinant Vaccinia Viruses that Display the HIV Type 1 Envelope Glycoprotein on the Surface of Infectious Virions (1997)

A chimeric protein, consisting of the extracellular domain of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein attached to the transmembrane and cytoplasmic domains of the vaccinia virus B5R glycoprotein, is displayed on the surface of extracellular recombinant vaccinia virus particles, whereas the unmodified full-length HIV-1 glycoprotein is not (Katz E, et al., J Virol 1997;71:3178-3187). Here, we report that rabbits and mice inoculated with recombinant vaccinia viruses that express the chimeric protein developed higher HIV-specific antibody responses than animals inoculated with vaccinia virus that expressed the unmodified HIV glycoprotein. These data suggest that the immunogenicity of recombinant proteins may be enhanced by their presentation on the surface of vaccinia virus particles.
Paradoxical Hypotension and Bradycardia after Intravenous Arginine Vasopressin (1998)

Standard therapy for variceal bleeding includes endoscopic sclerotherapy and esophageal balloon tamponade. In addition, pharmacologic therapies, including arginine vasopressin (AVP), are frequently used in hemodynamically unstable patients or where sclerotherapy has been unsuccessful. A case is described herein of a 30-year-old woman with a history of ethanol abuse, hematemeisis, and biopsy-proven hepatic cirrhosis in which the addition of AVP to an antivariceal regimen of octreotide was associated with a paradoxical episode of hypotension, bradycardia, and hypoxia. Indeed, within 15 minutes after initiation of an AVP infusion, the patient exhibited hypotension with a systolic blood pressure of 80 mmHg, a relative bradycardia to 76 beats per minute, and a desaturation of blood oxygen to 84%. The AVP infusion was discontinued 2 hours later and blood pressure, heart rate, and oxygen saturation rapidly returned to baseline. This temporal correlation between the onset and termination of the physiologic effects and the initiation and discontinuation of the AVP infusion suggests a causal relationship. The paradoxical physiologic effects might reflect cardiac ischemia secondary to vasospasm and/or central suppression of the autonomic nervous system induced by AVP.