gebhart/patrepeval huggingface dataset:
Somatostatin 14 and joint inflammation: evidence for intraarticular efficacy of prolonged administration in rheumatoid arthritis. (1995)

Previous studies with intraarticular administration of somatostatin (SST14) in rheumatoid arthritis showed an antiinflammatory and analgesic effect. The aim of the present study was to demonstrate the efficacy and tolerability of SST14 in rheumatoid arthritis (RA) patients for a longer period of treatment than previously scheduled. Forty-one patients with RA of the knee were treated with a cycle of intraarticular injection of 750 micrograms of SST14, every 15 days. The efficacy of SST14 was evaluated by determining acute phase parameters (erythrocyte sedimentation rate, C-reactive protein [CRP]) and by clinical assessment (pain at rest and on movement, joint tenderness, morning stiffness, spontaneous pain). Additionally, telethermography was performed to evaluate the intensity of the joint inflammation. The tolerability of the treatment was also assessed both by patients and physicians. SST14 produced a reduction in all parameters; this was already statistically significant after the second injection in terms of pain at rest and on movement, and after the third injection for all other symptoms. The treatment showed an excellent tolerability, both local and systemic. Our results indicate the analgesic property of SST14 and demonstrate its capacity to reduce progressively joint inflammation confirmed by thermography and by reduction of pain, after a month of therapy.
Agrobactrium tumefaciens-mediated transformation of Monascus ruber. (2008)

Agrobacterium tumefaciens-mediated transformation (ATMT) was successfully applied to Monascus ruber. The optimum cocultivation time was 84 h with an efficiency of 900 to 1,000 transformants when 1x106 spores were used with the same volume of bacteria. The stability of transformants was over 98% after five generations. When M. ruber was transformed with A. tumefaciens YL-63 containing the green fluorescent protein gene (egfp), the green fluorescent signal was observed throughout hyphae, confirming expression of the gene. This efficient transformation and expression system of M. ruber by ATMT will facilitate the study of this fungus at a molecular genetic level.
Role of Sphingosine Kinase 2 in Cell Migration toward Epidermal Growth Factor (2005)

Sphingosine 1-phosphate (S1P), produced by two sphingosine kinase isoenzymes, denoted SphK1 and SphK2, is the ligand for a family of five specific G protein-coupled receptors that regulate cytoskeletal rearrangements and cell motility. Whereas many growth factors stimulate SphK1, much less is known of the regulation of SphK2. Here we report that epidermal growth factor (EGF) stimulated SphK2 in HEK 293 cells. This is the first example of an agonist-dependent regulation of SphK2. Chemotaxis of HEK 293 cells toward EGF was inhibited by N,N-dimethylsphingosine, a competitive inhibitor of both SphKs, implicating S1P generation in this process. Down-regulating expression of SphK1 in HEK 293 cells with a specific siRNA abrogated migration toward EGF, whereas decreasing SphK2 expression had no effect. EGF contributes to the invasiveness of human breast cancer cells, and EGF receptor expression is associated with poor prognosis. EGF also stimulated SphK2 in MDA-MB-453 breast cancer cells. Surprisingly, however, down-regulation of SphK2 in these cells completely eliminated migration toward EGF without affecting fibronectin-induced haptotaxis. Our results suggest that SphK2 plays an important role in migration of MDA-MB-453 cells toward EGF.
Directed ortho Metalation - Cross Coupling Connections. Nickel (0) - Catalyzed Cross Coupling of Aryl Triflates with Organozinc Reagents (1994)

Aryl zinc reagents, derived by directed ortho metalation, undergo cross coupling with aryl triflates under Ni(0) catalysis to provide a general, regiospecific method for the synthesis of diverse functionalized biaryls (Table).
Dynamic Stochastic Blockmodels for Time-Evolving Social Networks (2014)

Significant efforts have gone into the development of statistical models for analyzing data in the form of networks, such as social networks. Most existing work has focused on modeling static networks, which represent either a single time snapshot or an aggregate view over time. There has been recent interest in statistical modeling of dynamic networks, which are observed at multiple points in time and offer a richer representation of many complex phenomena. In this paper, we present a state-space model for dynamic networks that extends the well-known stochastic blockmodel for static networks to the dynamic setting. We fit the model in a near-optimal manner using an extended Kalman filter (EKF) augmented with a local search. We demonstrate that the EKF-based algorithm performs competitively with a state-of-the-art algorithm based on Markov chain Monte Carlo sampling but is significantly less computationally demanding.
A quantitative model for the in vivo assessment of drug binding sites with positron emission tomography (1984)

We propose an in vivo method for use with positron emission tomography (PET) that results in a quantitative characterization of neuroleptic binding sites using radiolabeled spiperone. The data are analyzed using a mathematical model that describes transport, nonspecific binding, and specific binding in the brain. The model demonstrates that the receptor quantities Bmax (i.e., the number of binding sites) and KD-1 (i.e., the binding affinity) are not separably ascertainable with tracer methodology in human subjects. We have, therefore, introduced a new term, the binding potential, equivalent to the product BmaxKD-1, which reflects the capacity of a given tissue, or region of a tissue, for ligand-binding site interaction. The procedure for obtaining these measurements is illustrated with data from sequential PET scans of baboons after intravenous injection of carrier-added [18F]spiperone. From these data we estimate the brain tissue nonspecific binding of spiperone to be in the range of 94.2 to 95.3%, and the regional brain spiperone permeability (measured as the permeability-surface area product) to be in the range of 0.025 to 0.036 cm3/(s X ml). The binding potential of the striatum ranged from 17.4 to 21.6; these in vivo estimates compare favorably to in vitro values in the literature. To our knowledge this represents the first direct evidence that PET can be used to characterize quantitatively, locally and in vivo, drug binding sites in brain. The ability to make such measurements with PET should permit the detailed investigation of diseases thought to result from disorders of receptor function.
Electrochemical Sensors and Biosensors (2011)

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTElectrochemical Sensors and BiosensorsDanielle W. Kimmel, Gabriel LeBlanc, Mika E. Meschievitz, and David E. Cliffel*View Author Information Department of Chemistry, Vanderbilt University, 7330 Stevenson Center, VU Station B 351822, Nashville, Tennessee 37235-1822, United States*Fax: (615) 343-1234. E-mail: [email protected]Cite this: Anal. Chem. 2012, 84, 2, 685–707Publication Date (Web):November 1, 2011Publication History Published online11 November 2011Published inissue 17 January 2012https://pubs.acs.org/doi/10.1021/ac202878qhttps://doi.org/10.1021/ac202878qreview-articleACS PublicationsCopyright © 2011 American Chemical SocietyRequest reuse permissionsArticle Views26979Altmetric-Citations731LEARN 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 SUBJECTS:Biotechnology,Carbon nanotubes,Electrodes,Peptides and proteins,Sensors Get e-Alerts
DNA specificity enhanced by sequential binding of protein monomers (1999)

Transcriptional activation often requires the rapid assembly of complexes between dimeric transcription factors and specific DNA sites. Here we show that members of the basic region leucine zipper and basic region helix-loop-helix zipper transcription factor families follow an assembly pathway in which two protein monomers bind DNA sequentially and form their dimerization interface while bound to DNA. Nonspecific protein or DNA competitors have little effect on the rate of assembly along this pathway, but slow a competing pathway in which preformed dimers bind DNA. The sequential monomer-binding pathway allows the protein to search for and locate a specific DNA site more quickly, resulting in greater specificity prior to equilibrium.
Decreased Plasma Levels of Orexin-A in Sleep Apnea (2004)

Orexin-A plasma levels are abnormally low in patients with OSAS, independently of the level of somnolence and/or presence of obesity. These results suggest that these low orexin-A levels may be related to the pathogenesis of OSAS.
Signaling lymphocytic activation molecule (SLAM) regulates T cellular cytotoxicity (2001)

Signaling lymphocytic activation molecule (SLAM) is a CD2-related surface receptor expressed by activated T cells and B cells. SLAM is a self ligand and enhances T cellular proliferation and IFN-gamma production. A defective SLAM associated protein (SAP) causes X-linked lymphoproliferative syndrome (XLP), a frequently lethal mononucleosis based on the inability to control EBV. We report that SLAM augments TCR-mediated cytotoxicity. In normal CD4(+) and CD8(+) T cells, SLAM enhanced TCR-mediated cytotoxicity. In CD4(+) and CD8(+) Herpesvirus saimiri (H.saimiri) infected T cells, SLAM engagement alone triggered cytotoxicity. Using H.saimiri-transformed T cells as a model system we found that SLAM-engagement promotes the release of lytic granules and a CD95-independent killing that requires extracellular Ca(2+), cytoskeletal rearrangements, and signaling mediated by mitogen-activated protein kinase kinases MEK1/2. SLAM-enhanced cytotoxicity implies an immunoregulatory function by facilitating the elimination of APC and a role in overcoming infections with pathogens requiring a cytotoxic immune response.
The membrane glycoprotein Ia-IIa (VLA-2) complex mediates the Mg++-dependent adhesion of platelets to collagen. (1989)

We have purified the platelet membrane glycoprotein Ia-IIa complex by detergent solubilization and sequential affinity chromatography on Concanavalin A-Sepharose and collagen-Sepharose. The complex, which is identical to the VLA-2 complex of lymphocytes and other cells and contains subunits of 160 and 130 kD on SDS-PAGE, was labeled with 125I and incorporated into phosphatidyl choline liposomes. The liposomes, like intact platelets, adhered to collagenous substrates in an Mg++-dependent manner with a K'a(Mg++) of 3.5 mM. Little adhesion of the liposomes to collagen occurred when Mg++ was replaced by Ca++ or EDTA. Calcium ions inhibited the Mg++-dependent adhesion with a K'i(Ca++) of 5.5 mM. Liposomes containing the Ia-IIa complex adhered to substrates composed of types I, II, III, and IV collagen, but did not effectively adhere to substrates composed of type V collagen or gelatin. Adhesion to collagen was specific. The liposomes did not adhere to fibronectin, vitronectin, laminin, thrombospondin, fibrinogen, or von Willebrand factor substrates. The monoclonal antibody P1H5, which specifically immunoprecipitated the Ia-IIa complex, also specifically inhibited the Mg++-dependent adhesion of both platelets and Ia-IIa-containing liposomes to collagen substrates. These findings provide additional evidence that the platelet membrane Ia-IIa complex is the mediator of Mg++-dependent platelet adhesion to collagen and suggest that the VLA-2 complex may also function as an Mg++-dependent collagen receptor in other cells.
Mathematical Modeling, Analysis, and Design of Magnetorheological (MR) Dampers (2009)

Most magnetorheological (MR) fluid dampers are designed as fixed-pole valve mode devices, where the MR fluid is forced to flow through a magnetically active annular gap. This forced flow generates the damping force, which can be continuously regulated by controlling the strength of the applied magnetic field. Because the size of the annular gap is usually very small relative to the radii of the annulus, the flow of the MR fluid through this annulus is usually approximated by the flow of fluid through two infinitely wide parallel plates. This approximation, which is widely used in designing and modeling of MR dampers, is satisfactory for many engineering purposes. However, the model does not represent accurately the physical processes and, therefore, expressions that correctly describe the physical behavior are highly desirable. In this paper, a mathematical model based on the flow of MR fluids through an annular gap is developed. Central to the model is the solution for the flow of any fluid model with a yield stress (of which MR fluid is an example) through the annular gap inside the damper. The physical parameters of a MR damper designed and fabricated at the University of Manchester are used to evaluate the performance of the damper and to compare with the corresponding predictions of the parallel plate model. Simulation results incorporating the effects of fluid compressibility are presented, and it is shown that this model can describe the major characteristics of such a device—nonlinear, asymmetric, and hysteretic behaviors—successfully.
Clinical experience of noninvasive prenatal testing with cell‐free DNA for fetal trisomies 21, 18, and 13, in a general screening population (2013)

NIPT has the potential to be a highly effective screening method as a standard test for risk assessment of fetal trisomies 21, 18, and 13 in general pregnant populations.
A scalable method for biochemical purification of Salmonella flagellin (2014)

Flagellins are the main structural proteins of bacterial flagella and potent stimulators of innate and adaptive immunity in mammals. The flagellins of Salmonella are virulence factors and protective antigens, and form the basis of promising vaccines. Despite broad interest in flagellins as antigens and adjuvants in vaccine formulations, there have been few advances towards the development of scalable and economical purification methods for these proteins. We report here a simple and robust strategy to purify flagellin monomers from the supernatants of liquid growth culture. Phase 1 flagellins from Salmonella enterica serovars Typhimurium (i epitope) and Enteritidis (g,m epitopes) were purified directly from conditioned fermentation growth media using sequential cation- and anion-exchange chromatography coupled with a final tangential flow-filtration step. Conventional porous chromatography resin was markedly less efficient than membrane chromatography for flagellin purification. Recovery after each process step was robust, with endotoxin, nucleic acid and residual host-cell protein effectively removed. The final yield was 200-300 mg/L fermentation culture supernatant, with ∼45-50% overall recovery. A final pH 2 treatment step was instituted to ensure uniformity of flagellin in the monomeric form. Flagellins purified by this method were recognized by monoclonal anti-flagellin antibodies and maintained capacity to activate Toll-like Receptor 5. The process described is simple, readily scalable, uses standard bioprocess methods, and requires only a few steps to obtain highly purified material.
Protein trans-Splicing and Cyclization by a Naturally Split Intein from the dnaE Gene ofSynechocystis Species PCC6803 (2000)

A naturally occurring split intein from the dnaE gene of Synechocystis sp. PCC6803 (Ssp DnaE intein) has been shown to mediate efficient in vivo and in vitro trans-splicing in a foreign protein context. A cis-splicing Ssp DnaE intein construct displayed splicing activity similar to the trans-splicing form, which suggests that the N- and C-terminal intein fragments have a high affinity interaction. An in vitro trans-splicing system was developed that used a bacterially expressed N-terminal fragment of the Ssp DnaE intein and either a bacterially expressed or chemically synthesized intein C-terminal fragment. Unlike artificially split inteins, the Ssp DnaE intein fragments could be reconstituted in vitro under native conditions to mediate splicing as well as peptide bond cleavage. This property allowed the development of an on-column trans-splicing system that permitted the facile separation of reactants and products. Furthermore, the trans-splicing activity of the Ssp DnaE intein was successfully applied to the cyclization of proteins in vivo. Also, the isolation of the unspliced precursor on chitin resin allowed the cyclization reaction to proceed in vitro. The Ssp DnaE intein thus represents a potentially important protein for in vivo and in vitro protein manipulation.
Human papillomavirus type 18 E6*, E6, and E7 protein synthesis in cell-free translation systems and comparison of E6 and E7 in vitro translation products to proteins immunoprecipitated from human epithelial cells (1991)

Expression of the E6 and E7 transforming genes of human papillomavirus type 18 (HPV18) occurs via structurally bicistronic mRNAs in which the downstream open reading frame (ORF) E7 is preceded either by the full-length ORF E6 or by a spliced ORF, E6*. We have used in vitro transcription and translation of HPV18 cDNAs in order to analyze the synthesis of E6*, E6, and E7 proteins and to compare the E6 and E7 in vitro translation products with the authentic proteins immunoprecipitated from cervical cancer cells. In wheat germ extract, in vitro translation resulted in the production of all three proteins, E6*, E6, and E7. In rabbit reticulocyte lysate, however, only the E6 and E7 proteins were produced. The lack of E6* protein was due neither to template RNA degradation nor to an inhibitory influence of the RNA 5' leader sequences, thus indicating the possibility of either inhibition of synthesis or degradation of E6* protein in reticulocyte lysate. The E7 protein was synthesized from both E6*-E7 and E6-E7 RNAs. In vitro-synthesized and authentic HPV18 E7 proteins revealed identical electrophoretic mobilities in two-dimensional gel electrophoresis, thus indicating similar modifications. By using a monoclonal antibody against the N terminus of HPV18 E6* and E6, an 18-kDa protein was detected not only in HPV18-positive but also in HPV18-negative epithelial cells. The 18-kDa proteins and the in vitro-synthesized HPV18 E6 protein exhibited comparable electrophoretic characteristics in two-dimensional gels. These results suggest the possible existence of a cellular protein related to HPV18 E6.
Fusion-Competent Vaccines: Broad Neutralization of Primary Isolates of HIV (1999)

Current recombinant human immunodeficiency virus (HIV) gp120 protein vaccine candidates are unable to elicit antibodies capable of neutralizing infectivity of primary isolates from patients. Here, "fusion-competent" HIV vaccine immunogens were generated that capture the transient envelope-CD4-coreceptor structures that arise during HIV binding and fusion. In a transgenic mouse immunization model, these formaldehyde-fixed whole-cell vaccines elicited antibodies capable of neutralizing infectivity of 23 of 24 primary HIV isolates from diverse geographic locations and genetic clades A to E. Development of these fusion-dependent immunogens may lead to a broadly effective HIV vaccine.
Expression and replication of hepatitis B virus genome in transgenic mice. (1989)

We produced transgenic mice by microinjecting a partial tandem duplication of the complete hepatitis B virus (HBV) genome into fertilized eggs of C57BL/6 mice. One of eight transgenic mice was a high producer for HBV surface antigen (HBsAg) and HBV e antigen (HBeAg) in the serum. The HBV genomes were transmitted to the next generation and these F1 mice also produced HBsAg and HBeAg. mRNAs of 3.5, 2.1, and 0.8 kilobases were detected in the livers and the kidneys of these mice. In addition, a 0.8-kilobase RNA was detected in the testis. Single-stranded and partially double-stranded HBV DNAs were shown to be produced in the cytoplasm of the liver and kidneys. These HBV DNAs were associated with the core particles, indistinguishable from nucleocapsid produced in an infected human liver. Viral genome DNA was detected in the serum. These results demonstrate that the HBV genome integrated into the mouse chromosome acted as a template for viral gene expression, allowing viral replication. Thus, these transgenic mice should be useful for detailed studies of the replication and expression of HBV and for pathological studies of hepatitis, including the development of hepatocellular carcinoma.
The Use of a Subatmospheric Pressure Dressing to Salvage a Gustilo Grade IIIB Open Tibial Fracture with Concomitant Osteomyelitis to Avert a Free Flap (1998)

Greer, Steven MD; Kasabian, Armen MD; Thorne, Charles MD; Borud, Loren MD; Hsu, Milton MD Author Information
Consolidation Treatment With Chimeric Anti-GD2-Antibody ch14.18 in Children Older Than 1 Year With Metastatic Neuroblastoma (2004)

Consolidation treatment of stage 4 neuroblastoma with ch14.18 was associated with considerable but manageable side effects. Compared with oral maintenance chemotherapy and no consolidation treatment, ch14.18 had no clear impact on the outcome of patients.
The Relative Proportion of Stromal and Epithelial Hyperplasia is Related to the Development of Symptomatic Benign Prostate Hyperplasia (1992)

The specific features of the prostate adenoma predisposing to the development of symptomatic benign prostatic hyperplasia (BPH) are unknown. Our objective was to determine whether the histological composition of the prostate adenoma is related to the development of symptomatic BPH. Prostate adenomas were obtained from men with asymptomatic BPH undergoing cystoprostatectomy for invasive transitional cell carcinoma, and from men with symptomatic BPH undergoing open prostatectomy, transurethral resection of the prostate and pharmacotherapy. The severity of bladder outlet obstruction was evaluated with the Boyarsky symptom score and uroflowmetry. The percentages of stroma, epithelium and glandular lumen were determined in the prostate adenomas via quantitative image analysis on a computer-assisted morphometry system. The prostate adenomas from the 33 men with symptomatic BPH contained 62 +/- 1%, 15 +/- 1% and 23 +/- 1 of stroma, epithelium and glandular lumen, respectively. The prostate adenomas from 6 men with asymptomatic disease contained 54 +/- 1%, 21 +/- 1% and 25 +/- 1% of stroma, epithelium and glandular lumen, respectively. The ratios of stromal-to-epithelial hyperplasia in the prostate adenomas from men with symptomatic and asymptomatic disease were 4.6 +/- 0.3 and 2.7 +/- 0.1, respectively. The differences in percentage of stroma and epithelium, and the stromal-to-epithelial ratio in the prostate adenomas from men with symptomatic and asymptomatic BPH were statistically significant. Our study suggests that the histological composition of the prostate adenoma is related to the development of symptomatic BPH.