gebhart/patrepeval huggingface dataset:
Calibrating a novel multi-sensor physical activity measurement system (2011)

Advancing the field of physical activity (PA) monitoring requires the development of innovative multi-sensor measurement systems that are feasible in the free-living environment. The use of novel analytical techniques to combine and process these multiple sensor signals is equally important. This paper describes a novel multi-sensor 'integrated PA measurement system' (IMS), the lab-based methodology used to calibrate the IMS, techniques used to predict multiple variables from the sensor signals, and proposes design changes to improve the feasibility of deploying the IMS in the free-living environment. The IMS consists of hip and wrist acceleration sensors, two piezoelectric respiration sensors on the torso, and an ultraviolet radiation sensor to obtain contextual information (indoors versus outdoors) of PA. During lab-based calibration of the IMS, data were collected on participants performing a PA routine consisting of seven different ambulatory and free-living activities while wearing a portable metabolic unit (criterion measure) and the IMS. Data analyses on the first 50 adult participants are presented. These analyses were used to determine if the IMS can be used to predict the variables of interest. Finally, physical modifications for the IMS that could enhance the feasibility of free-living use are proposed and refinement of the prediction techniques is discussed.
Analogs of luteinizing hormone-releasing hormone containing derivatives of phenylalanine in place of tyrosine (1973)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAnalogs of luteinizing hormone-releasing hormone containing derivatives of phenylalanine in place of tyrosineDavid H. Coy, Esther J. Coy, and Andrew V. SchallyCite this: J. Med. Chem. 1973, 16, 7, 827–829Publication Date (Print):July 1, 1973Publication History Published online1 May 2002Published inissue 1 July 1973https://pubs.acs.org/doi/10.1021/jm00265a017https://doi.org/10.1021/jm00265a017research-articleACS PublicationsRequest reuse permissionsArticle Views50Altmetric-Citations21LEARN 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
Lack of association of Graves' disease with the A2 allele of the interleukin-1 receptor antagonist gene in a white European population (1998)

Our data do not support an association between the IL-1RA A2 allele and Graves' disease or Graves' ophthalmopathy in our study population. Thus the A2-type IL-1RA gene polymorphism does not appear to indicate an increased susceptibility to develop Graves' disease and Graves' ophthalmopathy. Mechanisms unrelated to the IL-1RA A2 allele may be responsible for altered IL-1RA production within the orbital tissues in Graves' ophthalmopathy.
Recent advances in dynamic covalent chemistry (2013)

Dynamic covalent chemistry (DCvC) has been strongly integrated into diverse research fields, and has enabled easy access to a variety of combinatorial libraries, 2-D macrocycles, and 3-D molecular cages that target many important applications, such as drug discovery, biotechnology, molecular separation, light harvesting, etc. DCvC relies on the reversible formation and breaking of rather strong covalent bonding within molecules. Therefore it combines the error-correction capability of supramolecular chemistry and the robustness of covalent bonding. Compared to those supramolecular interactions, dynamic covalent reactions usually have slower kinetics and require the assistance of catalysts to achieve rapid equilibrium. Although the scope of dynamic covalent reactions is rapidly expanding, the reversible reactions suitable for DCvC are still very limited. The identification and development of new dynamic reactions and catalysts would be critical for the further advancement of DCvC. This review covers the recent development of dynamic covalent reactions as well as their applications.
Recombinant Gaussia Luciferase. Overexpression, Purification, and Analytical Application of a Bioluminescent Reporter for DNA Hybridization (2002)

The cDNA for Gaussia luciferase (GLuc), the enzyme responsible for the bioluminescent reaction of the marine copepod Gaussia princeps, has been cloned recently. GLuc (MW = 19 900) catalyzes the oxidative decarboxylation of coelenterazine to produce coelenteramide and light. We report the first quantitative anaytical study of GLuc and examine its potential as a new reporter for DNA hybridization. A plasmid encoding both a biotin acceptor peptide-GLuc fusion protein as well as the enzyme biotin protein ligase (BPL) is engineered by using GLuc cDNA as a starting template. BPL catalyzes the covalent attachment of a single biotin to the fusion protein in vivo. Purification of GLuc is then accomplished by affinity chromatography using immobilized monomeric avidin. Moreover, the in vivo biotinylation enables subsequent complexation of GLuc with streptavidin (SA), thereby avoiding chemical conjugation reactions that are known to inactivate luciferases. Purified GLuc can be detected down to 1 amol with a signal-to-background ratio of 2 and a linear range extending over 5 orders of magnitude. The background luminescence of coelenterazine is the main limiting factor for even higher detectability of GLuc. Furthermore, the GLuc-SA complex is used as a detection reagent in a microtiter well-based DNA hybridization assay. The analytical range extends from 1.6 to 800 pmol/L of target DNA. Biotinylated GLuc produced from 1 L of bacterial culture is sufficient for 150,000 hybridization assays.
A Cytosolic Homomerization and a Modulatory Domain within STIM1 C Terminus Determine Coupling to ORAI1 Channels (2009)

In immune cells, generation of sustained Ca(2+) levels is mediated by the Ca(2+) release-activated Ca(2+) (CRAC) current. Molecular key players in this process comprise the stromal interaction molecule 1 (STIM1) that functions as a Ca(2+) sensor in the endoplasmic reticulum and ORAI1 located in the plasma membrane. Depletion of endoplasmic reticulum Ca(2+) stores leads to STIM1 multimerization into discrete puncta, which co-cluster with ORAI1 to couple to and activate ORAI1 channels. The cytosolic C terminus of STIM1 is sufficient to activate ORAI1 currents independent of store depletion. Here we identified an ORAI1-activating small fragment (OASF, amino acids 233-450/474) within STIM1 C terminus comprising the two coiled-coil domains and additional 50-74 amino acids that exhibited enhanced interaction with ORAI1, resulting in 3-fold increased Ca(2+) currents. This OASF, similar to the complete STIM1 C terminus, displayed the ability to homomerize by a novel assembly domain that occurred subsequent to the coiled-coil domains. A smaller fragment (amino acids 233-420) generated by a further deletion of 30 amino acids substantially reduced the ability to homomerize concomitant to a loss of coupling to as well as activation of ORAI1. Extending OASF by 35 amino acids (233-485) did not alter homomerization but substantially decreased efficiency in coupling to and activation of ORAI1. Expressing OASF in rat basophilic leukemia (RBL) mast cells demonstrated its enhanced plasma membrane targeting associated with 2.5-fold larger CRAC currents in comparison with the complete STIM1 C terminus. In aggregate, we have identified two cytosolic key regions within STIM1 C terminus that control ORAI1/CRAC activation: a homomerization domain indispensable for coupling to ORAI1 and a modulatory domain that controls the extent of coupling to ORAI1.
Steady State Kinetic Mechanism of Bruton’s Tyrosine Kinase (2006)

Bruton’s Tyrosine Kinase (BTK) is a member of the Tec non‐receptor tyrosine kinase family that is involved in regulating B cell proliferation. In order to better understand how both substrates and small molecule inhibitors interact with BTK, we studied the BTK steady‐state kinetic mechanism. We first developed a bead‐based, radioactive filtration assay to monitor BTK enzyme activity. We then used this assay to examine how BTK activity varied with the concentration of substrates ATP and S1 peptide (biotin‐Aca‐AAAEEIYGEI‐NH 2 ). These studies revealed that BTK employs a sequential mechanism with only modest communication between substrate binding sites (α = 2.4 ± 0.8). Maximum velocity was 121 ± 52 pmol/min/μ g, with K m (ATP) = 93 ± 13 μ M and K m (S1) = 45 ± 9 μ M. Dead‐end inhibition studies were also performed to examine the order of substrate binding. The inhibitors ADP and staurosporine were both found to be competitive with ATP and non‐competitive with S1, indicating binding of S1 to BTK is random. This kinetic characterization of BTK will aid in the identification of novel enzyme inhibitors that may be useful for treating rheumatoid arthritis or other inflammatory diseases.
Activation of ΔF508 CFTR in an epithelial monolayer (1998)

The DeltaF508 mutation leads to retention of cystic fibrosis transmembrane conductance regulator (CFTR) in the endoplasmic reticulum and rapid degradation by the proteasome and other proteolytic systems. In stably transfected LLC-PK1 (porcine kidney) epithelial cells, DeltaF508 CFTR conforms to this paradigm and is not present at the plasma membrane. When LLC-PK1 cells or human nasal polyp cells derived from a DeltaF508 homozygous patient are grown on plastic dishes and treated with an epithelial differentiating agent (DMSO, 2% for 4 days) or when LLC-PK1 cells are grown as polarized monolayers on permeable supports, plasma membrane DeltaF508 CFTR is significantly increased. Moreover, when confluent LLC-PK1 cells expressing DeltaF508 CFTR were treated with DMSO and mounted in an Ussing chamber, a further increase in cAMP-activated short-circuit current (i.e., approximately 7 microA/cm2; P < 0.00025 compared with untreated controls) was observed. No plasma membrane CFTR was detected after DMSO treatment in nonepithelial cells (mouse L cells) expressing DeltaF508 CFTR. The experiments describe a way to augment DeltaF508 CFTR maturation in epithelial cells that appears to act through a novel mechanism and allows insertion of functional DeltaF508 CFTR in the plasma membranes of transporting cell monolayers. The results raise the possibility that increased epithelial differentiation might increase the delivery of DeltaF508 CFTR from the endoplasmic reticulum to the Golgi, where the DeltaF508 protein is shielded from degradative pathways such as the proteasome and allowed to mature.
Differential mechanisms in the pathogenesis of autoimmune cholangitis versus inflammatory bowel disease in interleukin‐2Rα−/− mice† (2008)

Interleukin-2 (IL-2) receptor alpha knockout (IL-2Ralpha(-/-)) mice have a deficiency of CD25 and a corresponding functional defect in T regulatory cells (Tregs). These mice spontaneously develop portal inflammation with biliary ductular damage and colitis with features similar to human inflammatory bowel disease with T cell infiltrates in both the liver and colon. In humans, inflammatory bowel disease may be accompanied by primary sclerosing cholangitis (PSC), but seldom primary biliary cirrhosis (PBC). We hypothesized that the effector mechanism responsible for T cell infiltrates would differ for colon versus liver. To address this thesis, we developed three colonies of double-knockout mice including IL-2Ralpha(-/-) CD4(-/-), IL-2Ralpha(-/-) CD8(-/-), and IL-2Ralpha(-/-) T cell receptor (TCR)-beta(-/-). Tissue immunopathology, body weight, and serum levels of cytokines, immunoglobulins, and anti-mitochondrial antibodies (AMA) were assayed at 3 months of age. Relative to IL-2Ralpha(-/-) mice, IL-2Ralpha(-/-) CD4(-/-) mice had increased biliary ductular damage but reduced inflammation in the colon. In contrast, IL-2Ralpha(-/-) CD8(-/-) mice had increased colon inflammation but markedly attenuated biliary ductular damage. Both IL-2Ralpha(-/-) CD4(-/-) and IL-2Ralpha(-/-) CD8(-/-) mice demonstrated elevated serum levels of tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), interleukin-12p40 (IL-12p40), and interleukin-2 (IL-2) compared with C57BL/6J controls, but only IL-2Ralpha(-/-) CD8(-/-) mice had increased serum levels of immunoglobulin A (IgA), AMA and interleukin-17 (IL-17). Finally, and of importance, IL-2Ralpha(-/-) TCR-beta(-/-) mice had abrogation of liver and colon pathological conditions and lacked AMA. In conclusion, on loss of Treg function in mice, CD8 T cells mediate biliary ductular damage whereas CD4 T cells mediate induction of colon-specific autoimmunity.
T‐cadherin modulates hepatocyte functions in vitro (2008)

Primary hepatocytes from several different species rapidly lose viability and phenotypic functions on isolation from their native microenvironment of the liver. Stromal cells derived from both within and outside the liver can induce phenotypic functions in primary hepatocytes in vitro; however, the molecular mediators underlying this "coculture effect" have not been fully elucidated. We have previously developed a functional genomic screen utilizing cocultures of hepatocytes and 3T3 fibroblasts to identify such candidate hepatocyte-function-inducing molecules. In particular, truncated-cadherin (T-cadherin) was identified as a potential molecule of interest in induction of hepatic functions. Here we demonstrate that liver-specific functions of primary rat hepatocytes are induced on cocultivation with Chinese hamster ovary cells engineered to express T-cadherin on their surface as compared with wild-type controls. Additionally, culture of cells on substrata presenting recombinant T-cadherin protein (acellular presentation) enhanced hepatic functions in both pure hepatocyte cultures and in hepatocyte-stromal cocultures lacking endogenous T-cadherin expression. Collectively, these data indicate that both cellular and acellular presentation of T-cadherin can be used to modulate the hepatocyte phenotype in vitro for tissue engineering applications. Our work suggests potential avenues for investigating the role of T-cadherin on hepatocellular function in vivo in settings such as embryogenesis and liver pathology.
Anaplerotic Sequences in Microbial Metabolism (1965)

Abstract In addition to catabolic and anabolic pathways, which enable nutrients to enter and to be withdrawn from the central routes of metabolism, enzymic sequences operate to ensure that intermediates, removed from these central routes in the course of biosynthesis, are replenished. These obligatory pathways of replenishment are generically designated “anaplerotic sequences”. The nature of these sequences, operative in micro‐organisms growing on C 3 ‐ and C 2 ‐compounds, is discussed in outline, and the mode of regulation of one of them (the glyoxylate cycle) is examined in detail.
Nonsteroidal Anti-inflammatory Drugs Suppress Glioma via 15-Hydroxyprostaglandin Dehydrogenase (2008)

Studies have conjectured that nonsteroidal anti-inflammatory drugs (NSAID) inhibit growth of various malignancies by inhibiting cyclooxygenase-2 (COX-2) enzyme activity. Yet, several lines of evidence indicate that a COX-2-independent mechanism may also be involved in their antitumor effects. Here, we report that NSAIDs may inhibit the growth of glioblastoma multiforme (GBM) cells through COX-2-independent mechanisms, including up-regulation of both 15-hydroxyprostaglandin dehydrogenase (15-PGDH, the key prostaglandin catabolic enzyme) and the cell cycle inhibitor p21. Using Western blot and real-time PCR analysis in various GBM cell lines, we observed up-regulation of 15-PGDH and p21 after NSAIDs treatment. To elucidate the role of 15-PGDH in GBM, transfection assays were conducted using the T98G GBM cell line. Overexpression of 15-PGDH suppressed cell growth and was associated with increased expression of p21. In an attempt to investigate the roles of COX-2, 15-PGDH, and p21 in the inhibition of growth of GBM, small interfering RNA (siRNA) against each of these proteins was transfected into T98G cells. Inhibition of growth mediated by NSAIDs was partially reversed after knockdown of either 15-PGDH or p21, but not after COX-2 knockdown. Moreover, expression level of p21 was not affected in COX-2 siRNA transfected cells. Our studies provide evidence that the up-regulation of 15-PGDH induced by NSAIDs has the potential to inhibit growth of GBM, in part, by up-regulation of p21 possibly independent from COX-2 enzymatic function.
Differentiation of Marrow Stromal Cells into Photoreceptors in the Rat Eye (2003)

Retinal degenerations and dystrophies are the major causes of genetically inherited blindness that are characterized by the apoptotic death of the photoreceptor cell layer of the retina. To date, no treatment exists for these diseases and only recently have they been considered as candidates for gene and stem cell therapies. Here we report the ability of adult CD90+ marrow stromal cells (MSCs) to be induced by activin A, taurine, and EGF into cells (20-32%) expressing photoreceptor-specific markers rhodopsin, opsin, and recoverin in vitro. CD90+ cells were either transduced with recombinant adeno-associated virus expressing green fluorescent protein (GFP) or bromodeoxyuridine (BrdU) labeled and then injected into the subretinal space of adult Royal College of Surgeons rats. Fundus photography and angiography showed no adverse effects of CD90+ MSC transplantation. GFP-expressing cells or BrdU-positive cells covered approximately 30% of the entire retinal area. By 2 weeks after injection, CD90+ MSCs integrated into the host retina, forming structures similar to the photoreceptor layer and expressed a photoreceptor-specific marker. No teratoma formation was observed in the recipient retina. The subretinally delivered CD90+ MSCs did not stain for proliferating cell nuclear antigen, indicating that they primarily undergo differentiation rather than proliferation. In addition, we established that transplanted cells can attract synaptic vesicles and hence are potentially capable of signal transduction. This study demonstrates for the first time the partial differentiation of adult CD90+ MSCs into photoreceptors in vitro and in vivo. Our results establish a proof of concept for CD90+ MSC differentiation with autologous transplantation, which may provide a promising therapeutic strategy for the treatment of some forms of genetically inherited retinal degenerations.
Discovery and Evaluation of a Series of 3-Acylindole Imidazopyridine Platelet-Activating Factor Antagonists (1998)

Studies conducted with the goal of discovering a second-generation platelet-activating factor (PAF) antagonist have identified a novel class of potent and orally active antagonists which have high aqueous solubility and long duration of action in animal models. The compounds arose from the combination of the lipophilic indole portion of Abbott's first-generation PAF antagonist ABT-299 (2) with the methylimidazopyridine heterocycle moiety of British Biotechnology's BB-882 (1) and possess the positive attributes of both of these clinical candidates. Structure-activity relationship (SAR) studies indicated that modification of the indole and benzoyl spacer of lead compound 7b gave analogues that were more potent, longer-lived, and bioavailable and resulted in the identification of 1-(N, N-dimethylcarbamoyl)-4-ethynyl-3-[3-fluoro-4-[(1H-2-methylimidazo[4,5-c] pyrid-1-yl)methyl]benzoyl]indole hydrochloride (ABT-491, 22 m.HCl) which has been evaluated extensively and is currently in clinical development.
Characterization and sequence determination of six aprotinin homologues from bovine lungs. (1988)

Six Kunitz inhibitors, which are dissimilar to aprotinin, can be isolated from bovine lungs. These homologues cannot be distinguished from aprotinin, in respect to their inhibitory specificity. They have, however, different amino-acid compositions and a different degree of basicity. The entire primary structures of these inhibitors were elucidated by automated Edman sequencing. Besides the known Glp-1-aprotinin another aprotinin homologue (des-Ala58-aprotinin) was isolated, which could result from a different proteolytic processing of the bovine aprotinin precursor. The other homologues can be denoted as aprotinin isoinhibitors, showing several amino-acid replacements compared to aprotinin and which also appear in the area of the contact region.
Self-Assembled Monolayers Composed of Aromatic Thiols on Gold:  Structural Characterization and Thermal Stability in Solution (2002)

Self-assembled monolayers (SAMs) derived from 1,2-bis(mercaptomethyl)-4,5-dialkylbenzene (1), 1-mercaptomethyl-3,4-dialkylbenzene (2), 1-mercaptomethyl-4-alkylbenzene (3), 1-mercapto-4-alkylbenzene (4), and 4-mercaptomethyl-4‘-alkoxybiphenyl (5) were prepared by adsorption from solution onto evaporated gold. The SAMs were characterized by contact angle goniometry, optical ellipsometry, and polarization modulation infrared reflection absorption spectroscopy. Comparison of SAMs generated from 1 and 2 to well-known SAMs generated from normal alkanethiols (6) revealed that the former SAMs are densely packed and highly oriented. The alkyl chains of the SAMs derived from 1 and 2 are, however, less crystalline (i.e., less conformationally ordered) than those derived from 6. The adsorption of compounds 3, 4, and 5 onto gold yielded highly crystalline SAMs. Solution-phase thermal desorption of SAMs 1−6 at temperatures ranging from 60 to 110 °C was monitored using ex situ ellipsometry. The desorption profiles of SAMs derived from 1−6 revealed two distinct kinetic regimes: a fast initial desorption followed by a substantially slower desorption. The rates of film desorption in both regimes were observed to increase with increasing temperature. Comparison of the desorption profiles of SAMs 1−6 showed that the structure of the adsorbate strongly influenced the rate of desorption; the differences were more apparent during the advanced stages of desorption. These studies provided a framework for evaluating the structural features and the mechanistic pathways that dictate the thermal stability of SAMs on gold.