gebhart/patrepeval huggingface dataset:
A Deletion in the First Cysteine‐Rich Repeat of the Low‐Density‐Lipoprotein Receptor Leads to the Formation of Multiple Misfolded Isomers (1996)

The ligand-binding domain of the low-density-lipoprotein (LDL) receptor comprises seven cysteine-rich repeats, each approximately 40 amino acids long. The deletion of two amino acids (Asp26 and Gly27) from the first of these repeats (LB1), leads to a defective LDL receptor, and the clinical syndrome of familial hypercholesterolemia [Leitersdorf, E., Hobbs, H. H., Fourie, A. M., Jacobs, M., van der Westhuyzen, D.R. & Coetzee, G.A. (1988) Proc. Natl Acad. Sci. USA 85, 7912-7916]. Receptors which reach the cell surface fail to bind IgG-C7, a conformation-specific monoclonal antibody directed to LB1. To determine the effects of the two-amino-acid deletion on the folding of the LB1 of the LDL receptor, we have expressed LB1 and the mutant repeat, des-Asp26, Gly27-LB1, as recombinant (rLB1 and des-Asp26, Gly27-rLB1) peptides, and have determined their ability to fold in vitro. Unlike rLB1, which folded into a single isomer that was recognized by IgG-C7 and had three disulfide bonds, des-Asp26, Gly27-rLB1 folded into an equilibrium mixture of four isomers. Each of these isomers contained three disulfide bonds, but none were recognized by IgG-C7. We suggest that LDL receptors in the endoplasmic reticulum (ER) of the cell also fold into an equilibrium mixture of distinct receptor molecules, each with an abnormally folded isomer of des-Asp26, Gly27-LB1, and that the retarded transport of receptors to the cell surface arises because only a subset of the isomers reaches the cell surface.
Voltage-induced switching of nanoscale magnetic tunnel junctions (2012)

We demonstrate voltage-induced (non-STT) switching of nanoscale, high resistance voltage-controlled magnetic tunnel junctions (VMTJs) with pulses down to 10 ns. We show ~10x reduction in switching energies (compared to STT) with leakage currents <; 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">5</sup> A/cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> . Switching dynamics, from quasi-static to the nanosecond regime, are studied in detail. Finally, a strategy for eliminating the need for external magnetic-fields, where switching is performed by set/reset voltages of different amplitudes but same polarity, is proposed and verified experimentally.
The binding of Cellulomonas fimi endoglucanase C (CenC) to cellulose and Sephadex is mediated by the N‐terminal repeats (1992)

Endoglucanase C (CenC) from Cellulomonas fimi binds to cellulose and to Sephadex. The enzyme has two contiguous 150-amino-acid repeats (N1 and N2) at its N-terminus and two unrelated contiguous 100-amino-acid repeats (C1 and C2) at its C-terminus. Polypeptides corresponding to N1, N1N2, C1, and C1C2 were produced by expression of appropriate cenC gene fragments in Escherichia coli. N1N2, but not N1 alone, binds to Sephadex; both polypeptides bind to Avicel, (a heterogeneous cellulose preparation containing both crystalline and non-crystalline components). Neither C1 nor C1C2 binds to Avicel or Sephadex. N1N2 and N1 bind to regenerated ('amorphous') cellulose but not to bacterial crystalline cellulose; the cellulose-binding domain of C. fimi exoglucanase Cex binds to both of these forms of cellulose. Amino acid sequence comparison reveals that N1 and N2 are distantly related to the cellulose-binding domains of Cex and C. fimi endoglucanases A and B.
Discovery of 1-{4-[1-(2,6-Difluorobenzyl)-5-[(dimethylamino)methyl]-3-(6-methoxypyridazin-3-yl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3- d ]pyrimidin-6-yl]phenyl}-3-methoxyurea (TAK-385) as a Potent, Orally Active, Non-Peptide Antagonist of the Human Gonadotropin-Releasing Hormone Receptor (2011)

We previously discovered an orally active human gonadotropin-releasing hormone (GnRH) receptor antagonist, thieno[2,3-d]pyrimidine-2,4-dione derivative 1 (sufugolix). To reduce the cytochrome P450 (CYP) inhibitory activity and improve in vivo GnRH antagonistic activity, further optimization of this scaffold was carried out. We focused our synthetic efforts on chemical modification at the 5 and 3 positions of the thieno[2,3-d]pyrimidine-2,4-dione ring based on computational modeling, which resulted in the discovery of 1-{4-[1-(2,6-difluorobenzyl)-5-[(dimethylamino)methyl]-3-(6-methoxypyridazin-3-yl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl]phenyl}-3-methoxyurea (16b) as a highly potent and orally active GnRH antagonist. Compound 16b showed potent in vitro GnRH antagonistic activity in the presence of fetal bovine serum (FBS) without CYP inhibition. Oral administration of 16b maintained the suppressive effect of the plasma luteinizing hormone levels in castrated cynomolgus monkeys at a 3 mg/kg dose for more than 24 h. Compound 16b is currently under clinical development with the code name of TAK-385.
Long‐term synthesis rates of skeletal muscle DNA and protein are higher during aerobic training in older humans than in sedentary young subjects but are not altered by protein supplementation (2011)

Consuming protein following exercise has been shown to stimulate protein synthesis acutely in skeletal muscle and has been recommended to prevent sarcopenia. It is not known, however, whether acute stimulation persists long term or includes muscle cell division. We asked here whether consuming protein following exercise during aerobic training increases long-term protein and DNA synthesis rates in skeletal muscle of adult humans. Sixteen previously untrained participants (50 ± 8 yr) consumed either a carbohydrate or carbohydrate and protein drink following each session during 6 wk of treadmill training. A younger untrained group provided a nonexercising comparison. Participants were administered heavy water (²H₂O; deuterium oxide) continuously for 6 wk to isotopically label newly synthesized skeletal muscle proteins and DNA. Muscle biopsies were performed after 6 wk of training. Contrary to acute studies, consuming protein after exercise did not increase skeletal muscle protein synthesis rates. In contrast, muscle protein synthesis, DNA, and phospholipid synthesis were significantly higher in the older exercise groups than the younger sedentary group. The higher DNA replication rate could not be attributed to mitochondrial DNA and may be due to satellite cell activation. We conclude that postexercise protein supplementation does not increase rates of mixed protein synthesis over 6 wk and that aerobic exercise may stimulate long-term cell division (DNA synthesis) in skeletal muscle of humans. Measurements of long-term synthesis rates provide important insights into aging and exercise adaptations.
Inside Smalltalk: vol. 1 (1990)

Individuals with cystic fibrosis (CF) are commonly colonized with Pseudomonas aeruginosa. The chronic infections caused by P. aeruginosa are punctuated by acute exacerbations of the lung disease, which lead to significant morbidity and mortality. As regulators of virulence determinants, P. aeruginosa quorum-sensing systems may be active in the chronic lung infections associated with CF. We have examined the levels of autoinducer molecules and transcript accumulation from the bacterial populations found in the lungs of patients with CF. We detected biologically active levels of N-(3-oxododecanoyl)-L-homoserine (3-oxo-C12-HSL) and N-butyryl-L-homoserine lactone (C4-HSL) in sputum from CF patients. Interestingly, it appears that C4-HSL is less frequently detected than 3-oxo-C12-HSL in the lungs of patients with CF. We also examined the transcription of the autoinducer synthase gene lasI and showed that it is frequently expressed in the lungs of patients with CF. We observed a significant correlation between the expression of lasI and four target genes of the Las quorum-sensing system. Taken together, our results indicate that quorum-sensing systems are active and may control virulence factor expression in the lungs of patients with CF.
Upregulated expression of human membrane type-5 matrix metalloproteinase in kidneys from diabetic patients (2001)

Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that degrade the extracellular matrix (ECM). The membrane-type matrix metalloproteinases (MT-MMPs) are a new family of MMPs that differ from other MMPs in that they have a transmembrane domain that anchors them to the cell surface. MT-MMPs have been shown to function as receptors and activators for other MMPs and to localize extracellular matrix proteolysis at the pericellular region. Here we report on mRNA and protein expression of the fifth human MT-MMP (MT5-MMP), a 64-kDa protein that is capable of converting pro-MMP-2 to its active form, in human kidney as well as its upregulation in diabetes. We also demonstrate upregulation of the active form of MMP-2 in kidney samples from patients with diabetes. Through immunohistochemistry, MT5-MMP expression was localized to the epithelial cells of the proximal and distal tubules, the collecting duct, and the loop of Henle. Furthermore, the tubular epithelial cells that expressed MT5-MMP were associated with tubular atrophy. Because renal tubular atrophy is a significant factor in the pathogenesis of diabetic nephropathy and renal failure and the molecular mechanisms regulating this process remain unknown, it is hypothesized that the elevated expression of MT5-MMP contributes to the activation of pro-MMP-2, which participates in the remodeling of the proximal and distal tubules as well as in the collecting duct. These results provide the first evidence of the expression of a MT-MMP in diabetes and suggest a novel role for MT5-MMP in the pathogenesis of renal tubular atrophy and end-stage renal disease.
Curettage Alone with no Graft in Enchondroma of Hand (2012)

Background: Enchondroma is the most common benign bone tumor in hand, which can be seen in various manifestations such as swelling, pain, deformity and pathologic fracture. Different surgical treatments were reported for enchondroma to prevent the progressive deformity and pathological fractures. The purpose of this study was to investigate the result of treatment of enchondroma of hand with curettage alone. Methods: In a cross sectional study, 17 patients with average age of 32 years with enchondroma of hand who were operated in a 6-year period in a training hospital in Tehran-Iran were evaluated. The patients received the treatment of tumor removal without filling the resultant defect. The cases were evaluated for range of motion, grip power and radiographic Tordai classification.
EFFECT OF THE INTERFERENCE OF ALKALI AND ALKALINE EARTH METAL IONS ON THE EXTRACTION OF 90 SR FROM ACIDIC NUCLEAR WASTE SOLUTIONS BY 18-CROWN-6 DERIVATIVES (1995)

ABSTRACT The extraction of 90Sr from liquid sodium-bearing wastes (SBW) at the Idaho Chemical Processing Plant (ICPP) by 4', 4'(5')-di-(t-butyldicyclohexo)-18-crown-6 (DtBuCH18C6) and cis-dicyclohexano-l8-crown-6 (DCH18C6) in 1-octanol has been investigated. It has been shown mat the presence of group I and group II metal ions which are co-extracted by the organic solvent limits the extraction of Sr2+ from nitric acid solutions. For example, extraction experiments which were performed with 0.15 M DtBuCH18C6 in 1-octanol yielded DSr values which ranged from -20 in 3M nitric acid to -5 in a solution of 3M NaNO3 and 3M nitric acid. Furthermore, it has been shown that when the concentration of the Na+ is ≥ l.5M, an increase in the total concentration of NO3 ion has little effect on the value of Dsr The value of DSr has been studied as a function of the concentration of Li+, K+, Na+, Cs+, and Ca2+. Additionally, a comparative study of commercially available 18-crown-6 derivatives has been performed. It has been shown that although DtBuCH18C6 yields larger values of DSr in nitric acid solutions than DCH18C6, the extractants yield very similar results in SBW. This is explained by the observation mat me presence of group I and group II metal ions interferes wim the extraction of Sr2+ by DtBuCH18C6 to a greater extent than that of DCH18C6.
Tumor Eradication by Wild-type p53-specific Cytotoxic T Lymphocytes (1997)

The tumor suppressor protein p53 is overexpressed in close to 50% of all human malignancies. The p53 protein is therefore an attractive target for immunotherapy. Cytotoxic T lymphocytes (CTLs) recognizing a murine wild-type p53 peptide, presented by the major histocompatibility complex class I molecule H-2Kb, were generated by immunizing p53 gene deficient (p53 -/-) C57BL/6 mice with syngeneic p53-overexpressing tumor cells. Adoptive transfer of these CTLs into tumor-bearing p53 +/+ nude mice caused complete and permanent tumor eradication. Importantly, this occurred in the absence of any demonstrable damage to normal tissue. When transferred into p53 +/+ immunocompetent C57BL/6 mice, the CTLs persisted for weeks in the absence of immunopathology and were capable of preventing tumor outgrowth. Wild-type p53-specific CTLs can apparently discriminate between p53-overexpressing tumor cells and normal tissue, indicating that widely expressed autologous molecules such as p53 can serve as a target for CTL-mediated immunotherapy of tumors.
Epidermal Growth Factor Binds to a Receptor on Trypanosoma cruziAmastigotes Inducing Signal Transduction Events and Cell Proliferation (2002)

Host growth factors induce proliferation of Trypanosoma cruzi amastigotes by mechanisms that remain poorly defined. Here we examined human epidermal growth factor (EGF) for its ability to bind to the mammalian multiplicative forms of T. cruzi and to induce growth of the parasites. EGF stimulated incorporation of [3H] thymidine into DNA and growth of amastigotes both in a concentration-dependent manner. Radiolabeled EGF was found to bind to amastigotes in a concentration-dependent and saturable manner but it did not bind to trypomastigotes. Scatchard analysis showed a single class of receptors with a Kd of 0.8 nM and numbering 3.1 x 10(3) per amastigote. Results from internalization experiments provided evidence of receptor-mediated endocytosis of EGF. Northern analysis showed a 3.0-kb transcript for the putative EGF receptor (EGFR) homologue in amastigotes, but not trypomastigotes. Binding of EGF to amastigotes induced signal transduction events. EGF induced "in vitro" kinase activity as determined by gamma-[32P] ATP incorporation into amastigote proteins. EGF also increased protein kinase C activity in a concentration-dependent manner and Mitogen Activated Protein (MAP) kinase activity in a time- and concentration-dependent manner. A specific inhibitor (AG14782) of the EGFR and a MAP kinase inhibitor (PD98059) decreased EGF-dependent T. cruzi MAP kinase activity. These results describe a novel mechanism used by amastigotes to regulate their proliferation mediated by an EGF-dependent signal transduction pathway.
Studies on vitamin D (calciferol) and its analogs. 25. Studies on a convergent route to side-chain analogues of vitamin D: 25-hydroxy-23-oxavitamin D3 (1983)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStudies on vitamin D (calciferol) and its analogs. 25. Studies on a convergent route to side-chain analogues of vitamin D: 25-hydroxy-23-oxavitamin D3H. T. Toh and William H. OkamuraCite this: J. Org. Chem. 1983, 48, 9, 1414–1417Publication Date (Print):May 1, 1983Publication History Published online1 May 2002Published inissue 1 May 1983https://pubs.acs.org/doi/10.1021/jo00157a004https://doi.org/10.1021/jo00157a004research-articleACS PublicationsRequest reuse permissionsArticle Views684Altmetric-Citations63LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
ADS-5102 (Amantadine) Extended-Release Capsules for Levodopa-Induced Dyskinesia in Parkinson Disease (EASE LID Study) (2017)

clinicaltrials.gov Identifier: NCT02136914.
Cross-Species Sequence Comparisons: A Review of Methods and Available Resources (2003)

With the availability of whole-genome sequences for an increasing number of species, we are now faced with the challenge of decoding the information contained within these DNA sequences. Comparative analysis of DNA sequences from multiple species at varying evolutionary distances is a powerful approach for identifying coding and functional noncoding sequences, as well as sequences that are unique for a given organism. In this review, we outline the strategy for choosing DNA sequences from different species for comparative analyses and describe the methods used and the resources publicly available for these studies.
Inhibition of clot-bound alpha 2-antiplasmin enhances in vivo thrombolysis. (1990)

Recent experiments in vitro have shown that inhibition of human alpha 2-antiplasmin by a monoclonal antibody (MAb RWR) markedly enhances clot lysis by plasminogen activators. To extend these studies in vivo, we tested whether inhibition of clot or fibrin-bound alpha 2-antiplasmin by MAb RWR could enhance the lysis of a human clot by tissue-type plasminogen activator (t-PA) in a rabbit jugular vein thrombosis model. Compared with a saline placebo or a control antibody, MAb RWR significantly increased thrombolysis by endogenous plasminogen activator in rabbits to which no t-PA was administered (p less than 0.05). In rabbits that received t-PA, the combination of MAb RWR and t-PA caused significantly greater thrombolysis than equivalent doses of t-PA alone (p less than 0.05). However, compared with equipotent doses of t-PA alone, the combination of MAb RWR and t-PA did not increase the nonspecific consumption of fibrinogen. These experiments suggest that the combination of an alpha 2-antiplasmin inhibitor and a plasminogen activator could be a more potent thrombolytic strategy.
Morphology and Matrix Composition During Early Tendon to Bone Healing (1997)

This study outlines the early morphologic phenomenon of tendon to bone healing in the rabbit model. Twelve skeletally mature, male New Zealand White rabbits received transplantation of the hallucis longus tendon into a 2-mm calcaneal bone tunnel. The morphologic characteristics of the healing tendon to bone interface were evaluated at 1, 2, 4, and 6 weeks after surgery by the use of conventional histology and immunohistochemical localization of collagen Types I, II, and III. Histologic analysis illustrated progressive maturation and reorganization of the tendon to bone interface with subsequent development of tissue collagen fiber continuity between the tendon and bone. Initially, diffuse immunolocalization of all three collagen types was observed within the scar tissue filling the space between the tendon and bone. During a 6-week period, reorganization of the scar tissue into an interface occurred, similar to an indirect insertion. Although a definitive fibrocartilage region did not form, Type II collagen was localized at the remodeling insertion site throughout the first 6 weeks of repair. In addition, Type III collagen fibers, resembling Sharpey's fibers, were noted to span this interface. The characterization of the insertion between tendon and bone is important to the understanding of healing in commonly used orthopaedic grafting procedures, such as anterior cruciate ligament reconstructions.
Candida albicans SOU1 encodes a sorbose reductase required for L‐sorbose utilization (2005)

Previous work in our laboratory showed that L-sorbose utilization in Candida albicans is subject to a novel form of regulation which involves a reversible increase or decrease in the copy number of chromosome 5. Furthermore, the structural gene SOU1 is required for L-sorbose utilization and encodes a member of the short chain dehydrogenase family. However, the precise function of SOU1 was not known and neither was the pathway for L-sorbose utilization. We have now expressed SOU1 at a high level from a replicative plasmid having a constitutive ADH1 promoter and purified a version of Sou1p tagged with the FLAG epitope at the N-terminus. Sou1FLAGNp has a sorbose reductase activity which utilizes NADPH as a co-factor and converts L-sorbose to D-sorbitol. It can also less efficiently utilize fructose as a substrate with NADPH as a co-factor, converting fructose to mannitol. In agreement with prediction, the purified enzyme has a subunit molecular weight of 31 kDa and a pI of about 4.8. It probably consists of four identical subunits and has a pH optimum of 6.2. The L-sorbose utilization pathway in C. albicans probably converts L-sorbose to fructose-6-phosphate via D-sorbitol as an intermediate. The first step is catalysed by Sou1p. We also found that C. albicans extracts have a D-sorbitol-6-phosphate dehydrogenase activity, not encoded by SOU1, which utilizes NADP as a co-factor. This activity has not been described previously in yeasts and may be involved in the conversion of phosphorylated D-sorbitol to fructose-6-phosphate or glucose-6-phosphate.
Elevated Serum Interleukin-15 Level in Acute Graft-Versus-Host Disease After Hematopoietic Cell Transplantation (2003)

These changes point to a possible role of systemic cytokine secretion in the development of acute GVHD. Elevated levels of IL-15 early in the posttransplant period could be a helpful laboratory predictor of acute GVHD.
Insulin resistance in relation to melanoma risk (2011)

Obesity, deregulation of adipocytokines, and insulin resistance are interrelated and have been implicated in carcinogenesis. In search of novel risk factors for melanoma, we explored the association of this disease with insulin resistance in a small size, case-control study. Homeostasis Model Assessment for Insulin Resistance (HOMA-IR), serum leptin, and adiponectin levels were determined in 55 patients with incident melanoma and 165 age-matched and sex-matched controls. Odds ratios were derived after adjusting for skin type, medical history, sociodemographic, lifestyle, and anthropometric parameters. Among the controls, HOMA-IR correlated positively with BMI (r=0.34; P=0.0001), waist-to-hip ratio (r=0.20; P=0.01) and negatively with serum adiponectin (r=-0.21; P=0.006), whereas the correlation with leptin was essentially null (r=0.09; P=0.27). The mean HOMA-IR was approximately 1.5 times higher in cases than in controls (P=0.05). The established positive association of melanoma with skin type was evident in multiple logistic regression models and so was the association with increasing HOMA-IR quintile (odds ratio for the fifth quintile=3.68; 95% confidence intervals 1.15-11.79, P=0.02). The latter persisted after adjustment for anthropometric variables and adiponectin but was attenuated when leptin was introduced in the model. These findings point to insulin resistance as a potentially independent risk factor for melanoma and need to be confirmed by future larger studies, ideally allowing the control of the directionality of the association.