gebhart/patrepeval huggingface dataset:
N,N'-Carbonyldiimidazole in Peptide Synthesis. III.1 A Synthesis of Isoleucine-5 Angiotensin II Amide-I (1962)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTN,N'-Carbonyldiimidazole in Peptide Synthesis. III.1 A Synthesis of Isoleucine-5 Angiotensin II Amide-IRolf Paul and George W. AndersonCite this: J. Org. Chem. 1962, 27, 6, 2094–2099Publication Date (Print):June 1, 1962Publication History Published online1 May 2002Published inissue 1 June 1962https://pubs.acs.org/doi/10.1021/jo01053a046https://doi.org/10.1021/jo01053a046research-articleACS PublicationsRequest reuse permissionsArticle Views744Altmetric-Citations48LEARN 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
EXOSKELETON PROTOTYPE PROJECT. (1967)

This is the final report of Phase I of a three-phase project to develop a powered exoskeleton. This is a powered, jointed, loadbearing structure designed to be worn by man and augment his strength and endurance. While wearing the device, an operator will be able to life up to 1500 pounds as high as 6 feet. He will also be able to carry such a load at least 25 feet in 10 seconds at any height up to 6 feet. Typical applications for the powered exoskeleton will include loading and unloading cargo from vehicle to ground and vice versa, stacking and moving cargo from place to place, and similar associated tasks. The exoskeleton will be designed so that the wearer can walk, bend, turn, etc., with minimum restraint. (Author)
Skeletal Muscle Fiber-type Switching, Exercise Intolerance, and Myopathy in PGC-1α Muscle-specific Knock-out Animals (2007)

The transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha) is a key integrator of neuromuscular activity in skeletal muscle. Ectopic expression of PGC-1alpha in muscle results in increased mitochondrial number and function as well as an increase in oxidative, fatigue-resistant muscle fibers. Whole body PGC-1alpha knock-out mice have a very complex phenotype but do not have a marked skeletal muscle phenotype. We thus analyzed skeletal muscle-specific PGC-1alpha knock-out mice to identify a specific role for PGC-1alpha in skeletal muscle function. These mice exhibit a shift from oxidative type I and IIa toward type IIx and IIb muscle fibers. Moreover, skeletal muscle-specific PGC-1alpha knock-out animals have reduced endurance capacity and exhibit fiber damage and elevated markers of inflammation following treadmill running. Our data demonstrate a critical role for PGC-1alpha in maintenance of normal fiber type composition and of muscle fiber integrity following exertion.
Na,K-ATPase and phospholipid degradation in bovine and human lenses (1992)

Na,K-ATPase, an enzyme intrinsic to the membrane of most cells, is inhibited in cataract. Na,K-ATPase, activity in clear non-cataractous lenses is found predominantly in the lens epithelium. The lens fiber cells would appear to be unique, among mammalian cells in that Na,K-ATPase activity is low if not absent. The study presented here indicates that Na,K-ATPase is present, often in high concentration, but progressively more functionally compromised as the fiber cells mature. The membrane lipid environment as causative agent in the loss of normal function of Na,K-ATPase, is considered in this study. The data indicate a correlation between increasing cholesterol/phospholipid ratio, increasing phospholipase A2 activity and decreasing Na,K-ATPase activity in normal clear lenses. The phospholipase A2 activity is higher in cortex and nucleus than in the epithelium of normal bovine and human lenses. The phospholipase A2 is Ca2+ dependent and may be membrane associated.
Effects of pH treatments and deglycosylation of rabbit immunoglobulin G on the binding of C1q. (1980)

The abbreviations used are: Ig, immunoglobulin; Asn-GlcNAc, the N-glycosidic linked pair 1-L-0-aspartamido-2-acetamido-2-deoxy- /I-D-glucose found as the core-type linkage between the polypeptide backbone and oligosaccharides of certain glycoproteins; (BADL-pro)?-EDA, bis(a-bromoacetyl-~-2,4-dinitrophenyl proly1)ethylenediamine; BDPE, bis-2,4-dinitropheny1 pimelic ester; C' , complement; CF-saline, 0.15 M
Global burden of Shigella infections: implications for vaccine development and implementation of control strategies. (1999)

Few studies provide data on the global morbidity and mortality caused by infection with Shigella spp.; such estimates are needed, however, to plan strategies of prevention and treatment. Here we report the results of a review of the literature published between 1966 and 1997 on Shigella infection. The data obtained permit calculation of the number of cases of Shigella infection and the associated mortality occurring worldwide each year, by age, and (as a proxy for disease severity) by clinical category, i.e. mild cases remaining at home, moderate cases requiring outpatient care, and severe cases demanding hospitalization. A sensitivity analysis was performed to estimate the high and low range of morbid and fatal cases in each category. Finally, the frequency distribution of Shigella infection, by serogroup and serotype and by region of the world, was determined. The annual number of Shigella episodes throughout the world was estimated to be 164.7 million, of which 163.2 million were in developing countries (with 1.1 million deaths) and 1.5 million in industrialized countries. A total of 69% of all episodes and 61% of all deaths attributable to shigellosis involved children under 5 years of age. The median percentages of isolates of S. flexneri, S. sonnei, S. boydii, and S. dysenteriae were, respectively, 60%, 15%, 6%, and 6% (30% of S. dysenteriae cases were type 1) in developing countries; and 16%, 77%, 2%, and 1% in industrialized countries. In developing countries, the predominant serotype of S. flexneri is 2a, followed by 1b, 3a, 4a, and 6. In industrialized countries, most isolates are S. flexneri 2a or other unspecified type 2 strains. Shigellosis, which continues to have an important global impact, cannot be adequately controlled with the existing prevention and treatment measures. Innovative strategies, including development of vaccines against the most common serotypes, could provide substantial benefits.
Phosphatidylinositol 3‐kinases are involved in the all‐trans retinoic acid‐induced upregulation of CD38 antigen on human haematopoietic cells (2002)

All-trans retinoic acid (ATRA) is a specific inducer of CD38 antigen on marrow CD34+ cells as well as on blast cells in acute promyelocytic and myeloblastic leukaemia. The CD38 antigen contributes to the control of blast cell proliferation, and the upregulation of CD38 might constitute an element in the pathogenesis of retinoic acid syndrome. The aim of this study was to determine whether phosphoinositide 3-kinase (PI3-K) is involved in the modification of CD38 antigen expression on myeloid cells, as PI3-K plays a major role in the ATRA-induced granulocytic differentiation of HL-60 cells. We evaluated the effects of PI3-K inhibitors (wortmannin and LY294002) on the levels of CD38 antigen and mRNA in HL-60 and normal marrow CD34+ cells exposed to ATRA (1 micromol/l). The inhibitors prevented increase in CD38 mRNA expression and the overexpression of membrane CD38 antigen, without modification of the cytoplasmic level of this antigen. Interestingly, PI3-K activity was also necessary for CD38 expression on normal marrow CD34+ cells and for the ATRA-induced upregulation of CD157, a CD38-related antigen. In conclusion, PI3-K activity plays an essential role in the regulation of CD38 expression on human haematopoietic cells, and might constitute an interesting therapeutic target in haematological disorders involving CD38 overexpression.
Hereditary Retinoblastoma: Host Resistance and Age at Onset<xref ref-type="fn" rid="FN2">2</xref><xref ref-type="fn" rid="FN3">3</xref> (1979)

Age-specific incidence data from 244 bilateral and 31 familial unlateral cases of retinoblastoma were analyzed. In the bilateral cases, a high intraclass correlation between ages of the patients at diagnosis in the right and left eyes was noted, even after removal of the bias due to the fact that the diagnosis for each eye is never independent. This finding indicated strongly that the age at onset was largely determined by host factors common to both eyes. The mean ages of the patients at diagnosis of the inherited cases among the bilateral or unilateral group varied consistently with parental phenotype. This finding implied that inherited host resistance played an important role in the latency period for the gene carriers. The fraction of cases not yet diagnosed fit well to a negative exponential distribution, and in the less susceptible group with hereditary unilateral cases, tumor formation may have been suppressed about twice that in the most susceptible group with bilateral cases. It was argued that the presumed second hit initiating tumor formation in the gene carriers was not a mutational process, but probably an error in the process of differentiation that could be suppressed completely in the most resistant group who could remain unaffected, but that could not be suppressed completely in the less resistant group.
Molecular characterization of the mouse gene encoding cellular retinaldehyde-binding protein. (1998)

To clone and characterize the mouse gene encoding cellular retinaldehyde-binding protein (CRALBP). CRALBP appears to modulate enzymatic generation and processing of 11-cis-retinol and regeneration of visual pigment in the vertebrate visual cycle. Mutations in human CRALBP segregate with autosomal recessive retinitis pigmentosa.A genomic clone encompassing the 5' end of the CRALBP gene through exon 6 was isolated from a mouse 129/Sv genomic DNA library. Exons 7 and 8 were PCR amplified from mouse eye cDNA and 129/SvJ genomic DNA. The gene structure was determined by automated DNA sequence analysis.The sequence of 6855 nucleotides was determined, including all 8 exons, 3 introns plus 3932 and 629 bases from the 5'- and 3'-flanking regions, respectively. The lengths of introns 3-6 were determined by PCR amplification. Northern analysis identifies a approximately 2.1 kb transcript in mouse eye; Southern analysis supports a single copy gene.The mouse CRALBP gene is similar to the human gene; the coding sequence is approximately 87% identical, the non-coding sequence approximately 65% identical. In contrast to the human gene, the mouse gene contains a consensus TATA box. One of two photoreceptor consensus elements important for CRALBP expression in human retinal pigment epithelium is also present in the mouse gene. Additional conserved and species-specific consensus sequences are identified. The mouse CRALBP genomic clones and structure provide valuable tools for developing an in vivo model to study protein function and gene regulation.
Novel Therapeutic Approaches to Eosinophilic Esophagitis. (2020)

Eosinophilic esophagitis is a chronic inflammatory condition that requires treatment to improve symptoms and prevent complications of esophageal remodeling, such as strictures and narrow-caliber esophagus. First-line treatments include proton pump inhibitors, topical corticosteroids, elimination or elemental diets, and esophageal dilation. Topical corticosteroids have typically required repurposing inhaled asthma medications by swallowing an aerosolized medication or mixing a nebulizer solution into a slurry. New topical corticosteroid formulations undergoing investigation include a premade budesonide oral suspension and disintegrating budesonide and fluticasone propionate tablets. The approach to an elimination diet is also changing, with an emphasis on patient preference when considering a traditional 6-food elimination diet compared with a step-up approach. This approach involves eliminating only 2 or 4 foods initially and expanding if necessary. While this method can be initially less effective for some patients, it generally involves fewer endoscopies and minimizes diet restriction. Beyond conventional therapies, a number of novel biologic agents are also under investigation. These include weekly subcutaneous injections or monthly intravenous infusions of RPC4046, dupilumab, antolimab, and benralizumab. The increasing number of approaches under development as well as anticipated submissions to the US Food and Drug Administration offer the potential of multiple specific therapies becoming available in the near future.
Heterocyclic aromatic anions with 4n + 2 .pi.-electrons (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTHeterocyclic aromatic anions with 4n + 2 .pi.-electronsFrederick G. Bordwell and Herbert E. FriedCite this: J. Org. Chem. 1991, 56, 13, 4218–4223Publication Date (Print):June 1, 1991Publication History Published online1 May 2002Published inissue 1 June 1991https://pubs.acs.org/doi/10.1021/jo00013a027https://doi.org/10.1021/jo00013a027research-articleACS PublicationsRequest reuse permissionsArticle Views3997Altmetric-Citations185LEARN 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
Whereof one cannot speak: When input distributions are unknown (1998)

One of the major criticisms of probabilistic risk assessment is that the requisite input distributions are often not available. Several approaches to this problem have been suggested, including creating a library of standard empirically fitted distributions, employing maximum entropy criteria to synthesize distributions from a priori constraints, and even using ‘default’ inputs such as the triangular distribution. Since empirical information is often sparse, analysts commonly must make assumptions to select the input distributions without empirical justification. This practice diminishes the credibility of the assessment and any decisions based on it. There is no absolute necessity, however, of assuming particular shapes for input distributions in probabilistic risk assessments. It is possible to make the needed calculations using inputs specified only as bounds on probability distributions. We describe such bounds for a variety of circumstances where empirical information is extremely limited, and illustrate how these bounds can be used in computations to represent uncertainty about input distributions far more comprehensively than is possible with current approaches.
Clinical pharmacological studies of concurrent infusion of 5-fluorouracil and thymidine in treatment of colorectal carcinomas. (1982)

The effects of thymidine (dThd) coadministration on the pharmacokinetics and metabolism of 5-fluorouracil (FUra) were investigated in 29 colorectal cancer patients. Five patients received 5-day i.v. infusion of FUra at 15 mg/kg/day and 24 patients received infusion of FUra (7.5 mg/kg/day, 5 days) and dThd (216 mg/kg/day, 6 days) preceded by a bolus dose of dThd (405 mg/kg). Plasma and urine concentrations of FUra, 5-fluorodeoxyuridine (FdUrd), thymine, and dThd were quantitated by a high-pressure liquid chromatographic assay. Concurrent dThd administration reduced the plasma clearance of FUra at steady state from 389.1 +/- 153.5 (S.D.) to 56.0 +/- 36.4 liters/kg/day. The mean steady-state plasma concentration of FUra in patients receiving FUra alone was 0.38 microM and was significantly lower than the 1.30 microM in patients receiving FUra-dThd. Plasma concentrations of FUra were linearly dependent on those of thymine. Furthermore, the metabolic and renal clearances of FUra decreased inversely with thymine concentrations indicating that the elimination of FUra was reduced by thymine. In contrast to the absence of FdUrd as a circulating metabolite in patients treated with FUra alone, microM concentrations of FdUrd were detected in plasma of most of the patients treated with FUra-dThd. This together with the linear correlation of FdUrd and dThd concentrations indicates that the interconversion of FUra to FdUrd was enhanced by dThd. The incidence of dose-limiting leukopenia in the FUra-dThd combination therapy was 40%. There is an inverse correlation between the plasma clearance of FUra at steady state and hematological toxicity. The plasma clearance of FUra in the toxic population was 32.0 +/- 16.8 liters/kg/day and was significantly lower than the clearance of 72.0 +/- 37.3 liters/kg/day in the nontoxic population (p less than 0.001). The corresponding critical toxic steady-state FUra plasma concentration was 1.5 microM. The biochemical effects of dThd on the incorporation of FUra and FdUrd into RNA and into acid-soluble 5-fluorodeoxyuridine monophosphate (FdUMP) in human colon tumor cells were studied in vitro. At 100 microM, dThd increased the incorporation of FUra into RNA up to 4-fold but diminished the acid-soluble FdUMP pool. Similarly, the incorporation of FdUrd into acid-soluble FdUMP was inhibited by dThd. The response rate of colorectal carcinoma to FUra was not improved by coadministration of dThd; only one of the 11 patients who had no prior FUra therapy achieved partial remission. The lack of clinical response in these patients may be partly due to the inhibition of anabolism of FUra and FdUrd to FdUMP by dThd.
Mutations of the platelet-derived growth factor receptor that cause a loss of ligand-induced conformational change, subtle changes in kinase activity, and impaired ability to stimulate DNA synthesis. (1989)

The wild-type and two mitogenic-defective mutants of the type beta receptor for platelet-derived growth factor (PDGF) were expressed in Chinese hamster ovary cells. In the first mutant, delta Ki, 82 of 104 amino acids in the kinase insert region were deleted. This mutant was recently reported to be defective in mediating DNA synthesis. In the second mutant, Y825F, tyrosine 825 was converted to phenylalanine by a point mutation. We report here that this mutant is also defective in mediating PDGF-stimulated DNA synthesis. Both mutants were capable of eliciting many of the early responses to PDGF, including receptor autophosphorylation. However, neither mutant was capable of undergoing PDGF-stimulated change in receptor conformation or of phosphorylating exogenous substrate in an in vitro assay. These data suggest that changes in receptor conformation and efficient utilization of specific tyrosine kinase substrates are important for the stimulation of cell proliferation of PDGF and that phosphorylation of tyrosine 825 may be involved in signal transduction.
Choosing a Gliptin (2011)

The treatment of type 2 diabetes mellitus (T2DM) has included the use of metformin and sulfonylurea (SU) as first-line anti-diabetic therapies world over since years. This remains, despite the knowledge that the combination results in a progressive decline in [beta]-cell function and by 3 years up to 50% of diabetic patients can require an additional pharmacological agent to maintain the glycosylated hemoglobin (HbA1c) <7.0% (UKPDS). Gliptins represent a novel class of agents that improve beta cell health and suppress glucagon, resulting in improved post-prandial and fasting hyperglycemia. They function by augmenting the incretin system (GLP-1 and GIP) preventing their metabolism by dipeptidyl peptidase-4 (DPP-4). Not only are they efficacious but also safe (weight neutral) and do not cause significant hypoglycemia, making it a unique class of drugs. This review focuses on gliptins (sitagliptin, vildagliptin, saxagliptin, linagliptin, and alogliptin) discussing pharmacokinetics, pharmacodynamics, efficacy, and safety.
Achieving High Field‐Effect Mobility in Amorphous Indium‐Gallium‐Zinc Oxide by Capping a Strong Reduction Layer (2012)

An effective approach to reduce defects and increase electron mobility in a-IGZO thin-film transistors (a-IGZO TFTs) is introduced. A strong reduction layer, calcium, is capped onto the back interface of a-IGZO TFT. After calcium capping, the effective electron mobility of a-IGZO TFT increases from 12 cm(2) V(-1) s(-1) to 160 cm(2) V(-1) s(-1). This high mobility is a new record, which implies that the proposed defect reduction effect is key to improve electron transport in oxide semiconductor materials.
Derivation and Maintenance of Embryonic Stem Cell Cultures (2003)

The ability to derive permanent tissue-culture lines (1) of pluripotential stem cell lines (ES cells) from mouse embryos has provided a valuable model system for fundamental research into the cellular differentiation processes occuring in the normal embryo. Perhaps the most attractive feature of embryonic stem cell lines is that they can be manipulated to differentiate into a diversity of cell types either directly in the tissue-culture dish or within the context of the normal developing embryo following their return to the embryonic environment.
Human DNA polymerase α: predicted functional domains and relationships with viral DNA polymerases (1989)

The primary sequence of human DNA polymerase alpha deduced from the full-length cDNA contains regions of striking similarity to sequences in replicative DNA polymerases from Escherichia coli phages PRD1 and T4, Bacillus phage phi 19, yeast DNA polymerase I, yeast linear plasmid pGKL1, maize S1 mitochondrial DNA, herpes family viruses, vaccinia virus, and adenovirus. The conservation of these homologous regions across this vast phylogenetic expanse indicates that these prokaryotic and eukaryotic DNA polymerases may all have evolved from a common primordial gene. Based on the sequence analysis and genetic results from yeast and herpes simplex virus studies, these consensus sequences are suggested to define potential sites that subserve essential roles in the DNA polymerase reaction. Two of these conserved regions appear to participate directly in the active site required for substrate deoxynucleotide interaction. One region toward the carboxyl-terminus has the potential to be the DNA interacting domain, whereas a potential DNA primase interaction domain is predicted toward the amino-terminus. The provisional assignment of these domains can be used to identify unique or dissimilar features of functionally homologous catalytic sites in viral DNA polymerases of pathogenetic significance and thereby serve to guide more rational antiviral drug design.