gebhart/patrepeval huggingface dataset:
Antisense RNA and DNA. (1992)

Partial table of contents: ANTISENSE RNA Regulation of Gene Expression and Function by Antisense RNA in Bacteria (C. Thomas) Use of Antisense RNA to Study Gene Expression in the Mammalian Preimplantation Embryo (B. Levy, et al.) Manipulation of Myelin Formation in Transgenic Mice (M. Kimura, et al.) Use of Antisense RNA Technology to Engineer Virus Resistance in Plants (E. Bejarano, et al.) The Double-Stranded RNA Unwinding/Modifying Activity (B. Bass) ANTISENSE DNA Anticancer Drug Design Using Modified Antisense Oligonucleotides (D. Tidd) Transmembrane Passage and Cell Targeting of Antiviral Synthetic Oligonucleotides (G. Degols, et al.) CASE STUDIES Alternative Antiviral Approaches to Influenza Virus: Antisense RNA and DNA (S. Agrawal & J. Leiter) RIBOZYMES Selective Amplification Techniques for Optimization of Ribozyme Function (G. Joyce) Index.
Few bicyclic acetals at reducing end of low-molecular-weight heparins: might they restrict specification of pharmacopoeia? (2005)

The alkaline hydrolysis of heparin benzyl ester originates enoxaparin. The depolymerization by beta-elimination is the primary effect of reaction; but side reactions can happen and the bicyclic acetal at the reducing end of glucosamine N,6-disulphate, called 1,6-anhydro ring, is a product of a side reaction. The amount of this predictable moiety of enoxaparin can be controlled to a lowest extent (6%) and to extent higher than 40% by modulating the alkalinity and duration of the reaction of hydrolysis. With the exclusion of the beta-elimination effects and of these non significative side reactions, the chemical structure of the parent heparin is entirely maintained in enoxaparin as it results by the same profiles of constituent disaccharides. The content of 1,6-anhydro rings is assessed by a not yet validated NMR method. The chains of enoxaparin bearing, at their reducing end, 1,6-anhydro rings could be regarded as Related Substances of enoxaparin. If present, even in an amount less than, or equal to, 30% of chains, these "related substances" affect neither activities nor safety of enoxaparin.
Self assembly driven by hydrophobic interactions at alkanethiol monolayers: mechanism of formation of hybrid bilayer membranes (1998)

The mechanism for the formation of biomimetic model cell membranes consisting of bilayers composed of alkanethiols and phospholipids was probed with a kinetic study using surface plasmon resonance. The kinetics of formation of a monolayer of phospholipid from vesicles in solution onto a hydrophobic alkanethiol monolayer is described by a model that takes into account the lipid concentration, diffusion, and a surface reorganization rate constant. Monomer phospholipid apparently does not play a direct role in determining the kinetics of bilayer formation. Expressions for the limiting cases of this model describe the behavior of two distinct vesicle concentration conditions. At high concentrations of lipid vesicles the formation of the bilayer appears to be limited by the diffusion of vesicles to the surface; at lower concentrations of vesicles, the rate-limiting step is apparently the surface reorganization of lipid. This kinetic model can also be used to describe the formation of a biomimetic bilayer from an alkanethiol monolayer and cell membranes.
Cyclophosphamide versus Placebo in Scleroderma Lung Disease (2006)

One year of oral cyclophosphamide in patients with symptomatic scleroderma-related interstitial lung disease had a significant but modest beneficial effect on lung function, dyspnea, thickening of the skin, and the health-related quality of life. The effects on lung function were maintained through the 24 months of the study.
Topical Review: Role of Instrumented Fetal Sheep Preparations in Defining the Pathogenesis of Human Periventricular White-Matter Injury (2006)

Periventricular white-matter injury is the major form of brain injury associated with prematurity and the leading cause of cerebral palsy in survivors of premature birth. Progress in understanding the pathogenesis of periventricular white-matter injury requires the development of animal models that are relevant to the unique physiology of the preterm human brain and that replicate the major neuropathologic features of human injury. The sheep is the most extensively studied true fetal preparation. The neurodevelopment of the preterm sheep fetus (0.65 gestation) is comparable to that of the preterm human between approximately 24 and 28 weeks. The size of the fetal sheep permits chronic instrumentation so that well-defined insults can be studied with reliable measurements of blood flow and metabolism in cerebral white-matter. We review here recent developments in the understanding of the role of cerebral hypoxia-ischemia and vulnerable oligodendrocyte progenitors in the pathogenesis of periventricular white-matter injury in the immature sheep fetus. We focus on recent developments in high-resolution spatially defined cerebral blood flow measurements in utero. We determined ovine white-matter maturation between 90 and 120 days' gestation, as defined by immunohistochemical localization of oligodendrocyte lineage-specific antibodies. There was considerable spatial and temporal heterogeneity in oligodendrocyte maturation in the immature periventricular white-matter. Oligodendrocyte maturation in the 90- to 105-day fetal sheep closely coincided with that of the preterm human during the high-risk period for white-matter injury. Hence, the immature state of the 90- to 105-day fetal periventricular white-matter is an optimal and dynamic developmental window to study the role of cellular-maturational factors in the pathogenesis of white-matter injury. We conclude with a review of the significant advantages of the instrumented fetal sheep to accelerate progress in the translation of preventive therapies for periventricular white-matter injury and cerebral palsy.
Characterization of Insulin Degrading Enzyme and Other Amyloid-β Degrading Proteases in Human Serum: A Role in Alzheimer's Disease? (2012)

Sporadic Alzheimer's disease (AD) patients have low amyloid-β peptide (Aβ) clearance in the central nervous system. The peripheral Aβ clearance may also be important but its role in AD remains unclear. We aimed to study the Aβ degrading proteases including insulin degrading enzyme (IDE), angiotensin converting enzyme (ACE) and others in blood. Using the fluorogenic substrate V (a substrate of IDE and other metalloproteases), we showed that human serum degraded the substrate V, and the activity was inhibited by adding increasing dose of Aβ. The existence of IDE activity was demonstrated by the inhibition of insulin, amylin, or EDTA, and further confirmed by immunocapture of IDE using monoclonal antibodies. The involvement of ACE was indicated by the ability of the ACE inhibitor, lisinopril, to inhibit the substrate V degradation. To test the variations of substrate V degradation in humans, we used serum samples from a homebound elderly population with cognitive diagnoses. Compared with the elderly who had normal cognition, those with probable AD and amnestic mild cognitive impairment (amnestic MCI) had lower peptidase activities. Probable AD or amnestic MCI as an outcome remained negatively associated with serum substrate V degradation activity after adjusting for the confounders. The elderly with probable AD had lower serum substrate V degradation activity compared with those who had vascular dementia. The blood proteases mediating Aβ degradation may be important for the AD pathogenesis. More studies are needed to specify each Aβ degrading protease in blood as a useful biomarker and a possible treatment target for AD.
High throughput digital quantification of mRNA abundance in primary human acute myeloid leukemia samples (2009)

Acute promyelocytic leukemia (APL) is characterized by the t(15;17) chromosomal translocation, which results in fusion of the retinoic acid receptor alpha (RARA) gene to another gene, most commonly promyelocytic leukemia (PML). The resulting fusion protein, PML-RARA, initiates APL, which is a subtype (M3) of acute myeloid leukemia (AML). In this report, we identify a gene expression signature that is specific to M3 samples; it was not found in other AML subtypes and did not simply represent the normal gene expression pattern of primary promyelocytes. To validate this signature for a large number of genes, we tested a recently developed high throughput digital technology (NanoString nCounter). Nearly all of the genes tested demonstrated highly significant concordance with our microarray data (P < 0.05). The validated gene signature reliably identified M3 samples in 2 other AML datasets, and the validated genes were substantially enriched in our mouse model of APL, but not in a cell line that inducibly expressed PML-RARA. These results demonstrate that nCounter is a highly reproducible, customizable system for mRNA quantification using limited amounts of clinical material, which provides a valuable tool for biomarker measurement in low-abundance patient samples.
Excitatory and inhibitory autaptic currents in isolated hippocampal neurons maintained in cell culture. (1991)

Individual rat hippocampal neurons, grown in isolation from other neurons on small spots of permissive substrate, were studied in order to characterize the electrical properties of the synapses that such cells formed with themselves (autapses). Excitatory (probably glutamatergic) or inhibitory (probably type A gamma-aminobutyratergic) autapses were frequently found. Excitatory autaptic currents reversed near the potential expected for monovalent cations were blocked by the glutamatergic antagonist kynurenic acid, and possessed a slow component with the pharmacological profile of N-methyl-D-aspartate-type channels. These currents also exhibited trial-to-trial statistical fluctuations in their amplitudes, this being well-described by quantal analysis. Inhibitory autaptic currents reversed at hyperpolarized potentials, as expected for chloride-permeable pores and were blocked by picrotoxin, a type A gamma-aminobutyric receptor antagonist. It is concluded that autaptic currents in culture are identical to those found at synapses.
Preferential Induction of EphB4 over EphB2 and Its Implication in Colorectal Cancer Progression (2009)

The receptor tyrosine kinase EphB2 is expressed by colon progenitor cells; however, only 39% of colorectal tumors express EphB2 and expression levels decline with disease progression. Conversely, EphB4 is absent in normal colon but is expressed in all 102 colorectal cancer specimens analyzed, and its expression level correlates with higher tumor stage and grade. Both EphB4 and EphB2 are regulated by the Wnt pathway, the activation of which is critically required for the progression of colorectal cancer. Differential usage of transcriptional coactivator cyclic AMP-responsive element binding protein-binding protein (CBP) over p300 by the Wnt/beta-catenin pathway is known to suppress differentiation and increase proliferation. We show that the beta-catenin-CBP complex induces EphB4 and represses EphB2, in contrast to the beta-catenin-p300 complex. Gain of EphB4 provides survival advantage to tumor cells and resistance to innate tumor necrosis factor-related apoptosis-inducing ligand-mediated cell death. Knockdown of EphB4 inhibits tumor growth and metastases. Our work is the first to show that EphB4 is preferentially induced in colorectal cancer, in contrast to EphB2, whereby tumor cells acquire a survival advantage.
Enteric infections, diarrhea, and their impact on function and development (2008)

Enteric infections, with or without overt diarrhea, have profound effects on intestinal absorption, nutrition, and childhood development as well as on global mortality. Oral rehydration therapy has reduced the number of deaths from dehydration caused by infection with an enteric pathogen, but it has not changed the morbidity caused by such infections. This Review focuses on the interactions between enteric pathogens and human genetic determinants that alter intestinal function and inflammation and profoundly impair human health and development. We also discuss specific implications for novel approaches to interventions that are now opened by our rapidly growing molecular understanding.
Synthetic “interface” peptides alter dimeric assembly of the HIV 1 and 2 proteases (1992)

Retroviral proteases are obligate homodimers and play an essential role in the viral life cycle. Dissociation of dimers or prevention of their assembly may inactivate these enzymes and prevent viral maturation. A salient structural feature of these enzymes is an extended interface composed of interdigitating N- and C-terminal residues of both monomers, which form a four-stranded beta-sheet. Peptides mimicking one beta-strand (residues 95-99), or two beta-strands (residues 1-5 plus 95-99 or 95-99 plus 95-99) from the human immunodeficiency virus 1 (HIV1) interface were shown to inhibit the HIV1 and 2 proteases (PRs) with IC50's in the low micromolar range. These interface peptides show cognate enzyme preference and do not inhibit pepsin, renin, or the Rous sarcoma virus PR, indicating a degree of specificity for the HIV PRs. A tethered HIV1 PR dimer was not inhibited to the same extent as the wild-type enzymes by any of the interface peptides, suggesting that these peptides can only interact effectively with the interface of the two-subunit HIV PR. Measurements of relative dissociation constants by limit dilution of the enzyme show that the one-strand peptide causes a shift in the observed Kd for the HIV1 PR. Both one- and two-strand peptides alter the monomer/dimer equilibrium of both HIV1 and HIV2 PRs. This was shown by the reduced cross-linking of the HIV2 PR by disuccinimidyl suberate in the presence of the interface peptides. Refolding of the HIV1 and HIV2 PRs with the interface peptides shows that only the two-strand peptides prevent the assembly of active PR dimers. Although both one- and two-strand peptides seem to affect dimer dissociation, only the two-strand peptides appear to block assembly. The latter may prove to be more effective backbones for the design of inhibitors directed toward retroviral PR dimerization in vivo.
MOSAIK: A Hash-Based Algorithm for Accurate Next-Generation Sequencing Short-Read Mapping (2014)

MOSAIK is a stable, sensitive and open-source program for mapping second and third-generation sequencing reads to a reference genome. Uniquely among current mapping tools, MOSAIK can align reads generated by all the major sequencing technologies, including Illumina, Applied Biosystems SOLiD, Roche 454, Ion Torrent and Pacific BioSciences SMRT. Indeed, MOSAIK was the only aligner to provide consistent mappings for all the generated data (sequencing technologies, low-coverage and exome) in the 1000 Genomes Project. To provide highly accurate alignments, MOSAIK employs a hash clustering strategy coupled with the Smith-Waterman algorithm. This method is well-suited to capture mismatches as well as short insertions and deletions. To support the growing interest in larger structural variant (SV) discovery, MOSAIK provides explicit support for handling known-sequence SVs, e.g. mobile element insertions (MEIs) as well as generating outputs tailored to aid in SV discovery. All variant discovery benefits from an accurate description of the read placement confidence. To this end, MOSAIK uses a neural-network based training scheme to provide well-calibrated mapping quality scores, demonstrated by a correlation coefficient between MOSAIK assigned and actual mapping qualities greater than 0.98. In order to ensure that studies of any genome are supported, a training pipeline is provided to ensure optimal mapping quality scores for the genome under investigation. MOSAIK is multi-threaded, open source, and incorporated into our command and pipeline launcher system GKNO (http://gkno.me).
Experimental and therapeutic approaches to muscular dystrophies (2002)

This panoply of experimental approaches covered all the current possibilities of attacking the problem of treating muscular dystrophies. It is expected that one or more will progress to provide efficient tools for the ultimate clinical goal: to prolong function and life in severe muscular dystrophy patients.
Minor groove binding of SN6999 to an alkylated DNA: Molecular structure of d(CGC[e6G]AATTCGCG)-SN6999 complex (1993)

The interaction between a potent synthetic antitumor and antiviral minor groove binding drug 1-methyl-4-[4-[4-(4-(1-methylquinolinium)amino)benzamido]anilino] pyridinium dichloride (SN6999) and an alkylated DNA d(CGC[e6G]AATTCGCG) dodecamer has been studied by X-ray crystallography. The complex forms a new crystal lattice in the space group P2(1)2(1)2(1) with unit cell dimensions of a = 28.48 A, b = 36.11 A, and c = 69.60 A. The structure has been solved by the molecular replacement method and refined to an R-factor of 17.0% at approximately 2.5 A resolution using 1618 reflections. In the complex, the SN6999 covers almost six base pairs in the narrow minor groove with the 1-methylquinolinium (Q) ring near T8-A17 and the 1-methylpyridinium (P) ring near the C3-G22 base pair. The central benzamido (BQ) and anilino (BP) rings are essentially coplanar, with the Q and P rings having large dihedral angles of 38 degrees and 39 degrees, respectively, to the plane of BQ/BP. There is only one direct hydrogen bond between the amide NH of SN6999 to T20O2 of DNA. The drug-DNA interaction is stabilized by stacking interaction of sugar oxygens from T20O4' to BQ and C21O4' to BP. There is charge-induced dipole interaction between the positively charged nitrogen atom of 1-methylquinolinium with C9O4' and that of 1-methylpyridinium with G22O4'. The crystal structure of the complex can be used to explain the NMR results. SN6999 lacks the crescent shape observed in other minor groove binding drugs and distorts the DNA duplex upon binding. The complex packs in the lattice using the G-N2:G-N3 interlocking base pairs at both ends of the helix. As in earlier cases, the two independent e6G:C base pairs adopt different base pairing schemes. The e6G16:C9 base pair adopts a previously observed bifurcated configuration involving three-centered hydrogen bonds and is similar to a Watson-Crick pairing. In contrast, the e6G4:C21 base pair adopts a novel "reverse wobble" configuration with C21 being pushed toward the major groove side. The ethyl group is in the proximal orientation (to N7) in both base pairs. Taken together with the observations found in the same DNA complexed to Hoechst 33258, Hoechst 33342, and retropsin from different crystal lattices, the results suggest that the e6G:C base pairing is weak and polymorphic when compared to a normal G:C base pair and the DNA duplex containing this lesion is readily distorted.
Methotrexate for systemic lupus erythematosus: a retrospective analysis of 17 unselected cases. (1992)

We report a retrospective study of 17 patients with systemic lupus erythematosus who were treated with oral methotrexate given as a mean weekly dose of 8.47 +/- 1.72 mg. Methotrexate treatment resulted in symptomatic improvement in 57% of patients and allowed the reduction of the mean daily dose of prednisone from 16.66 mg initially to 8.99 mg at one year follow-up. Twelve of 17 patients (70.6%) experienced at least one episode of toxicity. Factors which might be associated with toxicity are analyzed. Because of its potential as a corticosteroid-sparing agent, controlled studies of methotrexate for the treatment of systemic lupus erythematosus are indicated.
Why Is Tetrazole Formation by Addition of Azide to Organic Nitriles Catalyzed by Zinc(II) Salts? (2003)

The mechanism by which zinc(II) catalyzes the union of an azide ion with organic nitriles to form tetrazoles is investigated by means of density functional theory using the hybrid functional B3LYP. The calculations indicate that coordination of the nitrile to the zinc ion is the dominant factor affecting the catalysis; this coordination substantially lowers the barrier for nucleophilic attack by azide. Relative reaction rates of catalyzed and uncatalyzed tetrazole formation also provide experimental support for this conclusion.
Selection on Somatic Cell Score to Improve Resistance to Mastitis in the United States (1994)

Increased genetic susceptibility to mastitis has accompanied the rapid genetic increase in milk yield, and genetic selection for mastitis resistance should be considered. Somatic cell score is recommended as an indicator trait to achieve genetic improvement for mastitis resistance. Heritability of somatic cell score is around 10%, and genetic correlation between somatic cell score and clinical mastitis is around .6 to .8. Selection for lower somatic cell score is consistent with the goal of maximizing genetic improvement for total economic merit and should be included in breeding programs. National genetic evaluations for somatic cells scores will use the same animal models and methods as are currently used for milk yield traits. Reliabilities of PTA for somatic cell scores will be smaller than for yield traits because of lower heritability and availability of records from fewer cows. Several forms are proposed for reporting genetic evaluations of somatic cells to producers, and advantages and disadvantages are discussed. Using somatic cell scores for breeding decisions would marginally decrease genetic gain for milk yield and increase total economic merit. Optimal selection indexes would slow the rate of increase in mastitis, rather than decrease its incidence.
Azide solid phase peptide synthesis (1970)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAzide solid phase peptide synthesisArthur M. Felix and R. B. MerrifieldCite this: J. Am. Chem. Soc. 1970, 92, 5, 1385–1391Publication Date (Print):March 1, 1970Publication History Published online1 May 2002Published inissue 1 March 1970https://pubs.acs.org/doi/10.1021/ja00708a046https://doi.org/10.1021/ja00708a046research-articleACS PublicationsRequest reuse permissionsArticle Views1135Altmetric-Citations78LEARN 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