gebhart/patrepeval huggingface dataset:
Corticosteroids for the treatment of Duchenne muscular dystrophy (2016)

Moderate quality evidence from RCTs indicates that corticosteroid therapy in DMD improves muscle strength and function in the short term (twelve months), and strength up to two years. On the basis of the evidence available for strength and function outcomes, our confidence in the effect estimate for the efficacy of a 0.75 mg/kg/day dose of prednisone or above is fairly secure. There is no evidence other than from non-randomised trials to establish the effect of corticosteroids on prolongation of walking. In the short term, adverse effects were significantly more common with corticosteroids than placebo, but not clinically severe. A weekend-only prednisone regimen is as effective as daily prednisone in the short term (12 months), according to low to moderate quality evidence from a single trial, with no clear difference in BMI (low quality evidence). Very low quality evidence indicates that deflazacort causes less weight gain than prednisone after a year's treatment. We cannot evaluate long-term benefits and hazards of corticosteroid treatment or intermittent regimens from published RCTs. Non-randomised studies support the conclusions of functional benefits, but also identify clinically significant adverse effects of long-term treatment, and a possible divergence of efficacy in daily and weekend-only regimens in the longer term. These benefits and adverse effects have implications for future research and clinical practice.
Antibodies specific for the polyoma virus middle-size tumor antigen. (1981)

We have obtained antibodies specific for the polyoma virus middle-size tumor antigen (middle T antigen) by immunizing rabbits with a synthetic peptide, Lys-Arg-Ser-Arg-His-Phe, corresponding to the six carboxy-terminal amino acids of the middle T antigen predicted from the nucleotide sequence of polyoma DNA. The antipeptide serum precipitates the polyoma middle T antigen but not the small or large tumor antigens, and precipitation is inhibited in the presence of the peptide. Two cellular proteins, 30,000 and 26,000 daltons, are also precipitated specifically by the antipeptide serum and may have amino acid sequences related to the peptide. Two other cellular proteins, 33,000 and 25,000 daltons, are precipitated only in the presence of the peptide and may associate with it in cell extracts. Antisera directed against synthetic peptides are likely to be important in various ways, including the production of antibodies directed against particular determinants and the recognition of unknown proteins whose genes have been analyzed.
The role of structure, energy landscape, dynamics, and allostery in the enzymatic function of myoglobin (2001)

The grail of protein science is the connection between structure and function. For myoglobin (Mb) this goal is close. Described as only a passive dioxygen storage protein in texts, we argue here that Mb is actually an allosteric enzyme that can catalyze reactions among small molecules. Studies of the structural, spectroscopic, and kinetic properties of Mb lead to a model that relates structure, energy landscape, dynamics, and function. Mb functions as a miniature chemical reactor, concentrating and orienting diatomic molecules such as NO, CO, O 2 , and H 2 O 2 in highly conserved internal cavities. Reactions can be controlled because Mb exists in distinct taxonomic substates with different catalytic properties and connectivities of internal cavities.
In Vivo Sampling: A Promising Technique for Detecting and Profiling Endogenous Substances in Living Systems (2019)

Endogenous substances, naturally occurring in living organisms, are critical components with physiological and biological functions. Discovery and quantitative measurement of endogenous substances in living biotas are important for food analysis, crop cultivation, and quality assessment. Low or non-invasive in vivo sampling techniques offer the advantages of minimal perturbation to the investigated system and potentially obtain more accurate feedback compared to in vitro sampling. In this perspective, we summarize the up-to-date progress in the development of microdialysis and solid-phase microextraction as valuable tools for in vivo sampling of endogenous substances in food and agriculture chemistry. We discuss their feasibility for on-site and real-time in vivo monitoring and highlight the prospects in searching for highly specific coatings, miniaturized sampling devices, and instruments that well meet the trend for high-efficient and high-throughput analyses.
Accumulation of 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone in alkaloid genotypes of burley tobacco during postharvest processing: comparisons with N'-nitrosonornicotine and probable nitrosamine precursors. (1985)

Recent work showed that 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) was present in some cured tobacco and was more carcinogenic than N'-nitrosonornicotine (NNN). In the present investigation, the concentration relationships of NNK, NNN, and their probable precursors, i.e., nitrite, nitrate, and alkaloids, were determined: (a) after the growth of Ky 14 burley tobacco under different shade conditions followed by air curing; and (b) during preparation of air-cured and homogenized-leaf-cured (HLC) burley tobaccos from conventionally grown tobaccos of different alkaloid genotypes. A capillary gas chromatography-nitrogen-phosphorus detector procedure was developed and utilized for quantitative determinations of NNK and NNN. NNK contents ranged from 0.2 to 0.5 micrograms/g in air-cured Ky 14 tobacco lamina from leaves grown under 0 to 65% shade (100, 65, and 35% of natural daylight). The highest NNK concentrations were from 45% shade-grown lamina from lower leaf positions on stalks. Concentrations of NNK did not correlate significantly with those of either nitrate or total alkaloids calculated over all shade treatments and stalk positions. During HLC tobacco processing, the following significant correlations of NNK with precursor content changes were found for each of four burley alkaloid genotypes calculated over the four successive stages of processing: NNN (r = 1.0); and nitrate (r = -0.9). NNK also correlated negatively with nicotine concentration changes (r = -0.9) in the low-alkaloid and high-alkaloid isolines during processing. After a 20-h incubation period under aerobic conditions followed by a 1-h standing period without aeration, substantial increases of NNK were observed in each burley line. The increased NNK contents ranged from 9-fold for the low-alkaloid isoline to 99-fold for the nornicotine-converter line. Increases in NNK content (27 to 69%) also occurred during the air drying stage; further increases occurred during a 15-month storage period at ambient conditions. After the HLC process and prolonged storage, maximal NNK contents were observed in each tobacco genotype in the following order of increasing NNK content: Ky 14 cultivar, 79 micrograms/g; low-alkaloid line, 80 micrograms/g; nornicotine converter line, 102 micrograms/g; and high-alkaloid line, 177 micrograms/g. At the beginning of a controlled environmental storage period used for high-alkaloid and low-alkaloid isoline air-cured and HLC tobaccos, NNK contents correlated with nitrite (r = 1.0) and nitrate (r = -0.9) calculated over the two curing regimens.(ABSTRACT TRUNCATED AT 400 WORDS)
The Alpha 21264 microprocessor (1999)

Alpha microprocessors have been performance leaders since their introduction in 1992. The first generation 21064 and the later 21164 raised expectations for the newest generation-performance leadership was again a goal of the 21264 design team. Benchmark scores of 30+ SPECint95 and 58+ SPECfp95 offer convincing evidence thus far that the 21264 achieves this goal and will continue to set a high performance standard. A unique combination of high clock speeds and advanced microarchitectural techniques, including many forms of out-of-order and speculative execution, provide exceptional core computational performance in the 21264. The processor also features a high-bandwidth memory system that can quickly deliver data values to the execution core, providing robust performance for a wide range of applications, including those without cache locality. The advanced performance levels are attained while maintaining an installed application base. All Alpha generations are upward-compatible. Database, real-time visual computing, data mining, medical imaging, scientific/technical, and many other applications can utilize the outstanding performance available with the 21264.
4-Aryl-2,4-dioxobutanoic Acid Inhibitors of HIV-1 Integrase and Viral Replication in Cells (2000)

ADVERTISEMENT RETURN TO ISSUELetterNEXT4-Aryl-2,4-dioxobutanoic Acid Inhibitors of HIV-1 Integrase and Viral Replication in CellsJohn S. Wai, Melissa S. Egbertson, Linda S. Payne, Thorsten E. Fisher, Mark W. Embrey, Lekhanh O. Tran, Jeffrey Y. Melamed, H. Marie Langford, James P. Guare,, Linghang Zhuang, Vanessa E. Grey, Joseph P. Vacca, M. Katharine Holloway, Adel M. Naylor-Olsen, Daria J. Hazuda, Peter J. Felock, Abigail L. Wolfe, Kara A. Stillmock, William A. Schleif, Lori J. Gabryelski, and Steven D. YoungView Author Information Departments of Medicinal Chemistry, Molecular Systems, and Antiviral Research, Merck Research Laboratories, West Point, Pennsylvania 19486 Cite this: J. Med. Chem. 2000, 43, 26, 4923–4926Publication Date (Web):November 28, 2000Publication History Received19 April 2000Published online28 November 2000Published inissue 1 December 2000https://pubs.acs.org/doi/10.1021/jm000176bhttps://doi.org/10.1021/jm000176brapid-communicationACS PublicationsCopyright © 2000 American Chemical SocietyRequest reuse permissionsArticle Views1562Altmetric-Citations197LEARN 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 SUBJECTS:Cell culture,DNA replication,Genetics,Inhibition,Inhibitors Get e-Alerts
Drosophila rugoseIs a Functional Homolog of MammalianNeurobeachinand Affects Synaptic Architecture, Brain Morphology, and Associative Learning (2012)

Neurobeachin (Nbea) is implicated in vesicle trafficking in the regulatory secretory pathway, but details on its molecular function are currently unknown. We have used Drosophila melanogaster mutants for rugose (rg), the Drosophila homolog of Nbea, to further elucidate the function of this multidomain protein. Rg is expressed in a granular pattern reminiscent of the Golgi network in neuronal cell bodies and colocalizes with transgenic Nbea, suggesting a function in secretory regulation. In contrast to Nbea(-/-) mice, rg null mutants are viable and fertile and exhibit aberrant associative odor learning, changes in gross brain morphology, and synaptic architecture as determined at the larval neuromuscular junction. At the same time, basal synaptic transmission is essentially unaffected, suggesting that structural and functional aspects are separable. Rg phenotypes can be rescued by a Drosophila rg+ transgene, whereas a mouse Nbea transgene rescues aversive odor learning and synaptic architecture; it fails to rescue brain morphology and appetitive odor learning. This dissociation between the functional redundancy of either the mouse or the fly transgene suggests that their complex composition of numerous functional and highly conserved domains support independent functions. We propose that the detailed compendium of phenotypes exhibited by the Drosophila rg null mutant provided here will serve as a test bed for dissecting the different functional domains of BEACH (for beige and human Chediak-Higashi syndrome) proteins, such as Rugose, mouse Nbea, or Nbea orthologs in other species, such as human.
Wnt/β-Catenin Signaling Regulates Telomerase in Stem Cells and Cancer Cells (2012)

Telomerase activity controls telomere length and plays a pivotal role in stem cells, aging, and cancer. Here, we report a molecular link between Wnt/β-catenin signaling and the expression of the telomerase subunit Tert. β-Catenin-deficient mouse embryonic stem (ES) cells have short telomeres; conversely, ES cell expressing an activated form of β-catenin (β-cat(ΔEx3/+)) have long telomeres. We show that β-catenin regulates Tert expression through the interaction with Klf4, a core component of the pluripotency transcriptional network. β-Catenin binds to the Tert promoter in a mouse intestinal tumor model and in human carcinoma cells. We uncover a previously unknown link between the stem cell and oncogenic potential whereby β-catenin regulates Tert expression, and thereby telomere length, which could be critical in human regenerative therapy and cancer.
Melatonin and its agonists: an update (2008)

The pineal hormone melatonin is able to shift the timing of circadian rhythms, including the sleep-wake cycle, and to promote sleep. Melatonin agonists with similar properties have therapeutic potential for the treatment of circadian rhythm sleep disorders. Depression is specifically targeted by agomelatine, which is also a serotonin-2C (5-HT(2C)) antagonist.
Optimum fourier filtering of cardiac data: a minimum-error method: concise communication. (1983)

Random fluctuations limit the accuracy of quantities derived from cardiac time-activity curves (TACs). To overcome this problem, TACs are often fitted with a truncated Fourier series giving rise to two sources of error: (a) the truncated series may not adequately describe the TAC shape, causing errors in parameters calculated from the fit: and (b) successive TACs acquired from the same subject under identical circumstances will fluctuate due to limited counts, causing the Fourier fits (and parameters derived from them) to fluctuate. These two errors, respectively, decrease and increase as the number of harmonics increases, suggesting the existence of a minimum in total error. This number of harmonics for minimum error (NHME) was calculated for each of six common parameters used to describe LV TACs. The "true" value of each parameter was determined from TACs of very high statistical precision. Poisson noise was added to simulate lower count rates. For low-count TACs, use of either a smaller or a larger number of harmonics resulted in significantly greater error. NHME was found to occur at two harmonics for the systolic parameters studied, regardless of the noise level present in the TAC. For diastolic parameters, however, NHME was a strong function of the noise present in the TAC, varying from three harmonics for noise levels typical of regional TACs, to five or six harmonics for high-count global TACs.
Induced Response of the Siebold's Beech (Fagus crenataBlume) to Manual Defoliation (1996)

Siebold's beech (Fagus crenata) was manually defoliated for two successive years. The beech caterpillar (Quadricalcarifera punctatella) was used in a bioassay to determine insect performance. Survival and body size were low on foliage from defoliated trees. Reduced foliar nitrogen and increased tannin content were probably the main causes of the low insect performance. Leaves were less tough on defoliated trees than in controls. Two sucessive years of manual defoliation caused stronger induced resistance than one year defoliation. The quanlity, as well as the quality of the foliage, decreased the year following manual defoliation; total weight of leaves on a tree was less than one half of that before treatment. Severe defoliation may cause a decrease of leaves the following year and starvation may limit populations. Delayed induced resistance of beech trees is proposed as a possible cause of the cyclical population dynamics of Q. punctatella. The delayed induced response also affected folivorous insects other than Q. punctatella.
TALE-Like Effectors Are an Ancestral Feature of the Ralstonia solanacearum Species Complex and Converge in DNA Targeting Specificity (2016)

Ralstonia solanacearum, a species complex of bacterial plant pathogens divided into four monophyletic phylotypes, causes plant diseases in tropical climates around the world. Some strains exhibit a broad host range on solanaceous hosts, while others are highly host-specific as for example some banana-pathogenic strains. Previous studies showed that transcription activator-like (TAL) effectors from Ralstonia, termed RipTALs, are capable of activating reporter genes in planta, if these are preceded by a matching effector binding element (EBE). RipTALs target DNA via their central repeat domain (CRD), where one repeat pairs with one DNA-base of the given EBE. The repeat variable diresidue dictates base repeat specificity in a predictable fashion, known as the TALE code. In this work, we analyze RipTALs across all phylotypes of the Ralstonia solanacearum species complex. We find that RipTALs are prevalent in phylotypes I and IV but absent from most phylotype III and II strains (10/12, 8/14, 1/24, and 1/5 strains contained a RipTAL, respectively). RipTALs originating from strains of the same phylotype show high levels of sequence similarity (>98%) in the N-terminal and C-terminal regions, while RipTALs isolated from different phylotypes show 47-91% sequence similarity in those regions, giving rise to four RipTAL classes. We show that, despite sequence divergence, the base preference for guanine, mediated by the N-terminal region, is conserved across RipTALs of all classes. Using the number and order of repeats found in the CRD, we functionally sub-classify RipTALs, introduce a new simple nomenclature, and predict matching EBEs for all seven distinct RipTALs identified. We experimentally study RipTAL EBEs and uncover that some RipTALs are able to target the EBEs of other RipTALs, referred to as cross-reactivity. In particular, RipTALs from strains with a broad host range on solanaceous hosts cross-react on each other's EBEs. Investigation of sequence divergence between RipTAL repeats allows for a reconstruction of repeat array biogenesis, for example through slipped strand mispairing or gene conversion. Using these studies we show how RipTALs of broad host range strains evolved convergently toward a shared target sequence. Finally, we discuss the differences between TALE-likes of plant pathogens in the context of disease ecology.
Coronary vasoactivity of adenosine in the conscious dog. (1979)

Intracoronary adenosine infusions in conscious dogs produced half-maximal coronary vasodilation at 0.57 +/- 0.18 (SD) microns and at 1.01 +/- 0.25 microns in open-chest dogs. In both preparations, adenosine at concentrations in the range found in cardiac muscle by direct analysis produced coronary vasodilation equal to that attained during a maximum reactive hyperemic response. The quantitative structure-activity relationship technique was applied to data on the coronary vasoactivity of 68 adenosine analogs to identify the chemical features of this molecule that determine its vasoactivity. These are: (1) the size of the purine base; (2) the inductive effect of C-2 substituent; (3) the electron-withdrawing effect of the C-6 substituent; (4) the glycosylic torsion angle; (5) the ability of the C-2' and C-3' hydroxyls to participate in hydrogen bonding; (7) the absence of sterically hindering groups in the vicinity of C-2' and, more importantly, C-3'; and (8) the inductive effect of the C-5' substituent. The hydrophobicity of these analogs did not correlate with vasoactivity, suggesting that the hydrophilicity of the ribose moiety overshadows any hydrophobic influence of the very weakly aromatic purine base.
Domain structure of vitronectin. Alignment of active sites. (1984)

The structure of vitronectin, an adhesive protein isolated from human plasma, was studied by chemical fragmentation. Partial cleavage of vitronectin with cyanogen bromide in 70% formic acid generated four main fragments with masses of 53,000, 43,000, 35,000, and 12,000 daltons arising from both the 75- and 65-kDa vitronectin polypeptides and a 10-kDa fragment arising only from the 75-kDa polypeptide. By varying the reaction conditions, four BrCN cleavage sites and one acid cleavage site could be identified. The latter site gave rise to 40-, 32-, and 26-kDa fragments. The order of these fragments within the vitronectin polypeptides was determined by comparison of the NH2-terminal sequences of the polypeptides and their fragments, by further cleavage of the largest fragments with BrCN or 70% formic acid, and by assaying for heparin-binding and cell-attachment activities. The NH2-terminal sequences of the intact vitronectin polypeptides are the same and identical to a 44-amino acid serum peptide called somatomedin B, indicating that vitronectin may be the precursor of somatomedin B. The cell-attachment site appears to be located within approximately 5 kDa of the NH2 terminus, but it is distinct from the somatomedin B domain. The heparin-binding site is contained in the 12-kDa fragment near the COOH terminus. This fragment was shown to bind to a chondroitin sulfate proteoglycan in addition to heparin. The NH2-terminal amino acid sequence of this glycosaminoglycan-binding fragment is remarkably rich in basic amino acids. The NH2-terminal sequences of this and the other vitronectin fragments showed no homology with the amino acid sequence of the heparin-binding domain of fibronectin or other known sequences from fibronectin. These results show that the biological activities of vitronectin are located in distinct parts of both of the vitronectin polypeptides, which appear to be identical except for the presence of an additional 10-kDa fragment near or at the COOH terminus of the 75-kDa polypeptide.
Structure elucidation of everninomicin-6, a new oligosaccharide antibiotic, by chemical degradation and FAB-MS methods (1997)

The structural characterization of a new oligosaccharide antibiotic, Everninomicin-6 (EV-6), is described. Detailed fast-atom bombardment mass spectrometry (FAB-MS) studies along with NMR and chemical degradation methods were conducted to elucidate the structure of EV-6. The effects of the use of various matrices, including salt addition, on the quality of the FAB-MS were explored. The use of 3-nitro benzyl alcohol, dimethyl sulfoxide (DMSO), and NaCl produced the best results: an intense sodiated molecular ion plus structurely informative fragmentation. FAB-MS yields information providing the complete sugar sequence information for everninomicins, which is quite valuable to the elucidation of the structure of this complex oligosaccharide antibiotic. In addition, the results of accurate mass work with the molecular ion are consistent with the assigned structure. The use of electrospray ionization mass spectrometry (ESI-MS) and ESI-MS/MS for the study of EV-6 was investigated and was found to produce an abundant molecular ion with limited structural information. These results revealed that EV-6 resembled EV-D quite closely except for the absence of the nitrosugar and the replacement on ring g of the -CH2OCH3 group with a -CH2OH group.
Data for: 3608774 (2020)

IPUMS CPS extract and do file for brief calculations on unemployment and incomes (individuals/households projected to have high incomes but now unemployed for April 2020).