gebhart/patrepeval huggingface dataset:
Measurement of the binding of transcription factor Sp1 to a single GC box recognition sequence (1989)

The equilibrium constant was determined for the binding of the transcription factor Sp1 to a single consensus GC box DNA recognition site, (5'-GGGGCGGGGC-3'). For these experiments, single copies of the recognition site were synthesized and cloned in a standard plasmid background. Binding was measured either by a footprinting assay modified so that the binding reaction was at equilibrium, or by a gel mobility shift assay. The concentration of active Sp1 in the reactions and the dissociation constant were determined by computer-assisted fitting to theoretical curves. Values for the dissociation constant obtained in different experiments ranged from 4.1 X 10(-10) M to 5.3 X 10(-10) M. Several variants of the consensus recognition site were also tested. An A-substituted variant (5'-GGGGAGGGGC-3') and a T-substituted variant (5'-GGGGTGGGGC-3') were bound 3-fold and 6-fold more weakly than the consensus site, respectively. A G-substituted variant (5'-GGGGGGGGGC-3') was bound at least 30-fold more weakly than the consensus site. These findings help distinguish between alternative models for Sp1-DNA recognition. They are consistent with the presence of specific hydrogen-bond contacts between Sp1 and the central C-G base pair, but provide no particular evidence to support a model where local DNA structure is the dominant factor in the interaction.
Improving Cancer Vaccine Efficiency by Nanomedicine (2019)

Cancer vaccines, which have been widely investigated in the past few decades, are one of the most attractive strategies for cancer immunotherapy. Through the precise delivery of antigens and adjuvants to lymphoid organs or lymphocytes via nanotechnology, innate and adaptive immunity can be boosted to prevent the growth and relapse of malignant tumors. Indeed, nanomedicine offers great opportunities to improve the efficiency of vaccines. Various functional platforms are used to deliver small molecules, peptides, nucleic acids, and even whole cell antigens to the target area of interest, achieving enhanced antitumor immunity and durable therapeutic benefits. Herein, the recent progress in cancer vaccines based on nanotechnology is summarized. Novel platforms used for delivering tumor antigens, promoting adjuvant functions, and combining other therapeutic strategies are discussed. Moreover, possible striving directions and major challenges of nanomedicine for vaccination are also reviewed.
Dithioether-containing cyclic peptides (1985)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDithioether-containing cyclic peptidesHenry I. Mosberg and John R. OmnaasCite this: J. Am. Chem. Soc. 1985, 107, 10, 2986–2987Publication Date (Print):May 1, 1985Publication History Published online1 May 2002Published inissue 1 May 1985https://pubs.acs.org/doi/10.1021/ja00296a033https://doi.org/10.1021/ja00296a033research-articleACS PublicationsRequest reuse permissionsArticle Views183Altmetric-Citations32LEARN 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
Five Years of Progress on Cyclin-Dependent Kinases and other Cellular Proteins as Potential Targets for Antiviral Drugs (2006)

In 1997-1998, the pharmacological cyclin-dependent kinase (CDK) inhibitors (PCIs) were independently discovered to inhibit replication of human cytomegalovirus, herpes simplex virus type 1 and HIV-1. The results from small clinical trials against cancer were then suggesting that PCIs could be safe enough to be used clinically. It was thus hypothesized that PCIs could have the potential to be developed as novel antivirals targeting cellular proteins. Consequently, Antiviral Chemistry & Chemotherapy published in 2001 the first review on the potential of CDKs, and cellular proteins in general, as potential targets for antivirals. The viral functions inhibited by PCIs, or their cellular targets, were then just starting to be characterized. The antiviral spectrum of PCIs and their effects on viral disease were still mostly untested. Even their actual specificity was not yet completely characterized. In addition, cellular proteins were not accepted as valid targets for antivirals. Significant progress has been made in the last 5 years in understanding the antiviral activities of PCIs and the potential roles of cellular proteins in general as targets for antivirals. The first clinical trials of the antiviral activities of PCIs and other inhibitors of cellular protein kinases have now been scheduled. Herein, we review the progress made since the publication of the first review on PCIs as potential antiviral drugs and on CDKs, and cellular proteins in general, as potential targets for antiviral drugs. We also highlight the major issues that still need to be addressed before PCIs or other drugs targeting cellular proteins can be developed as clinical antivirals.
Identification of the DNA Binding Site for NGFI-B by Genetic Selection in Yeast (1991)

An in vivo selection system for isolating targets of DNA binding proteins in yeast was developed and used to identify the DNA binding site for the NGFI-B protein, a member of the steroid-thyroid hormone receptor superfamily. The feasibility of the technique was verified by selecting DNA fragments that contained binding sites for GCN4, a well-characterized yeast transcriptional activator. The DNA binding domain of NGFI-B, expressed as part of a LexA-NGFI-B-GAL4 chimeric activator, was then used to isolate a rat genomic DNA fragment that contained an NGFI-B binding site. The NGFI-B response element (NBRE) is similar to but functionally distinct from elements recognized by the estrogen and thyroid hormone receptors and the hormone receptor-like proteins COUP-TF, CF1, and H-2RIIBP. Cotransfection experiments in mammalian cells demonstrated that NGFI-B can activate transcription from the NBRE with or without its putative ligand binding domain.
Incorporation of heparin‐binding peptides into fibrin gels enhances neurite extension: an example of designer matrices in tissue engineering (1999)

The goal of this work was to improve the potential of fibrin to promote nerve regeneration by enzymatically incorporating exogenous neurite-promoting heparin-binding peptides. The effects on neurite extension of four different heparin-binding peptides, derived from the heparin-binding domains of antithrombin III, neural cell adhesion molecule and platelet factor 4, were determined. These exogenous peptides were synthesized as bi-domain peptide chimeras, with the second domain being a substrate for factor XIIIa. This coagulation transglutaminase covalently bound the peptides within the fibrin gel during coagulation. The heparin-binding peptides enhanced the degree of neurite extension from embryonic chick dorsal root ganglia through 3-dimensional fibrin gels, and the extent of enhancement was found to correlate positively with the heparin-binding affinity of the individual domains. The enhancement could be inhibited by competition with soluble heparin, by degradation of cell-surface proteoglycans, and by inhibition of the covalent immobilization of the peptide. These results demonstrate an important potential role for proteoglycan-binding components of the extracellular matrix in neurite extension and suggest that fibrin gels modified with covalently bound heparin-binding peptides could serve as a therapeutic agent to enhance peripheral nerve regeneration through nerve guide tubes. More generally, the results demonstrate that the biological responses to fibrin, the body's natural wound healing matrix, can be dramatically improved by the addition of exogenous bioactive peptides in a manner such that they become immobilized during coagulation.-Sakiyama, S. E., Schense, J. C., Hubbell, J. A. Incorporation of heparin-binding peptides into fibrin gels enhances neurite extension: an example of designer matrices in tissue engineering.
Parametric generalized Gaussian density estimation (1989)

The primary objective of this paper is to compare the large-sample as well as the small-sample properties of different methods for estimating the parameters of a three-parameter generalized Gaussian distribution. Three estimators, namely, the moment method (MM), the maximum-likelihood (ML), and the moment/Newton-step (MNS) estimators, are considered. The applicability of general asymptotic optimality results of the efficient ML and MNS estimation techniques is studied in the generalized Gaussian context. The asymptotic normal distributions of the estimators are obtained. The asymptotic relative superiority of the ML estimator or its variant, the MNS estimator, over the moment method is studied in terms of asymptotic relative efficiency. Based on this study, it is concluded that deviations from normality in the underlying distribution of the data necessitate the use of the efficient ML or MNS methods. In the small-sample case, a detailed comparative study of the estimators is made possible by extensive Monte Carlo simulations. From this study, it is concluded that the maximum-likelihood method is found to be significantly superior for heavy-tailed distributions. In a region of the parameter space corresponding to the vicinity of the Gaussian distribution, the moment method compares well with the other methods. Further, the MNS estimator is shown to perform best for light-tailed distributions. The simulation results are shown to lend support to analytically derived asymptotic results for each of the methods.
Tumor-targeting chemotherapy by a xanthine oxidase-polymer conjugate that generates oxygen-free radicals in tumor tissue. (2000)

Xanthine oxidase (XO) mediates anticancer activity because of its ability to generate cytotoxic reactive oxygen species (ROS), including superoxide anion radical and hydrogen peroxide. However, the high binding affinity of XO to blood vessels would cause systemic vascular damage and hence limits the use of native XO in clinical settings. We demonstrate here that chemical conjugation of XO with poly(ethylene glycol) (PEG; the conjugates hereafter referred to as PEG-XO) significantly enhanced the tumor-targeting efficacy and the antitumor activity of XO. By using a succinimide-activated PEG derivative, PEG was conjugated to epsilon-amino groups of lysine residues of XO, which play a crucial role in binding of XO to blood vessels. PEG-XO administered i.v. showed a 2.8-fold higher accumulation in solid tumor compared with that of native XO 24 h after injection, whereas a slight or negligible increase in accumulation of PEG-XO was observed in normal organs. The highest PEG-XO enzyme activity was detected in tumor compared with normal organs or tissues except blood; enzyme activity in tumor was 5.0, 3.9, and 9.4 times higher than that in liver, kidney, and spleen, respectively. Intratumor activity remained high for >48 h. Administration of hypoxanthine, a substrate of XO, at 33 mg/kg body weight i.p. 12 h after the administration of PEG-XO (0.6 unit/mouse, i.v.) resulted in significant suppression of tumor growth (P < 0.001), with no tumor growth even after 52 days. However, either PEG-XO or hypoxanthine alone, or native XO with hypoxanthine, showed no effect on the inhibition of tumor growth under present experimental conditions. These findings suggest that PEG-XO, which accumulates preferentially in tumor tissue, warrants further investigation as a novel anticancer agent.
Obesity : preventing and managing the global epidemic : report of a WHO Consulation (2000)

This report issues a call for urgent action to combat the growing epidemic of obesity, which now affects developing and industrialized countries alike. Adopting a public health approach, the report responds to both the enormity of health problems associated with obesity and the notorious difficulty of treating this complex, multifactorial disease. With these problems in mind, the report aims to help policy-makers introduce strategies for prevention and management that have the greatest chance of success. The importance of prevention as the most sensible strategy in developing countries, where obesity coexists with undernutrition, is repeatedly emphasized. Recommended lines of action, which reflect the consensus reached by 25 leading authorities, are based on a critical review of current scientific knowledge about the causes of obesity in both individuals and populations. While all causes are considered, major attention is given to behavioural and societal changes that have increased the energy density of diets, overwhelmed sophisticated regulatory systems that control appetite and maintain energy balance, and reduced physical activity. Specific topics discussed range from the importance of fat content in the food supply as a cause of population-wide obesity, through misconceptions about obesity held by both the medical profession and the public, to strategies for dealing with the alarming prevalence of obesity in children. ...the volume is clearly written, and carries a wealth of summary information that is likely to be invaluable for anyone interested in the public health aspects of obesity and fatness, be they students, practitioner or researcher. - Journal of Biosocial Science
A 90-Min Cardiac Biorhythm Methodology and Data Analysis Using Modified Periodograms and Complex Demodulation (1974)

Since the discovery of an approximate 90-min oscillation in rapid eye movement (REM) or dream sleep, much interest has been expressed in the physiological and behavioral parameters associated with this phenomenon. One of the often stated theories is that this 90-min rhythm is an endogenous biorhythm present throughout the 24-h day, perhaps representing a rest-activity cycle of the nervous system. An approximate 90-min biorhythm in resting human heart rate is assessed and described using the techniques of periodogram analysis and complex demodulation. The techniques employed found evidence for this rhythm in all subjects; in-addition, the amplitude of the 90-min ultradian rhythm seemed to be modulated by a circadian (24-h) rhythm. However, the modulating circadian rhythm was not usually phase locked to the circadian rhythm fixed by the waking/sleeping cycle of each subject.
Evolution of the first metabolic cycles. (1990)

There are two alternatives concerning the origin of life: the origin may be heterotrophic or autotrophic. The central problem within the theory of an autotrophic origin is the first process of carbon fixation. I here propose the hypothesis that this process is an autocatalytic cycle that can be retrodictively constructed from the extant reductive citric acid cycle by replacing thioesters by thioacids and by assuming that the required reducing power is obtained from the oxidative formation of pyrite (FeS2). This archaic cycle is strictly chemoautotrophic: photoautotrophy is not required. The cycle is catalytic for pyrite formation and autocatalytic for its own multiplication. It is a consequence of this hypothesis that the postulated cycle cannot exist as a single isolated cycle but must be a member of a network of concatenated homologous cycles, from which all anabolic pathways appear to have sprung.
Purification and Characterization of the Commercialized, Cloned Bacillus megaterium α‐Amylase. Part II: Transferase Properties (1991)

Abstract Using an assay procedure based on reduction of iodine binding to starch. Bacillus megaterium , α‐amylase (BMA) demonstrated transferase activity using a wide range of acceptors. The enzyme had an absolute requirement for glucose or glucosides for acceptor molecules. Maltose acted as a transferase acceptor at low concentrations and as an inhibitor of starch hydrolysis at high concentrations. Kinetic analysis indicated that, in the presence of a suitable acceptor, the mechanism of starch hydrolysis is Ping Pong Bi Bi. The products of the transferase reaction have been determined using p‐nitro‐α‐D‐glucopyranoside as acceptor combined with a novel HPLC‐based system for product detection.
Rapid selection of organisms with increasing resistance on subinhibitory concentrations of norfloxacin in agar (1983)

Serial passage of Pseudomonas aeruginosa ATCC 27853 or Escherichia coli ATCC 25922 on agar with subinhibitory concentrations of norfloxacin rapidly produced isolates with minimal inhibitory concentrations (MICs) of norfloxacin up to 512-fold higher than that for the original strain. Although MICs of seven unrelated antibiotics were unchanged, increasing MICs occurred in parallel with norfloxacin, cinoxacin, and nalidixic acid regardless of which of these three organic acids was used to select for increased resistance. P. aeruginosa with a norfloxacin MIC of greater than 256 micrograms/ml could be selected; however, E. coli with MICs greater than the clinically achievable level of 16 micrograms/ml could not be produced.
Mechanisms of obesity-associated insulin resistance: many choices on the menu (2007)

Obesity-associated insulin resistance is a major risk factor for type 2 diabetes and cardiovascular disease. In the past decade, a large number of endocrine, inflammatory, neural, and cell-intrinsic pathways have been shown to be dysregulated in obesity. Although it is possible that one of these factors plays a dominant role, many of these factors are interdependent, and it is likely that their dynamic interplay underlies the pathophysiology of insulin resistance. Understanding the biology of these systems will inform the search for interventions that specifically prevent or treat insulin resistance and its associated pathologies.
Affinity Purification and Microcharacterization of Recombinant DNA-Derived Human Growth Hormone Isolated from an in Vivo Model (1995)

A procedure has been developed for the isolation and purification of trace amounts of unlabeled proteins from biological solutions. Using a combination of affinity chromatography and reversed-phase HPLC, microgram amounts of recombinant DNA-derived human growth hormone (rhGH) were purified from an in vivo rat model. Microcharacterization techniques were developed, and picomole amounts of the recovered protein were digested with trypsin and characterized using capillary HPLC peptide mapping. The described procedures were used to study the chemical changes that occur in rhGH following intravenous administration. The study demonstrated that both deamidation and oxidation can occur in vivo, although the former would occur to a significant extent only in proteins with an extended half-life.
Expression of OX40 (CD134) on CD4+ T-cells from patients with myasthenia gravis (2005)

Myasthenia gravis (MG) is commonly regarded as the prototype of an antibody-mediated, organ-specific autoimmune disease. Antibodies against the acetylcholine receptor (AChR) on the muscle endplate trigger its typical clinical manifestations of weakness and fatiguability. T-B cell interactions are thought to play a crucial role in the pathogenesis of MG. OX40 (CD134), a costimulatory molecule that is expressed on activated CD4+ T-cells, might contribute to the development or pathogenesis of immune-mediated diseases such as rheumatoid arthritis and graft-versus-host disease. In the present study, we investigated the expression of OX40 on CD4+ T-cells from patients with MG and healthy individuals. Results from 36 MG patients and 28 healthy controls revealed that more freshly isolated CD4+ T-cells from MG patients expressed OX40 than cells from healthy individuals. High levels of antibodies against the AChR, thymic hyperplasia and onset at an early age were associated with elevated expression of OX40. Upon activation by various concentrations of anti-CD3 antibodies, CD4+ T-cells from MG patients showed a tendency toward higher levels of OX40 expression than cells from healthy individuals. Given the role of OX40 in the immune system, we conclude that OX40 might contribute to the development of MG.
National trends in the mortality of children with sickle cell disease, 1968 through 1992. (1997)

Survival of Black children with sickle cell disease has improved markedly since 1968. A substantial proportion of deaths continue to occur prior to hospital admission. Trends in sickle cell mortality can be monitored inexpensively with death-certificate data.
Genomic and Proteomic Characterization of the Broad-Host-Range Salmonella Phage PVP-SE1: Creation of a New Phage Genus (2011)

(Bacterio)phage PVP-SE1, isolated from a German wastewater plant, presents a high potential value as a biocontrol agent and as a diagnostic tool, even compared to the well-studied typing phage Felix 01, due to its broad lytic spectrum against different Salmonella strains. Sequence analysis of its genome (145,964 bp) shows it to be terminally redundant and circularly permuted. Its G+C content, 45.6 mol%, is lower than that of its hosts (50 to 54 mol%). We found a total of 244 open reading frames (ORFs), representing 91.6% of the coding capacity of the genome. Approximately 46% of encoded proteins are unique to this phage, and 22.1% of the proteins could be functionally assigned. This myovirus encodes a large number of tRNAs (n=24), reflecting its lytic capacity and evolution through different hosts. Tandem mass spectrometric analysis using electron spray ionization revealed 25 structural proteins as part of the mature phage particle. The genome sequence was found to share homology with 140 proteins of the Escherichia coli bacteriophage rV5. Both phages are unrelated to any other known virus, which suggests that an "rV5-like virus" genus should be created within the Myoviridae to contain these two phages.
Stability of Drugs and Dosage Forms (2002)

Drug products are complex mixtures of drugs and excipients and, as such, their chemical and physical stability kinetics are complex. This book discusses the stability of these dosage forms with prefor
Time course of performance changes and fatigue markers during intensified training in trained cyclists (2002)

To study the cumulative effects of exercise stress and subsequent recovery on performance changes and fatigue indicators, the training of eight endurance cyclists was systematically controlled and monitored for a 6-wk period. Subjects completed 2 wk of normal (N), intensified (ITP), and recovery training. A significant decline in maximal power output (N = 338 +/- 17 W, ITP = 319 +/- 17 W) and a significant increase in time to complete a simulated time trial (N = 59.4 +/- 1.9 min, ITP = 65.3 +/- 2.6 min) occurred after ITP in conjunction with a 29% increase in global mood disturbance. The decline in performance was associated with a 9.3% reduction in maximal heart rate, a 5% reduction in maximal oxygen uptake, and an 8.6% increase in perception of effort. Despite the large reductions in performance, no changes were observed in substrate utilization, cycling efficiency, and lactate, plasma urea, ammonia, and catecholamine concentrations. These findings indicate that a state of overreaching can already be induced after 7 days of intensified training with limited recovery.