gebhart/patrepeval huggingface dataset:
PPAR‐gamma agonist pioglitazone modifies craving intensity and brain white matter integrity in patients with primary cocaine use disorder: a double‐blind randomized controlled pilot trial (2017)

Compared with placebo, patients receiving pioglitazone show a higher likelihood of reduced cocaine craving and improved brain white matter integrity as a function of time in treatment. Pioglitazone shows good feasibility as a treatment for cocaine use disorder.
Synthesis of 2′-Modified Cyclic Bis(3′–5′)diadenylic Acids (c-di-AMPs) and Their Promotion of Cell Division in a Freshwater Green Alga (2012)

Abstract Three 2′-modified cyclic bis(3′–5′)diadenylic acids (c-di-AMPs) were synthesized from commercially available adenosine phosphoramidites and the effects of c-di-AMP derivatives on the cell division of Chlamydomonas reinhardtii, a kind of freshwater green algae, were investigated. This structure–activity relationship study suggests that the di(2′-O-methyl)-c-di-AMP showed the highest activity and that 2′-substituents influenced the cell division of C. reinhardtii.
Binding of Cibacron blue F3GA to proteins containing the dinucleotide fold. (1976)

A simple, convenient, and sensitive spectrophotometric procedure is described for quantitative measurement of nucleoside phosphate binding sites constructed by the dinucleotide fold. The procedure involves difference spectral titration of such enzymes with the dye Cibacron blue F3GA in a spectral region remote from the intrinsic absorbance of proteins or natural ligands. The titration curves can be analyzed to determine the affinity of nucleoside phosphate binding sites for both the dye and the natural ligand over a potentially wide range of experimental conditions. The interaction of the dye with two proteins which contain the dinucleotide fold, lactate dehydrogenase (L-lactate:NAD+ oxidoreductase, EC 1.1.1.27) and phosphoglycerate kinase (ATP:3-phospho-D-glycerate 1-phosphotransferase, EC 2.7.2.3), is illustrated.
Monoclonal Antibody Process Development Using Medium Concentrates (1994)

A fed-batch process using concentrated medium was evaluated for its ability to improve cell culture longevity and final monoclonal antibody (MAb) titers for two monoclonal antibody producing cell lines. It was found to result in up to 7-fold increases in final antibody titers compared to batch culture controls. Although the development cell line specific fed-batch protocols is critical to the development of cost-efficient large-scale production processes, the use of complete medium concentrates provided us with a quick and simple method for producing large quantities of antibodies in the early stages of process development, thus accelerating early work on purification process development, analytical development, biochemical characterization, and safety studies. Insights gained from the concentrated medium fed-batch approach were valuable for the development of refined, cell line specific feeding strategies yielding final MAb titers on the order of 1-2 g/L. Process development data on the effects of inhibitory growth byproducts, medium osmolarity, and the mode of nutrient feed addition on culture longevity and MAb production and information on culture metabolic behavior were successfully incorporated in the development of the optimized fed-batch protocols.
CXCR4 is a prognostic marker in acute myelogenous leukemia (2006)

CXCR4 chemokine receptors retain hematopoietic progenitors and leukemia cells within the marrow microenvironment. We prospectively evaluated the prognostic implication of CXCR4 in 90 consecutive patients with acute myelogenous leukemia (AML) by flow cytometry. Patients were divided into groups with low (n=32), intermediate (n=26), or high (n=32) CXCR4 expression, as defined by CXCR4 mean fluorescence intensity ratio thresholds of less than 5, 5 to 10, or more than 10, respectively. We found that low CXCR4 expression on AML cells correlated with a better prognosis, resulting in a longer relapse-free and overall survival of 24.3+/-2.9 months for low CXCR4-expressing patients, compared with 17.4+/-3.4 months for intermediate and 12.8+/-2 months (mean+/-SEM) for patients with high expression. In univariate analyses, CXCR4 expression, cytogenetics, white blood cell count, and serum lactate dehydrogenase (LDH) predicted for shorter survival. Multivariate analysis revealed CXCR4 expression and unfavorable cytogenetics as independent prognostic factors. We conclude that CXCR4 expression in AML is an independent prognostic predictor for disease relapse and survival that can rapidly and easily be determined at disease presentation. These findings warrant further investigation into the role of CXCR4 in AML and suggest that CXCR4 should be incorporated into the risk assessment of AML patients.
Cold-adapted poliovirus mutants bypass a postentry replication block (1997)

In the current model of poliovirus entry, the initial interaction of the native virion with its cellular receptor is followed by a transition to an altered form, which then acts as an intermediate in viral entry. While the native virion sediments at 160S in a sucrose gradient, the altered particle sediments at 135S, has lost the coat protein VP4, and has become more hydrophobic. Altered particles can be found both associated with cells and in the culture medium. It has been hypothesized that the cell-associated 135S particle releases the viral genome into the cell cytoplasm and that nonproductive transitions to the 135S form are responsible for the high particle-to-PFU ratio observed for polioviruses. At 25 degrees C, a temperature at which the transition to 135S particles does not occur, the P1/Mahoney strain of poliovirus was unable to replicate, and cold-adapted (ca) mutants were selected from the population. These mutants have not gained the ability to convert to 135S particles at 25 degrees C, and the block to wild-type (wt) infection at low temperatures is not at the level of cellular entry. The particle-to-PFU ratio of poliovirus does not change at 25 degrees C in the absence of alteration. Three independent amino acid changes in the 2C coding region were identified in ca mutants, at positions 218 (Val to Ile), 241 (Arg to Ala), and 309 (Met to Val). Introduction of any of these mutations individually into wt poliovirus by site-directed mutagenesis confers the ca phenotype. All three serotypes of the Sabin vaccine strains and the P3/Leon strain of poliovirus also exhibit the ca phenotype. These results do not support a model of poliovirus entry into cells that includes an obligatory transition to the 135S particle.
HMG‐CoA reductase inhibitors (statins), inflammation, and endothelial progenitor cells—New mechanistic insights of atherosclerosis (2014)

Statins have been shown to favorably affect the prognosis of patients with risk factors to atherosclerosis-both as a primary and a secondary prevention. The beneficial effects observed with statin therapy are not merely related to changes in lipid profile but also are due to a positive effect on vascular inflammation and on immune-modulation of T lymphocytes and endothelial progenitor stem cells (EPCs). This dual effect has been demonstrated mainly in clinical trials where a change in endothelial function was observed within hours, much earlier than the effects of statins on the lipid profile (weeks). Based on all the knowledge that we have today questions were raised as to the mechanistic pathways that may explain the process of atherosclerosis and through this pathway to find better solutions and therapies to prevent and fight atherosclerosis. Our review will focus on the new updates in the field of inflammation and stem cells in vascular biology-in relation with atherosclerosis.
Conditional Lethality of Null Mutations in RTH1 That Encodes the Yeast Counterpart of a Mammalian 5′- to 3′-Exonuclease Required for Lagging Strand DNA Synthesis in Reconstituted Systems (1995)

A 5'- to 3'-exonuclease of about 45 kDa has been purified from various mammalian sources and shown to be required for the completion of lagging strand synthesis in reconstituted DNA replication systems. RTH1 encodes the yeast Saccharomyces cerevisiae counterpart of the mammalian enzyme. To determine the in vivo biological role of RTH1-encoded 5'- to 3'-exonuclease, we have examined the effects of an rth1 delta mutation on various cellular processes. rth1 delta mutants grow poorly at 30 degrees C, and a cessation in growth occurs upon transfer of the mutant to 37 degrees C. At the restrictive temperature, the rth1 delta mutant exhibits a terminal cell cycle morphology similar to that of mutants defective in DNA replication, and levels of spontaneous mitotic recombination are elevated in the rth1 delta mutant even at the permissive temperature. The rth1 delta mutation does not affect UV or gamma-ray sensitivity but enhances sensitivity to the alkylating agent methyl methanesulfonate. The role of RTH1 in DNA replication and in repair of alkylation damage is discussed.
Branch nucleophile selection in pre-mRNA splicing: evidence for the bulged duplex model. (1994)

Selection of the nucleophile for the first step of nuclear pre-mRNA splicing was probed by site-specific incorporation into splicing substrates of nucleotides modified at the 2' position. The differing abilities of ribose, 2'-deoxyribose, and arabinose nucleotides to base-pair within an RNA.RNA duplex and to contribute a nucleophilic 2'-OH group were exploited to analyze the paired/unpaired disposition of the branch site nucleotide. The results provide direct evidence for a bulged duplex model in which either of two adjacent purines within the consensus branch site sequence may shift into a bulged position and contribute the 2'-OH group for the first step of splicing. Furthermore, the presence of a consensus branch site that cannot present a reactive nucleophile suppresses splicing, including the use of cryptic branch sites elsewhere. We conclude that the branch site region base-pairing with U2 snRNA determines the first step nucleophile and persists at the time of the first transesterification reaction.
Coupled Wave Theory for Thick Hologram Gratings (1969)

A coupled wave analysis is given of the Bragg diffraction of light by thick hologram gratings, which is analogous to Phariseau's treatment of acoustic gratings and to the “dynamical” theory of X-ray diffraction. The theory remains valid for large diffraction efficiencies where the incident wave is strongly depleted. It is applied to transmission holograms and to reflection holograms. Spatial modulations of both the refractive index and the absorption constant are allowed for. The effects of loss in the grating and of slanted fringes are also considered. Algebraic formulas and their numerical evaluations are given for the diffraction efficiencies and the angular and wavelength sensitivities of the various hologram types.
Polymer-supported solution synthesis of oligosaccharides (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPolymer-supported solution synthesis of oligosaccharidesStephen P. Douglas, Dennis M. Whitfield, and Jiri J. KrepinskyCite this: J. Am. Chem. Soc. 1991, 113, 13, 5095–5097Publication Date (Print):June 1, 1991Publication History Published online1 May 2002Published inissue 1 June 1991https://pubs.acs.org/doi/10.1021/ja00013a075https://doi.org/10.1021/ja00013a075research-articleACS PublicationsRequest reuse permissionsArticle Views522Altmetric-Citations122LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Self‐Assembly of a Tripod Aromatic Rod into Stacked Planar Networks (2015)

Threefold symmetric rigid-core molecules with an internally grafted poly(ethylene oxide) (PEO) chain were synthesized, and their self-assembled structures were characterized using differential scanning calorimetry, TEM, and 1D and 2D X-ray scatterings in the solid state. The tripod compounds based on short PEO chains (n=8, 13, 17, 21), self-assemble into 2D channel-like network structures, whereas the compound with the longest PEO chain (n=34) forms a lamellar liquid crystalline phase. The interiors of the channel structures are filled with flexible PEO chains along the double-walled aromatic circumference. In these channel-like networks, three aromatic rods connected in the meta-position to each other are superimposed in parallel to other adjacent molecules to form the double-walled aromatic frameworks stacked perpendicular to the resulting channels. These are novel examples of supramolecular channel-like structures developed using amphiphilic diblock molecules based on a threefold symmetric rigid scaffold.
The role of oxidative damage in the neuropathology of organic acidurias: Insights from animal studies (2004)

Organic acidurias represent a group of inherited disorders resulting from deficient activity of specific enzymes of the catabolism of amino acids, carbohydrates or lipids, leading to tissue accumulation of one or more carboxylic (organic) acids. Patients affected by organic acidurias predominantly present neurological symptoms and structural brain abnormalities, of which the aetiopathogenesis is poorly understood. However, in recent years increasing evidence has emerged suggesting that oxidative stress is possibly involved in the pathology of some organic acidurias and other inborn errors of metabolism. This review addresses some of the recent developments obtained mainly from animal studies indicating oxidative damage as an important determinant of the neuropathophysiology of some organic acidurias. Recent data showing that various organic acids are capable of inducing free radical generation and decreasing brain antioxidant defences is presented. The discussion focuses on the relatively low antioxidant defences of the brain and the vulnerability of this tissue to reactive species. This offers new perspectives for potential therapeutic strategies for these disorders, which may include the early use of appropriate antioxidants as a novel adjuvant therapy, besides the usual treatment based on removing toxic compounds and using special diets and pharmacological agents, such as cofactors and L-carnitine.
Lysine acetylation and the bromodomain: a new partnership for signaling (2004)

Lysine acetylation has been shown to occur in many protein targets, including core histones, about 40 transcription factors and over 30 other proteins. This modification is reversible in vivo, with its specificity and level being largely controlled by signal-dependent association of substrates with acetyltransferases and deacetylases. Like other covalent modifications, lysine acetylation exerts its effects through "loss-of-function" and "gain-of-function" mechanisms. Among the latter, lysine acetylation generates specific docking sites for bromodomain proteins. For example, bromodomains of Gcn5, PCAF, TAF1 and CBP are able to recognize acetyllysine residues in histones, HIV Tat, p53, c-Myb or MyoD. In addition to the acetyllysine moiety, the flanking sequences also contribute to efficient recognition. The relationship between acetyllysine and bromodomains is reminiscent of the specific recognition of phosphorylated residues by phospho-specific binding modules such as SH2 domains and 14-3-3 proteins. Therefore, lysine acetylation forges a novel signaling partnership with bromodomains to govern the temporal and spatial regulation of protein functions in vivo.
Calcium, ATP, and ROS: a mitochondrial love-hate triangle (2004)

The mitochondrion is at the core of cellular energy metabolism, being the site of most ATP generation. Calcium is a key regulator of mitochondrial function and acts at several levels within the organelle to stimulate ATP synthesis. However, the dysregulation of mitochondrial Ca(2+) homeostasis is now recognized to play a key role in several pathologies. For example, mitochondrial matrix Ca(2+) overload can lead to enhanced generation of reactive oxygen species, triggering of the permeability transition pore, and cytochrome c release, leading to apoptosis. Despite progress regarding the independent roles of both Ca(2+) and mitochondrial dysfunction in disease, the molecular mechanisms by which Ca(2+) can elicit mitochondrial dysfunction remain elusive. This review highlights the delicate balance between the positive and negative effects of Ca(2+) and the signaling events that perturb this balance. Overall, a "two-hit" hypothesis is developed, in which Ca(2+) plus another pathological stimulus can bring about mitochondrial dysfunction.
Protein partners of deubiquitinating enzymes (2008)

Protein modification by ubiquitin and ubiquitin-like molecules is a critical regulatory process. Like most regulated protein modifications, ubiquitination is reversible. Deubiquitination, the reversal of ubiquitination, is quickly being recognized as an important regulatory strategy. Nearly one hundred human DUBs (deubiquitinating enzymes) in five different gene families oppose the action of several hundred ubiquitin ligases, suggesting that both ubiquitination and its reversal are highly regulated and specific processes. It has long been recognized that ubiquitin ligases are modular enzyme systems that often depend on scaffolds and adaptors to deliver substrates to the catalytically active macromolecular complex. Although many DUBs bind ubiquitin with reasonable affinities (in the nM to microM range), a larger number have little affinity but exhibit robust catalytic capability. Thus it is apparent that these DUBs must acquire their substrates by binding the target protein in a conjugate or by associating with other macromolecular complexes. We would then expect that a study of protein partners of DUBs would reveal a variety of substrates, scaffolds, adaptors and ubiquitin receptors. In the present review we suggest that, like ligases, much of the regulation and specificity of deubiquitination arises from the association of DUBs with these protein partners.
Dose-Fractionated Radioimmunotherapy in Non-Hodgkin's Lymphoma Using DOTA-Conjugated, 90Y-Radiolabeled, Humanized Anti-CD22 Monoclonal Antibody, Epratuzumab (2005)

Radioimmunotherapy with weekly 185 MBq/m2 [90Y]epratuzumab achieved a high objective response rate (62%) across lymphoma subtypes, including durable CRs. The findings that three weekly infusions (555 MBq/m2, total dose) can be administered safely with only minor toxicity, that antibody levels increased during treatment weeks, and that therapeutic response predominantly occurs in patients with unequivocal CD22 tumor expression provide guidance for future studies.
Salicylic Acid Decreases Extracellular Biofilm Production by Staphylococcus epidermidis: Electron Microscopic Analysis (1993)

Journal Article Salicylic Acid Decreases Extracellular Biofilm Production by Staphylococcus epidermidis: Electron Microscopic Analysis Get access Saul Teichberg, Saul Teichberg Departments of Pediatrics, Laboratories, and Medicine, North Shore University Hospital-Cornell Medical College, Manhasset, New York Search for other works by this author on: Oxford Academic PubMed Google Scholar Bruce F. Farber, Bruce F. Farber Departments of Pediatrics, Laboratories, and Medicine, North Shore University Hospital-Cornell Medical College, Manhasset, New York Reprints or correspondence: Dr. Bruce F. Farber, Division of Infectious Disease, North Shore University Hospital-Cornell University Medical College, 300 Community Dr., Manhasset, NY 11030. Search for other works by this author on: Oxford Academic PubMed Google Scholar Arlene G. Wolff, Arlene G. Wolff Departments of Pediatrics, Laboratories, and Medicine, North Shore University Hospital-Cornell Medical College, Manhasset, New York Search for other works by this author on: Oxford Academic PubMed Google Scholar Beth Roberts Beth Roberts Departments of Pediatrics, Laboratories, and Medicine, North Shore University Hospital-Cornell Medical College, Manhasset, New York Search for other works by this author on: Oxford Academic PubMed Google Scholar The Journal of Infectious Diseases, Volume 167, Issue 6, June 1993, Pages 1501–1503, https://doi.org/10.1093/infdis/167.6.1501 Published: 01 June 1993
Learned helplessness: Theory and evidence. (1976)

\, SUMMARY In 1967, Overmier and Seligman found that dogs exposed to inescapable and unavoidable electric shocks in one situation later failed to learn to escape shock in a different situation where escape was possible. Shortly thereafter Seligman and Maier (1967) demonstrated that this effect was caused by the uncontrollability of the original shocks. In this article we review the effects of exposing organisms to aversive events which they cannot control, and we review the explanations which have been offered. There seem to be motivational, cognitive, and emotional effects of uncontrollability. (a) Motivation. Dogs that have been exposed to inescapable shocks do not subsequently initiate escape response in the presence of shock. We review parallel phenomena in cats, fish, rats, and man. Of particular interest is the discussion of learned helplessness in rats and man. Rats are of interest because learned helplessness has been difficult to demonstrate in rats. However, we show that inescapably shocked rats do fail to learn to escape if the escape task is reasonably difficult. With regard to man, we review a variety of studies using inescapable noise and unsolvable problems as agents which produce learned helplessness effects on both instrumental and cognitive tasks, (b) Cognition. We argue that exposure to uncontrollabl e events interferes with the organism's tendency to perceive contingent relationships between its behavior and outcomes. Here we review a variety of studies showing such a cognitive set. (c) Emotion. We review a variety of experiments which show that uncontrollable aversive events produce greater emotional disruption than do controllable aversive events. We have proposed an explanation for these effects, which we call the learned helplessness hypothesis. It argues that when events are uncontrollable the organism learns that its behavior and outcomes are independent, and that this learning produces the motivational, cognitive, and emotional effects of uncontrollabi lity. We describe the learned helplessness hypothesis and research which supports it. Finally, we describe and discuss in detail alternative hypotheses which have been offered as accounts of the learned helplessness effect. One set of hypotheses argues that organisms learn motor responses during exposure to uncontrollabl e shock that compete with the response required in the test task. Another explanation holds that uncontrollable shock is a severe stressor and depletes a neurochemical necessary for the mediation of movement. We examine the logical structure of these explanations and present a variety of evidence which bears on them directly.
Imaging Hypoxia in Orthotopic Rat Liver Tumors with Iodine 124–labeled Iodoazomycin Galactopyranoside PET (2008)

Regions of high (124)I-IAZGP uptake in orthotopic rat liver tumors are consistent with independent measures of hypoxia; visualization of hypoxia with (124)I-IAZGP PET is optimal 6 hours after injection.