gebhart/patrepeval huggingface dataset:
Glyceraldehyde-3-phosphate dehydrogenase from the hyperthermophilic archaebacterium Pyrococcus woesei: characterization of the enzyme, cloning and sequencing of the gene, and expression in Escherichia coli (1990)

The glyceraldehyde-3-phosphate dehydrogenase from the hyperthermophilic archaebacterium Pyrococcus woesei (optimal growth temperature, 100 to 103 degrees C) was purified to homogeneity. This enzyme was strictly phosphate dependent, utilized either NAD+ or NADP+, and was insensitive to pentalenolactone like the enzyme from the methanogenic archaebacterium Methanothermus fervidus. The enzyme exhibited a considerable thermostability, with a 44-min half-life at 100 degrees C. The amino acid sequence of the glyceraldehyde-3-phosphate dehydrogenase from P. woesei was deduced from the nucleotide sequence of the coding gene. Compared with the enzyme homologs from mesophilic archaebacteria (Methanobacterium bryantii, Methanobacterium formicicum) and an extremely thermophilic archaebacterium (Methanothermus fervidus), the primary structure of the P. woesei enzyme exhibited a strikingly high proportion of aromatic amino acid residues and a low proportion of sulfur-containing residues. The coding gene of P. woesei was expressed at a high level in Escherichia coli, thus providing an ideal basis for detailed structural and functional studies of that enzyme.
Concise Review: MSC-Derived Exosomes for Cell-Free Therapy (2017)

Mesenchymal stem cell transplantation is undergoing extensive evaluation as a cellular therapy in human clinical trials. Because MSCs are easily isolated and amenable to culture expansion in vitro there is a natural desire to test MSCs in many diverse clinical indications. This is exemplified by the rapidly expanding literature base that includes many in vivo animal models. More recently, MSC-derived extracellular vesicles (EVs), which include exosomes and microvesicles (MV), are being examined for their role in MSC-based cellular therapy. These vesicles are involved in cell-to-cell communication, cell signaling, and altering cell or tissue metabolism at short or long distances in the body. The exosomes and MVs can influence tissue responses to injury, infection, and disease. MSC-derived exosomes have a content that includes cytokines and growth factors, signaling lipids, mRNAs, and regulatory miRNAs. To the extent that MSC exosomes can be used for cell-free regenerative medicine, much will depend on the quality, reproducibility, and potency of their production, in the same manner that these parameters dictate the development of cell-based MSC therapies. However, the MSC exosome's contents are not static, but rather a product of the MSC tissue origin, its activities and the immediate intercellular neighbors of the MSCs. As such, the exosome content produced by MSCs appears to be altered when MSCs are cultured with tumor cells or in the in vivo tumor microenvironment. Therefore, careful attention to detail in producing MSC exosomes may provide a new therapeutic paradigm for cell-free MSC-based therapies with decreased risk. Stem Cells 2017;35:851-858.
Treatment update: nonallergic rhinitis. (2002)

Chronic nonallergic rhinitis is a diagnosis of exclusion. The pathophysiology underlying this disorder is unknown. There probably are several mechanisms involved and several different variations of this condition. Therapies which have been approved for use in the treatment of chronic nonallergic rhinitis include topical corticosteroids and azelastine. Topical corticosteroid preparations that have received approval are fluticasone, budesonide, and beclomethasone. Topical nasal saline also has been established as a beneficial adjunct to therapy in some instances. Other therapies have included capsaicin, silver nitrate, botulin toxin, and various surgical procedures. These procedures include turbinate reduction, which has been performed by a number of techniques including submucosal diathermy, cryosurgery, laser cautery, and classic resection. Ethmoidal and vidian neurectomies have been performed by excision, diathermy, and cryotherapy. These procedures have met with varying degrees of success.
Incidence of Tardive Dyskinesia With Atypical Versus Conventional Antipsychotic Medications (2010)

The incidence of tardive dyskinesia with recent exposure to atypical antipsychotics alone was more similar to that for conventional antipsychotics than in most previous studies. Despite high penetration of atypical antipsychotics into clinical practice, the incidence and prevalence of tardive dyskinesia appeared relatively unchanged since the 1980s. Clinicians should continue to monitor for tardive dyskinesia, and researchers should continue to pursue efforts to treat or prevent it.
Validation Study of a Quantitative Multigene Reverse Transcriptase–Polymerase Chain Reaction Assay for Assessment of Recurrence Risk in Patients With Stage II Colon Cancer (2011)

The continuous 12-gene RS has been validated in a prospective study for assessment of recurrence risk in patients with stage II colon cancer after surgery and provides prognostic value that complements T stage and MMR. The TS was not predictive of chemotherapy benefit.
Experience with the elective transfer of two embryos under the conditions of the German embryo protection law: results of a retrospective data analysis of 2573 transfer cycles (2000)

The German embryo protection law (Embryonenschutzgesetz, ESchG) does not allow embryo selection. Therefore, only as many oocytes at the pronuclear stage (PN), as are planned to be transferred, are allowed to be cultured. It is not known whether, under these conditions, it is possible to reduce the number of embryos for transfer without a corresponding reduction of the overall pregnancy rate (PR). We retrospectively analysed 2573 consecutive transfer cycles following either in-vitro fertilization (IVF) or IVF/intracytoplasmic sperm injection. Out of these cycles, 234, 329 and 792 were performed with one, two, and three embryos respectively, because only that number was available (non-elective transfer). Another 123 and 1095 transfer cycles were performed with two and three embryos, respectively, which were selected from a higher number of PN oocytes (elective transfer). The clinical ongoing PR were 3.9, 9.1 and 17.7% respectively for the groups with non-elective transfer of 1, 2 and 3 embryos, and 22.0 and 22.5% for the groups with elective transfers with two and three embryos, respectively. There was no statistically significant difference in PR between the two elective embryo transfer groups up to the age of 40 years. The multiple pregnancy rate was reduced by 7.9%. The reduction of the number of embryos transferred from three to two can be performed even under the conditions of the ESchG without an effect on the overall PR.
Designing bimetallic catalysts for a green and sustainable future (2012)

This Critical Review provides an overview of the recent developments in the synthesis and characterization of bimetallic nanoparticles. Initially the review follows a materials science perspective on preparing bimetallic nanoparticles with designer morphologies, after which the emphasis shifts towards recent developments in using these bimetallic particles for catalysing either oxidation or reduction. In the final part of this review we present an overview of the utilization of bimetallic catalyst systems for the transformation of bio-renewable substrates and reactions related to the realization of a bio-refinery. Because of the sheer number of examples of transformations in this area, a few key examples, namely selective oxidation, hydrogenation/hydrogenolysis and reforming of biomass derived molecules, have been chosen for this review. Reports of bimetallic catalysts being used for the aforementioned transformations are critically analysed and the potential for exploiting such bimetallic catalysts have also been highlighted. A specific objective of this review article is to motivate researchers to synthesize some of the "designer" bimetallic catalysts with specific nanostructures, inspired from recent advances in the area of materials chemistry, and to utilize them for the transformation of biomass derived materials that are very complex and pose different challenges compared to those of simple organic molecules. We consider that supported bimetallic nanoparticles have an important role to play as catalysts in our quest for a more green and sustainable society.
Dithiobenzoatotetracarbonylmanganese(I) (1964)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDithiobenzoatotetracarbonylmanganese(I)Irwin A. Cohen and Fred BasoloCite this: Inorg. Chem. 1964, 3, 11, 1641–1642Publication Date (Print):November 1, 1964Publication History Published online1 May 2002Published inissue 1 November 1964https://pubs.acs.org/doi/10.1021/ic50021a039https://doi.org/10.1021/ic50021a039research-articleACS PublicationsRequest reuse permissionsArticle Views73Altmetric-Citations15LEARN 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
The Transfer of Heavy Chains from Bikunin Proteins to Hyaluronan Requires Both TSG-6 and HC2 (2008)

Tumor necrosis factor-stimulated gene-6 protein (TSG-6) is involved in the transfer of heavy chains (HCs) from inter-alpha-inhibitor (IalphaI), pre-alpha-inhibitor, and as shown here HC2.bikunin to hyaluronan through the formation of covalent HC.TSG-6 intermediates. In contrast to IalphaI and HC2.bikunin, pre-alpha-inhibitor does not form a covalent complex in vitro using purified proteins but needs the presence of another factor (Rugg, M. S., Willis, A. C., Mukhopadhyay, D., Hascall, V. C., Fries, E., Fülöp, C., Milner, C. M., and Day, A. J. (2005) J. Biol. Chem. 280, 25674-25686). In the present study we purified the required component from human plasma and identified it as HC2. Proteins containing HC2 including IalphaI, HC2.bikunin, and free HC2 promoted the formation of HC3.TSG-6 and subsequently HC3.hyaluronan complexes. HC1 or HC3 did not possess this activity. The presented data reveal that both HC2 and TSG-6 are required for the transesterification reactions to occur.
Experimental anti-tumor therapy in 3-D: Spheroids – old hat or new challenge? (2007)

Cell-based assays have become an integral component in many stages of routine anti-tumor drug testing. However, they are almost always based on homogenous monolayer or suspension cultures and thus represent a rather artificial cellular environment. 3-D cultures--such as the well established spheroid culture system--better reflect the in vivo behavior of cells in tumor tissues and are increasingly recognized as valuable advanced tools for evaluating the efficacy of therapeutic intervention. The present article summarizes past and current applications and particularly discusses technological challenges, required improvements and recent progress with the use of the spheroid model in experimental therapeutics, as a basis for sophisticated drug/therapy screening. A brief overview is given focusing on the nomenclature of spherical 3-D cultures, their potential to mimic many aspects of the pathophysiological situation in tumors, and currently available protocols for culturing and analysis. A list of spheroid-forming epithelial cancer cell lines of different origin is provided and the recent trend to use spheroids for testing combination treatment strategies is highlighted. Finally, various spheroid co-culture approaches are presented that have been established to study heterologous cell interactions in solid tumors and thereby are able to reflect the cellular tumor environment with increasing accuracy. The intriguing observation that in order to retain certain tumor initiating cell properties, some primary tumor cell populations must be maintained exclusively in 3-D culture is mentioned, adding a new but fascinating challenge for future therapeutic campaigns.
Induction of intercellular adhesion molecule 1 on primary and continuous cell lines by pro-inflammatory cytokines. Regulation by pharmacologic agents and neutralizing antibodies. (1988)

The expression of intercellular adhesion molecule-1 (ICAM-1) on primary human fibroblasts, a human fibrosarcoma, chondrosarcoma, and adenocarcinoma cell line in response to IL-1, TNF-alpha, or IFN-gamma was studied using an ELISA with anti-ICAM-1 mAb. The induction of ICAM-1 by these cytokines was neutralized by cytokine-specific antisera as well as some steroids and the glycosylation inhibitor, tunicamycin. Cyclohexamide up-regulated the expression of ICAM-1 on chondrosarcoma cells but had little or no effect on carcinoma cells. These data indicate different mechanisms in the regulation and expression of ICAM-1 on the various cell types and provide some insight into the anti-inflammatory effects of some pharmacologic agents.
The Role of Tau in Neurodegenerative Diseases and Its Potential as a Therapeutic Target (2012)

The abnormal deposition of proteins in and around neurons is a common pathological feature of many neurodegenerative diseases. Among these pathological proteins, the microtubule-associated protein tau forms intraneuronal filaments in a spectrum of neurological disorders. The discovery that dominant mutations in the MAPT gene encoding tau are associated with familial frontotemporal dementia strongly supports abnormal tau protein as directly involved in disease pathogenesis. This and other evidence suggest that tau is a worthwhile target for the prevention or treatment of tau-associated neurodegenerative diseases, collectively called tauopathies. However, it is critical to understand the normal biological roles of tau, the specific molecular events that induce tau to become neurotoxic, the biochemical nature of pathogenic tau, the means by which pathogenic tau exerts neurotoxicity, and how tau pathology propagates. Based on known differences between normal and abnormal tau, a number of approaches have been taken toward the discovery of potential therapeutics. Key questions still remain open, such as the nature of the connection between the amyloid- β protein of Alzheimer's disease and tau pathology. Answers to these questions should help better understand the nature of tauopathies and may also reveal new therapeutic targets and strategies.
Islet Amyloid: A Critical Entity in the Pathogenesis of Type 2 Diabetes (2004)

Islet amyloid deposition is a pathogenic feature of type 2 diabetes, and these deposits contain the unique amyloidogenic peptide islet amyloid polypeptide. Autopsy studies in humans have demonstrated that islet amyloid is associated with loss of beta-cell mass, but a direct role for amyloid in the pathogenesis of type 2 diabetes cannot be inferred from such studies. Animal studies in both spontaneous and transgenic models of islet amyloid formation have shown that amyloid forms in islets before fasting hyperglycemia and therefore does not arise merely as a result of the diabetic state. Furthermore, the extent of amyloid deposition is associated with both loss of beta-cell mass and impairment in insulin secretion and glucose metabolism, suggesting a causative role for islet amyloid in the islet lesion of type 2 diabetes. These animal studies have also shown that beta-cell dysfunction seems to be an important prerequisite for islet amyloid formation, with increased secretory demand from obesity and/or insulin resistance acting to further increase islet amyloid deposition. Recent in vitro studies suggest that the cytotoxic species responsible for islet amyloid-induced beta-cell death are formed during the very early stages of islet amyloid formation, when islet amyloid polypeptide aggregation commences. Interventions to prevent islet amyloid formation are emerging, with peptide and small molecule inhibitors being developed. These agents could thus lead to a preservation of beta-cell mass and amelioration of the islet lesion in type 2 diabetes.
Magnetic resonance studies of polypeptides adsorbed on silica and hydroxyapatite surfaces (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMagnetic resonance studies of polypeptides adsorbed on silica and hydroxyapatite surfacesVeronica L. Fernandez, Jeffrey A. Reimer, and Morton M. DennCite this: J. Am. Chem. Soc. 1992, 114, 24, 9634–9642Publication Date (Print):November 1, 1992Publication History Published online1 May 2002Published inissue 1 November 1992https://pubs.acs.org/doi/10.1021/ja00050a051https://doi.org/10.1021/ja00050a051research-articleACS PublicationsRequest reuse permissionsArticle Views270Altmetric-Citations53LEARN 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
Methylthioadenosine Reprograms Macrophage Activation through Adenosine Receptor Stimulation (2014)

Regulation of inflammation is necessary to balance sufficient pathogen clearance with excessive tissue damage. Central to regulating inflammation is the switch from a pro-inflammatory pathway to an anti-inflammatory pathway. Macrophages are well-positioned to initiate this switch, and as such are the target of multiple therapeutics. One such potential therapeutic is methylthioadenosine (MTA), which inhibits TNFα production following LPS stimulation. We found that MTA could block TNFα production by multiple TLR ligands. Further, it prevented surface expression of CD69 and CD86 and reduced NF-KB signaling. We then determined that the mechanism of this action by MTA is signaling through adenosine A2 receptors. A2 receptors and TLR receptors synergized to promote an anti-inflammatory phenotype, as MTA enhanced LPS tolerance. In contrast, IL-1β production and processing was not affected by MTA exposure. Taken together, these data demonstrate that MTA reprograms TLR activation pathways via adenosine receptors to promote resolution of inflammation.
SELECTIVE COGNITIVE IMPAIRMENT DURING FOCAL AND GENERALIZED EPILEPTIFORM EEG ACTIVITY (1984)

It is well established that generalized epileptiform EEG discharges unaccompanied by overt clinical change may nevertheless be associated with transitory cognitive impairment (TCI) detectable by appropriate psychological testing. However, the tests employed in most research studies of this phenomenon are of little use for routine clinical application. They are suitable for administration only over short periods of time and are therefore applicable only to patients with a high discharge rate, a serious limitation, as the discharges are generally depressed by the tests themselves. We have developed two short-term memory tasks, one using verbal, the other nonverbal material presented in the form of television games which patients are generally prepared to perform for up to an hour or longer. Forty-six patients with subclinical EEG discharges have been studied. They were screened by video monitoring before and during testing to exclude any with overt clinical changes during the discharges. Despite this rigorous selection, in 50 per cent TCI was demonstrable with a confidence level (within the individual patient) of 10 per cent. Discharges during stimulus presentation were most disruptive of performance and those confined to the period when the patient was responding were without demonstrable effect. A significant association was found between the laterality of focal or asymmetrical generalized discharges and impairment of one or other task, left-sided discharges being associated with errors in the verbal task and right-sided with impairment of the nonverbal test. Two case histories are cited illustrating patients who were clearly handicapped by TCI and whose functioning improved when the subclinical discharges were suppressed by medication. To determine how many patients suffer such disabilities or can be helped by appropriate medication, further prospective studies are required.
Synthesis and Characterization of PAMAM Dendrimer-Based Multifunctional Nanodevices for Targeting α v β 3 Integrins (2007)

We have synthesized a stable and clinically relevant nanodevice (cRGD-BT-ND; ND for short) that exhibits superior binding to the biologic target alphavbeta3 integrins, when either compared to the same free cRGD peptide or to the biotinylated nanodevice without covalently attached peptides (BT-ND). Selective targeting of alphavbeta3 integrins was achieved by coupling cyclic cRGD peptides to the nanodevice (ND) surface, while biotin groups (BT) were used for amplified detection of bound cRGD-BT-ND by anti-biotin antibody or avidin linked to horseradish peroxidase after binding. The synthesis involved the following steps: the amino-terminated ethylenediamine core generation 5 poly(amidoamine) (PAMAM_E5.NH2) dendrimer was first partially acetylated and then biotinylated, and residual primary amine termini were converted to succinamic acid groups (SAH), some of which finally were conjugated with cRGD peptide residues through the amino group of the lysine side chain. The starting material and all derivatives were extensively characterized by polyacrylamide gel electrophoresis (PAGE), size exclusion chromatography (SEC), potentiometric acid-base titration, MALDI-TOF, and NMR. Cytotoxicity of all dendrimer derivatives was examined in B16F10 melanoma cell cultures using the XTT colorimetric assay for cellular viability. Binding of nanodevices to the biological target was determined using plates coated with human alphavbeta3 integrin and alphavbeta3 receptor expressing human dermal microvascular endothelial cells (HDMECs). The PAMAM_E5.(NHAc)72(NHBT)8(NHSAH)35(NHSA-cR GD)4 nanodevice is nontoxic within physiologic concentration ranges and specifically binds to the alphavbeta3 integrins, apparently much stronger than the cyclic cRGD peptide itself.