gebhart/patrepeval huggingface dataset:
Pathogenesis of Fasting and Postprandial Hyperglycemia in Type 2 Diabetes: Implications for Therapy (2010)

The objective of this research is to gain a greater understanding of the cause of fasting and postprandial hyperglycemia in people with type 2 diabetes. Endogenous glucose production is excessive before eating and fails to appropriately suppress after eating in people with type 2 diabetes. This is due in part to impaired insulin-induced suppression of endogenous glucose production, which is observed early in the evolution of type 2 diabetes. Increased rates of gluconeogenesis and perhaps glycogenolysis contribute to hepatic insulin resistance. Insulin-induced stimulation of hepatic glucose uptake and hepatic glycogen synthesis are reduced in people with type 2 diabetes primarily due to decreased uptake of extracellular glucose presumably because of inadequate activation of hepatic glucokinase. Delayed insulin secretion results in higher peak glucose concentrations particularly when suppression of glucagon is impaired, whereas insulin resistance prolongs the duration of hyperglycemia, which can be marked when both hepatic and extra-hepatic insulin resistance are present. The premise of these studies, as well as those performed by many other investigators, is that an understanding of the pathogenesis of type 2 diabetes will enable the development of targeted therapies that are directed toward correcting specific metabolic defects in a given individual. I, as well as many other investigators, believe that such therapies are likely to be more effective and to have a lower risk than would occur if everyone were treated the same regardless of the underlying cause of their hyperglycemia. While we do not yet have sufficient knowledge to truly individualize therapy, in my opinion this approach will be the norm in the not too distant future.
Logistic Regression, Conditional (2014)

Abstract This section describes the conditional logistic regression model. This model is appropriate when one wishes to model a binary outcome variable with matched or highly stratified data and when one is not interested in matched sets or stratum effects. The resulting fitted model may be used to estimate odds ratios in the same manner as is done with the usual logistic regression model. Examples of estimation and interpretation are given.
mTOR Inhibitors Alone and in Combination with JAK2 Inhibitors Effectively Inhibit Cells of Myeloproliferative Neoplasms (2013)

These findings support mTOR inhibitors as novel potential drugs for the treatment of MPN and advocate for clinical trials exploiting the combination of mTOR and JAK2 inhibitor.
Structure-Based Design, Synthesis, and Biological Evaluation of Irreversible Human Rhinovirus 3C Protease Inhibitors. 6. Structure−Activity Studies of Orally Bioavailable, 2-Pyridone-Containing Peptidomimetics (2002)

The structure-based design, chemical synthesis, and biological evaluation of various 2-pyridone-containing human rhinovirus (HRV) 3C protease (3CP) inhibitors are described. These compounds are comprised of a peptidomimetic binding determinant and a Michael acceptor moiety, which forms an irreversible covalent adduct with the active site cysteine residue of the 3C enzyme. The 2-pyridone-containing inhibitors typically display improved 3CP inhibition properties relative to related peptide-derived molecules along with more favorable antiviral properties. The cocrystal structure of one pyridone-derived 3CP inhibitor complexed with HRV-2 3CP is also described along with certain ab initio conformation analyses. Optimization of the 2-pyridone-containing compounds is shown to provide several highly active 3CP inhibitors (k(obs)/[I] > 500,00 M(-1) s(-1)) that function as potent antirhinoviral agents (EC(50) = <0.05 microM) against multiple virus serotypes in cell culture. One 2-pyridone-containing 3CP inhibitor is shown to be bioavailable in the dog after oral dosing (F = 48%).
A Gain-of-Function Mutation in the HIF2A Gene in Familial Erythrocytosis (2008)

Hypoxia-inducible factor (HIF) alpha, which has three isoforms, is central to the continuous balancing of the supply and demand of oxygen throughout the body. HIF-alpha is a transcription factor that modulates a wide range of processes, including erythropoiesis, angiogenesis, and cellular metabolism. We describe a family with erythrocytosis and a mutation in the HIF2A gene, which encodes the HIF-2alpha protein. Our functional studies indicate that this mutation leads to stabilization of the HIF-2alpha protein and suggest that wild-type HIF-2alpha regulates erythropoietin production in adults.
Nonpeptide antigens, presentation mechanisms, and immunological memory of human Vγ2Vδ2 T cells: discriminating friend from foe through the recognition of prenyl pyrophosphate antigens (2007)

Human Vgamma2Vdelta2 T cells play important roles in mediating immunity against microbial pathogens and have potent anti-tumor activity. Vgamma2Vdelta2 T cells recognize the pyrophosphorylated isoprenoid intermediates (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP), an intermediate in the foreign 2-C-methyl-d-erythritol 4-phosphate (MEP) pathway, and isopentenyl pyrophosphate (IPP), an intermediate in the self-mevalonate pathway. Infection with bacteria and protozoa using the MEP pathway leads to the rapid expansion of Vgamma2Vdelta2 T cells to very high numbers through preferential recognition of HMBPP. Activated Vgamma2Vdelta2 T cells produce proinflammatory cytokines and chemokines, kill infected cells, secrete growth factors for epithelial cells, and present antigens to alphabeta T cells. Vgamma2Vdelta2 T cells can also recognize high levels of IPP in certain tumors and in cells treated with pharmacological agents, such as bisphosphonates and alkylamines, that block farnesyl pyrophosphate synthase. Activated Vgamma2Vdelta2 T cells are able to kill most tumor cells because of recognition by T-cell receptor and natural killer receptors. The ubiquitous nature of the antigens converts essentially all Vgamma2Vdelta2 T cells to memory cells at an early age. Thus, primary infections with HMBPP-producing bacteria are perceived by Vgamma2Vdelta2 T cells as a repeat infection. Extensive efforts are underway to harness these cells to treat a variety of cancers and to provide microbial immunity.
Is clonidine useful for treatment of clozapine-induced sialorrhea? (2005)

Clozapine has shown superior efficacy in treatment of refractory schizophrenia, but its use is limited by emergent side-effects. Among other adverse effects, sialorrhea is a troublesome side-effect, its stigmatizing nature results in poor treatment compliance. Several hypotheses have been put forward in the etiology of clozapine-induced sialorrhea. 2 adrenergic antagonism is hypothesized to be involved in its pathophysiology, based on the response to clonidine and lofexidine. Oral clonidine (50 to 100 g/day) was tried on 12 stable outpatients of schizophrenia maintained on clozapine. Wet area over the pillow as reported by the patients was recorded at baseline and at 4 weeks of treatment along with the subjective response after the treatment. Most of the patients reported a decrease in sialorrhea without any adverse events. We describe encouraging results in an open case series of oral clonidine for clozapine-induced sialorrhea.
Human mononuclear cells contain an endoglycosidase specific for heparan sulphate glycosaminoglycan demonstrable with the use of a specific solid-phase metabolically radiolabelled substrate (1989)

Xyloside-initiated 35SO4(2-)-labelled glycosaminoglycans were isolated from the medium of cultured bovine glomeruli and covalently coupled to Sepharose 4B to construct a solid-phase substrate suitable for the detection of endoglycosidases. The substrate is rendered specific for heparitinase by prior digestion with chondroitin sulphate ABC lyase and is insensitive to proteinase, neuraminidase and hyaluronidase. Normal human mononuclear cells are shown to contain a heparitinase. This enzyme appears to be cell-associated and can be partially purified from human spleen by heparin affinity chromatography.
Arrayed narrow linewidth erbium-doped waveguide-distributed feedback lasers on an ultra-low-loss silicon-nitride platform (2013)

We demonstrate an array of erbium-doped waveguide-distributed feedback lasers on an ultra-low-loss Si(3)N(4) platform. Sidewall gratings providing the lasing feedback are defined in the silicon-nitride layer using 248 nm stepper lithography, while the gain is provided by a reactive co-sputtered erbium-doped aluminum-oxide layer. We observe lasing output over a 12 nm wavelength range (1531-1543 nm) from the array of five separate lasers. Output powers of 8 μW and lasing linewidths of 501 kHz are obtained. Single-mode operation is confirmed, with side-mode suppression ratios over 35 dB for all designs.
ENHANCEMENT OF THE INFECTIVITY OF ARBOVIRUSES BY SPECIFIC ANTISERA PRODUCED IN DOMESTIC FOWLS (1964)

Summary The apparent infectivity of certain arboviruses is increased by the action of specific antisera prepared in domestic fowls when assayed on chick embryo fibroblast (CEF) monolayers or the chorioallantoic membrane of the developing chick embryo. Of the viruses tested, Murray Valley encephalitis (MVE), West Nile (WNV) and Japanese encephalitis viruses from Casals group B, and Getah virus from group A demonstrate this enhancement, but Sindbis and SFV from group A do not. The virus plaque count is increased by up to 12 times the control plaque count, depending on the potency of the antiserum. Enhancement could not be demonstrated with rabbit or mouse antisera to MVE on the CEF monolayer, nor with fowl antiserum on PK‐2a cells or in suckling mice. Cross enhancing activity could be demonstrated between viruses within group B (MVE and WNV), but not between viruses from different groups (MVE and Getah). Preliminary work indicates that 19S antibody is involved, as well as antibody not susceptible to depolymerisation with mercaptoethanol.
Mutant p53 promotes ovarian cancer cell adhesion to mesothelial cells via integrin β4 and Akt signals (2015)

Missense mutations in the TP53 gene resulting in the accumulation of mutant proteins are extremely common in advanced ovarian cancer, which is characterised by peritoneal metastasis. Attachment of cancer cells to the peritoneal mesothelium is regarded as an initial, key step for the metastatic spread of ovarian cancer. In the present study, we investigated the possible role of a p53 mutant in the mesothelial adhesion of ovarian cancer cells. We found that OVCAR-3 cells with the R248 TP53 mutation (p53(R248)) were more adhesive to mesothelial Met5A cells than were A2780 cells expressing wild-type p53. In addition, ectopic expression of p53(R248) in p53-null SKOV-3 cells significantly increased adhesion to Met5A cells. Knockdown of mutant p53 significantly compromised p53(R248)-induced cell adhesion to Met5A cells. Microarray analysis revealed that several adhesion-related genes, including integrin β4, were markedly up-regulated, and certain signalling pathways, including PI3K/Akt, were activated in p53(R248) transfectants of SKOV-3 cells. Inhibition of integrin β4 and Akt signalling using blocking antibody and the inhibitor LY294002, respectively, significantly attenuated p53(R248)-mediated ovarian cancer-mesothelial adhesion. These data suggest that the p53(R248) mutant endows ovarian cancer cells with increased adhesiveness and that integrin β4 and Akt signalling are associated with the mutation-enhanced ovarian cancer-mesothelial cell adhesion.
Rat Muc4 (sialomucin complex) reduces binding of anti‐ErbB2 antibodies to tumor cell surfaces, a potential mechanism for herceptin resistance (2002)

Muc4 (also called sialomucin complex), the rat homolog of human MUC4, is a heterodimeric glycoprotein complex that consists of a peripheral O-glycosylated mucin subunit, ASGP-1, tightly but noncovalently linked to a N-glycosylated transmembrane subunit, ASGP-2. The complex is expressed in a number of normal, vulnerable epithelial tissues, including mammary gland, uterus, colon, cornea and trachea. Muc4/SMC is also overexpressed or aberrantly expressed on a number of human tumors including breast tumors. Overexpression of Muc4/SMC has been shown to block cell-cell and cell-matrix interactions, protect tumor cells from immune surveillance and promote metastasis. In addition, as a ligand for ErbB2, Muc4/SMC can potentiate phosphorylation of ErbB2 and potentially alter signals generated from this receptor. Using A375 human melanoma cells and MCF7 human breast adenocarcinoma cells stably transfected with tetracycline regulatable Muc4, we have investigated whether overexpression of Muc4/SMC can repress antibody binding to cell surface-expressed ErbB2. Overexpression of Muc4/SMC does not affect the level of ErbB2 expression in either cell line, but it does reduce binding of a number of anti-ErbB2 antibodies, including Herceptin. Interestingly, overexpression of ErbB2 does not block binding of other unrelated antibodies of the same isotype, suggesting that the reduction in ErbB2 antibody binding is due to complex formation of Muc4/SMC and ErbB2. Furthermore, capping of Muc4/SMC with anti-Muc4/SMC antibodies reduces antibody binding to ErbB2 instead of increasing binding, again suggesting that reduced antibody binding to ErbB2 is due to steric hindrance from complex formation of Muc4/SMC and ErbB2. Thus, overexpression of Muc4/SMC on tumor cells may have both prognostic and therapeutic relevance.
Effects of Abiraterone Acetate on Androgen Signaling in Castrate-Resistant Prostate Cancer in Bone (2011)

The observed pretreatment androgen-signaling signature is consistent with persistent androgen signaling in CRPC bone metastases. This is the first evidence that abiraterone acetate achieves sustained suppression of testosterone in both blood and bone marrow aspirate to less than picograms-per-milliliter levels. Potential admixture of blood with bone marrow aspirate limits our ability to determine the origin of measured testosterone.
Silicon Direct Opals (2009)

The use of magnesiothermic reduction and CVD to obtain Si spheres is reported. The porous structures of the Si spheres after the former process and the infilling of their pores after the latter one are observed. The optical properties of opals formed with these spheres are used to assess the power of the method and the quality of the final product.
Cell association of complexes of chymase, heparin proteoglycan, and protein after degranulation by rat mast cells. (1981)

Abstract Complexes of chymase, heparin, and certain undefined proteins that reside in rat mast cell secretory granules are poorly soluble in physiologic buffer and remain associated with mast cells after coupled activation and secretion of dissociable soluble mediators, such as β-hexosaminidase and histamine. Purified mast cells activated immunologically or with the calcium ionophore A23187 retain granule core material in cell surface labyrinths as demonstrated by electron microscopy. In order to solubilize and extract this core material, activated mast cells were washed with 1 M NaCI, a procedure that does not impair the integrity of plasma membrane barriers as assessed by the failure to release lactate dehydrogenase (LDH) from resting or activated mast cells. High salt treatment of resting cells caused swelling of cytoplasmic granules, whereas high salt treatment of activated cells caused the extruded granule core material to lose structure and become disassociated from the mast cell surface, as revealed by electron microscopy. Salt treatment of activated mast cells with anti-IgE also increased the net percent release ratios of chymase and heparin to β-hexosaminidase from 0.17 to 0.76 and from 0.24 to 0.51, respectively, indicating either that complexes of heparin and protein were only partially solubilized by the high salt conditions or that there was some re-uptake after release. Furthermore, net protein detected as released material from mast cells activated in a protein deficient medium with A23187 increased from 30 to 53 µg/106 mast cells with salt treatment. Resting and activated mast cells have the same content of chymase activity, 0.56 ± 0.15 U or 24 ± 6 µg, indicating that there is no significant activation of enzyme precursor forms with mast cell activation and that chymase accounts for about 40% of the secretory granule protein in these cells. Twenty-eight micrograms of heparin and 1.3 U of β-hexosaminidase (&amp;lt;1 µg) were also detected in 106 mast cells. Thus, approximately one-half of the secretory granule proteins are functionally undefined, and these as well as the concentration and prolonged presentation of complexes containing heparin and chymase at the cell surface of activated mast cells may be important in the chronicity of the host response to mast cell activation.
HsMCM6: a new member of the human MCM/P1 family encodes a protein homologous to fission yeast Mis5 (1997)

The results indicate that the behaviour of HsMcm6 is reminiscent of replication licensing factor like other Mcm/P1 family members.
Functional Genomics: It's All How You Read It (1997)

Hieter and Boguski describe the new era of functional genomics that is being entered as the mapping and sequencing (structural genomics) phase of the Human Genome Project draws to a close. Functional genomics involves the development of global experimental approaches for analyzing gene function by utilizing information and reagents provided by structural genomics. Functional genomic data needs to be generated by rigorous experiments to allow a fair evaluation of the emerging technologies. The data should also be made publicly accessible in order for the scientific community to gain maximum benefit.
Fatty acid binding proteins (2014)

In addition to their traditional role as fatty acid trafficking proteins, increasing evidence supports the role of FABPs as important controllers of global metabolism, with their dysregulation being linked to a host of metabolic diseases.
THE CHOLINERGIC HYPOTHESIS—TEN YEARS ON (1986)

The cholinergic hypothesis of Alzheimer's disease originally postulated a connection between some of the cognitive impaiments of this disorder, particularly memory, and a disturbance in cerebral cholinergic neurotransmission. A decade of neurochemical, anatomical, pathological and psychopharmacological research has since reinforced and refined the hypothesis. Current evidence suggests a critical role for cortical cholinergic projections, originating in the basal forebrain, in the memory component (possibly via activation of encoding mechanisms) of both Alzheimer and Parkinson types of dementia. In more advanced stages of Alzheimer's disease, the involvement of other transmitters extends the search for potential long-term therapy beyound the cholinergic system. Nevertheless, the cholinergic hypothesis still merits investigation today with a view to obtaining more precise information on the role of the human cerebral cholinergic system memory and, with the advent of novel approaches to cholinergic therapy, to improving the management of at least mildly demented patients.
COMBINATION THALIDOMIDE AND CYCLOSPORINE FOR CARDIAC ALLOGRAFT REJECTION (1990)

Combination CsA with corticosteroids is the most commonly used maintenance immunosuppressive regimen after cardiac transplantation, although their high-toxicity profiles frequently limit their clinical benefit. Immunosuppressive agents that would act synergistically with CsA but without the toxicity profile of corticosteroids would be clinically useful. Thalidomide was removed from the market due to its teratogenic effects, although it has known immunomodulatory activity. The purpose of this study was (1) to determine whether maintenance immunosuppression with thalidomide and subtherapeutic doses of CsA can help prevent rat cardiac allograft rejection; and (2) to compare its synergism with CsA to the commonly used corticosteroid, methylprednisolone. ACI-LEW allografts were all treated with subtherapeutic doses of CsA (10 mg/g/day, s.c.) for 4 days. When CsA was then discontinued, severe rejection developed by posttransplant day 14. Group 1 received CsA alone. Group 2 received in addition oral thalidomide 100 mg/day for 14 days. Groups 3, 4, and 5 received CsA and methylprednisolone (low dose: 0.2 mg/kg/day s.c.; moderate dose: 2.0 mg/kg/day s.c.; and high dose: 20 mg/kg/day s.c. Twelve histologic parameters of rejection were semiquantitatively graded 0-4, and total pathology scores were determined. The combination of thalidomide and subtherapeutic CsA significantly reduced the severity of myocardial necrosis, interstitial inflammation, interstitial edema, and the total pathology score. Thalidomide was found to be equally as effective as low-, moderate-, and high-dose methylprednisolone. The results of this study suggest the potential clinical role of CsA and thalidomide in maintenance immunosuppressive regimens, thereby avoiding the use of corticosteroids.
A X-band switched-line 5-bit phase shifter with RF MEMS multithrow switches (2013)

In this paper, a 5-bit switched-line phase shifter is designed, processed and tested for X-band application, which is based on packaged RF MEMS single-pole double-throw(SPDT) and single-pole four-throw(SP4T) switches to get an compact structure. The design and optimization are carried out by analyzing the non-ideal performance of packaged RF MEMS switches and extracting their circuit model parameters. The effects of the bonding-wire connecting RF MEMS switches and peripheral circuits are also analyzed and modeled. The 5-bit phase shifter shows the average measured insertion loss of -3.1 dB, the average return loss of -21.1 dB, and the average absolute phase error of 2.2° at 10GHz. By comparison of simulations and measurements, this paper proposes that the main factors to effect the performances of phase shifters with packaged MEMS switches are parasitic inductances introduced by the bonding-wire and limited isolation of the used switches.
Abbreviations and symbols for nucleic acids, polynucleotides, and their constituents (1970)

ADVERTISEMENT RETURN TO ISSUEPREVArticleAbbreviations and symbols for nucleic acids, polynucleotides, and their constituents IUPAC-IUB Comm. on Biochem. Nomenclature (CBN)Cite this: Biochemistry 1970, 9, 20, 4022–4027Publication Date (Print):September 29, 1970Publication History Published online1 May 2002Published inissue 29 September 1970https://pubs.acs.org/doi/10.1021/bi00822a023https://doi.org/10.1021/bi00822a023research-articleACS PublicationsRequest reuse permissionsArticle Views533Altmetric-Citations60LEARN 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