gebhart/patrepeval huggingface dataset:
Colocalization and coassembly of two human brain M-type potassium channel subunits that are mutated in epilepsy (2000)

Acetylcholine excites many central and autonomic neurons through inhibition of M-channels, slowly activating, noninactivating voltage-gated potassium channels. We here provide information regarding the in vivo distribution and biochemical characteristics of human brain KCNQ2 and KCNQ3, two channel subunits that form M-channels when expressed in vitro, and, when mutated, cause the dominantly inherited epileptic syndrome, benign neonatal familial convulsions. KCNQ2 and KCNQ3 proteins are colocalized in a somatodendritic pattern on pyramidal and polymorphic neurons in the human cortex and hippocampus. Immunoreactivity for KCNQ2, but not KCNQ3, is also prominent in some terminal fields, suggesting a presynaptic role for a distinct subgroup of M-channels in the regulation of action potential propagation and neurotransmitter release. KCNQ2 and KCNQ3 can be coimmunoprecipitated from brain lysates. Further, KCNQ2 and KCNQ3 are coassociated with tubulin and protein kinase A within a Triton X-100-insoluble protein complex. This complex is not associated with low-density membrane rafts or with N-methyl-d-aspartate receptors, PSD-95 scaffolding proteins, or other potassium channels tested. Our studies thus provide a view of a signaling complex that may be important for cognitive function as well as epilepsy. Analysis of this complex may shed light on the unknown transduction pathway linking muscarinic acetylcholine receptor activation to M-channel inhibition.
The contribution of obesity to prescription opioid use in the United States (2019)

The prevalence of obesity has grown rapidly over the past several decades and has been accompanied by an increase in the prevalence of chronic pain and prescription opioid use. Obesity, through its association with pain, may represent an important contributor to opioid use. This cross-sectional study investigated the relationship between obesity and prescription opioid use among adults aged 35 to 79 years using data from the National Health and Nutrition Examination Survey (NHANES, 2003-2016). Relative to normal weight, body mass indices in the overweight {odds ratio (OR), 1.11 (confidence interval [CI], 0.88-1.39)}, obese I (OR, 1.26 [CI, 1.01-1.57]), obese II (OR, 1.69 [CI, 1.34-2.12]), and obese III (OR, 2.33 [CI, 1.76-3.08]) categories were associated with elevated odds of prescription opioid use. The association between excess weight and opioid use was stronger for chronic opioid use than for use with a duration of less than 90 days (P-value, <0.001). We estimated that 14% (CI, 9%-19%) of prescription opioid use at the population level was attributable to obesity, suggesting there might have been 1.5 million fewer opioid users per year under the hypothetical scenario where obese individuals were instead nonobese (CI, 0.9-2.0 million users). Back pain, joint pain, and muscle/nerve pain accounted for the largest differences in self-reported reasons for prescription opioid use across obesity status. Although interpretation is limited by the cross-sectional nature of the associations, our findings suggest that the obesity epidemic may be partially responsible for the high prevalence of prescription opioid use in the United States.
FluBlok, a recombinant hemagglutinin influenza vaccine (2008)

FluBlok, a recombinant trivalent hemagglutinin (HA) vaccine produced in insect cell culture using the baculovirus expression system, provides an attractive alternative to the current egg-based trivalent inactivated influenza vaccine (TIV) manufacturing process. FluBlok contains three times more HA than TIV and does not contain egg-protein or preservatives. This review discusses the four main clinical studies that were used to support licensure of FluBlok under the 'Accelerated Approval' mechanism in the United States.
Melanoma-associated markers expression in blood: MUC-18 is associated with advanced stages in melanoma patients (2008)

MUC-18 RT-PCR assay could be proposed as an adjunctive molecular method in the management of melanoma patients and is useful in the monitoring of study protocols.
Highly Crystalline Spindle-Shaped Mesoporous Anatase Titania Particles: Solution-Phase Synthesis, Characterization, and Photocatalytic Properties (2010)

Spindlelike mesoporous anatase titania particles were directly synthesized at a low temperature (95 degrees C) by using an aqueous peroxotitanium solution with polyacrylamide (PAM). The mesoporous titania had a BET-specific surface area of 89.6 m(2) g(-1) and showed high crystallinity, thermal stability, and good photocatalytic activity in the degradation of rhodamine B. PAM, as an additive, was confirmed to be crucial in the evolution of the specific structure, morphology, and crystalline phase, and a possible formation mechanism was suggested.
Glucagon-Like Peptide-1-(7–36)Amide Is Transformed to Glucagon-Like Peptide-1-(9–36)Amide by Dipeptidyl Peptidase IV in the Capillaries Supplying the L Cells of the Porcine Intestine1 (1999)

The insulinotropic hormone glucagon-like peptide-1 (GLP-1) is stored in the intestinal L cell in an active form, GLP-1-(7-36)amide, but more than half of the endogenous peptide circulates in an inactive, N-terminally truncated form, GLP-1-(9-36)amide. This study examined the GLP-1 newly secreted from the porcine ileum, in vitro (isolated perfused preparation) and in vivo (anesthetized pig), to determine where this conversion occurs. Although the GLP-1 extractable from the porcine ileum is predominantly the intact peptide (94.6+/-1.7%), a large proportion of the GLP-1 that is secreted has already been degraded to the truncated form both in vitro (53.8+/-0.9% intact) and in vivo (32.9+/-10.8% intact). In the presence of a specific dipeptidyl peptidase IV (DPP IV) inhibitor (valine-pyrrolidide), the proportion of intact GLP-1 released from the perfused ileum was increased under both basal (99% intact; P < 0.05) and stimulated (86-101% intact; P < 0.05) conditions. Immunohistochemical and histochemical studies revealed specific DPP IV staining in the brush border epithelium as well as in the capillary endothelium. Double staining showed juxtapositioning of DPP IV-positive capillaries and GLP-1-containing L cells. From these results, we suggest that GLP-1 is degraded as it enters the DPP IV containing blood vessels draining the intestinal mucosa.
Design and synthesis of a knot from single-stranded DNA (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDesign and synthesis of a knot from single-stranded DNAJohn E. Mueller, Shou Ming Du, and Nadrian C. SeemanCite this: J. Am. Chem. Soc. 1991, 113, 16, 6306–6308Publication Date (Print):July 1, 1991Publication History Published online1 May 2002Published inissue 1 July 1991https://pubs.acs.org/doi/10.1021/ja00016a077https://doi.org/10.1021/ja00016a077research-articleACS PublicationsRequest reuse permissionsArticle Views507Altmetric-Citations89LEARN 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
Upper bound to the thermal conductivity of carbon nanotube pellets (2009)

Using atomistic Green’s function calculations, we find that the phonon thermal conductivity of pellets composed of ∼μm long carbon nanotubes has an upper bound of a few W/m K. This is in striking contrast with the extremely high thermal conductivity of individual nanotubes (∼3000 W/m K). We show that, at room temperature, this upper bound does not depend on the nanotube diameter. Conversely, for low temperatures, an inverse proportionality with nanotube diameter is predicted. We present concrete results as a function of nanotube length and chirality, pellet density, and temperature. These results imply that carbon nanotube pellets belong to the category of thermal insulators, contrasting with the good conducting properties of parallel nanotube arrays, or individual nanotubes.
Determination of glucose oxidase oxidation-reduction potentials and the oxygen reactivity of fully reduced and semiquinoid forms. (1978)

The oxidation-reduction potential values for the two electron transfers to glucose oxidase were obtained at pH 5.3, where the neutral radical is the stable form, and at pH 9.3, where the anion radical is the stable form. The midpoint potentials at 25 degrees were: pH 5.3 EFl1ox + e- H+ equilibrium EFlH. Em1 = -0.063 +/- 0.011 V EFlH. + e- + H+ equilibrium EFlredH2 Em2 = -0.065 +/- 0.007 V pH 9.3 EFlox + e- EFi- Em1 = -0.200 +/- 0.010 V EFi- + e- + H+ equilibrium EFlredH- Em2 = -0.240 +/- 0.005 V All potentials were measured versus the standard hydrogen electrode (SHE). The potentials indicated that glucose oxidase radicals are stabilized by kinetic factors and not by thermodynamic energy barriers. The pK for the glucose oxidase radical was 7.28 from dead time stopped flow measurements and the extinction coefficient of the neutral semiquinone was 4140 M-1 cm-1 at 570 nm. Both radical forms reacted with oxygen in a second order fashion. The rate at 25 degrees for the neutral semiquinone was 1.4 X 10(4) M-1 s-1; that for the anion radical was 3.5 X 10(4) M-1 s-1. The rate of oxidation of the neutral radical changed by a factor of 9 for a temperature difference of 22 degrees. For the anion radical, the oxidation rate changed by a factor of 6 for a 22 degrees change in temperature. We studied the oxygen reactivity of the 2-electron reduced form of the enzyme over a wide wavelength range and failed to detect either oxygenated flavin derivatives or semiquinoid forms as intermediates. The rate of reoxidation of fully reduced glucose oxidase at pH 9.3 was dependent on ionic strength.
A new method for non‐parametric multivariate analysis of variance (2001)

Abstract Hypothesis‐testing methods for multivariate data are needed to make rigorous probability statements about the effects of factors and their interactions in experiments. Analysis of variance is particularly powerful for the analysis of univariate data. The traditional multivariate analogues, however, are too stringent in their assumptions for most ecological multivariate data sets. Non‐parametric methods, based on permutation tests, are preferable. This paper describes a new non‐parametric method for multivariate analysis of variance, after McArdle and Anderson (in press). It is given here, with several applications in ecology, to provide an alternative and perhaps more intuitive formulation for ANOVA (based on sums of squared distances) to complement the description provided by McArdle and Anderson (in press) for the analysis of any linear model. It is an improvement on previous non‐parametric methods because it allows a direct additive partitioning of variation for complex models. It does this while maintaining the flexibility and lack of formal assumptions of other non‐parametric methods. The test‐statistic is a multivariate analogue to Fisher’s F ‐ratio and is calculated directly from any symmetric distance or dissimilarity matrix. P ‐values are then obtained using permutations. Some examples of the method are given for tests involving several factors, including factorial and hierarchical (nested) designs and tests of interactions.
Specific progressive cAMP reduction implicates energy deficit in presymptomatic Huntington's disease knock-in mice (2003)

Defects in gene transcription and mitochondrial function have been implicated in the dominant disease process that leads to the loss of striatal neurons in Huntington's disease (HD). Here we have used precise genetic HD mouse and striatal cell models to investigate the hypothesis that decreased cAMP responsive element (CRE)-mediated gene transcription may reflect impaired energy metabolism. We found that reduced CRE-signaling in Hdh(Q111) striatum, monitored by brain derived neurotrophic factor and phospho-CRE binding protein (CREB), predated inclusion formation. Furthermore, cAMP levels in Hdh(Q111) striatum declined from an early age (10 weeks), and cAMP was significantly decreased in HD postmortem brain and lymphoblastoid cells, attesting to a chronic deficit in man. Reduced CRE-signaling in cultured STHdh(Q111) striatal cells was associated with cytosolic CREB binding protein that mirrored diminished cAMP synthesis. Moreover, mutant cells exhibited mitochondrial respiratory chain impairment, evidenced by decreased ATP and ATP/ADP ratio, impaired MTT conversion and heightened sensitivity to 3-nitropropionic acid. Thus, our findings strongly suggest that impaired ATP synthesis and diminished cAMP levels amplify the early HD disease cascade by decreasing CRE-regulated gene transcription and altering energy dependent processes essential to neuronal cell survival.
Synthesis of rac‐ar‐Curcumen‐15‐al (1997)

Abstract Starting from p ‐tolunitrile ( 4 ) via alkylation with the bromoacetal 12 (→ 8 ), and with MeI (→ 9 ), hydrolysis to 10 , Wittig reaction (→ 7 ) and DIBAH reduction, the rac‐ar ‐curcumen‐15‐al ( 2 ) was obtained. The cumin‐like, citrus odor of rac ‐ 2 is similar to that of the isolated (−)‐ 2 .
Intracellular mechanism of penile erection in monkeys (1994)

To elucidate the sequence of events between the release of neurotransmitters and cavernous smooth muscle relaxation in erection, we studied the role of the cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) systems. In a well-established simian model, the effects of specific agonists and antagonists of the intracellular sequence for smooth muscle relaxation and potassium channel openers on the intracavernous pressure were examined. Sodium nitroprusside (10(-3) M), a nitric oxide releaser and thus a stimulant of the cGMP system, caused an increase in the intracavernous pressure from 82 to 115 cm H2O for 7 to 19 min and penile diameter from 24.8 +/- 2.28 to 43 +/- 4.87 mm. When nitroprusside was injected after methylene blue (10(-3) M), a specific antagonist of the enzyme guanylate cyclase, intracavernous pressure rise decreased significantly, but cromakalin, a potassium channel opener, provoked excellent increases after the block. A smaller dose of sodium nitroprusside (10(-4) M) caused an increase in intracavernous pressure from 35 to 85 cm H2O for 7 to 11.5 min. When nitroprusside was injected after zaprinast, a phosphodiesterase inhibitor, the increase in pressure ranged from 80 to 116 cm H2O for 15 to 30 min. Prostaglandin E1, an activator of the cAMP system, caused an increase in the intracavernous pressure of 20-80 cm H2O for 5 to 10 min, and an increase in penile diameter from 25 +/- 2.22 to 35 +/- 3.48 mm. The erectile response to PGE1, but not to cromakalin, was nearly abolished by ethylmaleimide, an adenylate cyclase blocker. The response to nitroprusside was significantly greater (P < 0.05) than to PGE1. Both systems, cAMP and cGMP, may be involved in cavernous smooth muscle relaxation, and cGMP is probably the predominant intracellular second messenger in penile erection in monkeys. Stimulants of the cGMP system, such as nitric oxide releasers, could represent a more physiological and effective approach in the treatment of erectile dysfunction.
Oxygen affinity of haemoglobin and red cell acid-base status in patients with severe chronic obstructive lung disease. (1977)

The oxygen affinity of hemoglobin and the factors determining the position of the oxygen dissociation curve were investigated in twenty-five patients with severe chronic obstructive lung disease. Patients have been separated into three groups: group I showed a normal or mild decrease of PaO2, group II a moderate fall in arterial oxygen pressure, and group III a severe hypoxia with balanced acid-base equilibrium and hypercapnia. Blood hemoglobin exhibited a significant increase in all groups, indicating an improved oxygen transport. In most patients a leftward shifting of the oxygen dissociation curve occurred. It is discussed that the tendency to left shifting is based upon alkalosis inside the red cells, evidently demonstrated in all groups studied. 2,3-diphosphoglycerate showed no close relation to evaluated oxygen affinity of hemoglobin. The evidence for an increased oxygen affinity may reveal a further compensatory mechanism in oxygen transport in patients with pulmonary disorders. Additionally the alkalosis inside the cells may counterbalance too great a right shifting of oxygen dissociation curve in vivo when severe hypoxia and hypercapnia occur.
Selective neuronal vulnerability to oxidative stress in the brain (2010)

Oxidative stress (OS), caused by the imbalance between the generation and detoxification of reactive oxygen and nitrogen species (ROS/RNS), plays an important role in brain aging, neurodegenerative diseases, and other related adverse conditions, such as ischemia. While ROS/RNS serve as signaling molecules at physiological levels, an excessive amount of these molecules leads to oxidative modification and, therefore, dysfunction of proteins, nucleic acids, and lipids. The response of neurons to this pervasive stress, however, is not uniform in the brain. While many brain neurons can cope with a rise in OS, there are select populations of neurons in the brain that are vulnerable. Because of their selective vulnerability, these neurons are usually the first to exhibit functional decline and cell death during normal aging, or in age-associated neurodegenerative diseases, such as Alzheimer's disease. Understanding the molecular and cellular mechanisms of selective neuronal vulnerability (SNV) to OS is important in the development of future intervention approaches to protect such vulnerable neurons from the stresses of the aging process and the pathological states that lead to neurodegeneration. In this review, the currently known molecular and cellular factors that contribute to SNV to OS are summarized. Included among the major underlying factors are high intrinsic OS, high demand for ROS/RNS-based signaling, low ATP production, mitochondrial dysfunction, and high inflammatory response in vulnerable neurons. The contribution to the selective vulnerability of neurons to OS by other intrinsic or extrinsic factors, such as deficient DNA damage repair, low calcium-buffering capacity, and glutamate excitotoxicity, are also discussed.
Prednisolone and danazol for treatment of immune-mediated anemia, thrombocytopenia, and ineffective erythroid regeneration in a dog (1990)

Immune-mediated anemia and thrombocytopenia were diagnosed in an 8-year-old spayed Miniature Schnauzer. The initial CBC indicated poor erythroid regeneration and concurrent leukopenia. The results of a Coombs test and ANA titer were strongly positive. Examination of a bone marrow specimen revealed erythrophagocytosis and a maturation arrest in the RBC series. Treatment with transfusion plus prednisolone and an attenuated androgen (danazol) resulted in stabilization of the PCV and the development of reticulocytosis.
An open-label trial of the PPARγ ligand rosiglitazone for active ulcerative colitis (2001)

OBJECTIVES: Previous research has demonstrated that ligands for the γ subtype of peroxisome proliferator-activated receptors (PPARs) reduce inflammation in two different murine models of colitis. This study was designed to examine the potential efficacy of rosiglitazone, a ligand for the γ subtype of PPARs, as a therapy for active ulcerative colitis. METHODS: Fifteen patients with mild to moderately active ulcerative colitis despite therapy with 5-aminosalicylic acid compounds were enrolled in an open-label study of rosiglitazone (4 mg b.i.d. p.o.) for 12 wk. Thirteen of 15 patients were receiving concomitant therapy with corticosteroids and/or immunomodulator medications. Disease activity was measured with the Disease Activity Index. RESULTS: After 12 wk of therapy, four patients (27%) had achieved clinical remission, of whom three (20%) also had an endoscopic remission. Four additional patients (27%) had a clinical response without achieving remission. Two patients were hospitalized with worsened disease activity, and one patient was withdrawn for nephrotic syndrome. CONCLUSIONS: These data suggest that ligands for the γ subtype of PPARs may represent a novel therapy for ulcerative colitis. A double blind, placebo-controlled, randomized trial is warranted.
A narcoleptic patient exhibiting hallucinations and delusion (2000)

A female narcoleptic patient with persistent auditory hallucinations and delusion is reported. These psychotic symptoms appeared before the diagnosis of narcolepsy and before the use of pemoline and clomipramine. On admission to the Department of Neuropsychiatry at the Kurume University school of Medicine, the patient's auditory hallucinations were almost the same as the previous hallucinations. The patient's delusional state improved smoothly after haloperidol administration. After that, the patient related well socially. The persistent auditory hallucinations were correlated with rapid eye movement sleep symptoms during her disease process so that we concluded that her persistent auditory hallucinations and delusion of observation were due to narcoleptic symptoms.
RNA target specificity of the embryonic cell fate determinant POS-1 (2008)

Specification of Caenorhabditis elegans body axes and cell fates occurs prior to the activation of zygotic transcription. Several CCCH-type tandem zinc finger (TZF) proteins coordinate local activation of quiescent maternal mRNAs after fertilization, leading to asymmetric expression of factors required for patterning. The primary determinant of posterior fate is the TZF protein POS-1. Mutants of pos-1 are maternal effect lethal with a terminal phenotype that includes excess pharyngeal tissue and no endoderm or germline. Here, we delineate the consensus POS-1 recognition element (PRE) required for specific recognition of its target mRNAs. The PRE is necessary but not sufficient to pattern the expression of a reporter. The PRE is distinct from sequences recognized by related proteins from both mammals and nematodes, demonstrating that variants of this protein family can recognize divergent RNA sequences. The PRE is found within the 3' untranslated region of 227 maternal transcripts required for early development, including genes involved in endoderm and germline specification. The results enable prediction of novel targets that explain the pleiotropy of the pos-1 phenotype.
Oxides and nitrides as alternative plasmonic materials in the optical range [Invited] (2011)

As alternatives to conventional metals, new plasmonic materials offer many advantages in the rapidly growing fields of plasmonics and metamaterials. These advantages include low intrinsic loss, semiconductor-based design, compatibility with standard nanofabrication processes, tunability, and others. Transparent conducting oxides such as Al:ZnO, Ga:ZnO and indium-tin-oxide (ITO) enable many high-performance metamaterial devices operating in the near-IR. Transition-metal nitrides such as TiN or ZrN can be substitutes for conventional metals in the visible frequencies. In this paper we provide the details of fabrication and characterization of these new materials and discuss their suitability for a number of metamaterial and plasmonic applications. (C) 2011 Optical Society of America