gebhart/patrepeval huggingface dataset:
Comparison of Airway Remodeling in Acute, Subacute, and Chronic Models of Allergic Airways Disease (2007)

The relationship between airway inflammation and structural changes of airway remodeling, and their relative effects on airway function, are poorly understood. Remodeling is thought to result from chronic repetitive injury to the airway wall caused by airway inflammation; however, the mechanisms regulating remodeling changes have not been clearly defined. We examined the sequence of events in remodeling using three commonly used mouse models of allergic airways disease in which mice are exposed to nebulized ovalbumin for four consecutive days (acute), seven consecutive days (subacute), or three times a week for 6 wk (chronic). Surprisingly, we found that a very short period of exposure to ovalbumin was sufficient to elicit early changes of remodeling. Goblet cell hyperplasia and epithelial thickening were evident after just 4 d. In chronically challenged mice, these changes persisted and, in addition, subepithelial collagen deposition was significantly increased. This collagen deposition was associated with a failure to upregulate matrix metalloproteinase (MMP)-2, in conjunction with increased transforming growth factor-beta and MMP-9 expression. The relationship between inflammation, remodeling changes, and airway hyperresponsiveness (AHR) were examined. The acute and subacute models exhibited marked airway inflammation, whereas the chronic model had very modest inflammation. Conversely, airway fibrosis was only evident in the chronic model. AHR was present in all three models; however, it was significantly higher in the chronic model compared with the acute (P<0.05) and subacute (P<0.05) models. These data demonstrate that both airway inflammation and airway fibrosis may contribute to AHR, with airway fibrosis leading to the greatest increases in AHR.
Patch-clamp recordings of rat neurons from acute brain slices of the somatosensory cortex during magnetic stimulation (2014)

Although transcranial magnetic stimulation (TMS) is a popular tool for both basic research and clinical applications, its actions on nerve cells are only partially understood. We have previously predicted, using compartmental modeling, that magnetic stimulation of central nervous system neurons depolarized the soma followed by initiation of an action potential in the initial segment of the axon. The simulations also predict that neurons with low current threshold are more susceptible to magnetic stimulation. Here we tested these theoretical predictions by combining in vitro patch-clamp recordings from rat brain slices with magnetic stimulation and compartmental modeling. In agreement with the modeling, our recordings demonstrate the dependence of magnetic stimulation-triggered action potentials on the type and state of the neuron and its orientation within the magnetic field. Our results suggest that the observed effects of TMS are deeply rooted in the biophysical properties of single neurons in the central nervous system and provide a framework both for interpreting existing TMS data and developing new simulation-based tools and therapies.
Viewpoint: Race for Majorana fermions (2010)

The race for realizing Majorana fermions—elusive particles that act as their own antiparticles—heats up, but we still await ideal materials to work with.
Pursuit of Optimal Carbohydrate-Based Anticancer Vaccines:  Preparation of a Multiantigenic Unimolecular Glycopeptide Containing the Tn, MBr1, and Lewisy Antigens (2001)

A novel preparation of nonnatural glycoamino acids starting from n-pentenyl glycosides is described. The approach involves a Horner-Emmons olefination with a suitably protected glycine-derived phosphonate, followed by catalytic asymmetric hydrogenation, which proceeds with excellent diastereomeric selectivity. The synthetic methodology was useful for the preparation of glycoamino acids containing the Tn antigen, the MBr1 antigen (Globo-H), the Le(y) antigen, and lactose. These glycoamino acids can also serve as units for peptide synthesis. The synthesis of polyvalent glycopeptides containing three different antitumor antigens is described (28 and 29), and these have been prepared for conjugation to carrier protein in order to access the immunogenicity for tumor immunotherapy applications.
Evaluation of self-treatment of mild-to-moderate facial acne with a blue light treatment system. (2011)

The blue light treatment system offers effective, rapid, convenient and well tolerated treatment of inflammatory and non-inflammatory acne lesions. The majority of subjects consider it much gentler than traditional acne treatments and it facilitates effective treatment without the need for antibiotic exposure. The blue light treatment system and blue light therapy alone are attractive treatment options for acne vulgaris, both as alternatives to traditional acne treatments and as adjunctive treatments to complement existing therapies.
Expression and function of periostin‐isoforms in bone (2004)

Periostin was originally identified in MC3T3-E1 osteoblast-like cells. We have identified an isoform of periostin referred to as periostin-like-factor (PLF). It is homologous to other proteins such as fasciclin I (fas I), MPB70, betaIG-H3, and Algal-CAMs. All of these proteins are implicated in regulating cell adhesion. PLF and the other isoforms of periostin differ in their C-terminal sequences. PLF and periostin differ in two specific regions, between 673 and 699 amino acids (aa) and 785-812 aa. Periostin isoforms are expressed in vivo and in vitro during the stages of osteoblast differentiation and maturation. Their mRNAs are present in pre-osteoblast cells as detected by in situ hybridization, and the proteins are between 86 and 93 kD in size as determined by Western blot analysis. Antisense oligonucleotides and antibodies directed against the isoforms of periostin were used to block the activity of these proteins. In both cases, the levels of osteoblast-specific-differentiation markers were markedly reduced suggesting a role for these proteins in osteoblast differentiation.
Regulation of NRT1 and NRT2 Gene Families of Arabidopsis thaliana: Responses to Nitrate Provision (2003)

Four low-affinity (NRT1), and seven high-affinity (NRT2) nitrate transporter gene homologues have been identified in Arabidopsis thaliana. We investigated the transcript abundances of all eleven genes in shoot and root tissues in response to the provision of 1 mM NO(3)(-), using relative quantitative RT-PCR. Based upon this criterion, genes were classified as nitrate-inducible, nitrate-repressible, or nitrate-constitutive. AtNRT1.1, 2.1, and 2.2 were strongly induced by NO(3)(-), peaking at 3-12 h and subsequently declining. By contrast AtNRT2.4 showed only modest induction both in shoots and roots. Expression of AtNRT2.5, one of the nitrate-repressible genes, was strongly suppressed by nitrate provision in both roots and shoots. The last group, characterized by a constitutive expression pattern, included AtNRT1.2, 1.4, 2.3, 2.6, and 2.7. Correlation coefficients between (13)NO(3)(-) influx from 100 micro M and 5 mM [NO(3)(-)], suggest that high- and low-affinity transport systems are mediated primarily by AtNRT2.1 and AtNRT1.1, respectively. Functional roles for the other members of these families remain uncertain.
Carbon nanotube atomic force microscopy tips: Direct growth by chemical vapor deposition and application to high-resolution imaging (2000)

Carbon nanotubes are potentially ideal atomic force microscopy probes because they can have diameters as small as one nanometer, have robust mechanical properties, and can be specifically functionalized with chemical and biological probes at the tip ends. This communication describes methods for the direct growth of carbon nanotube tips by chemical vapor deposition (CVD) using ethylene and iron catalysts deposited on commercial silicon-cantilever-tip assemblies. Scanning electron microscopy and transmission electron microscopy measurements demonstrate that multiwalled nanotube and single-walled nanotube tips can be grown by predictable variations in the CVD growth conditions. Force-displacement measurements made on the tips show that they buckle elastically and have very small (</= 100 pN) nonspecific adhesion on mica surfaces in air. Analysis of images recorded on gold nanoparticle standards shows that these multi- and single-walled carbon nanotube tips have radii of curvature of 3-6 and 2-4 nm, respectively. Moreover, the nanotube tip radii determined from the nanoparticle images are consistent with those determined directly by transmission electron microscopy imaging of the nanotube ends. These molecular-scale CVD nanotube probes have been used to image isolated IgG and GroES proteins at high-resolution.
Parkin reverses intracellular β‐amyloid accumulation and its negative effects on proteasome function (2009)

The significance of intracellular beta-amyloid (Abeta(42)) accumulation is increasingly recognized in Alzheimer's disease (AD) pathogenesis. Abeta removal mechanisms that have attracted attention include IDE/neprilysin degradation and antibody-mediated uptake by immune cells. However, the role of the ubiquitin-proteasome system (UPS) in the disposal of cellular Abeta has not been fully explored. The E3 ubiquitin ligase Parkin targets several proteins for UPS degradation, and Parkin mutations are the major cause of autosomal recessive Parkinson's disease. We tested whether Parkin has cross-function to target misfolded proteins in AD for proteasome-dependent clearance in SH-SY5Y and primary neuronal cells. Wild-type Parkin greatly decreased steady-state levels of intracellular Abeta(42), an action abrogated by proteasome inhibitors. Intracellular Abeta(42) accumulation decreased cell viability and proteasome activity. Accordingly, Parkin reversed both effects. Changes in mitochondrial ATP production from Abeta or Parkin did not account for their effects on the proteasome. Parkin knock-down led to accumulation of Abeta. In AD brain, Parkin was found to interact with Abeta and its levels were reduced. Thus, Parkin is cytoprotective, partially by increasing the removal of cellular Abeta through a proteasome-dependent pathway.
Progress in high-speed and high-resolution CMOS data converters (2002)

This paper presents an overview of the status of high-speed and high-resolution CMOS data converters. Techniques and achieved performance are compared using power consumption per step of resolution as a key parameter. The effort in optimizing this quality factor is evident, because of the urgency of portable system requirements. Trends towards low-power design and bit-stream processing are also considered.
Forebrain Fatty Acid Composition during Development in Protein-Calorie and Essential Fatty Acid Deficiencies in the Rat (1979)

Rats were fed three different dietary levels of essential fatty acids (EFA), 3.0, 0.75 and 0.1 cal%, representing normal, subnormal and severely deficient dietary intakes. From the animals kept on these diets, with a protein content of 16 cal%, 3-month-old females were randomly selected to be fed diets with only 6 cal% protein but with unchanged amounts of EFA. The rats were then mated, and the effects of the diets were studied in the forebrains of their offspring. The growth and the fatty acid patterns of the ethanolamine phosphoglyceride and total phosphoglyceride fractions were studied during the first 60 days of life. Addition of protein-calorie deficiency to rats severely undernourished in EFA mitigated the biochemical signs of EFA deficiency. In EPG the developmental pattern with a decrease of 20:4 (n-6) and an increase of 22:6 (n-3) was retarded between 11 and 21 days of age in the protein-calorie deficient groups suggesting a delay in the maturation of the forebrain.
Carrier-specific suppression of antibody responses by antigen-specific glycosylation-inhibiting factors. (1987)

We previously established an ovalbumin (OA)-specific T cell clone from spleen cells of BDF1 mice, which had been treated by i.v. injections of OA, and constructed antigen-specific T cell hybridomas from the T cell clone. One of the hybridomas constitutively released glycosylation-inhibiting factor (GIF) which lacked affinity for OA, and was called non-specific GIF. Incubation of the same hybridoma cells with OA-pulsed syngeneic macrophages or OA-pulsed B lymphoblastoid cells of BALB/c origin resulted in the formation of GIF molecules that had affinity for OA but not for bovine serum albumin or keyhole limpet hemocyanin. Both the OA-specific GIF and nonspecific GIF bound to monoclonal anti-lipocortin and possessed I-Jb determinants. The OA-specific GIF consisted of two species of molecules, of m.w. 80,000 and 30,000 to 40,000, respectively, whereas the nonspecific GIF from unstimulated cells had an m.w. of 15,000. Intravenous injections of OA-specific GIF or nonspecific GIF into BDF1 mice suppressed both the IgE and IgG1 anti-hapten antibody responses of the animals to dinitrophenyl derivatives of OA (DNP-OA), but OA-specific GIF was much more effective than nonspecific GIF in suppressing the antibody responses. When the same preparations of GIF were injected into DNP-KHL-primed mice, OA-specific GIF and nonspecific GIF were comparable in suppressing the anti-DNP antibody response. In contrast to the 40,000 m.w. species of OA-specific GIF, the 80,000 m.w. OA-specific GIF had carrier-specific suppressive effects. The similarities of antigen-specific GIF to antigen-specific TsF suggest that the phospholipase-inhibiting activity of the molecules may be involved in the immunosuppressive effects of some antigen-specific TsF.
Phase-transfer catalysis. I. Heterogeneous reactions involving anion transfer by quaternary ammonium and phosphonium salts (1971)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPhase-transfer catalysis. I. Heterogeneous reactions involving anion transfer by quaternary ammonium and phosphonium saltsCharles M. StarksCite this: J. Am. Chem. Soc. 1971, 93, 1, 195–199Publication Date (Print):January 1, 1971Publication History Published online1 May 2002Published inissue 1 January 1971https://pubs.acs.org/doi/10.1021/ja00730a033https://doi.org/10.1021/ja00730a033research-articleACS PublicationsRequest reuse permissionsArticle Views9771Altmetric-Citations800LEARN 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
MODELS OF AMYLOID SEEDING IN ALZHEIMER'S DISEASE AND SCRAPIE: Mechanistic Truths and Physiological Consequences of the Time-Dependent Solubility of Amyloid Proteins (1997)

Ordered protein aggregation in the brain is a hallmark of Alzheimer's disease and scrapie. The disease-specific amyloid fibrils comprise primarily a single protein, amyloid beta, in Alzheimer's disease, and the prion protein in scrapie. These proteins can be induced to form aggregates in vitro that are indistinguishable from brain-derived fibrils. Consequently, much effort has been invested in the development of in vitro model systems to study the details of the aggregation processes and the effects of endogenous molecules that have been implicated in disease. Selected studies of this type are reviewed herein. A simple mechanistic model has emerged for both processes that involves a nucleation-dependent polymerization. This mechanism dictates that aggregation is dependent on protein concentration and time. Furthermore, amyloid formation can be seeded by a preformed fibril. The physiological consequences of this mechanism are discussed.
Traversing a wormhole to combat Parkinson’s disease (2008)

Human movement disorders represent a significant and unresolved societal burden. Among these, the most prevalent is Parkinson's disease (PD), a disorder afflicting millions worldwide. Despite major advances, stemming primarily from human genetics, there remains a significant gap in our understanding of what factors underlie disease susceptibility, onset, and progression. Innovative strategies to discern specific intracellular targets for subsequent drug development are needed to more rapidly translate basic findings to the clinic. Here we briefly review the recent contributions of research using the nematode roundworm Caenorhabditis elegans as a model system for identifying and characterizing gene products associated with PD. As a microscopic but multicellular and genetically tractable animal with a well-defined nervous system and an experimentally tenable lifespan, C. elegans affords significant advantages to researchers attempting to determine causative and therapeutic factors that influence neuronal dysfunction and age-associated neurodegeneration. The rapidity with which traditional genetic, large-scale genomic, and pharmacological screening can be applied to C. elegans epitomizes the utility of this animal for disease research. Moreover, with mature bioinformatic and functional genomic data readily available, the nematode is well positioned to play an increasingly important role in PD-associated discoveries.
New Antipsychotics and Schizophrenia: A Review on Efficacy and Side Effects (2004)

The first compounds showing efficacy in the treatment of schizophrenia and other psychotic disorders was chlorpromazine, an anti-histaminic compound casually observed to possess antipsychotic effects. The discovery of the real mechanism of action of antipsychotic substances dates back to the 1960s, when researchers found that these compounds act as dopamine receptor antagonists. Unfortunately, this type of drugs cannot block the D2 receptors only in the mesolimbic dopaminergic pathway (which mediates their therapeutic effects), because of their non-selective D2 receptor blockage in both the mesolimbic and striatal regions, and the consequent appearance of side effects related to striatal interaction in the same dosage range as is needed for the therapeutical effects. Clozapine, discovered in the early 1970s, seemed to represent the solution to contrast these side effects, as it possesses antipsychotic activity without inducing extrapyramidal disorders in humans or catalepsy in rats; for this reason, it was defined as an "atypical" antipsychotic drug. Later, other beneficial properties, such as improvement of negative symptoms and of cognitive dysfunction and efficacy in neuroleptic-resistant schizophrenia, were included in the definition of "atypical". In recent years, the appearance of new atypical antipsychotics (risperidone, olanzapine, quetiapine, ziprasidone) has opened new ways to therapy. The aim of this paper is to review literature about newer antipsychotics, focusing on their advantages in terms of efficacy and side effect profiles when compared to classical and older atypical antipsychotics, and to evaluate the efficacy of the different new antipsychotics when compared to one another.
Molecular basis of the diagnosis and treatment of polycythemia vera and essential thrombocythemia (2006)

Recent insights into the molecular mechanisms of polycythemia vera (PV) and essential thrombocythemia (ET) are challenging the traditional diagnostic classification of these myeloproliferative disorders (MPDs). Clonality analysis using X-chromosome inactivation patterns has revealed apparent heterogeneity among the MPDs. The recently discovered single somatic activating point mutation in the JAK2 gene (JAK2-V617F) is found in the great majority of patients with PV, but also in many patients with phenotypically classified ET and other MPDs. In contrast to the acquired MPDs, mutations of the erythropoietin receptor and thrombopoietin receptor have been identified in familial forms of nonclonal erythrocytosis and thrombocytosis, respectively. The mechanisms of major clinical complications of PV and ET remain poorly understood. Quantitative or qualitative abnormalities of red cells and platelets do not provide clear explanations for the thrombotic and bleeding tendency in these MPDs, suggesting the need for entirely new lines of research in this area. Recently reported randomized clinical trials have demonstrated the efficacy and safety of low-dose aspirin in PV, and an excess rate of arterial thrombosis, major bleeding, and myelofibrotic transformation, but decreased venous thrombosis, in patients with ET treated with anagrelide plus aspirin compared to hydroxyurea plus aspirin.
Systemic nicotine‐induced dopamine release in the rat nucleus accumbens is regulated by nicotinic receptors in the ventral tegmental area (1994)

Stimulation of the mesolimbic dopamine (DA) system is considered of major importance for the rewarding and dependence producing properties of nicotine (NIC). To identify the site of this stimulatory action, simultaneous microdialysis was performed in the ventral tegmental area (VTA) and the ipsilateral nucleus accumbens (NAC) of awake rats. Extracellular concentrations of DA and its metabolites were measured in the NAC. NIC (0.5 mg/kg, s.c.) increased DA and its metabolites by approximately 50%. Concomitant infusion of the nicotinic receptor antagonist mecamylamine (MEC, 100 microM) through the VTA probe, starting 40 min before NIC injection, antagonized the NIC induced increases of DA and its metabolites. In contrast, similar MEC pretreatment (40 or 140 min) in the NAC did not affect DA or metabolite responses to systemic NIC. Infusion of NIC (1,000 microM) in the NAC or the VTA increased DA release by 49% and 48%, respectively, whereas only the VTA infusion increased metabolite concentrations by approximately 25%. MEC infusion (1-1,000 microM) in the VTA did not affect DA or its metabolites, whereas the 1,000 microM concentration infused in the NAC increased DA by 77%. These results suggest that nicotinic receptors in the somatodendritic region may be of greater importance than those located in the terminal area for the stimulatory action of systemic NIC on the mesolimbic DA system. Furthermore, our findings support the notion that the mesolimbic dopaminergic system is phasically rather than tonically regulated by nicotinic receptor activation within the VTA.
Management of Hepatic Encephalopathy (2011)

Hepatic encephalopathy (HE), the neuropsychiatric presentation of liver disease, is associated with high morbidity and mortality. Reduction of plasma ammonia remains the central therapeutic strategy, but there is a need for newer novel therapies. We discuss current evidence supporting the use of interventions for both the general management of chronic HE and that necessary for more acute and advanced disease.