gebhart/patrepeval huggingface dataset:
Voicedraw (2007)

We present VoiceDraw, a voice-driven drawing application for people with motor impairments that provides a way to generate free-form drawings without needing manual interaction. VoiceDraw was designed and built to investigate the potential of the human voice as a modality to bring fluid, continuous direct manipulation interaction to users who lack the use of their hands. VoiceDraw also allows us to study the issues surrounding the design of a user interface optimized for non-speech voice-based interaction. We describe the features of the VoiceDraw application, our design process, including our user-centered design sessions with a 'voice painter', and offer lessons learned that could inform future voice-based design efforts. In particular, we offer insights for mapping human voice to continuous control.
Effect of frequency and amplitude of FES pulses on muscle fatigue during toning of muscles (2008)

This study presents effects of frequency and amplitude of stimulation pulses on muscle contraction. The experiments are on a complete paraplegic patient with injury level between T4 and T5. Number of contraction episode before fatigue has been more for low frequency and low voltage stimulation.
Development of Mullerian Inhibiting Substance as an Anti-cancer Drug (1986)

Normal animal cell proliferation is a precisely controlled process, which when disrupted leads to malignant transformation and uncontrolled growth. The concept of autocrine stimulation of cellular proliferation has been proposed to explain malignant transformation: Normal cells require exogenous growth factors, whereas transformed cells have gained autonomy due to the endogenous production of these factors (Todaro et al. 1977; Sporn and Todaro 1980). Many examples can be cited in support of this hypothesis (De Larco and Todaro 1978; Kaplan et al. 1982; Waterfield et al. 1983; Lang et al. 1985). Recently, the autocrine hypothesis has been extended to include growth inhibitors: Transformation may also result from failure to express or respond to specific growth-inhibitory substances that may be released by cells to regulate their orderly growth (Sporn and Roberts 1985). Consistent with this, transforming growth factor (TGF-β) can suppress the growth of the monkey kidney cells that produce this peptide (Tucker...
Post-translational Processing and Oligomerization of the Fusion Glycoprotein of Human Respiratory Syncytial Virus (1991)

The post-translational maturation of the fusion protein (F) of human respiratory syncytial virus was investigated. Chemical cross-linking experiments indicated that F forms homotetramers and provided evidence that the intermonomer contacts involve primarily the F1 subunit. Homooligomerization as measured by sedimentation in sucrose gradients was insensitive to carbonyl cyanide m-chlorophenylhydrazone, indicating that it occurs in the endoplasmic reticulum. Cleavage of the F0 precursor to yield the F1 and F2 subunits was blocked by monensin or brefeldin A, indicating that it takes place in distal cisternae of the trans Golgi compartment or in the more distal trans Golgi network. The F0 precursor was not detected at the cell surface in surface immunoprecipitation experiments, indicating that cleavage is intracellular. The appearance of the cleaved F1 protein at the cell surface was concurrent with that of the attachment glycoprotein (G); this and other information indicated that the type 2 membrane orientation of G is not obligatorily associated with a reduced transit rate. Examination of F maturation in the presence of tunicamycin provided evidence that its expression at the cell surface depends upon cleavage and not directly upon glycosylation.
Studies on the immunoglobulin-G Fc-fragment receptor from neonatal rat small intestine (1980)

1. A method for preparing the small-intestinal brush-border membrane of neonatal rats is described in which enzymic methods are used to remove associated polysaccharide and cell nuclei. 2. 125I-labelled IgG (immunoglobulin G) and 125I-labelled IgG Fc fragment have high specific binding and low non-specific binding to brush borders prepared in this way. F(ab)'2 fragment however, does not bind, indicating the existence of a specific receptor for the Fc fragment of IgG. The receptor system is saturable, and the affinity (KA) for the binding of rat IgG was determined by both equilibrium and kinetic methods. 3. The binding of heterologous IgG species (human and bovine) was compared and demonstrated a close similarity between human IgG and rat IgG in their receptor affinities. 4. Kinetic results are presented that are consistent with previously proposed models of ligand-induced receptor aggregation.
Synthesis of Coumarins via Palladium-Catalyzed Carbonylative Annulation of Internal Alkynes by o-Iodophenols (2000)

A variety of substituted coumarins have been prepared in good yields by the palladium-catalyzed coupling of o-iodophenols with internal alkynes and 1 atm of carbon monoxide. Unlike most of the previous work on the palladium-catalyzed carbonylation of alkynes, the insertion of the internal alkyne occurs in preference to the insertion of CO.
Insulin sensitizers in treatment of nonalcoholic fatty liver disease: Systematic review (2006)

Current information indicates that the use of insulin sensitizers in NAFLD improves insulin resistance and liver function. Histological changes must be corroborated in randomized controlled trials.
Relationship between antibacterial activity and porin binding of lactoferrin in Escherichia coli and Salmonella typhimurium (1993)

The effect of lactoferrin (Lf) on bacterial growth was tested by measuring conductance changes in the cultivation media by using a Malthus-AT system and was compared with the magnitude of 125I-labeled Lf binding in 15 clinical isolates of Escherichia coli. The binding property was inversely related to the change in bacterial metabolic rate (r = 0.91) and was directly related to the degree of bacteriostasis (r = 0.79). The magnitude of Lf-bacterium interaction showed no correlation with the MIC of Lf. In certain strains, Lf at supraoptimal levels reduced the bacteriostatic effect. Thus, the Lf concentration in the growth media was critical for the antibacterial effect. The cell envelopes of Salmonella typhimurium 395MS with smooth lipopolysaccharide (LPS) and its five isogenic rough mutants revealed 38-kDa porin proteins as peroxidase-labeled-Lf-reactive components in sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot (ligand blot) analysis. However, in the whole cell binding assay, parent strain 395MS demonstrated a very low interaction with 125I-Lf. On the other hand, Lf interaction gradually increased in correspondence with the decrease in LPS polysaccharide moiety in the isogenic rough mutants. Conductance measurement studies revealed that the low-level-Lf-binding (low-Lf-binding) strain 395MS with smooth LPS was relatively insusceptible to Lf, while the high-Lf-binding mutant Rd was more susceptible to Lf. These data suggested a correlation between Lf binding to porins and the Lf-mediated antimicrobial effect. The polysaccharide moiety of LPS shielded porins from the Lf interaction and concomitantly decreased the antibacterial effect.
Sputum ECP Levels Correlate with Parameters of Airflow Obstruction (1992)

Growing evidence suggests that eosinophils play an important role as proinflammatory cells in asthma, possibly by releasing toxic cationic proteins. In this study concentrations of serum and sputum eosinophil cationic protein (ECP) from 134 patients with productive cough and a history suggestive of airflow obstruction were measured by radioimmunoassay. Small sputum volumes were suspended in saline, vortexed, and centrifuged and ECP measured in the supernatant. Serum ECP levels ranged from 0.002 to 0.095 mg/L (0.016 +/- 0.0014), whereas sputum ECP concentrations were between 0.024 and 5.66 mg/L ECP per g sputum (0.878 +/- 0.092). Only 17 of the 134 patients (14 asthma, one cystic fibrosis, one bronchiectasis, and one bronchitis) had not been pretreated with corticosteroids. Sputum but not serum ECP levels of the 14 patients with asthma were inversely correlated with impairment of FEV1 (r = -0.73). Airway resistance (Raw) (r = 0.71) as well as the change in FEV1 (r = 0.79) and Raw (r = 0.84) after inhalation of 0.2 mg albuterol were positively correlated. This relationship was not observed in the remaining 117 patients on topical and/or systemic corticosteroids, suggesting that corticosteroid treatment influences sputum ECP levels. Also, sputum ECP levels and the degree of sputum eosinophilia were not correlated in any of the patient groups. Neither did serum ECP levels predict sputum ECP concentrations. We conclude that sputum ECP concentrations serve as a marker of eosinophil degranulation in the sputum, and this marker correlates with airflow obstruction. Sputum ECP levels are more closely related to lung function parameters than serum ECP concentrations and/or microscopic sputum analysis.
Tn7 transposition: two transposition pathways directed by five Tn7-encoded genes. (1988)

The bacterial transposon Tn7 is capable of high-frequency transposition to a specific site in the Escherichia coli chromosome, attTn7, and of low-frequency transposition to sites other than attTn7. Using an in vitro insertional mutagenesis procedure, we have identified and characterized five tns (Tn seven) genes that are essential for Tn7 transposition. Three of these genes, tnsA, tnsB, and tnsC, are required, but are not sufficient, for all Tn7 transposition events. In addition, tnsD is specifically required for transposition to attTn7, whereas tnsE is specifically required for transposition to other sites. Thus, Tn7 is an elaborate transposon that encodes two distinct but overlapping transposition pathways.
Butyrate, neuroepigenetics and the gut microbiome: Can a high fiber diet improve brain health? (2016)

As interest in the gut microbiome has grown in recent years, attention has turned to the impact of our diet on our brain. The benefits of a high fiber diet in the colon have been well documented in epidemiological studies, but its potential impact on the brain has largely been understudied. Here, we will review evidence that butyrate, a short-chain fatty acid (SCFA) produced by bacterial fermentation of fiber in the colon, can improve brain health. Butyrate has been extensively studied as a histone deacetylase (HDAC) inhibitor but also functions as a ligand for a subset of G protein-coupled receptors and as an energy metabolite. These diverse modes of action make it well suited for solving the wide array of imbalances frequently encountered in neurological disorders. In this review, we will integrate evidence from the disparate fields of gastroenterology and neuroscience to hypothesize that the metabolism of a high fiber diet in the gut can alter gene expression in the brain to prevent neurodegeneration and promote regeneration.
A Roadside Scattering Model for the Vehicle-to-Vehicle Communication Channel (2013)

Achieving accurate and effective modeling of the vehicle-to-vehicle (V2V) communication channel has proven to be a challenging task, particularly owing to the highly dynamic nature of vehicular environments. V2V channels generally may have contributions from the line-of-sight path, reflections from large stationary and moving objects such as bridges and other vehicles, and a diffuse base from large numbers of small stationary objects in the environment. We propose a new geometrical model for the diffuse component based on scattering objects distributed along the roadside, and use this model to predict the Doppler spectrum and angle-of-arrival distribution associated with this component for various V2V scenarios. In contrast with previous roadside scattering models that sum the contributions from large numbers of randomly-generated scattering objects, our model assumes a uniform linear distribution along the roadside. This permits a computationally efficient, closed-form model. Comparisons with on-road measurement data as well as the double ring model demonstrate the validity and effectiveness of the proposed model.
A Critical Evaluation of Anti-IL-13 and Anti-IL-4 Strategies in Severe Asthma (2016)

Asthma is a high-prevalence disease, still accounting for mortality and high direct and indirect costs. It is now recognized that, despite the implementation of guidelines, a large proportion of cases remain not controlled. Certainly, adherence to therapy and the education of patients remain the primary objective, but the increasingly detailed knowledge about the pathogenic mechanisms and new biotechnologies offer the opportunity to better address and treat the disease. Interleukin (IL)-13 and IL-4 appear as the most suitable targets to treat the T helper 2 (TH2)-mediated forms (endotypes) of asthma. IL-13 and IL-4 partly share the same receptor and signaling pathways and both are deeply involved in immunoglobulin E (IgE) synthesis, eosinophil activation, mucus secretion and airways remodeling. Several anti-IL-13 strategies have been proposed (anrukinzumab, lebrikizunab and tralokinumab), with relevant clinical results reported with lebrikizumab. Such studies facilitate better definition of the possible predictive markers of response to a specific treatment (e.g. eosinophils, total IgE, fraction of exhaled nitric oxide and periostin). In parallel, anti-IL-4 strategies have been attempted (pascolizumab, pitakinra and dupilumab). So far, dupilumab was reported capable of reducing the severity of asthma and the rate of exacerbations. IL-13 and IL-4 are crucial in TH2-mediated inflammation in asthma, but it remains clear that only specific endotypes respond to these treatments. Although the use of anti-IL-14 and anti-IL-13 strategies is promising, the search for appropriate predictive biomarkers is urgently needed to better apply biological treatments.
A Novel Human CC Chemokine, Eotaxin-3, Which Is Expressed in IL-4-Stimulated Vascular Endothelial Cells, Exhibits Potent Activity Toward Eosinophils (1999)

IL-4 has been shown to be involved in the accumulation of leukocytes, especially eosinophils, at sites of inflammation by acting on vascular endothelial cells. To identify novel molecules involved in the IL-4-dependent eosinophil extravasation, cDNA prepared from HUVEC stimulated with IL-4 was subjected to differential display analysis, which revealed a novel CC chemokine designated as eotaxin-3. The human eotaxin-3 gene has been localized to chromosome 7q11.2, unlike most other CC chemokine genes. The predicted mature protein of 71 aa showed 27-42% identity to other human CC chemokines. The recombinant protein induced a transient increase in the cytosolic Ca2+ concentration and in vitro chemotaxis on eosinophils. Furthermore, in cynomolgus monkeys, the accumulation of eosinophils was observed at the sites where the protein was injected. Eotaxin-3 inhibited the binding of 125I-eotaxin, but not 125I-macrophage inflammatory protein-1alpha, to eosinophils and acted on cell lines transfected with CCR-3, suggesting that eotaxin-3 recognized CCR-3. IL-13 as well as IL-4 up-regulated eotaxin-3 mRNA in HUVEC, whereas neither TNF-alpha, IL-1beta, IFN-gamma, nor TNF-alpha plus IFN-gamma did. The expression profile of eotaxin-3 is different from those of eotaxin, RANTES, and monocyte chemoattractant protein-4, which are potent eosinophil-selective chemoattractants and are induced by either TNF-alpha or TNF-alpha plus IFN-gamma. These results suggest that eotaxin-3 may contribute to the eosinophil accumulation in atopic diseases.
Suppression of nonsense-mediated mRNA decay permits unbiased gene trapping in mouse embryonic stem cells (2005)

An international collaborative project has been proposed to inactivate all mouse genes in embryonic stem (ES) cells using a combination of random and targeted insertional mutagenesis techniques. Random gene trapping will be the first choice in the initial phase, and gene-targeting experiments will then be carried out to individually knockout the remaining 'difficult-to-trap' genes. One of the most favored techniques of random insertional mutagenesis is promoter trapping, which only disrupts actively transcribed genes. Polyadenylation (poly-A) trapping, on the other hand, can capture a broader spectrum of genes including those not expressed in the target cells, but we noticed that it inevitably selects for the vector integration into the last introns of the trapped genes. Here, we present evidence that this remarkable skewing is caused by the degradation of a selectable-marker mRNA used for poly-A trapping via an mRNA-surveillance mechanism, nonsense-mediated mRNA decay (NMD). We also report the development of a novel poly-A-trap strategy, UPATrap, which suppresses NMD of the selectable-marker mRNA and permits the trapping of transcriptionally silent genes without a bias in the vector-integration site. We believe the UPATrap technology enables a simple and straightforward approach to the unbiased inactivation of all mouse genes in ES cells.
Description of the mutations in 15 subjects with variant forms of maple syrup urine disease (2007)

The results of this study indicate that genotyping may be predictive of clinical severity of variant MSUD phenotypes and might be of prognostic value particularly in subjects with variant MSUD identified in newborn screening in whom early treatment fortunately slows the natural course of the disease.
Acute Experimental Allergic Encephalomyelitis in SJL/J Mice Induced by a Synthetic Peptide of Myelin Proteolipid Protein (1990)

Clinical, histologic, and ultrastructural characteristics of acute experimental allergic encephalomyelitis (EAE) induced by sensitization with a synthetic peptide corresponding to mouse myelin proteolipid protein (PLP) residues 139-151 HCLGKWLGHPDKF were studied in SJL/J mice. Groups of mice were immunized with 20, 50, or 100 nmol of the peptide and were killed from seven to 28 days after sensitization or when they were moribund. Beginning on Day 9, the mice showed signs of EAE and the disease progressed rapidly to paralysis. Central nervous system (CNS) inflammation, edema, gliosis, and demyelination were found in all mice killed between Days 10 and 28 and white matter lesion areas correlated with clinical score at the time the mice were killed. Peripheral nerve roots and the cauda equina did not have lesions. Within the range studied, the severity of clinical or histologic disease was the same regardless of the PLP peptide dose. Two of ten mice immunized with 100 nmol and none of 14 mice given smaller doses of a synthetic peptide of mouse myelin basic protein (MBP) showed clinical EAE. These mice had small numbers of CNS lesions that were indistinguishable from those in PLP peptide-sensitized mice. These findings demonstrate that immunization of SJL/J mice with PLP peptide 139-151 produces a disease with the clinical and morphologic features of CNS tissue-, whole PLP-, whole MBP-, and MBP peptide-induced acute EAE. Thus, PLP is a major encephalitogen and immune reactions to epitopes of different myelin proteins may induce identical patterns of injury in the CNS.
The Pathobiology of Amyotrophic Lateral Sclerosis: A Proteinopathy? (2005)

Amyotrophic lateral sclerosis (ALS) is increasingly considered to be a disorder of multiple etiologies that have in common progressive degeneration of both upper and lower motor neurons, ultimately giving rise to a relentless loss of muscle function. This progressive degeneration is associated with heightened levels of oxidative injury, excitotoxicity, and mitochondrial dysfunction--all occurring concurrently. In this article, we review the evidence that suggests, in common with other age-dependent neurodegenerative disorders, that ALS can be considered a disorder of protein aggregation. Morphologically, this is evident as Bunina bodies, ubiquitin-immunoreactive fibrils or aggregates, neurofilamentous aggregates, mutant copper/zinc superoxide dismutase (SOD1) aggregates in familial ALS variants harboring mutations in SOD1, peripherin-immunoreactive aggregates within spinal motor neurons and as neuroaxonal spheroids, and in an increasingly greater population of patients with ALS with cognitive impairment, both intra- and extraneuronal tau aggregates. We review the evidence that somatotopically specific patterns of altered kinase and phosphatase activity are associated with alterations in the phosphorylation state of these proteins, altering either solubility or assembly characteristics. The role of nonneuronal cells in mediating motor neuronal injury is discussed in the context of alterations in tyrosine kinase activity and enhanced protein phosphorylation.
Biochemical Approaches for Evaluating Drug—Receptor Interactions (1987)

A productive drug screening program entails various levels of analysis. Although it is ultimately necessary to demonstrate a bioogical response in intact animals, in vivo tests are labor-intensive and require significant quantities of compound, limiting their utility as primary screens. More desirable are simple, inexpensive tests that allow for the rapid identification of inactive or less active compounds. This can be achieved in many instances by measuring an in vitro biochemical response related to the action of a particular drug class. Such tests require only small amounts of sample and can be used for analyzing dozens of compounds in a matter of hours. By providing the pharmacologist and chemist with information about potency, efficacy, and structure-activity characteristics, this methodology enables them to select a few lead agents that can then be subjected to more detailed examination in secondary and tertiary screens.
Structural determinants of allosteric antagonism at metabotropic glutamate receptor 2: mechanistic studies with new potent negative allosteric modulators (2011)

This is the first complete molecular investigation of the allosteric binding pocket of mGlu₂ and Group II mGluRs and provides new information on what determines mGlu₂ NAMs selective interactions and effects.
Term Infants Fed Formula Supplemented With Selected Blends of Prebiotics Grow Normally and Have Soft Stools Similar to Those Reported for Breast‐fed Infants (2007)

Infants fed formula supplemented with a prebiotic mixture achieved normal growth and stool characteristics more similar to those of breast-fed infants in comparison with infants fed an unsupplemented formula. A pediatrician needs to consider the risk of possible intolerance against the benefits of prebiotics.