gebhart/patrepeval huggingface dataset:
Vav1/Rac-dependent actin cytoskeleton reorganization is required for lipid raft clustering in T cells (2001)

Formation of the immunological synapse (IS) in T cells involves large scale molecular movements that are mediated, at least in part, by reorganization of the actin cytoskeleton. Various signaling proteins accumulate at the IS and are localized in specialized membrane microdomains, known as lipid rafts. We have shown previously that lipid rafts cluster and localize at the IS in antigen-stimulated T cells. Here, we provide evidence that lipid raft polarization to the IS depends on an intracellular pathway that involves Vav1, Rac, and actin cytoskeleton reorganization. Thus, lipid rafts did not translocate to the IS in Vav1-deficient (Vav1-/-) T cells upon antigen stimulation. Similarly, T cell receptor transgenic Jurkat T cells also failed to translocate lipid rafts to the IS when transfected with dominant negative Vav1 mutants. Raft polarization induced by membrane-bound cholera toxin cross-linking was also abolished in Jurkat T cells expressing dominant negative Vav1 or Rac mutants and in cells treated with inhibitors of actin polymerization. However, Vav overexpression that induced F-actin polymerization failed to induce lipid rafts clustering. Therefore, Vav is necessary, but not sufficient, to regulate lipid rafts clustering and polarization at the IS, suggesting that additional signals are required.
Mesoscopic EMR Device Magnetic Sensitivity in $I$–$V$–$I$ –$V$ Configuration (2009)

Extraordinary magnetoresistance devices with critical dimensions below 50 nm have been developed in InAs 2-D electron gas (2DEG) quantum well heterostructures, and show the same magnetic sensitivity as Giant magnetoresistance magnetic recording sensors. A new device design, in which fingers of metal extend into the semiconductor mesa to form leads, yields higher signal and operating currents than the more conventional design with semiconductor tab contacts. Devices built with the 2DEG very close to the surface yield high-signal and high-current carrying capacity, as required for scanning probe and magnetic recording applications.
Optimized clinical performance of growth hormone with an expanded genetic code (2011)

The ribosomal incorporation of nonnative amino acids into polypeptides in living cells provides the opportunity to endow therapeutic proteins with unique pharmacological properties. We report here the first clinical study of a biosynthetic protein produced using an expanded genetic code. Incorporation of p -acetylphenylalanine (pAcF) at distinct locations in human growth hormone (hGH) allowed site-specific conjugation with polyethylene glycol (PEG) to produce homogeneous hGH variants. A mono-PEGylated mutant hGH modified at residue 35 demonstrated favorable pharmacodynamic properties in GH-deficient rats. Clinical studies in GH-deficient adults demonstrated efficacy and safety comparable to native human growth hormone therapy but with increased potency and reduced injection frequency. This example illustrates the utility of nonnative amino acids to optimize protein therapeutics in an analogous fashion to the use of medicinal chemistry to optimize conventional natural products, low molecular weight drugs, and peptides.
Myostatin inhibition induces muscle fibre hypertrophy prior to satellite cell activation (2012)

Muscle fibres are multinucleated post-mitotic cells that can change dramatically in size during adulthood. It has been debated whether muscle fibre hypertrophy requires activation and fusion of muscle stem cells, the satellite cells. Myostatin (MSTN) is a negative regulator of skeletal muscle growth during development and in the adult, and MSTN inhibition is therefore a potential therapy for muscle wasting diseases, some of which are associated with a depletion of satellite cells. Conflicting results have been obtained in previous analyses of the role of MSTN on satellite cell quiescence. Here, we inhibited MSTN in adult mice with a soluble activin receptor type IIB and analysed the incorporation of new nuclei using 5-bromo-2-deoxyuridine (BrdU) labelling by isolating individual myofibres. We found that satellite cells are activated by MSTN inhibition. By varying the dose and time course for MSTN inhibition, however, we found that myofibre hypertrophy precedes the incorporation of new nuclei, and that the overall number of new nuclei is relatively low compared to the number of total myonuclei. These results reconcile some of the previous work obtained by other methods. In contrast with previous reports, we also found that Mstn null mice do not have increased satellite cell numbers during adulthood and are not resistant to sarcopaenia. Our results support a previously proposed model of hypertrophy in which hypertrophy can precede satellite cell activation. Studies of the metabolic and functional effects of postnatal MSTN inhibition are needed to determine the consequences of increasing the cytoplasm/myonuclear ratio after MSTN inhibition.
User-calibration-free remote eye-gaze tracking system with extended tracking range (2011)

A novel general method to extend the tracking range of user-calibration-free remote eye-gaze tracking (REGT) systems that are based on the analysis of stereo-images from multiple cameras is presented. The method consists of two distinct phases. In the brief initial phase, estimates of the center of the pupil and corneal reflections in pairs of stereo images are used to estimate automatically a set of subject-specific eye parameters. In the second phase, these subject-specific eye parameters are used with estimates of the center of the pupil and corneal reflections in images from any one of the systems' cameras to compute the Point-of-Gaze (PoG). Experiments with a system that includes two cameras show that the tracking range for horizontal gaze directions can be extended from ±23.2° when the two cameras are used as a stereo pair to ±35.5° when the two cameras are used independently to estimate the POG.
Receptor Interaction Profiles of 4-Alkoxy-3,5-Dimethoxy-Phenethylamines (Mescaline Derivatives) and Related Amphetamines (2022)

3,4,5-Trimethoxyphenethylamine (mescaline) is a psychedelic alkaloid found in peyote cactus. Related 4-alkoxy-3,5-dimethoxy-substituted phenethylamines (scalines) and amphetamines (3C-scalines) are reported to induce similarly potent psychedelic effects and are therefore potential novel therapeutics for psychedelic-assisted therapy. Herein, several pharmacologically uninvestigated scalines and 3C-scalines were examined at key monoamine targets <i>in vitro</i>. Binding affinity at human serotonergic 5-HT<sub>1A</sub>, 5-HT<sub>2A</sub>, and 5-HT<sub>2C</sub>, adrenergic α<sub>1A</sub> and α<sub>2A</sub>, and dopaminergic D<sub>2</sub> receptors, rat and mouse trace amine-associated receptor 1 (TAAR1), and human monoamine transporters were assessed using target specific transfected cells. Furthermore, activation of human 5-HT<sub>2A</sub> and 5-HT<sub>2B</sub> receptors, and TAAR1 was examined. Generally, scalines and 3C-scalines bound with weak to moderately high affinity to the 5-HT<sub>2A</sub> receptor (<i>K</i> <sub>i</sub> = 150-12,000 nM). 3C-scalines showed a marginal preference for the 5-HT<sub>2A</sub> vs the 5-HT<sub>2C</sub> and 5-HT<sub>1A</sub> receptors whereas no preference was observed for the scalines. Extending the 4-alkoxy substituent increased 5-HT<sub>2A</sub> and 5-HT<sub>2C</sub> receptors binding affinities, and enhanced activation potency and efficacy at the 5-HT<sub>2A</sub> but not at the 5-HT<sub>2B</sub> receptor. Introduction of fluorinated 4-alkoxy substituents generally increased 5-HT<sub>2A</sub> and 5-HT<sub>2C</sub> receptors binding affinities and increased the activation potency and efficacy at the 5-HT<sub>2A</sub> and 5-HT<sub>2B</sub> receptors. Overall, no potent affinity was observed at non-serotonergic targets. As observed for other psychedelics, scalines and 3C-scalines interacted with the 5-HT<sub>2A</sub> and 5-HT<sub>2C</sub> receptors and bound with higher affinities (up to 63-fold and 34-fold increase, respectively) when compared to mescaline.
The Future of DNA Sequencing: Methods and Applications (1996)

The Human Genome Project entails the determination of the DNA sequence of a set of samples that will represent a single human genome. The identity of the particular base, A, T, C or G, at each position along 24 pieces of DNA encompassing one example of each of the human (H. sapiens) chromosomes, will be revealed. A total of about 3 billion bases will be identified. Along the way, the DNA sequence of several model genomes will be determined including a worm, C. elegans, a fly, D. melanogaster, a yeast, S. cerevisiae, and a bacterium, E. coli. All of these model genomes together amount to less than 20% of one human genome. In addition, depending on the efficiency and cost of the methods finally employed for most of the sequencing, we will also see revealed some or all of the DNA sequence of the common laboratory mouse, M. musculus. It is clear that, with the technology currently in hand, it will be possible to obtain the set of fragments needed for this DNA sequencing effort (this process is called physical mapping) and then read the sequence of each of these fragments for a total cost approximating the original estimate of $3 billion.
North of England evidence based guideline development project: guideline on the use of aspirin as secondary prophylaxis for vascular disease in primary care (1998)

Patients who have had cardiovascular disease and stroke are treated with aspirin to reduce their subsequent risk of vascular events or death and thereby to increase the length and quality of their life. This guideline aims to provide general practitioners with evidence linked recommendations on the use of aspirin as secondary prophylaxis for cardiovascular disease and stroke in patients at high risk of these disorders. It is assumed that doctors will use their knowledge and clinical judgment in managing individual patients in the light of available resources. Recommendations may not be appropriate for use in all circumstances. This is a summary of the full version of the guideline.1

#### Summary points

The use of aspirin in the secondary prophylaxis of vascular disease is cost effective

Aspirin should be used in patients with acute myocardial infarction, prior myocardial infarction, stable and unstable angina, and prior stroke or transient ischaemic attack

In acute myocardial infarction a dose of 150 mg daily should be used

In the other indications a dose of 75 mg daily should be used

In general practice, patients with a raised risk of vascular disease present with several disorders—acute or previous myocardial infarction, unstable or stable angina, transient ischaemic attacks, and peripheral vascular disease. The incidence and prevalence of these conditions and the workload associated with them in general practice can be estimated from the recent national morbidity survey in general practice for England and Wales, and is shown in the table.2

View this table:

Diseases associated with a raised risk of vascular events—incidence, prevalence, and workload in a general practice, assuming a list size of 2000 patients



Throughout this guideline the strength of statements on evidence and of recommendations is categorised according to the scheme discussed in the first paper in the series.3 The box below shows these categories in descending …
Heterogeneous Loss of Connexin43 Protein in Ischemic Dog Hearts (1999)

Cx43 undergoes both distribution and concentration changes following acute cardiac ischemia. The loss of Cx43 protein is heterogeneous. Cx43 dephosphorylation occurred within 1 hour following ischemia.
Uma História, Diversas Possibilidades : O Trabalho com Gênero da Literatura Infantil sob uma Perspectiva de Ensino Bilígue para Surdos no 1º ano do Ensino Fundamental (2000)

O presente artigo traz o relato de uma experiencia educacional com duas turmas do 1o ano das series iniciais do Colegio de Aplicacao do Instituto Nacionalde Educacao de surdos – Cap INES, tendo como ponto de partida a utilizacao da historia do genero da literatura infantil “Chapeuzinho vermelho”.
Transition Metals in Control of Gene Expression (1993)

Metalloproteins play structural and catalytic roles in gene expression. The metalloregulatory proteins are a subclass that exerts metal-responsive control of genes involved in respiration, metabolism, and metal-specific homeostasis or stress-response systems, such as iron uptake and storage, copper efflux, and mercury detoxification. Two allosteric mechanisms for control of gene expression were first discovered in metalloregulatory systems: an iron-responsive translational control mechanism for ferritin production and a mercury-responsive DNA-distortion mechanism for transcriptional control of detoxification genes. These otherwise unrelated mechanisms give rise to a rapid physiological response when metal ion concentrations exceed a dangerous threshold. Molecular recognition in these allosteric metal ion receptors is achieved through atypical coordination geometries, cluster formation, or complexes with prosthetic groups, such as sulfide and heme. Thus, many of the inorganic assemblies that otherwise buttress the structure of biopolymers or catalyze substrate transformation in active sites of enzymes have also been adapted to serve sensor functions in the metalloregulatory proteins. Mechanistic studies of these metal-sensor protein interactions are providing new insights into fundamental aspects of inorganic chemistry, molecular biology, and cellular physiology.
Crystal structure of Drosophila angiotensin I‐converting enzyme bound to captopril and lisinopril1 (2003)

Angiotensin I-converting enzymes (ACEs) are zinc metallopeptidases that cleave carboxy-terminal dipeptides from short peptide hormones. We have determined the crystal structures of AnCE, a Drosophila homolog of ACE, with and without bound inhibitors to 2.4 A resolution. AnCE contains a large internal channel encompassing the entire protein molecule. This substrate-binding channel is composed of two chambers, reminiscent of a peanut shell. The inhibitor and zinc-binding sites are located in the narrow bottleneck connecting the two chambers. The substrate and inhibitor specificity of AnCE appears to be determined by extensive hydrogen-bonding networks and ionic interactions in the active site channel. The catalytically important zinc ion is coordinated by the conserved Glu395 and histidine residues from a HExxH motif.
Pyruvate:NADP Oxidoreductase from the Mitochondrion of Euglena gracilis and from the Apicomplexan Cryptosporidium parvum: A Biochemical Relic Linking Pyruvate Metabolism in Mitochondriate and Amitochondriate Protists (2001)

Most eukaryotes perform the oxidative decarboxylation of pyruvate in mitochondria using pyruvate dehydrogenase (PDH). Eukaryotes that lack mitochondria also lack PDH, using instead the O(2)-sensitive enzyme pyruvate : ferredoxin oxidoreductase (PFO), which is localized either in the cytosol or in hydrogenosomes. The facultatively anaerobic mitochondria of the photosynthetic protist Euglena gracilis constitute a hitherto unique exception in that these mitochondria oxidize pyruvate with the O(2)-sensitive enzyme pyruvate : NADP oxidoreductase (PNO). Cloning and analysis of Euglena PNO revealed that the cDNA encodes a mitochondrial transit peptide followed by an N-terminal PFO domain that is fused to a C-terminal NADPH-cytochrome P450 reductase (CPR) domain. Two independent 5.8-kb full-size cDNAs for Euglena mitochondrial PNO were isolated; the gene was expressed in cultures supplied with 2% CO(2) in air and with 2% CO(2) in N(2). The apicomplexan Cryptosporidium parvum was also shown to encode and express the same PFO-CPR fusion, except that, unlike E. gracilis, no mitochondrial transit peptide for C. parvum PNO was found. Recombination-derived remnants of PNO are conserved in the genomes of Saccharomyces cerevisiae and Schizosaccharomyces pombe as proteins involved in sulfite reduction. Notably, Trypanosoma brucei was found to encode homologs of both PFO and all four PDH subunits. Gene organization and phylogeny revealed that eukaryotic nuclear genes for mitochondrial, hydrogenosomal, and cytosolic PFO trace to a single eubacterial acquisition. These findings suggest a common ancestry of PFO in amitochondriate protists with Euglena mitochondrial PNO and Cryptosporidium PNO. They are also consistent with the view that eukaryotic PFO domains are biochemical relics inherited from a facultatively anaerobic, eubacterial ancestor of mitochondria and hydrogenosomes.
Polyelectrolyte persistence length: Attractive effect of counterion correlations and fluctuations (2003)

The persistence length of a single, strongly charged, stiff polyelectrolyte chain is investigated theoretically. Path integral formulation is used to obtain the effective electrostatic interaction between the monomers. We find significant deviations from the classical Odijk, Skolnick and Fixman (OSF) result. An induced attraction between monomers is due to thermal fluctuations and correlations between bound counterions. The electrostatic persistence length is found to be smaller than the OSF value and indicates a possible mechanical instability (collapse) for highly charged polyelectrolytes with multivalent counterions. In addition, we calculate the amount of condensed counterions on a slightly bent polyelectrolyte. More counterions are found to be adsorbed as compared to the Manning condensation on a cylinder.
Abstract 2789: C-reactive protein and risk of lung cancer (2010)

Abstract Background: Chronic inflammation could act as a co-factor to tobacco smoke in increasing lung cancer risk, underscoring the potential for both lung cancer prevention and screening. We investigated the association of circulating high-sensitivity C-reactive protein (CRP) and CRP single nucleotide polymorphisms (SNPs) with prospective risk of lung cancer. Methods: We conducted a nested case-control study of 592 lung cancers and 670 controls with available pre-diagnostic serum and 378 cases and 447 controls with available DNA within the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (N=77,464). Controls were matched to cases on age, sex, entry year, follow-up time, and smoking status (cumulative amount and time since quitting). We measured CRP levels in baseline serum samples and genotyped 5 common CRP SNPs. Results: Elevated CRP levels were associated with increased lung cancer risk (odds ratio [OR] for individuals in the fourth quartile (Q4, ≥5.6 mg/L) vs. those in Q1 (&amp;lt;1.0 mg/L)=1.98; 95% CI=1.35-2.89), with a trend for increasing risk across CRP quartiles (p-trend&amp;lt;0.001). This association was most apparent for squamous cell carcinomas (OR=2.92; 95% CI=1.30-6.54), in the 2-5 years before lung cancer diagnosis (OR=2.33; 95% CI=1.24-4.39), and among former (OR=2.48; 95% CI=1.53-4.03) and current smokers (OR=1.90; 95% CI=1.06-3.41). Although CRP SNPs and haplotypes were associated with significant differences in CRP levels, they were not associated with lung cancer risk. Ten-year standardized absolute risks of lung cancer were higher with elevated CRP levels, among both former (Q4=2.55% vs. Q1=1.39%) and current smokers (Q4=7.37% vs. Q1=4.03%). Conclusions: Elevated CRP levels are associated with subsequently increased lung cancer risk, in support of an etiologic role for chronic pulmonary inflammation in lung carcinogenesis. The separation in lung cancer absolute risks across circulating CRP levels among former and current smokers provides preliminary evidence for the utility of CRP measurements in lung cancer risk stratification. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2789.
Pixel-Based Machine Learning in Medical Imaging (2012)

Machine learning (ML) plays an important role in the medical imaging field, including medical image analysis and computer-aided diagnosis, because objects such as lesions and organs may not be represented accurately by a simple equation; thus, medical pattern recognition essentially require "learning from examples." One of the most popular uses of ML is classification of objects such as lesions into certain classes (e.g., abnormal or normal, or lesions or nonlesions) based on input features (e.g., contrast and circularity) obtained from segmented object candidates. Recently, pixel/voxel-based ML (PML) emerged in medical image processing/analysis, which use pixel/voxel values in images directly instead of features calculated from segmented objects as input information; thus, feature calculation or segmentation is not required. Because the PML can avoid errors caused by inaccurate feature calculation and segmentation which often occur for subtle or complex objects, the performance of the PML can potentially be higher for such objects than that of common classifiers (i.e., feature-based MLs). In this paper, PMLs are surveyed to make clear (a) classes of PMLs, (b) similarities and differences within (among) different PMLs and those between PMLs and feature-based MLs, (c) advantages and limitations of PMLs, and (d) their applications in medical imaging.
Homology of the eyeless Gene of Drosophila to the Small eye Gene in Mice and Aniridia in Humans (1994)

A Drosophila gene that contains both a paired box and a homeobox and has extensive sequence homology to the mouse Pax-6 (Small eye) gene was isolated and mapped to chromosome IV in a region close to the eyeless locus. Two spontaneous mutations, ey2 and eyR, contain transposable element insertions into the cloned gene and affect gene expression, particularly in the eye primordia. This indicates that the cloned gene encodes ey. The finding that ey of Drosophila, Small eye of the mouse, and human Aniridia are encoded by homologous genes suggests that eye morphogenesis is under similar genetic control in both vertebrates and insects, in spite of the large differences in eye morphology and mode of development.
Demonstration of a semiconductor external cavitylaser using a UVwritten grating in a planar silica waveguide (1994)

The authors report the first demonstration of a semiconductor external cavity waveguide laser, modulated at 2.5 Gbit/s over 100 km of standard optical fibre using a UV written grating in a planar silica waveguide as the feedback element.