gebhart/patrepeval huggingface dataset:
The Medial Frontal Cortex and the Rapid Processing of Monetary Gains and Losses (2002)

We report the observation of neural processing that occurs within 265 milliseconds after outcome stimuli that inform human participants about gains and losses in a gambling task. A negative-polarity event-related brain potential, probably generated by a medial-frontal region in or near the anterior cingulate cortex, was greater in amplitude when a participant's choice between two alternatives resulted in a loss than when it resulted in a gain. The sensitivity to losses was not simply a reflection of detecting an error; gains did not elicit the medial-frontal activity when the alternative choice would have yielded a greater gain, and losses elicited the activity even when the alternative choice would have yielded a greater loss. Choices made after losses were riskier and were associated with greater loss-related activity than choices made after gains. It follows that medial-frontal computations may contribute to mental states that participate in higher level decisions, including economic choices.
Dural vasodilation causes a sensitization of rat caudal trigeminal neurones in vivo that is blocked by a 5‐HT1B/1D agonist (1999)

1. Migraine headache pain is thought to result from an abnormal distention of intracranial, extracerebral blood vessels and the consequent activation of the trigeminal nervous system. Migraine is also often accompanied by extracranial sensory disturbances from facial tissues. These experiments investigate whether meningeal dilation produces central sensitization of neurones that receive convergent input from the face. 2. Single unit extracellular activity was recorded from the trigeminal nucleus caudalis of anaesthetized rats in response to either noxious stimulation of the dura mater, innocuous stimulation of the vibrissae or to a transient dilation of the meningeal vascular bed. 3. Rat alpha-CGRP (calcitonin gene-related peptide; 1 microg kg(-1), i.v.) caused a dilation of the middle meningeal artery and facilitated vibrissal responses by 36+/-7%. 4. The 5-HT1B/1D agonist, L-741,604 (3 mg kg(-1), i.v.), inhibited responses to noxious stimulation of the dura mater (16+/-7% of control) and, in a separate group of animals, blocked the CGRP-evoked facilitation of vibrissal responses. 5. L-741,604 (3 mg kg(-1), i.v.) also inhibited responses to innocuous stimulation of the vibrissa (14+/-10% of control) with neurones that received convergent input from the face and from the dura mater, but not with cells that received input only from the face (70+/-12% of control). 6. These data show that dilation of meningeal blood vessels causes a sensitization of central trigeminal neurones and a facilitation of facial sensory processing which was blocked by activation of pre-synaptic 5-HT1B/1D receptors. 7. Sustained dural blood vessel dilation during migraine may cause a sensitization of trigeminal neurones. This may underlie some of the symptoms of migraine, such as the headache pain and the extracranial allodynia. Inhibition of this central sensitization may therefore offer a novel strategy for the development of acute and/or prophylactic anti-migraine therapies.
Severe Hypercholesterolemia, Impaired Fat Tolerance, and Advanced Atherosclerosis in Mice Lacking Both Low Density Lipoprotein Receptor-related Protein 5 and Apolipoprotein E (2003)

LDL receptor-related protein 5 (LRP5) plays multiple roles, including embryonic development and bone accrual development. Recently, we demonstrated that LRP5 is also required for normal cholesterol metabolism and glucose-induced insulin secretion. To further define the role of LRP5 in the lipoprotein metabolism, we compared plasma lipoproteins in mice lacking LRP5, apolipoprotein E (apoE), or both (apoE;LRP5 double knockout). On a normal chow diet, the apoE;LRP5 double knockout mice (older than 4 months of age) had approximately 60% higher plasma cholesterol levels compared with the age-matched apoE knockout mice. In contrast, LRP5 deficiency alone had no significant effects on the plasma cholesterol levels. High performance liquid chromatography analysis of plasma lipoproteins revealed that cholesterol levels in the very low density lipoprotein and low density lipoprotein fractions were markedly increased in the apoE;LRP5 double knockout mice. There were no apparent differences in the pattern of apoproteins between the apoE knockout mice and the apoE;LRP5 double knockout mice. The plasma clearance of intragastrically loaded triglyceride was markedly impaired by LRP5 deficiency. The atherosclerotic lesions of the apoE;LRP5 double knockout mice aged 6 months were approximately 3-fold greater than those in the age-matched apoE-knockout mice. Furthermore, histological examination revealed highly advanced atherosclerosis, with remarkable accumulation of foam cells and destruction of the internal elastic lamina in the apoE;LRP5 double knockout mice. These data suggest that LRP5 mediates both apoE-dependent and apoE-independent catabolism of plasma lipoproteins.
Role of satellite cells in altering myosin expression during avian skeletal muscle hypertrophy (1994)

This study examined whether satellite cells express an embryonic isoform of myosin upon fusion with hypertrophying muscle fibers. Anterior latissimus dorsi (ALD) muscle hypertrophy was induced in adult chickens by weighting one wing. One and 7 days of wing-weighting produced significant increases in ALD muscle wet weight and in the number of mature fibers expressing ventricular-like embryonic (V-EMB) myosin. V-EMB myosin expression could be an event during regeneration of fibers injured by overload or part of the hypertrophy process itself. Although there was an increase in both the number of damaged fibers and the number of mature fibers expressing embryonic myosin after wing-weighting, results from this study suggest that these two events were not necessarily related. The apparent health of fibers expressing V-EMB myosin and the lack of correlation between the numbers of damaged and V-EMB myosin positive fibers (r = 0.20) suggest that embryonic myosin expression in mature fibers was likely a feature of the hypertrophy process itself. The appearance of V-EMB myosin in mature fibers 1 day after wing-weighting suggests that the change in myosin expression did not involve satellite cells since 24 hr is too short a time to permit more than limited satellite cell fusion. The relationship between satellite cells and embryonic myosin expression was examined more closely by labeling dividing satellite cells and their progeny with 5-bromo-2-deoxyuridine, and then colocalizing labeled myofiber nuclei and embryonic myosin in consecutive transverse sections of hypertrophied ALD muscle. One week of wing-weighting resulted in marked increases in myofiber nuclear labeling index and myofiber nuclear density compared to contralateral control. V-EMB myosin was not expressed uniformly throughout individual fibers, but rather in discrete regions of varying length. Many V-EMB myosin positive regions had a higher labeled nuclear density than V-EMB myosin negative regions indicating that V-EMB myosin expression was associated with an accumulation of satellite cell progeny in a restricted area. However, it was also clear that satellite cell progeny were not the sole source of V-EMB myosin since labeled nuclei were completely absent from 41% of the V-EMB positive regions. Furthermore, the presence of new nuclei did not result in obligatory expression of embryonic myosin because many V-EMB negative regions had a high labeled nuclear density. Thus, recently incorporated nuclei arising by satellite cell division are implicated as one, but not the sole source of embryonic myosin in hypertrophying muscle.(ABSTRACT TRUNCATED AT 400 WORDS)
Critical role of X-box binding protein 1 in NADPH oxidase 4-triggered cardiac hypertrophy is mediated by receptor interacting protein kinase 1 (2016)

NADPH oxidase 4 (NOX4) and the NOX4-related redox signaling are implicated in cardiac hypertrophy. NOX4 is interrelated with endoplasmic reticulum stress (ERS). Spliced X-box binding protein 1 (Xbp1s) is a key mediator of ERS while its role in cardiac hypertrophy is still poorly understood. Recently, receptor interacting protein kinase 1(RIPK1) has been increasingly reported to be associated with ERS. Therefore, we aimed to test the hypothesis that Xbp1s mediates NOX4-triggered cardiac hypertrophy via RIPK1 signaling. In the heart tissue of transverse aortic constriction (TAC) rats and in primary cultured neonatal cardiomyocytes(NCMs) treated with angiotensinII(AngII) or isoproterenol (ISO), NOX4 expression and reactive oxygen species (ROS) generation, and expression of Xbp1s as well as RIPK1-related phosphorylation of P65 subunit of NF-κB were elevated. Gene silencing of NOX4 by specific small interfering RNA (siRNA) significantly blocked the upregulation of NOX4, generation of ROS, splicing of Xbp1 and activation of the RIPK1-related NF-κB signaling, meanwhile attenuated cardiomyocyte hypertrophy. In addition, ROS scavenger (N-acetyl-L-cysteine, NAC) and NOX4 inhibitor GKT137831 reduced ROS generation and alleviated activation of Xbp1 and RIPK1-related NF-κB signaling. Furthermore, splicing of Xbp1 was responsible for the increase in RIPK1 expression in AngII or ISO-treated NCMs. Upregulated RIPK1 in turn activates NF-κB signaling in a kinase activity-independent manner. These findings suggest that Xbp1s plays an important role in NOX4-triggered cardiomyocyte hypertrophy via activating its downstream effector RIPK1, which may prove significant for the development of future therapeutic strategies.
The PERMA-Profiler: A brief multidimensional measure of flourishing (2016)

In the book Flourish (2011), Seligman defined wellbeing in terms of five pillars: Positive emotion, Engagement, Relationships, Meaning, and Accomplishment, or PERMA. We developed the PERMA-Profiler as a brief measure of PERMA. We first compiled hundreds of theoretically relevant items. Three studies (N = 7,188) reduced, tested, and refined items, resulting in a final set of 15 questions (three items per PERMA domain). Eight additional filler items were added, which assess overall wellbeing, negative emotion, loneliness, and physical health, resulting in a final 23item measure. A series of eight additional studies (N = 31,966) were conducted to test the psychometrics of the measure. The PERMA-Profiler demonstrates acceptable model fit, internal and cross-time consistency, and evidence for content, convergent, and divergent validity. Scores are reported visually as a profile across domains, reflecting the multidimensional nature of flourishing. The PERMA-Profiler adds to the toolbox of wellbeing measures, allowing individuals to monitor their wellbeing across multiple psychosocial domains.
Polymers in Small-Interfering RNA Delivery (2011)

This review will cover the current strategies that are being adopted to efficiently deliver small interfering RNA using nonviral vectors, including the use of polymers such as polyethylenimine, poly(lactic-co-glycolic acid), polypeptides, chitosan, cyclodextrin, dendrimers, and polymers-containing different nanoparticles. The article will provide a brief and concise account of underlying principle of these polymeric vectors and their structural and functional modifications which were intended to serve different purposes to affect efficient therapeutic outcome of small-interfering RNA delivery. The modifications of these polymeric vectors will be discussed with reference to stimuli-responsiveness, target specific delivery, and incorporation of nanoconstructs such as carbon nanotubes, gold nanoparticles, and silica nanoparticles. The emergence of small-interfering RNA as the potential therapeutic agent and its mode of action will also be mentioned in a nutshell.
Comparative Study of Retinal Nerve Fiber Layer Measurement by StratusOCT and GDx VCC, II: Structure/Function Regression Analysis in Glaucoma (2005)

Description of structure/function relationships in glaucoma depends on the choice of perimetry scale, the type of RNFL measuring device, and the characteristics of the studied groups. The higher association with visual function in StratusOCT RNFL measurements compared with that in GDx VCC suggested optical coherence tomography might be a better approach for evaluating structure/function relationships. Curvilinear regression profiles found between StratusOCT RNFL thickness and MD/VF scores provide an explanation for those longitudinal observations, showing that VFs with higher AGIS/CIGTS VF scores or worse MD at baseline are at higher risk for deterioration. Regression analysis of the structure/function profile could provide important information in the assessment of the trend and pattern of glaucoma progression.
A crossover operator using independent component analysis for real-coded genetic algorithms (2002)

For real-coded genetic algorithms, there have been proposed many crossover operators. The blend crossover (BLX-/spl alpha/) proposed by L.J. Eshelman and J.D. Schaffer (1993) shows a good searching ability for separable fitness functions. However, because of its component-wise operation, BLX-/spl alpha/ faces difficulties in the optimization of non-separable fitness functions. This paper proposes a novel crossover operator that combines the BLX-/spl alpha/ with independent component analysis (ICA). By applying the ICA to the population, the coordinate system of the search space is transformed so as to increase the separability of the fitness function, and then the BLX-/spl alpha/ is applied. A computer simulation shows the good searching ability of the proposed method for non-separable fitness functions.
Microsatellite instability detection by targeted sequencing of cell-free DNA (2018)

Background: Microsatellite instability (MSI) is a guideline-recommended biomarker used in assessment of prognosis and treatment choices, including checkpoint inhibitors recently approved for cancers with MSI-high (MSI-H) status. Plasma-based next generation DNA sequencing (NGS) tests are increasingly used for comprehensive genomic profiling of cancer; however, sensitive methods to detect MSI status from cell-free DNA (cfDNA) are not available for clinical patient care. Additionally, the impact of variable tumor shedding on MSI detection has not been evaluated. Methods: We developed an accurate method to assess MSI status using targeted sequencing of cfDNA using the Guardant360® clinical platform across a many cancer types, which allows broad coverage of simple repeats. For each microsatellite locus, the number of differently-sized repeats in experimental samples is quantified using a probabilistic log likelihood-based score designed to accurately discriminate biological signal derived from cfDNA fragments of somatic origin from noise arising from technical artifacts. Loci are considered unstable if the likelihood score is greater than a threshold computed from a cohort of normal samples. MSI status of a sample is determined by the presence of a minimum 5 unstable microsatellite loci among the 91 scored. Results: We simulated MSI high (MSI-H) samples across a range of tumor fractions by combining data from 82 healthy donor samples with in silico spike-ins of differentially sized repeats. Simulated data demonstrates a sensitivity of 94% at 0.2% (limit of detection) tumor content for an expected specificity of 99.9% estimated from healthy donor samples. When applied to a prospective test set of 134 advanced cancer samples, this method demonstrated 98.5% (125/127) specificity and 86% sensitivity (6/7) relative to standard tissue PCR-based MSI assessment across a ctDNA range of 0.1%-15%. Conclusions: Targeted sequencing of cfDNA data can enable highly accurate detection of MSI in cancer samples, even for samples with low tumor shedding. This novel approach enables non-invasive assessment of MSI status concurrent with comprehensive genomic profiling and allows potential access to immunotherapies for patients whose tumor types are not routinely tested for MSI. Legal entity responsible for the study: Guardant Health, Inc. Funding: Guardant Health, Inc. Disclosure: A. Artyomenko, M. Sikora, M. Lefterova, V.M. Raymond, D. Gavino, C. Barbacioru, C. Artieri, E. Helman, D. Chudova, R.B. Lanman, J. Odegaard, A. Talasaz: Employee: Guardant Health, Inc. All other authors have declared no conflicts of interest.
Anatomy of a cortical simulator (2007)

Insights into brain's high-level computational principles will lead to novel cognitive systems, computing architectures, programming paradigms, and numerous practical applications. An important step towards this end is the study of large networks of cortical spiking neurons.
Mostly lock-free malloc (2002)

Modern multithreaded applications, such as application servers and database engines, can severely stress the performance of user-level memory allocators like the ubiquitous malloc subsystem. Such allocators can prove to be a major scalability impediment for the applications that use them, particularly for applications with large numbers of threads running on high-order multiprocessor systems.This paper introduces Multi-Processor Restartable Critical Sections, or MP-RCS. MP-RCS permits user-level threads to know precisely which processor they are executing on and then to safely manipulate CPU-specific data, such as malloc metadata, without locks or atomic instructions. MP-RCS avoids interference by using upcalls to notify user-level threads when preemption or migration has occurred. The upcall will abort and restart any interrupted critical sections.We use MP-RCS to implement a malloc package, LFMalloc (Lock-Free Malloc). LFMalloc is scalable, has extremely low latency, excellent cache characteristics, and is memory efficient. We present data from some existing benchmarks showing that LFMalloc is often 10 times faster than Hoard, another malloc replacement package.
A National Bill of Patients' Rights (1998)

In one of the most enthusiastically received proposals in his January State of the Union address, President Bill Clinton called on Congress to enact a national bill of rights in health care. The President said, “You have the right to know all your medical options, not just the cheapest. You have the right to choose the doctor you want for the care you need. You have the right to emergency room care, wherever and whenever you need it. You have the right to keep your medical records confidential.”1 The President's proposal is a follow-up to his November 1997 announcement that . . .
Efficient transformation of Bacillus thuringiensis requires nonmethylated plasmid DNA (1991)

The transformation efficiency of Bacillus thuringiensis depends upon the source of plasmid DNA. DNA isolated from B. thuringiensis, Bacillus megaterium, or a Dam- Dcm- Escherichia coli strain efficiently transformed several B. thuringiensis strains, B. thuringiensis strains were grouped according to which B. thuringiensis backgrounds were suitable sources of DNA for transformation of other B. thuringiensis strains, suggesting that B. thuringiensis strains differ in DNA modification and restriction. Efficient transformation allowed the demonstration of developmental regulation of cloned crystal protein genes in B. thuringiensis.
Neighboring-group study in solvolyses of cyclopentyl and cyclohexyl tosylates (1969)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNeighboring-group study in solvolyses of cyclopentyl and cyclohexyl tosylatesDonald Duane Roberts and William HendricksonCite this: J. Org. Chem. 1969, 34, 8, 2415–2417Publication Date (Print):August 1, 1969Publication History Published online1 May 2002Published inissue 1 August 1969https://pubs.acs.org/doi/10.1021/jo01260a034https://doi.org/10.1021/jo01260a034research-articleACS PublicationsRequest reuse permissionsArticle Views124Altmetric-Citations3LEARN 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
CD40, an extracellular receptor for binding and uptake of Hsp70–peptide complexes (2002)

Tumor and viral antigens elicit a potent immune response by heat shock protein-dependent uptake of antigenic peptide with subsequent presentation by MHC I. Receptors on antigen-presenting cells that specifically bind and internalize a heat shock protein-peptide complex have not yet been identified. Here, we show that cells expressing CD40, a cell surface protein crucial for B cell function and autoimmunity, specifically bind and internalize human Hsp70 with bound peptide. Binding of Hsp70-peptide complex to the exoplasmic domain of CD40 is mediated by the NH(2)-terminal nucleotide-binding domain of Hsp70 in its ADP state. The Hsp70 cochaperone Hip, but not the bacterial Hsp70 homologue DnaK, competes formation of the Hsp70-CD40 complex. Binding of Hsp70-ADP to CD40 is strongly increased in the presence of Hsp70 peptide substrate, and induces signaling via p38. We suggest that CD40 is a cochaperone-like receptor mediating the uptake of exogenous Hsp70-peptide complexes by macrophages and dendritic cells.
Exploiting retrograde transport of Shiga‐like toxin 1 for the delivery of exogenous antigens into the MHC class I presentation pathway (1999)

Shiga-like toxin 1 (SLT) from Escherichia coli O157:H7 enters mammalian cells by endocytosis from the cell surface to the endoplasmic reticulum before translocating into the cytosol. Here, SLT was engineered at its N- or C-terminus to carry a peptide derived from influenza virus Matrix protein for delivery to major histocompatibility complex (MHC) class I molecules. We show that SLT N-Ma was capable of sensitising cells for lysis by appropriate cytotoxic T-lymphocytes whilst no killing of SLT-resistant cells was observed. Our results demonstrate that peptide was liberated intracellularly and that retrograde transport of a disarmed cytotoxic protein can intersect the MHC class 1 presentation pathway.
Low-dose ultrasound effects on wound healing: a controlled study with Yucatan pigs. (1992)

This study reports on the effect of low-dose ultrasound in accelerating wound healing in matched pairs of surgically induced incisions and full-thickness and partial-thickness lesions in 11 Yucatan mini-pigs after 7 days of healing and 5 days of sonation. Tensile strength, collagen deposition (hydroxyproline), reduction in wound size (full-thickness lesion), and mast-cell degranulation were significantly greater in the sonated lesions than in the sham-treated controls (p = 0.01). Sonation enhanced strength by 24% and collagen deposition by 29%, when compared with controls. There were no significant differences in the quality of healing as measured by an ordinal scale. The results suggest that within the first week of healing, low-dose ultrasound facilitates wound healing. More research is needed to confirm the most effective dose, frequency, and treatment duration and intervention time for maximum healing.