Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of the Extracellular Signal-Regulated Protein Kinase Cascade in Human Neutrophil Killing of Staphylococcus aureus andCandida albicans and in Migration

ABSTRACT Killing of Staphylococcus aureus and Candida albicans by neutrophils involves adherence of the microorganisms, phagocytosis, and a collaborative action of oxygen reactive species and components of the granules. While a number of intracellular signalling pathways have been proposed to regulate neutrophil responses, the extent to which each pathway contributes to the killing of S. aureus and C. albicans has not been clearly defined. We have therefore examined the effect of blocking one such pathway, the extracellular signal-regulated protein kinase (ERK) cascade, using the specific inhibitor of the mitogen-activated protein kinase/ERK kinase, PD98059, on the ability of human neutrophils to killS. aureus and C. albicans. Our data demonstrate the presence of ERK2 and a 43-kDa form of ERK but not ERK1 in human neutrophils. Upon stimulation with formyl methionyl leucyl phenylalanine (fMLP), the activities of both ERK2 and the 43-kDa form were stimulated. Despite abrogating the activity of both ERK forms, PD98059 only slightly reduced the ability of neutrophils to killS. aureus or C. albicans. This is consistent with our finding that PD98059 had no effect on neutrophil adherence or degranulation, although pretreatment of neutrophils with PD98059 inhibited fMLP-stimulated superoxide production by 50%, suggesting that a change in superoxide production per se is not strictly correlated with microbicidal activity. However, fMLP-stimulated chemokinesis was markedly inhibited, while random migration and fMLP-stimulated chemotaxis were partially inhibited, by PD98059. These data demonstrate, for the first time, that the ERK cascade plays only a minor role in the microbicidal activity of neutrophils and that the ERK cascade is involved primarily in regulating neutrophil migration in response to fMLP.
The Pleasure of Making a Difference: Perceived Social Contribution Explains the Relation Between Extraverted Behavior and Positive Affect

Why are trait extraversion and extraverted behaviors both associated with greater positive affect? Across 3 studies, we examined whether 2 aspects of social experience—perceived social contribution and social power—mediate the relation between extraversion and positive affect. Study 1 (N = 205) showed that trait measures of social contribution and power mediated the relation between trait extraversion and trait positive affect. Study 2 (N = 78) showed that state social contribution and power helped to explain the greater levels of state positive affect reported by participants who were instructed to enact extraverted behaviors. Finally, Study 3 (N = 62) showed that social contribution and power mediated the relation between natural fluctuations in extraverted behavior and positive affect states in daily life. In all 3 studies, multiple-mediator models showed that social contribution, but not power, independently mediated the relations that trait and state extraversion had with positive affect. This suggests that perceptions of positive influence—more so than a general sense of power—help to explain why extraverts and extraverted moments are happier. We link these findings to emerging trends in the study of personality dynamics and the potential benefits of acting “out of character. ”
RNA expression microarray analysis in mouse prospermatogonia: Identification of candidate epigenetic modifiers

The mammalian totipotent and pluripotent lineage exhibits genome‐wide dynamics with respect to DNA methylation content. The first phase of global DNA demethylation and de novo remethylation occurs during preimplantation development and gastrulation, respectively, while the second phase occurs in primordial germ cells and primary oocytes/prospermatogonia, respectively. These dynamics are indicative of a comprehensive epigenetic resetting or reprogramming of the genome in preparation for major differentiation events. To gain further insight into the mechanisms driving DNA methylation dynamics and other types of epigenetic modification, we performed an RNA expression microarray analysis of fetal prospermatogonia at the stage when they are undergoing rapid de novo DNA remethylation. We have identified a number of highly or specifically expressed genes that could be important for determining epigenetic change in prospermatogonia. These data provide a useful resource in the discovery of molecular pathways involved in epigenetic reprogramming in the mammalian germ line. Developmental Dynamics 237:1082–1089, 2008. © 2008 Wiley‐Liss, Inc.
Representation of Confidence in Assurance Cases Using the Beta Distribution

Assurance cases are used to document an argument that a system -- such as a critical software system -- satisfies some desirable property (e.g., safety, security, or reliability). Demonstrating high confidence that the claims made based on an assurance case can be trusted is crucial to the success of the case. Researchers have proposed quantification of confidence as a Baconian probability ratio of eliminated concerns about the assurance case to the total number of identified concerns. In this paper, we extend their work by mapping this discrete ratio to a continuous probability distribution -- a beta distribution -- enabling different visualizations of the confidence in a claim. Further, the beta distribution allows us to quantify and visualize theuncertainty associated with the expressed confidence. Additionally, by transforming the assurance case into a reasoning structure, we show how confidence calculations can be performed using beta distributions.
Inflammatory etiopathogenesis of systemic lupus erythematosus: an update

The immune system struggles every day between responding to foreign antigens and tolerating self-antigens to delicately maintain tissue homeostasis. If self-tolerance is broken, the development of autoimmunity can be the consequence, as it is in the case of the chronic inflammatory autoimmune disease systemic lupus erythematosus (SLE). SLE is considered to be a multifactorial disease comprising various processes and cell types that act abnormally and in a harmful way. Oxidative stress, infections, or, in general, tissue injury are accompanied by massive cellular demise. Several processes such as apoptosis, necrosis, or NETosis (formation of Neutrophil Extracellular Traps [NETs]) may occur alone or in combination. If clearance of dead cells is insufficient, cellular debris may accumulate and trigger inflammation and leakage of cytoplasmic and nuclear autoantigens like ribonucleoproteins, DNA, or histones. Inadequate removal of cellular remnants in the germinal centers of secondary lymphoid organs may result in the presentation of autoantigens by follicular dendritic cells to autoreactive B cells that had been generated by chance during the process of somatic hypermutation (loss of peripheral tolerance). The improper exposure of nuclear autoantigens in this delicate location is consequently prone to break self-tolerance to nuclear autoantigens. Indeed, the germline variants of autoantibodies often do not show autoreactivity. The subsequent production of autoantibodies plays a critical role in the development of the complex immunological disorder fostering SLE. Immune complexes composed of cell-derived autoantigens and autoantibodies are formed and get deposited in various tissues, such as the kidney, leading to severe organ damage. Alternatively, they may also be formed in situ by binding to planted antigens of circulating autoantibodies. Here, we review current knowledge about the etiopathogenesis of SLE including the involvement of different types of cell death, serving as the potential source of autoantigens, and impaired clearance of cell remnants, causing accumulation of cellular debris.
SGR 0418+5729—HOW DOES A YOUNG NEUTRON STAR SPIN DOWN TO A 9 s PERIOD WITH A DIPOLE FIELD LESS THAN 1013 G?

The period derivative bound for the soft gamma-ray repeater SGR 0418+5729 establishes the magnetic dipole moment to be distinctly lower than the magnetar range, placing the source beyond the regime of isolated pulsar activity in the diagram and giving a characteristic age >2 × 107 yr, much older than the 105 yr age range of SGRs and anomalous X-ray pulsars. So the spin-down must be produced by a mechanism other than dipole radiation in vacuum. A fallback disk will spin down a neutron star with surface dipole magnetic field in the 1012 G range and initial rotation period P0 ∼ 100 ms to the 9.1 s period of SGR 0418+5729 in a few 104 to ∼105 yr. The current upper limit to the period derivative gives a lower limit of ∼105 yr to the age that is not sensitive to the neutron star's initial conditions. The total magnetic field on the surface of SGR 0418+5729 could be significantly larger than its 1012 G dipole component.
The Environmental “Riskscape” and Social Inequality: Implications for Explaining Maternal and Child Health Disparities

Background Research indicates that the double jeopardy of exposure to environmental hazards combined with place-based stressors is associated with maternal and child health (MCH) disparities. Objective and Discussion Our aim is to present evidence that individual-level and place-based psychosocial stressors may compromise host resistance such that environmental pollutants would have adverse health effects at relatively lower doses, thus partially explaining MCH disparities, particularly poor birth outcomes. Allostatic load may be a physiologic mechanism behind the moderation of the toxic effect of environmental pollutants by social stressors. We propose a conceptual framework for holistic approaches to future MCH research that elucidates the interplay of psychosocial stressors and environmental hazards in order to better explain drivers of MCH disparities. Conclusion Given the complexity of the link between environmental factors and MCH disparities, a holistic approach to future MCH research that seeks to untangle the double jeopardy of chronic stressors and environmental hazard exposures could help elucidate how the interplay of these factors shapes persistent racial and economic disparities in MCH.
Cosmological imprint of an energy component with general equation of state

We examine the possibility that a significant component of the energy density of the Universe has an equation of state different from that of matter, radiation, or cosmological constant ({Lambda} ). An example is a cosmic scalar field evolving in a potential, but our treatment is more general. Including this component alters cosmic evolution in a way that fits current observations well. Unlike {Lambda} , it evolves dynamically and develops fluctuations, leaving a distinctive imprint on the microwave background anisotropy and mass power spectrum. {copyright} {ital 1998} {ital The American Physical Society}
On Higher Dimensional Window Query: Revisited using BITS-Tree

We present a dynamic index structure using Balanced Inorder Threaded Segment Tree to store orthogonal rectangles in R2 and an efficient method of finding rectangle intersections. Although PR-Trees is known to be the best known data structure in the I/O model for this problem and performs window query in O((N/B)1-1/d + T/B) I/Os, where N is the number of d-dimensional rectangles, B is the disk block size, and T is the output size, the dynamic insertion of rectangles requires reconstruction of the tree. In the pointer machine model, since the Balanced Inorder Threaded Segment Tree (BITS-Tree) permits dynamic updates of one dimensional segments in logarithmic time, we store the horizontal and vertical segment information of rectangles into two separate BITS-Trees and solve the rectangle intersection problem in O(log n + k) time where k is the maximum number of rectangles reported, with support for dynamic updates in O(log n) time. Also, this is extended to d (d > 2) dimensional objects with a query time of O(d(log n + m)) where k is the maximum number of nodes of rectangles and update time of O(d log n) that shows an improvement over query time of range trees of O(log n + m) where m is the number of rectangles reported.
Cerebral hemodynamic impairment

Article abstract Stenosis or occlusion of the major arteries of the head and neck may cause hemodynamic impairment of the distal cerebral circulation. Hemodynamic factors may play an important role in the pathogenesis of ischemic stroke for patients with cerebrovascular disease. Several neuroimaging methods are currently available for the indirect assessment of the hemodynamic effect of atherosclerotic stenosis or occlusion on the distal cerebrovasculature. Because these methods rely on different underlying physiologic mechanisms, they are not interchangeable. Two basic categories of hemodynamic impairment can be assessed with these techniques: Stage 1, in which autoregulatory vasodilation secondary to reduced perfusion pressure is inferred by the measurement of either increased blood volume or an impaired blood flow response to a vasodilatory stimulus; and Stage 2, in which increased oxygen extraction fraction (OEF) is noninvasively but directly measured. The correlation of different Stage 1 methods with each other and with Stage 2 techniques is quite variable. Clinical studies associating different manifestations of hemodynamic impairment with stroke risk often suffer from methodologic problems. The best evidence to date for such an association is for increased OEF measured in patients with symptomatic carotid occlusion. In the absence of data demonstrating improvement in patient outcome, there is currently no role for the routine use of these tools to guide clinical management in patients with cerebrovascular disease.
Asymptotic tracking control for a class of reference signals for linear differential inclusions

Tracking control for linear differential inclusions with disturbances is investigated in this paper. Based on the convex hull Lyapunov function, a feedback control law is designed such that the output of the closed-loop system without disturbances globally asymptotically tracks the desired reference signal. Under the bounded disturbances, the tracking error is bounded. An example is given to illustrate how to make the output of the closed-loop system track a sinusoidal signal, a cosine signal and a circular signal. The simulation shows the effectiveness of the proposed method.
Terrain-Influenced tornadogenesis in the Northeastern United States: An examination of the 29 May 1995 Great Barrington, Massachusetts, tornado

On 29 May 1995, a supercell thunderstorm traveling a corridor across prominent topographic landforms in the northeastern United States (US) produced an almost continuous 50 km track tornado that caused damage of up to F3 intensity (Grazulus 1997). The damage swath ranged up to 1 km in width, with severe forest destruction and structural damage reported. Maximum impact was felt in Great Barrington (GBR), Massachusetts, where widespread structural damage occurred and 3 people were killed when a vehicle was thrown more than 500 m by the tornado (Storm Data, 1995). The purpose of this paper is to conduct a detailed examination of the evolution of the GBR storm and its interaction with the complex terrain. A terrain and station/county location map with the GBR tornado track superimposed appears in Fig. 1. In its size, intensity, longevity, and most significantly, its occurrence over complex terrain, the GBR tornado represents a rare event, though it is far from unique. On occasion, tornadic storms will form over relatively flat terrain but then propagate into hilly or mountainous regions with their tornadic circulations remaining intact. Examples include the long-track Adirondack tornado in New York State in 1845 (Ludlam 1970), the Shinnston,
Paralanguage in Computer Mediated Communication

This paper reports on some of the components of person to person communication mediated by computer conferenceing systems. Transcripts from two systems were analysed: the Electronic Information and Exchange System (EIES), based at the New Jersey Institute of Technology; and Planet, based at Infomedia Inc. in Palo Alto, California. The research focused upon the ways in which expressive communication is encoded by users of the medium
Sequential Designs for Phase I Clinical Trials with Late‐Onset Toxicities

Summary. Traditional designs for phase I clinical trials require each patient (or small group of patients) to be completely followed before the next patient or group is assigned. In situations such as when evaluating late‐onset effects of radiation or toxicities from chemopreventive agents, this may result in trials of impractically long duration. We propose a new method, called the time‐to‐event continual reassessment method (TITE‐CRM), that allows patients to be entered in a staggered fashion. It is an extension of the continual reassessment method (CRM; O'Quigley, Pepe, and Fisher, 1990, Biometrics46, 33–48). We also note that this time‐to‐toxicity approach can be applied to extend other designs for studies of short‐term toxicities. We prove that the recommended dose given by the TITE‐CRM converges to the correct level under certain conditions. A simulation study shows our method's accuracy and safety are comparable with CRM's while the former takes a much shorter trial duration: a trial that would take up to 12 years to complete by the CRM could be reduced to 2–4 years by our method.
Histone Demethylase KDM6B Promotes Epithelial-Mesenchymal Transition*

Background: TGF-β induces EMT to regulate tumor invasion and metastasis. Results: TGF-β induces KDM6B and promotes EMT by activating SNAI1 via removing H3K27me3 marks. Conclusion: KDM6B is required for TGF-β-induced EMT and breast cancer cell invasion. Significance: Our findings highlight a novel epigenetic mechanism regulating EMT and cancer cell invasion and have potential implications in targeting metastatic breast cancer. Epithelial-mesenchymal transition (EMT) is a critical event that occurs in embryonic development, tissue repair control, organ fibrosis, and carcinoma invasion and metastasis. Although significant progress has been made in understanding the molecular regulation of EMT, little is known about how chromatin is modified in EMT. Chromatin modifications through histone acetylation and methylation determine the precise control of gene expression. Recently, histone demethylases were found to play important roles in gene expression through demethylating mono-, di-, or trimethylated lysines. KDM6B (also known as JMJD3) is a histone demethylase that might activate gene expression by removing repressive histone H3 lysine 27 trimethylation marks from chromatin. Here we report that KDM6B played a permissive role in TGF-β-induced EMT in mammary epithelial cells by stimulating SNAI1 expression. KDM6B was induced by TGF-β, and the knockdown of KDM6B inhibited EMT induced by TGF-β. Conversely, overexpression of KDM6B induced the expression of mesenchymal genes and promoted EMT. Chromatin immunoprecipitation (ChIP) assays revealed that KDM6B promoted SNAI1 expression by removing histone H3 lysine trimethylation marks. Consistently, our analysis of the Oncomine database found that KDM6B expression was significantly increased in invasive breast carcinoma compared with normal breast tissues. The knockdown of KDM6B significantly inhibited breast cancer cell invasion. Collectively, our study uncovers a novel epigenetic mechanism regulating EMT and tumor cell invasion, and has important implication in targeting cancer metastasis.
Debate: challenges in sports cardiology; US versus European approaches

For practitioners working with elite athletes, the field of sports cardiology provides clinical, academic, administrative and fiscal challenges. These challenges are exemplified and reinforced by the lack of consistency and consensus both in the literature and academic presentations. Through the presentation of a series of clinical questions, this debate attempts to ‘cut to the chase’ on cardiovascular issues relevant to the clinician dealing with elite athletes. In so doing, we hope to crystallize some of the most important elements of the complex cardiological management of elite athletes, in a concise, readable format. Frequently over the last 10 years, many of the controversies in this field have been (rightly or wrongly) presented in a Europe versus USA paradigm. We have chosen to test whether there really are polarised views across the Atlantic, by deliberately pitting specialists from the USA against those from the UK. Professors Levine and Thompson are both internationally recognised sports cardiologists, with immense academic and clinical credibility, and who will represent the ‘US approach’. Professor Whyte and Doctor Wilson are cardiac physiologists with a wealth of experience in the testing, evaluation and screening of elite athletes, and who have equally impressive academic credibility and for the purposes of this debate, they will be representing the ‘European approach’. To initiate this process, each team was required to provide a concise answer (circa 200–300 words) to a series of five clinical conundrums. Subsequently, each team had the opportunity to provide a rebuttal to the opposing team's answers, and the following reflects the consolidation of those answers. A popular debate in the literature and the conference podium is the clinical utility of the ECG in the preparticipation screening of athletes. If one assumes that the overall cost:benefit of cardiac screening for athletes remains to be determined, is it now established that the …
Reduced Testosterone During Puberty Results in a Midspermiogenic Lesion

Abstract The aim of this study was to determine the role of testosterone, as reflected in the testicular interstitial fluid, in the completion of the first wave of spermatogenesis and to further elucidate its role in spermiogenesis. At weekly intervals beginning with 26-day-old rats, body and testis weights were obtained, testicular interstitial fluid testosterone (TIF-T) was assayed, daily sperm production (DSP) was determined, and testicular tissue was structurally analyzed by light and electron microscopy. At 40 days postpartum, half the rats were treated with ethane dimethanesulphonate (EDS) to temporarily reduce Leydig cells. The other half served as controls and were treated with the vehicle. The timing of EDS treatment was just prior to the elongation of spermatids. At Day 47 (1 week after EDS treatment), TIF-T, testis weight, DSP, and number of Leydig cells were significantly reduced. At Day 54 (2 weeks after treatment), TIF-T had returned to the normal adult level, Leydig cell repopulation was apparent, and testis weight was normal. The DSP returned to normal by Day 61 (3 weeks after treatment). At 1 and 2 weeks after treatment, Step 8-9 spermatids were partially or completely detached from Sertoli cells. Results indicate that a temporary reduction of testosterone during the peripubertal period leads to a temporary reduction of the DSP approximately 1 week later. It is suggested that reduced testosterone is associated with a mid-spermiogenic lesion interfering with stable attachment of Step 8–9 spermatids to Sertoli cells during Stage VIII-IX of the spermatogenic cycle.