Miracle-dz/UniFAR-FTUs huggingface dataset:
Reactivation of latent Epstein-Barr virus by methotrexate: a potential contributor to methotrexate-associated lymphomas.

BACKGROUND Patients with rheumatoid arthritis or polymyositis treated with methotrexate (MTX) develop Epstein-Barr virus (EBV)-positive lymphomas more frequently than patients treated with other, equally immunosuppressive regimens. Here we determined whether MTX, in contrast to other commonly used medications for rheumatoid arthritis or polymyositis, is unique in its ability to induce the release of infectious EBV from latently infected cells. METHODS The effect of MTX and other immunosuppressant drugs on EBV replication in vitro was assessed using latently infected EBV-positive lymphoblastoid and gastric carcinoma cell lines. Inhibitors of signal transduction pathways were used to define requirements for induction of lytic infection. Drug effects on transcription of the two EBV immediate-early promoters (BRLF1 and BZLF1) and on promoter constructs lacking cis-acting sequences required for activation by other effectors was examined using reporter gene assays. EBV viral load in rheumatoid arthritis and polymyositis patients receiving MTX was compared with that in patients receiving other immunosuppressive medications. Statistical tests were two-sided. RESULTS MTX activated the release of infectious EBV from latently infected cell lines in vitro, and MTX treatment was associated with activation of the two viral immediate-early promoters in reporter gene assays. Induction of lytic EBV infection by MTX required the p38 MAP kinase, PI3 kinase, and MEK pathways and specific cis-acting motifs in the two viral immediate-early promoters. Patients treated with MTX-containing regimens had statistically significantly higher mean EBV loads in their blood than patients treated with immunosuppressing regimens that did not include MTX (40 EBV copies per 10(6) cellular genomes versus 5.1 copies; geometric mean fold difference in copies = 10.8, 95%, confidence interval = 3.0 to 38; P = . 011). CONCLUSION MTX may promote EBV-positive lymphomas in rheumatoid arthritis and polymyositis patients by its immunosuppressive properties as well as by reactivating latent EBV.
Higher-order Models in Computer Vision Image Processing and Analysing Graphs: Theory and Practice Higher-order Models in Computer Vision 1.2 Higher-order Random Fields

1.1 Introduction Many computer vision problems such as object segmentation, disparity estimation, and 3D reconstruction can be formulated as pixel or voxel labeling problems. The conventional methods for solving these problems use pairwise Conditional and Markov Random Field (CRF/MRF) formulations [1], which allow for the exact or approximate inference of Maximum a Posteriori (MAP) solutions. MAP inference is performed using extremely efficient algorithms such as combinatorial methods (e.g. graph-cut [2, 3, 4] or the BHS-algorithm [5, 6]), or message passing based techniques (e.g. The classical formulations for image labelling problems represent all output elements using random variables. An example is the problem of interactive object cutout where each pixel is represented using a random variable which can take two possible labels: foreground or background. The conventionally used pairwise random field models introduce a statistical relationship between pairs of random variables, often only among the immediate 4 or 8 neighboring pixels. Although such models permit efficient inference, they have restricted expressive power. In particular, they are unable to enforce the high-level structural dependencies between pixels that have been shown to be extremely powerful for image labeling problems. For instance, while segmenting an object in 2D or 3D, we might know that all its pixels (or parts) are connected. Standard pairwise MRFs or CRFs are not able to guarantee that their solutions satisfy such a constraint. To overcome this problem, a global potential function is needed which assigns all such invalid solutions a zero probability or an infinite energy. Despite substantial work from several communities, pairwise MRF and CRF models for computer vision problems have not been able to solve image labelling problems such as object segmentation fully. This has led researchers to question the richness of these classical pairwise energy function based formulations, which in turn has motivated the development of more sophisticated models. Along these lines, many have turned to the use of higher-order models that are more expressive, thereby enabling the capture of statistics of natural images more closely. The last few years have seen the successful application of higher-order CRFs and MRFs to some low-level vision problems such as image restoration, disparity estimation and object segmentation Researchers have used models composed of new families of higher-order potentials i.e. potentials defined over multiple variables, which have higher modelling power and lead to more accurate models of the problem. Researchers have also investigated incorporation of constraints such as connectivity of …
CONTINUED COOLING OF THE CRUST IN THE NEUTRON STAR LOW-MASS X-RAY BINARY KS 1731−260

Some neutron star low-mass X-ray binaries have very long outbursts (lasting several years) which can generate a significant amount of heat in the neutron star crust. After the system has returned to quiescence, the crust then thermally relaxes. This provides a rare opportunity to study the thermal properties of neutron star crusts, putting constraints on the thermal conductivity and hence the structure and composition of the crust. KS 1731−260 is one of only four systems where this crustal cooling has been observed. Here, we present a new Chandra observation of this source approximately eight years after the end of the last outburst and four years since the last observation. We find that the source has continued to cool, with the cooling curve displaying a simple power-law decay. This suggests that the crust has not fully thermally relaxed yet and may continue to cool further. A simple power-law decay is in contrast to theoretical cooling models of the crust, which predict that the crust should now have cooled to the same temperature as the neutron star core.
Educators' ambivalence and managing anxiety in providing sex education for people with learning disabilities

Little is known about how HIV/AIDS affects people with disabilities, although international literature suggests that people with learning disabilities and other disabilities may be at increased vulnerability to HIV infection. One factor that increases vulnerability to HIV is the lack of sex education and resulting knowledge about safe sex. People with learning disabilities have historically been excluded from sex education as they have often been perceived as being either asexual or over-sexed, and this sex education is either irrelevant or potentially dangerous. For those that work with people with learning disabilities, they may have to work with notions of damage, vulnerability and dependency, which may be disavowed aspects of the self which are projected on to people with disabilities. The work is made more difficult by the anxieties that issues of sex and sexuality raise. This article reports on a study exploring the experiences of educators providing sex education for people with learning disabilities in South Africa. The interview narratives were subject to a psychosocial analysis, drawing on a psychoanalytic framework to explore possible unconscious emotional aspects of participants' work. The analysis reveals ambivalent feelings about providing sex education for people with disabilities, where on the one hand the need for sex education is recognised, but there is some anxiety about the potential to cause harm or that providing sex education will lead to inappropriate sexual behaviour.
Rewiring MAP kinases in Saccharomyces cerevisiae to regulate novel targets through ubiquitination

Evolution has often copied and repurposed the mitogen-activated protein kinase (MAPK) signaling module. Understanding how connections form during evolution, in disease and across individuals requires knowledge of the basic tenets that govern kinase-substrate interactions. We identify criteria sufficient for establishing regulatory links between a MAPK and a non-native substrate. The yeast MAPK Fus3 and human MAPK ERK2 can be functionally redirected if only two conditions are met: the kinase and substrate contain matching interaction domains and the substrate includes a phospho-motif that can be phosphorylated by the kinase and recruit a downstream effector. We used a panel of interaction domains and phosphorylation-activated degradation motifs to demonstrate modular and scalable retargeting. We applied our approach to reshape the signaling behavior of an existing kinase pathway. Together, our results demonstrate that a MAPK can be largely defined by its interaction domains and compatible phospho-motifs and provide insight into how MAPK-substrate connections form. DOI: http://dx.doi. org/10.7554/eLife.15200. 001
AIK 1 , A Mitogen-Activated Protein Kinase , Modulates Abscisic Acid Responses through the MKK 5-MPK 6 Kinase Cascade 1 [ OPEN ]

The mitogen-activated protein kinase (MAPK) cascade is an evolutionarily conserved signal transduction module involved in transducing extracellular signals to the nucleus for appropriate cellular adjustment. This cascade essentially consists of three components: a MAPK kinase kinase (MAPKKK), a MAPK kinase, and a MAPK, connected to each other by the event of phosphorylation. Here, we report the characterization of a MAPKKK, ABA-INSENSITIVE PROTEIN KINASE1 (AIK1), which regulates abscisic acid (ABA) responses in Arabidopsis (Arabidopsis thaliana). T-DNA insertion mutants of AIK1 showed insensitivity to ABA in terms of both root growth and stomatal response. AIK1 functions in ABA responses via regulation of root cell division and elongation, as well as stomatal responses. The activity of AIK1 is induced by ABA in Arabidopsis and tobacco (Nicotiana benthamiana), and the Arabidopsis protein phosphatase type 2C, ABI1, a negative regulator of ABA signaling, restricts AIK1 activity by dephosphorylation. Bimolecular fluorescence complementation analysis showed that MPK3, MPK6, and AIK1 interact with MKK5. The single mutant seedlings of mpk6 and mkk5 have similar phenotypes to aik1, but mkk4 does not. AIK1 was localized in the cytoplasm and shown to activate MKK5 by protein phosphorylation, which was an ABA-activated process. Constitutively active MKK5 in aik1 mutant seedlings complements the ABA-insensitive root growth phenotype of aik1. The activity of MPK6 was increased by ABA in wild-type seedlings, but its activation by ABA was impaired in aik1 and aik1 mkk5 mutants. These findings clearly suggest that the AIK1-MKK5-MPK6 cascade functions in the ABA regulation of primary root growth and stomatal response.
Preparation of Pure Hepatocytes and Reticuloendothelial Cells in High Yield From a Single Rat Liver by Means of Percoll Centrifugation and Selective Adherence

A rapid method for mass isolation of functionally intact hepatocytes and reticuloendothelial cells from a single rat liver is described. The technique is based on collagenase perfusion of the liver, isopycnic sedimentation in Percoll, and selective adherence of the cells. The Kupffer cells (KC) attach and spread on glass or plastic in serum‐free medium 15 min following seeding. Cultures of KC are 90%–95% pure with about 5% liver endothelial cells (LEC), <1% parenchymal cells (PC) and a maximum of 5% stellate cells (SC). The LEC adhere and spread on fibronectin 60–120 min following seeding, forming cultures that are contaminated with 5–10% SC and <1% KC and PC. The yield of plated LEC is 50–60 × 106 per 200‐g rat. Ultrastructural analysis shows that Percoll does not associate with the cells during the separation procedure.
Tracking Women’s Transitions to Adulthood

Theories suggest curricular tracking is linked to racial/ethnic inequality. However, prior studies largely examine cognitive outcomes like standardized test scores and neglect behavioral outcomes. They also overlook potential racial/ethnic differences within curricular tracks. This study asks the following questions: (a) Is curricular tracking associated with young women’s social and behavioral outcomes during the transition to adulthood (dropping out of high school, teen motherhood, and poverty)? and (b) Are there racial/ethnic differences in these associations? Using National Longitudinal Survey of Youth data and logistic regression, results show that all women reduce risks of negative outcomes in the college and vocational tracks compared with the general track. However, college track coursework buffers White women from dropping out and teen motherhood (but not poverty) significantly more than it does Black and Latina women. Thus, racial gaps are greatest within the college track rather than lower tracks, suggesting that the college track may be a site for opportunity hoarding among Whites.
Optical Images of an Exosolar Planet 25 Light-Years from Earth

Fomalhaut, a bright star 7.7 parsecs (25 light-years) from Earth, harbors a belt of cold dust with a structure consistent with gravitational sculpting by an orbiting planet. Here, we present optical observations of an exoplanet candidate, Fomalhaut b. Fomalhaut b lies about 119 astronomical units (AU) from the star and 18 AU of the dust belt, matching predictions of its location. Hubble Space Telescope observations separated by 1.73 years reveal counterclockwise orbital motion. Dynamical models of the interaction between the planet and the belt indicate that the planet's mass is at most three times that of Jupiter; a higher mass would lead to gravitational disruption of the belt, matching predictions of its location. The flux detected at 0.8 μm is also consistent with that of a planet with mass no greater than a few times that of Jupiter. The brightness at 0.6 μm and the lack of detection at longer wavelengths suggest that the detected flux may include starlight reflected off a circumplanetary disk, with dimension comparable to the orbits of the Galilean satellites. We also observe variability of unknown origin at 0.6 μm.
Mass-mortality in green striped tree dragons (Japalura splendida) associated with multiple viral infections

In spring 2011, high mortality in association with skin lesions, systemic haemorrhages and necrosis occurred in a group of green striped tree dragons (Japalura splendida) which were imported from southwestern China via Florida to Germany. Infections with various endoparasites were diagnosed in coprological examinations. Different antiparasitic and antibiotic treatments over a period of three months did not reduce the mortality rate. The remaining animals were therefore euthanased and submitted for additional testing. Predominant findings in pathological examination were granulomatous and necrotising inflammation of the skin, vacuolar tubulonephrosis of the distal renal tubules, hyperaemia and liver necrosis. Eosinophilic intranuclear and basophilic intracytoplasmic inclusion bodies were detected in the liver. Virological testing (PCR and virus isolation methods) demonstrated the presence of ranavirus, adenovirus and invertebrate iridovirus.
Keeping up with the Joneses: Interpersonal Prediction Errors and the Correlation of Behavior in a Tandem Sequential Choice Task

In many settings, copying, learning from or assigning value to group behavior is rational because such behavior can often act as a proxy for valuable returns. However, such herd behavior can also be pathologically misleading by coaxing individuals into behaviors that are otherwise irrational and it may be one source of the irrational behaviors underlying market bubbles and crashes. Using a two-person tandem investment game, we sought to examine the neural and behavioral responses of herd instincts in situations stripped of the incentive to be influenced by the choices of one's partner. We show that the investments of the two subjects correlate over time if they are made aware of their partner's choices even though these choices have no impact on either player's earnings. We computed an “interpersonal prediction error”, the difference between the investment decisions of the two subjects after each choice. BOLD responses in the striatum, implicated in valuation and action selection, were highly correlated with this interpersonal prediction error. The revelation of the partner's investment occurred after all useful information about the market had already been revealed. This effect was confirmed in two separate experiments where the impact of the time of revelation of the partner's choice was tested at 2 seconds and 6 seconds after a subject's choice; however, the effect was absent in a control condition with a computer partner. These findings strongly support the existence of mechanisms that drive correlated behavior even in contexts where there is no explicit advantage to do so.
Population Representative Gait Speed and Its Determinants

Purpose: Although gait speed is an important measure to obtain from older adults, much is uncertain about the measure. Therefore, using a large population‐based sample, I sought to: (1) gain an indication of “normal” gait speed, (2) compare speed measured over 8 and 20 feet, (3) determine the relationship of several independent variables with gait speed. Methods: The National Health and Nutrition Examination Survey (NHANES) 2001–2002 provided the following data for individuals (≥ 50 years, n = 1923): gait speed over 8 and 20 feet, age, stature, adiposity, and isokinetic knee extension force. Estimates of normal gait speed were calculated for gender and age strata. Speeds over 8 and 20 feet were compared using a paired t‐test and a Pearson correlation. The relationship between the independent variables and gait speed were examined using Pearson correlations and forward multiple regression analysis. Results: Mean gait speeds were 3.26 ft/sec and 3.29 ft/sec over 8 and 20 feet, respectively. Speeds over the distances differed significantly (p = .002) but not meaningfully; they were correlated strongly (r = .933, p < .001). Age, stature, knee extension force, and waist circumference correlated significantly (p < .004) with gait speed over both distances. Age, gender, knee extension force, waist circumference, and stature were shown by multiple regression to predict walking speed over both 8 feet (R = .459, p < .001) and 20 feet (R = .506, p < .001). Conclusions: The estimates of normal gait speed provided are slower than many of those previously published but may be more representative of the population. As gait speed measured over 8 and 20 feet are comparable, using the shorter distance appears justifiable. Individuals walk faster who are younger, male, taller, stronger, and have smaller waists.
Die Bevorzugung von genetischen Verwandten im Lebenslauf

Zusammenfassung: Das Konzept der verwandtschaftlichen Orientierung bezieht sich auf einen evolvierten Mechanismus der Bevorzugung von genetisch verwandten gegenuber nichtverwandten und genetisch naher verwandten gegenuber genetisch entfernter verwandten Personen. Die verwandtschaftliche (nepotistische) Orientierung wird durch die Korrelation zwischen genetischer Verwandtschaft und emotionaler Nahe innerhalb individueller sozialer Netzwerke indiziert (Neyer & Lang, 2003). In dieser Studie wurde die 4-Jahresstabilitat der nepotistischen Orientierung mit unterschiedlichen Methoden in 2 unabhangigen Stichproben untersucht (489 junge Erwachsene und 206 Hochbetagte im Durchschnittsalter von 28 bzw. 84 Jahren). Die Befunde stutzen die Annahme einer relativ stabilen nepotistischen Orientierung als evolvierter psychologischer Adaptation, die aber auf individueller Ebene angesichts der hohen Plastizitat des menschlichen Sozialverhaltens je nach Umweltbedingungen einigen Schwankungen unterliegt.
Reconsidering the Low-Fear Explanation for Primary Psychopathy

Lykken's book, The Antisocial Personalities, is an informative and entertaining book with much to commend it. Written by a senior scientist with established expertise in psychophysiology, behavior genetics, and psychopathy, Lykken's experience and expertise enable him to provide clear and concise tutorials on evolution, genetics, and the relevance of temperament-related traits to the socialization process. Especially valuable is Lykken's emphasis on the heterogeneity of criminal behavior that, it follows, requires diverse explanations. With this background, the reader is prepared to understand that antisocial behavior results from a complex and continuous interaction of innate characteristics and environment. Lykken defines his subject matter by subdividing antisocial behavior into three broad categories: normal, psychopathic, and sociopathic. He goes on to outline alternative etiological explanations for these syndromes. One of the two major goals of his book, according to Lykken, is to review the experimental literature concerning a specific psychopathic subtype, the primary psychopath. The focus of this review includes: (a) differentiating primary psychopathy from the related syndromes of sociopathy and secondary psychopathy, (b) a reanalysis of the low-fear hypothesis that stems from his classic 1957 study on psychopathy, and (c) consideration of alternative explanations for this syndrome. Lykken concludes that primary psychopathy may result from "the rearing by typical parents of a child who is normal in all respects save for a below-average endowment of innate fearlessness" (p. 154). He argues that his proposal is superior to alternative models and states that "the time is ripe for the low-fear hypothesis of primary psychopathy to be reconsidered" (p. 155). Our goal is to evaluate Lykken's conclusions regarding the primary psychopath. Distinguishing Psychopathy and Sociopathy
Perspective Taking Through Narratives

This study investigated the use of a narrative-based language intervention program for teaching perspective-taking skills to students with autism spectrum disorders (ASD). The participants consisted of 18 students between the ages of 9 years 7 months and 12 years 2 months (M = 10:8) who had a diagnosis of an ASD. Students received 500 minutes of either a narrative-based intervention that focused on teaching perspective taking (PTI) or a traditional narrative-based language intervention (NBLI) that focused on story elements and semantics. Intervention was provided in small groups consisting of five students and one speech-language pathologist. The participants who received the PTI demonstrated greater growth in their ability to retell the story from the perspective of different characters compared to those who participated in the NBLI. Clinical implications are included.