Miracle-dz/UniFAR-FTUs huggingface dataset:
Sindbis Virus Nonstructural Protein nsP2 Is Cytotoxic and Inhibits Cellular Transcription

ABSTRACT Replication of alphaviruses in vertebrate cells strongly affects cell physiology and ultimately leads to development of a cytopathic effect (CPE) and cell death. Sindbis virus (SIN) replication causes major changes in cellular macromolecular synthesis, in which the strong downregulation of transcription of cellular mRNAs and rRNAs plays a critical role. SIN nonstructural protein nsP2 was previously proposed as one of the main regulators of virus-host cell interactions, because point mutations in the carboxy-terminal part of nsP2 could make SIN and other alphaviruses and replicons less cytopathic and capable of persisting in some vertebrate cell lines. These mutants were incapable of inhibiting transcription and downregulating a viral stress-induced cell response. In the present work, we demonstrate that (i) SIN nsP2 is critically involved in CPE development, not only during the replication of SIN-specific RNAs, but also when this protein is expressed alone from different expression cassettes; (ii) the cytotoxic effect of SIN nsP2 appears to be at least partially determined by its ability to cause transcriptional shutoff; (iii) these functions of SIN nsP2 are determined by the integrity of the carboxy-terminal peptide of this protein located outside its helicase and protease domains, rather than by its protease activity; and (iv) the cytotoxic activity of SIN nsP2 depends on the presence of this protein in a free form, and alterations in P123 processing abolish the ability of nsP2 to cause CPE.
Movement characteristics using a mouse with tactile and force feedback

Abstract A multi-modal mouse incorporating tactile and force feedback was tested in a target selection task with 12 subjects. Four feedback conditions (normal, tactile, force, tactile+force) were combined with three target distances and three target sizes. We found significant reductions in the overall movement times and in the time to stop the cursor after entering the target. This effect was particularly pronounced for the tactile condition and for small targets. However, compared to normal feedback, error rates were higher with the tactile and tactile+force conditions. The motor-sensory bandwidth calculated using Fitt's law, normalized for spatial variability, was highest in the presence of tactile feedback (6.4 bits/s). This was followed by tactile+force (6.2 bits/s), normal (5.9 bits /s), and force feedback (5.8 bits/s). These results indicate that modifying a mouse to include tactile feedback, and to a lesser extent, force feedback, offers performance advantages in target selection tasks.
Brief Intervention for Medical Inpatients with Unhealthy Alcohol Use

TO THE EDITOR: In their article, Saitz and colleagues (1) conclude that the brief intervention is inadequate for medical inpatients with unhealthy alcohol use. We fear that their main finding is old wine in new skins: Brief intervention is ineffective in alcohol-dependent individuals. As the authors discuss, a central issue deals with the representativeness of their sample. Compared with the at-risk drinkers who declined to participate in the study, the 35% of at-risk drinkers who enrolled in the intervention study tended to report higher values on the Alcohol Use Disorders Identification Test (AUDIT) and reported a substantially higher number of drinks per drinking occasion and per week. This indicates a sample bias toward individuals with more severe problems, for whom brief interventions are not effective in outpatient settings (2). In addition, failure to identify intervention effects in nondependent inpatients in the study does not necessarily mean that the intervention was ineffective. It may also reflect problems of statistical power because data were based on only 80 at-risk drinkers without alcohol dependence. Because brief interventions are assumed to produce small to medium effects (3), detecting differences between the control and the intervention group in this study is unlikely. Most studies on brief interventions in general hospital settings did not systematically diagnose and exclude alcohol-dependent individuals (4); therefore, more research using larger samples of nondependent, at-risk drinkers is needed before we can draw evidence-based conclusions. There are also remarkable differences compared with findings from intervention studies in outpatient settings. The rates of utilization of formal help among alcohol-dependent patients (44% to 49%) and the reduction in drinking in both groups were much higher than we would expect from the results of studies with outpatients. This finding is in line with results from other studies in general hospital settings (4) and is supported by data indicating a greater motivation to change among alcohol-dependent individuals in general hospitals compared with those in the general population (5). Because remission from alcohol problems is a widespread phenomenon and health problems are an important trigger for unassisted recovery from alcohol dependence (6), data indicate that these processes are more common in inpatients than in outpatients. In addition, hospitalization due to somatic crisis may be a window of opportunity for self-initiated change, especially when an extensive assessment has been conducted.
Simultaneous multiplexed stripping voltammetric monitoring of marine toxins in seafood based on distinguishable metal nanocluster-labeled molecular tags.

Marine toxins from microscopic algae can accumulate through the food chain and cause various neurological and gastrointestinal illnesses for human health. Herein, we designed a new ultrasensitive multiplexed immunoassay protocol for simultaneous electrochemical determination of brevetoxin B (BTX-2) and dinophysistoxin-1 (DTX-1) in seafood using distinguishable metal nanocluster-labeled molecular tags as traces on bifunctionalized magnetic capture probes. To construct such a bifunctionalized probe, monoclonal mouse anti-BTX-2 (mAb(1)) and anti-DTX-1 (mAb(2)) antibodies were co-immobilized on a magnetic bead (MB-mAb(1,2)). The distinguishable metal nanoclusters including cadmium nanoclusters (CdNC) and copper nanoclusters (CuNC) were synthesized using the artificial peptides with amino acid sequence CCCYYY, which were used as distinguishable signal tags for the label of the corresponding bovine serum albumin-BTX-2 and bovine serum albumin-DTX-1 conjugates. A competitive-type immunoassay format was adopted for the online simultaneous monitoring of BTX-2 and DTX-1 on a homemade flow-through magnetic detection cell. The assay was based on the stripping voltammetric behaviors of the labeled CdNC and CuNC at the various peak potentials in pH 2.5 HCl containing 0.01 M KCl using square wave anodic stripping voltammetry (SWASV). Under optimal conditions, the multiplexed immunoassays enabled simultaneous detection of BTX-2 and DTX-1 in a single run with wide working ranges of 0.005-5 ng mL(-1) for two marine toxins. The limit of detection (LOD) and limit of quantification (LOQ) were 1.8 and 6.0 pg mL(-1) for BTX-2, while those for DTX-1 were 2.2 and 7.3 pg mL(-1), respectively. No non-specific adsorption and electrochemical cross-talk between neighboring sites were observed during a series of procedures to detect target analytes. The covalent conjugation of biomolecules onto the nanoclusters and magnetic beads resulted in good repeatability and intermediate precision down to 9.5%. The method featured unbiased identification of negative (blank) and positive samples. No significant differences at the 0.05 significance level were encountered in the analysis of 12 spiked samples, including Sinonovacula constricta , Musculista senhousia , and Tegillarca granosa , between the multiplexed immunoassay and commercially available enzyme-linked immunosorbent assay (ELISA) for analysis of BTX-2 and DTX-1.
Microstructural Characterization of Co-Cr-Mo-W Alloy as Casting for Odontological Application

Interest in the analysis and material characterization is rising due to the necessity of the adequate material selection based on system performance in study. The analysis and knowledge of the microstructure and the mechanical properties of any material are of utmost importance since it aims primarily to estimate the performance during the material life span, minimizing the possibility of degradation and undesirable flaws during product utilization. Co-Cr-Mo-W alloys have been well accepted in odontology as prosthesis material, due to its high mechanical resistance, good corrosion resistance and exceptional biocompatibility properties. This study aims to characterize the microstructure of a cobalt based alloy (Co-Cr-Mo-W) obtained through vacuum casting process. Optical microscopy, electronic sweeping microscopy and X-ray were employed and Vickers hardness test with loads of 100 gf, 500 gf and 1000 gf during 10 s. Microstructure casting is characterized by a Co-fcc dendritic matrix with a secondary phase, as well as M23C6 precipitate carbides in the interdendritics zones and grain boundaries. The precipitation of carbides represents the main device of strengthening in the cast state for these types of alloys and is also responsible for its lower mechanical properties. The material attained hardness between 25 and 35 HRC, meeting the ASTM F75 standards.
Intraoperative No Go Donor Hepatectomy in Living Donor Liver Transplantation

We read the article titled ‘No Go Donor Hepatectomy in Living Donor Liver Transplantation’ by Guba et al. in the March 2010 issue of AJT with great interest (1). Twelve donor procedures (4.7%) were aborted in their series of 257 transplants. Reasons for aborting the donor procedures were unsuitable biliary or vascular anatomy (seven), poor graft quality (three) and unexpected intraoperative events (two). Incidence of 4.7% was slightly higher than incidence of 3.2% in A2ALL multicenter group trial (2).
Winning their trust.

The ranks of the U.S. medical profession will soon grow by 16,000 physicians, as the class of 2011 graduates from medical schools throughout the country. These new physicians will go on to receive graduate medical training that is superb by global standards. Once in practice, they will be encouraged to uphold high quality standards through licensing and certification, activities of specialty societies, and participation in a growing array of incentive programs (e.g., quality-measure reporting, meaningful use of information technology, and care models fostering enhanced communication and coordination of care). All this emphasis on the quality of care aims to maximize .
Ein Modell für Finanzkrisen bei Moral Hazard und Überinvestition

Die von der Asienkrise (1997-99) betroffenen Staaten wiesen im Vorfeld der Krise positive Fundamentaldaten auf. Traditionelle Krisentheorien konnten deshalb nicht zur Erklarung der Krise herangezogen werden. In diesem Paper wird ein alternativer Erklarungsansatz fur Finanzkrisen in offenen Volkswirtschaften dargelegt. Kern dieses Ansatzes ist eine staatliche Garantie auf Kredite, die Moral Hazard Verhalten bei privaten Akteuren bewirkt. Daraus entsteht eine ubermasige Kreditnahme und Uberinvestition in der betrachteten Volkswirtschaft. Es wird gezeigt, wie dadurch eine Krise entstehen kann, die durch Unternehmensinsolvenzen, Outputruckgang und einen starken Verlust von staatlichen Wahrungsreserven gekennzeichnet ist.
Disambiguation of Prepositional Phrases in Automatically Labelled Technical Text

A system is described for semi-automatically tagging a large body of technical English with domain-specific syntactic/semantic labels. These labels have been used to disambiguate prepositional phrase attachments for a 10,000-word body of text containing more than 1,000 prepositions, and to provide case role information for about half of the phrases.
Sticking the Landing : A Simple Reduced-Variance Gradient for ADVI

Compared to the REINFORCE gradient estimator, the reparameterization trick usually gives lower-variance estimators. We propose a simple variant of the standard reparameterized gradient estimator for the evidence lower bound that has even lower variance under certain circumstances. Specifically, we decompose the derivative with respect to the variational parameters into two parts: a path derivative and the score function. Removing the second term produces an unbiased gradient estimator whose variance approaches zero as the approximate posterior approaches the exact posterior. We propose that the removed term has arbitrarily high variance when the variational posterior has a complex form, as when using adaptive posteriors such as given by normalizing flows or stochastic Hamiltonian inference. 1 Estimators of the Evidence Lower Bound Variational inference posits a family of distributions Q and attempts to find an approximate posterior qφ by optimizing the evidence lower bound (ELBO): L(φ) = Ez∼q[log p(x, z)− log qφ(z |x)] (ELBO) An unbiased approximation of the gradient of the ELBO allows stochastic gradient descent to scalably learn complex models. When the joint distribution p(x, z) can be evaluated by p(x|z) and p(z) separately, the ELBO can be written in the following three forms: L(φ) = Ez∼q[log p(x|z) + log p(z)− log qφ(z|x)] (1) = Ez∼q[log p(x|z) + log p(z))] +H[qφ] (2) = Ez∼q[log p(x|z)]−KL(qφ(z|x)||p(z)) (3) By sampling z ∼ q(z), equations (1), (2), and (3) can be used to construct Monte-Carlo estimates of the ELBO. When p(z) and q(z|x) are multivariate Gaussians, using (3) is appealing because it analytically integrates out terms that would otherwise have to be estimated by Monte Carlo. Intuitively, we might that using exact integrals wherever possible will give lower-variance estimators. Surprisingly, though, there are circumstances under which (1), which we call the full Monte Carlo estimator of the ELBO, has lower variance than the estimator based on (3) which calculates the KL divergence exactly. Specifically, when q(z|x) = p(z|x), i.e. the variational approximation is exact, then the variance of the full Monte Carlo estimator is exactly zero, since its value is a constant
Community Aware Influence Maximization on Large Scale Networks Using Mapreduce

Influence maximization problem is a well known problem to find the top-k seed users who can maximize the spread of information in a social network. The primary concern is monte carlo simulations method is suffering with scalability issues while the selection of seed users . It takes days to find potential seed users in large datasets. In this paper, we propose a highly scalable algorithm for identifying Influential nodes on largescale graph using the Map Reduce framework. We perform a combined community detection algorithm and consider the most influential users in the community as the candidate for the top-k seeds. This approximation allows us to divide the whole graph into multiple sub graphs that can be processed independently. Then, for each sub graph, a Map Reduce based algorithm is designed to identify the minimum-sized influential vertices for the whole graph. This original approach contrasts with previous influence propagation models, which did not use similarity opportunities among members of communities to maximize influence propagation. The performance results show that the model activates a higher number of overall nodes in contemporary social networks, as compared to existing landmark approaches.
Oncolytic adenovirus and doxorubicin‐based chemotherapy results in synergistic antitumor activity against soft‐tissue sarcoma

Despite originating from several different tissues, soft‐tissue sarcomas (STS) are often grouped together as they share mesenchymal origin and treatment guidelines. Also, with some exceptions, a common denominator is that when the tumor cannot be cured with surgery, the efficacy of current therapies is poor and new treatment modalities are thus needed. We have studied the combination of a capsid‐modified oncolytic adenovirus CGTG‐102 (Ad5/3‐D24‐GMCSF) with doxorubicin, with or without ifosfamide, the preferred first‐line chemotherapeutic options for most types of STS. We show that CGTG‐102 and doxorubicin plus ifosfamide together are able to increase cell killing of Syrian hamster STS cells over single agents, as well as upregulate immunogenic cell death markers. When tested in vivo against established STS tumors in fully immunocompetent Syrian hamsters, the combination was highly effective. CGTG‐102 and doxorubicin (without ifosfamide) resulted in synergistic antitumor efficacy against human STS xenografts in comparison with single agent treatments. Doxorubicin increased adenoviral replication in human and hamster STS cells, potentially contributing to the observed therapeutic synergy. In conclusion, the preclinical data generated here support clinical translation of the combination of CGTG‐102 and doxorubicin, or doxorubicin plus ifosfamide, for the treatment of STS, and provide clues on the mechanisms of synergy.
Diagnosis of renal osteodystrophy

The idiom renal osteodystrophy (ROD) represents a heterogeneous pattern of bone disturbances caused by chronic renal insufficiency and concomitant diseases. For the clinical decision of therapy it is most important to differentiate between high and low or adynamic turnover ROD because the therapeutically consequences of these two ends of the ROD spectrum are fundamentally different.
EARTHENWARE FROM A FIRING SITE IN MYANMAR (BURMA) DATES TO MORE THAN 4,500 YEARS AGO

A radiocarbon date range of 2,890 to 2,470 BC for an earthenware firing site at Halin in Upper Myanmar (Burma) puts a solid timeframe around an assemblage that includes incised and burnished wares, and a spout. While earthenware is often found associated with burials in this region (Pautreau 2007 ; Pautreau, Coupey et al. 2010), this site provides a rare glimpse of early earthenware pottery production. Initial finds call for some reappraisal of approaches to Myanmar’s material culture in the pre-metal and pre-urban periods.
Context Specificity in Stability of Hyperactivity–Impulsivity

This paper exemplifies a secondary data analysis of context–specific differences in children's hyperactivity–impulsivity while controlling for informant–specific effects. Participants were boys and girls from the NICHD Study of Early Child Care and Youth Development whose behaviours were measured in 1st, 3rd and 5th grades. Latent factor models were structured using multi–informant reports including mothers, fathers, teachers and observers. Temporal stability within a context was stronger than cross–context consistency, and the magnitude of longitudinal stability was higher in the home context compared to the school context. Controlling for informant–specific effects resulted in a significantly improved model fit and increased within–context stability. Our findings highlight the importance of considering both context and informant effects when studying longitudinal stability and change in personality development. Copyright © 2010 John Wiley & Sons, Ltd.
Rapid Inhibition of Vasoconstriction in Renal Afferent Arterioles by Aldosterone

Abstract— Aldosterone has been suggested to elicit vessel contraction via a nongenomic mechanism. We tested this proposal in microdissected, perfused rabbit renal afferent arterioles. Aldosterone had no effect on internal diameter in concentrations from 10−10 to 10−5 mol/L, but aldosterone abolished the ability of 100 mmol/L KCl to induce vascular contraction. The inhibitory effect of aldosterone was observed from 1 pmol/L. The inhibitory effect was significant after 5 minutes and maximal after 20 minutes and was fully reversible. Actinomycin D (10−6 mol/L) prolonged the effect of aldosterone. The effect was abolished by the mineralocorticoid receptor antagonist spironolactone (10−7 mol/L) but not by the glucocorticoid receptor antagonist mifepristone (10−6 mol/L). The K+-mediated increase of intracellular calcium concentration in afferent arterioles was not affected by aldosterone. Mineralocorticoid receptor was detected by reverse transcription–polymerase chain reaction and immunohistochemistry in rat renal vasculature and rabbit endothelial cells. Inhibition of phosphatidylinositol (PI)-3 kinase with LY 294002 (3×10−6 mol/L) restored sensitivity to K+ in the presence of aldosterone, and afferent arterioles were immunopositive for PI-3 kinase subunit p110&agr;. Inhibition of NO formation by L-NAME (10−4 mol/L) or inhibition of soluble guanylyl cyclase with 1H-(1,2,4)Oxadiazolo[4,3-a]quinoxaline-1-one restored K+-induced vasoreactivity in the presence of aldosterone. Similar to aldosterone, the NO donor sodium nitroprusside inhibited K+-induced vascular contraction. Geldanamycin (10−6 mol/L), an inhibitor of heat shock protein 90, abolished aldosterone-induced vasorelaxation. We conclude that aldosterone inhibits depolarization-induced vasoconstriction in renal afferent arterioles by a rapid nongenomic mechanism that is initiated by mineralocorticoid receptor activation and involves PI-3 kinase, protein kinase B, and heat shock protein 90–mediated stimulation of NO generation.
Structural abnormalities in the frontal system in schizophrenia. A magnetic resonance imaging study.

Thirty-eight schizophrenics and 49 normal controls underwent magnetic resonance imaging. Midline sagittal cuts indicated that the schizophrenics had significantly smaller frontal lobes, as well as smaller cerebrums and craniums. The findings are consistent with some type of early developmental abnormality that might retard brain growth and therefore skull growth. These findings are confirmed on a smaller sample of patients on whom we have coronal cuts. Decreased cerebral and cranial size are associated with prominent negative symptoms, although decreased frontal size is not. Decreased cranial and cerebral size was also associated with impairment on some cognitive tests. These findings are consistent with the hypothesis that some schizophrenics may have a type of early developmental abnormality associated with prominent negative symptoms and cognitive impairment. Further, the results suggest that schizophrenics may have a type of structural frontal system impairment. Thus, they provide anatomic evidence for the "hypofrontality hypothesis. "
Plant species radiations: where, when, why?

The spatial and temporal patterns of plant species radiations are largely unknown. I used a nonlinear regression to estimate speciation and extinction rates from all relevant dated clades. Both are surprisingly high. A high species richness can be the result of either little extinction, thus preserving the diversity that dates from older radiations (a ‘mature radiation’), or a ‘recent and rapid radiation’. The analysis of radiations from different regions (Andes, New Zealand, Australia, southwest Africa, tropics and Eurasia) revealed that the diversity of Australia may be largely the result of mature radiations. This is in sharp contrast to New Zealand, where the flora appears to be largely the result of recent and rapid radiations. Mature radiations are characteristic of regions that have been climatically and geologically stable throughout the Neogene, whereas recent and rapid radiations are more typical of younger (Pliocene) environments. The hyperdiverse Cape and Neotropical floras are the result of the combinations of mature as well as recent and rapid radiations. Both the areas contain stable environments (the Amazon basin and the Cape Fold Mountains) as well as dynamic landscapes (the Andes and the South African west coast). The evolution of diversity can only be understood in the context of the local environment.