Miracle-dz/UniFAR-FTUs huggingface dataset:
N- and C-terminal Upf1 phosphorylations create binding platforms for SMG-6 and SMG-5:SMG-7 during NMD

Nonsense-mediated mRNA decay (NMD) is a surveillance mechanism that detects and degrades mRNAs containing premature termination codons (PTCs). SMG-1-mediated Upf1 phosphorylation takes place in the decay inducing complex (DECID), which contains a ribosome, release factors, Upf1, SMG-1, an exon junction complex (EJC) and a PTC-mRNA. However, the significance and the consequence of Upf1 phosphorylation remain to be clarified. Here, we demonstrate that SMG-6 binds to a newly identified phosphorylation site in Upf1 at N-terminal threonine 28, whereas the SMG-5:SMG-7 complex binds to phosphorylated serine 1096 of Upf1. In addition, the binding of the SMG-5:SMG-7 complex to Upf1 resulted in the dissociation of the ribosome and release factors from the DECID complex. Importantly, the simultaneous binding of both the SMG-5:SMG-7 complex and SMG-6 to phospho-Upf1 are required for both NMD and Upf1 dissociation from mRNA. Thus, the SMG-1-mediated phosphorylation of Upf1 creates a binding platforms for the SMG-5:SMG-7 complex and for SMG-6, and triggers sequential remodeling of the mRNA surveillance complex for NMD induction and recycling of the ribosome, release factors and NMD factors.
The effects of self-monitoring on the Facebook user experience

THE EFFECTS OF SELF-MONITORING ON THE FACEBOOK USER EXPERIENCE by Pamela Eden T. Ong Self-monitoring, or the individual differences in the extent to which people observe, regulate, and control their public appearances, has been studied in a variety of face-to-face domains such as friendships, romantic relationships, and work and organizational settings. The purpose of this study was to assess whether high and low self-monitors construct their identities on an online social networking site, such as Facebook, in ways that are consistent with their self-monitoring preferences for the faceto-face world. Social networking sites allow individuals to have members of all of their social networks present in a common setting at any particular time. This may lead to a predicament for people who are high self-monitors if they prefer to fit their behavior to a particular situation and a particular group of people. In Part 1, participants completed a self-report measure, which consisted of the Self-Monitoring Questionnaire, the Big Five Inventory, and an extended version of the Facebook Questionnaire. In Part 2, participants provided access to their Facebook profile for additional comparison between high and low self-monitors. High self-monitors were more concerned about and actively engaged in image management on Facebook, and image control concerns distinguished high selfmonitors from extraverts. Contrary to predictions, low self-monitors were less active and interested in using Facebook. Findings suggested that high self-monitors adapt their image control desires to the limits and opportunities that currently exist in social networking on social networking sites.
XDISTRIBUTE * : A PROCESSDISTRIBUTION SYSTEM

Powerful, single-user workstations now common in the workplace spend most of their time sitting idle. In an attempt to find low-cost computational power researchers have attempted to take advantage of these idle machines. Many systems ha ve been designed, ranging fr om simple process distribution like Condor [1], to completely new operating systems lik e Sprite [2] and Amoeba [3]. Although very powerful, these systems ar e out of reach of the typical user they r equire special privileges, and require specialized installation, set-up and maintenance. W e propose a simpler way to utilize these idle machines using a r emote execution en vir onment. We have written an application, xdistribute, that is extremely portable, simple to use, requires no changes to any source code, leaves no residual dependencies on the local machine, and can be used by any user without modification to the operating system or installation of any network daemons.
ZAP-70 Promotes the Infiltration of Malignant B-Lymphocytes into the Bone Marrow by Enhancing Signaling and Migration after CXCR4 Stimulation

ZAP-70 in chronic lymphocytic leukemia (CLL) is associated with enhanced response to microenvironmental stimuli. We analyzed the functional consequences of ZAP-70 ectopic expression in malignant B-cells in a xenograft mouse model of disseminated B-cell leukemia. Mice injected with B-cells expressing ZAP-70 showed a prominently higher infiltration of the bone marrow. In vitro analysis of the response of malignant B-cells to CXCL12, the main attracting chemokine regulating trafficking of lymphocytes to the bone marrow, or to bone marrow stromal cells, revealed that ZAP-70 induces an increased response in terms of signaling and migration. These effects are probably mediated by direct participation of ZAP-70 in CXCL12-CXCR4 signaling since CXCR4 stimulation led to activation of ZAP-70 and downstream signaling pathways, such as MAPK and Akt, whereas ZAP-70 did not alter the expression of the CXCR4 receptor. In addition, subclones of primary CLL cells with high expression of ZAP-70 also showed increased migrative capacity toward CXCL12. Neutralization of CXCR4 with a monoclonal antibody resulted in impaired in vitro responses to CXCL12 and bone marrow stromal cells. We conclude that ZAP-70 enhances the migration of malignant B-cells into the supportive microenvironment found in the bone marrow mainly by enhancing signaling and migration after CXCR4 stimulation.
Cardiac PPARα Protein Expression is Constant as Alternate Nuclear Receptors and PGC-1 Coordinately Increase During the Postnatal Metabolic Transition

Gene expression data obtained in mouse heart indicate that increased expression for the nuclear receptor, peroxisomal proliferator activated receptor α (PPARα), prompts the postnatal transition from predominantly carbohydrate to fatty acid oxidation preference. However, no phenotypic or proteomic data are available to confirm downstream signaling and metabolic transition in mice. We studied the hypothesis that shifts in nuclear receptor expression trigger the newborn metabolic switch in a newborn sheep. This species is well characterized with regards to developmental changes in substrate oxidative metabolism. Heart tissues from fetal (130 days gestation), newborn ≤24 hours, and 30-day old lambs were evaluated for protein expression from multiple enzymes controlling oxidative metabolism as well as principal nuclear receptors and coactivators. Although muscle and liver type carnitine palmitoyl transferases I showed no significant changes to correspond to the metabolic transition, hexokinase II protein content showed a profound transient drop, and pyruvate dehydrogenase kinase steadily increased. PPARα showed no increases preceding or during the transition, while peroxisomal proliferator activated receptor gamma coactivator-1 (PGC-1) increased approximately 20-fold transiently in newborn heart in conjunction with significant increases in thyroid hormone receptor α1 and retinoid-activated receptor α. These data challenge the paradigm that increases in PPARα prompt the postnatal metabolic switch, and suggest that other nuclear receptors play a major role. As thyroid hormone (TH) modulates PGC-1 expression in sheep during development, these data further suggest that well-characterized perinatal TH surge in sheep contributes to this metabolic switch.
Evaluation of a Near-Infrared Spectrometer (NIRO 300) for the Detection of Intracranial Oxygenation Changes in the Adult Head

Background and Purpose— The clinical application of intracranial near-infrared spectroscopy in adults has been hampered by concerns over contamination from extracranial tissues. The NIRO 300 (Hamamatsu Photonics) provides continuous online measurements of hemoglobin and cytochrome oxidase concentrations and a calculated tissue oxygen index (TOI). The present study seeks confirmation of the anatomic source of TOI in the adult cranium. Methods— Sixty patients undergoing carotid endarterectomy were studied. The NIRO 300 was incorporated into an established multimodal monitoring system. TOI, oxyhemoglobin, and deoxyhemoglobin changes were assessed and compared with (1) frontal cutaneous laser-Doppler flowmetry and (2) transcranial Doppler measurement of the ipsilateral middle cerebral artery flow velocity. Results— Changes in TOI were seen during cross-clamping of the carotid vessels in 49 patients (mean &Dgr;TOI=−9.4%, SD=7.1). Significant correlation was seen between TOI and flow velocity (r =0.56) but not with laser-Doppler flowmetry (r =0.13). In 31 patients, oxyhemoglobin and deoxyhemoglobin concentrations were recorded, showing significant changes during both external carotid artery and internal carotid artery clamping. A change in TOI was predominantly associated with internal carotid artery clamping (n=41). When TOI changed during external carotid artery clamping (n=8), significant blood pressure changes occurred, or extracranial-to-intracranial anastomosis was evident. In the absence of such variables, the sensitivity of TOI to intracranial and extracranial changes was 87.5% and 0%, respectively, and specificity was 100% and 0%, respectively. Conclusions— The NIRO 300 reflects changes in cerebral tissue oxygenation when TOI is calculated, with a high degree of sensitivity and specificity.
Genetic Polymorphisms in Folate Metabolism and the Risk of Stomach Cancer

Folate deficiency has been implicated in the etiology of stomach cancer through abnormal DNA methylation and disrupted DNA synthesis and repair. Enzyme-coding genes involved in folate metabolism are often polymorphic. In a population-based study of 305 cases and 427 controls in Warsaw, Poland, we evaluated the risk of stomach cancer in relation to polymorphisms in folate-metabolizing genes, including MTHFR (Ex5+79C>T and Ex8−62A>C), MTR (Ex26−20A>G), and MTRR (Ex2−64A>G, Ex5+123C>T, Ex15+572C>T, Ex15−405A>T, Ex9−85C>T, Ex15−526G>A, and Ex14+14C>T). Polymorphisms in the MTHFR gene were not associated with stomach cancer risk. No notable effect was found for polymorphisms in MTR or MTRR either, although MTR Ex26−20 A>G and MTRR Ex5+123C>T polymorphisms were associated with a borderline increased risk of stomach cancer (MTR Ex26−20A>G, AG/GG versus AA: odds ratio, 1.35; 95% confidence interval, 0.96-1.90; MTRR Ex5+123C>T, CT/TT versus CC: odds ratio, 1.30; 95% confidence interval, 0.93-1.82). We did not find significant interactions between polymorphisms in MTHFR, MTR, and MTRR genes and dietary folate and alcohol consumption. Our study did not identify strong genetic determinants in the folate metabolism pathway for stomach cancer risk. (Cancer Epidemiol Biomarkers Prev 2007;16(1):115–21)
Mutual coupling cancelation for compact transmit antenna arrays

Mutual coupling between elements in compact transmit antenna arrays is taken into account in performance prediction and system design of multiple-input multi-output (MIMO) systems. The transmitter-end coupling matrix comprised of array impedance matrix and effective load impedance matrix is derived. The impact of transmitter-end mutual coupling on spatial correlation, radiated power, and system capacity is studied. It is shown that for MIMO systems with compact transmit antenna arrays, transmitter-end mutual coupling seriously degrades system capacity. To mitigate the capacity degradation, a simple transmitter-end coupling cancelation method is proposed. It is shown through numerical experiments that the proposed method can significantly improve system capacity in the case that transmit antennas are placed closely.
Cloud-based e-learning infrastructures with load forecasting mechanism based on Exponential Smoothing: A use case

The development of cloud technologies allows the implementation of scalable, versatile, and customized systems, constructed on-demand. This allows more efficient use of computing resources, improving the revenue of the system and enhancing the Quality of Service (QoS) received by users while minimizing the power consumption of the machines. Several research works conclude that in order to efficiently manage a cloud-based infrastructure (meaning, deploy computing resources when needed without affecting negatively to the QoS perceived by users), accurate predictions on the load of machines should be made. Thanks to this, resources can be ready to use when users need them, and shutdown when they are not needed — thus reducing the power consumption and enhancing the revenue of the system. This paper presents algorithms to perform forecasts of the load of machines based on Exponential Smoothing (ES), so that the machines of the technological infrastructure of our University can be efficiently managed. Furthermore, algorithms to perform monitoring and provision of resources based on load forecasts are presented. The usefulness of these algorithms is illustrated by means of a use case based on the e-learning facilities of our University. This use case shows that thanks to the use of cloud technologies, enhanced with the developed algorithms for load forecasting and provision of resources, better use of resources and lower power consumption can be achieved, without affecting the QoS received by user.
Neutralization resistance of hepatitis C virus can be overcome by recombinant human monoclonal antibodies

Immunotherapy and vaccine development for hepatitis C virus (HCV) will depend on broadly reactive neutralizing antibodies (NAbs). However, studies in infectious strain JFH1‐based culture systems expressing patient‐derived Core‐NS2 proteins have suggested neutralization resistance for specific HCV strains, in particular, of genotype 2. To further examine this phenomenon, we developed a panel of HCV genotype 2 recombinants for testing of sensitivity to neutralization by chronic‐phase patient sera and lead human monoclonal antibodies (HMAbs). The novel Core‐NS2 recombinants, with patient‐derived genotype 2a (strain T9), 2b (strains DH8 and DH10), and 2c (strain S83) consensus sequences, were viable in Huh7.5 hepatoma cells without requirement for adaptive mutations, reaching HCV infectivity titers of 3.9‐4.5 log10 focus‐forming units per milliliter. In in vitro neutralization assays, we demonstrated that the novel genotype 2 viruses as well as prototype strains J6/JFH1(2a) and J8/JFH1(2b), all with authentic envelope proteins, were resistant to neutralization by genotype 2a, 2b, 2c, 2j, 2i, and 2q patient sera. However, these patient sera had high titers of HCV‐specific NAbs, because they efficiently reduced the infectivity of J6(2a) and J8(2b) with deleted hypervariable region 1. The genotype 2a, 2b, and 2c viruses, found resistant to polyclonal patient sera neutralization, were efficiently neutralized by two lead HMAbs (AR4A and HC84.26). Conclusion: Using novel 2a, 2b, and 2c cell‐culture systems, expressing authentic envelope proteins, we demonstrated resistance of HCV to patient‐derived polyclonal high‐titer NAbs. However, the same genotype 2 culture viruses were all sensitive to HMAbs recognizing conformational epitopes, indicating that neutralization resistance of HCV can be overcome by applying recombinant antibodies. These findings have important implications for HCV immunotherapy and vaccine development. (Hepatology 2013;58:1587–1597)
Stable Non-Gaussian Random Processes : Stochastic Models with Infinite Variance

Stable random variables on the real line Multivariate stable distributions Stable stochastic integrals Dependence structures of multivariate stable distributions Non-linear regression Complex stable stochastic integrals and harmonizable processes Self-similar processes Chentsov random fields Introduction to sample path properties Boundedness, continuity and oscillations Measurability, integrability and absolute continuity Boundedness and continuity via metric entropy Integral representation Historical notes and extensions.
Mobilizing medical information and knowledge: some insights from a survey

The mobile medical information system investigated in the study is developed for mobilizing medical information and knowledge and for matching physicians’ multiple needs, including mobility, reliability and time efficiency. This paper is set to investigate physicians’ perceptions, intentions and actual use regarding the system in a pilot trial conducted in the Finnish health care sector started from April to September 2003. The results from this empirical survey (N=500, returned N=379) indicate that physicians have rather positive perceptions of the system and future intentions to use it in their work practice. Mobile evidence-based medical guidelines-EBMG and mobile textbooks were the most favourite information sources that physicians might use through a mobile device. Mostly, they would search information about certain treatments, drugs and diseases. Mobile EBMG, Pharmaca Fennica and ICD-10 were their most wanted mobile information contents in the system. The physicians were highly motivated to use mobile Internet in order to access the Internet-based EBMG as well as the Finnish Internet medical portal— Terveysportti. Mobile prescription also gained a high probability for being adopted. Individual differences do matter physicians’ perceptional assessments and future intentions to use the system. These findings indicate some potential to mobilize “personalized” medical information and knowledge in order to create knowledge freedom to physicians by taking full advantage of mobile technologies. Mobile prescription might be a step further towards mobilizing medical information but with political difficulty. Implications for future system improvement are discussed briefly.
The evolution of phylogenetic differences in the efficiency of digestion in ruminants

This study investigates, for the first time (to our knowledge) for any animal group, the evolution of phylogenetic differences in fibre digestibility across a wide range of feeds that differ in potential fibre digestibility (fibre to lignin ratio) in ruminants. Data, collated from the literature, were analysed using a linear mixed model that allows for different sources of random variability, covariates and fixed effects, as well as controlling for phylogenetic relatedness. This approach overcomes the problem of defining boundaries to separate different ruminant feeding styles (browsers, mixed feeders and grazers) by using two covariates that describe the browser–grazer continuum (proportion of grass and proportion of browse in the natural diet of a species). The results indicate that closely related species are more likely to have similar values of fibre digestibility than species that are more distant in the phylogenetic tree. Body mass did not have any significant effect on fibre digestibility. Fibre digestibility is estimated to increase with the proportion of grass and to decrease with the proportion of browse in the natural diet that characterizes the species. We applied an evolutionary model to infer rates of evolution and ancestral states of fibre digestibility; the model indicates that the rate of evolution of fibre digestibility accelerated across time. We suggest that this could be caused by a combination of increasing competition among ruminant species and adaptation to diets rich in fibre, both related to climatically driven environmental changes in the past few million years.
Unsupervised Grammar Induction by Distribution and Attachment

Distributional approaches to grammar induction are typically inefficient, enumerating large numbers of candidate constituents. In this paper, we describe a simplified model of distributional analysis which uses heuristics to reduce the number of candidate constituents under consideration. We apply this model to a large corpus of over 400000 words of written English, and evaluate the results using EVALB. We show that the performance of this approach is limited, providing a detailed analysis of learned structure and a comparison with actual constituent-context distributions. This motivates a more structured approach, using a process of attachment to form constituents from their distributional components. Our findings suggest that distributional methods do not generalize enough to learn syntax effectively from raw text, but that attachment methods are more successful.
Direct Association of the Gap Junction Protein Connexin-43 with ZO-1 in Cardiac Myocytes*

The gap junction protein connexin-43 is normally located at the intercalated discs of cardiac myocytes, and it plays a critical role in the synchronization of their contraction. The mechanism by which connexin-43 is localized within cardiac myocytes is unknown. However, localization of connexin-43 likely involves an interaction with the cytoskeleton; immunofluorescence microscopy showed that in cardiac myocytes, connexin-43 specifically colocalizes with the cytoskeletal proteins ZO-1 and α-spectrin. In transfected HEK293 cells, immunoprecipitation experiments using coexpressed epitope-tagged connexin-43 and ZO-1 indicated that ZO-1 links connexin-43 with α-spectrin. The domains responsible for the protein-protein interaction between connexin-43 and ZO-1 were identified using affinity binding assays with deleted ZO-1 and connexin-43 fusion proteins. Immunoblot analysis of associated proteins showed that the C-terminal domain of connexin-43 binds to the N-terminal domain of ZO-1. The role of this linkage in gap junction formation was examined by a dominant-negative assay using the N-terminal domain of ZO-1. Overexpression of the N-terminal domain of ZO-1 in connexin-43-expressing cells resulted in redistribution of connexin-43 from cell-cell interfaces to cytoplasmic structures; this intracellular redistribution of connexin-43 coincided with a loss of electrical coupling. We therefore conclude that the linkage between connexin-43 and α-spectrin, via ZO-1, may serve to localize connexin-43 at the intercalated discs, thereby generating functional gap junctions in cardiac myocytes.
Observer design for simultaneous robust actuator and sensor faults reconstruction

This paper describes a robust fault reconstruction and estimation design for a class of nonlinear system described by Takagi-Sugeno structure subject to faults affecting actuators, sensor faults and disturbances. The premise variables are assumed to be unmeasurable. The main innovation is focused primarily to conceive Sliding Mode Observer (SMO) designed to compensate faults behaviors from the system states estimation. In formalism of multi-objective optimisation, we derive sufficient conditions to guarantee the states estimation error stability and to obtain the observer gains. Simulation result is given to evaluate the proposed approach performances.
Edge covering with budget constrains

We study two related problems: finding a set of k vertices and minimum number of edges (kmin) and finding a graph with at least m' edges and minimum number of vertices (mvms). Goldschmidt and Hochbaum \cite{GH97} show that the mvms problem is NP-hard and they give a 3-approximation algorithm for the problem. We improve \cite{GH97} by giving a ratio of 2. A 2(1+\epsilon)-approximation for the problem follows from the work of Carnes and Shmoys \cite{CS08}. We improve the approximation ratio to 2. algorithm for the problem. We show that the natural LP for \kmin has an integrality gap of 2-o(1). We improve the NP-completeness of \cite{GH97} by proving the pronlem are APX-hard unless a well-known instance of the dense k-subgraph admits a constant ratio. The best approximation guarantee known for this instance of dense k-subgraph is O(n^{2/9}) \cite{BCCFV}. We show that for any constant \rho>1, an approximation guarantee of \rho for the \kmin problem implies a \rho(1+o(1)) approximation for \mwms. Finally, we define we give an exact algorithm for the density version of kmin.