Miracle-dz/UniFAR-FTUs huggingface dataset:
NDRG1 is down‐regulated in the early apoptotic event induced by camptothecin analogs: The potential role in proteolytic activation of PKCδ and apoptosis

We previously reported that NSC606985, a new camptothecin analog, induces apoptosis of acute myeloid leukemic cells, which is triggered by proteolytic activation of protein kinase C delta (PKCδ). Here, we performed quantitative proteomic analysis of NSC606985‐treated and untreated leukemic U937 cells with two‐dimensional fluorescence difference gel electrophoresis (2‐D DIGE) in combination with matrix‐assisted laser desorption/ionization time‐of‐flight/time‐of‐flight tandem mass spectrometry. Thirty‐three proteins were found to be deregulated. Then, we focused on N‐myc downstream regulated gene 1 (NDRG1) down‐regulated during apoptosis induction. The results demonstrated that the down‐regulation of NDRG1 protein but not its mRNA was an early event prior to proteolytic activation of PKCδ in U937 cells under treatments of NSC606985 as well as other camptothecin analogs. With the ectopic expression of NDRG1, the proteolytic activation of PKCδ in NSC606985‐treated leukemic cells was delayed and the cells were less sensitive to apoptosis. On the contrary, the suppression of NDRG1 expression by specific small interfering RNA significantly enhanced NSC606985‐induced activation of PKCδ and apoptosis of U937 cells. In summary, our study suggests that the down‐regulation of NDRG1 is involved in proteolytic activation of PKCδ during apoptosis induction, which would shed new light on the understanding the apoptotic process initiated by camptothecin.
Comorbidity of mental disorders with substance misuse

facilities for treatment of patients with comorbidity in such services. Ten residen tial rehabilitation addiction services were contacted and admission staff questioned on their attitudes to new referrals who were on medication for comonbid psychiatric disorders. The therapeutic orientation ran ged from a therapeutic community to a skills-based programme; half were based on the abstinence 12-step approach. Only one of the 10 had psychiatric input and two had general practitioner support. The other seven could call on general practitioner services when necessary. Six would not accept patients on hypnotics, anxiolytics or antidepnessants; the other four would work towards the reduction of such medication. Six would accept patients on antipsycho tics, four refused. Five would accept pa tients on mood stabilisation, five refused. All would accept referrals on anti-epileptic medication. We also asked about attitudes to medication prescribed to help maintain abstinence. Only two of the 10 would accept clients taking acamprosate calcium or naltrexone. Poor outcome is associated with the failure to identify and address comorbid psychiatric disorders in patients with sub stance use disorders. Such patients would benefit from long-term residential rehabili tation. However, this is made difficult as many rehabilitation units refuse to take patients on medication. In addition, pa tients may be denied the benefits of new pharmacological treatments for addiction to reduce cravings, such as acamprosate calcium and naltrexone.
11 p VANets : Experimental evaluation of packet inter-reception time ✩

Periodic exchange of situational information (beacons) is at the basis of most active safety applications in vehicular environments, and understanding its performance in real-world situations is very important. However, existing studies are focused on measuring the packet delivery rate (PDR), while disregarding the packet inter-reception (PIR) time which has recently been shown to be more relevant than PDR to characterize active safety application performance. In this paper, we fill this gap by presenting an extensive study of the PIR times observed in real-world highway scenarios. We start by showing that PIR cannot be reliably estimated from PDR, since the two metrics are only weakly correlated. Motivated by this finding, we present a thorough characterization of the PIR time distribution, which is shown to be a power law in a variety of configurations. The shape of the PIR time distribution indicates that potentially dangerous “situational awareness” blackouts are relatively frequent and positively time correlated. We then evaluate the effect of vehicle configuration and line-of-sight conditions on the PIR time, and show that relatively simple multi-hop beaconing techniques can substantially improve PIR statistics and, hence, safety. A final contribution of this paper is promoting the Gilbert–Elliot model, previously proposed to model bit-error bursts in packet switched networks, as a very accurate model of beacon reception behavior observed in real-world scenarios. © 2015 Elsevier B.V. All rights reserved.
A case of multiple congenital anomalies in association with Rett syndrome confirmed by MECP2 mutation screening

Rett syndrome (RTT) is a severe neurodevelopmental disorder. Apparently normal at birth, girls with RTT undergo developmental regression and acquire a neurological and behavioural phenotype that has been used to define clinical diagnostic criteria for the disorder. Recently mutations in the methyl-CpG binding protein 2 gene (MECP2), located on Xq28 have been identified in females with RTT. We report a girl whose clinical course was complicated by congenital abnormalities of the respiratory tract and gastrointestinal system. In addition neurological abnormalities were evident in the newborn period. By the age of 3 years she had developed a phenotype very suggestive of RTT, but had not demonstrated deceleration of head growth and the development of expressive language was prevented by the presence of the tracheostomy. The clinical impression of RTT was confirmed by the recent finding of a mutation in the MECP2 gene. This case report highlights the importance of considering the clinical diagnosis of RTT even in the presence of other conditions and emphasises that girls with RTT may not be normal from birth.
Uptake and elimination of hydrophobic organic contaminants in estuarine copepods: An experimental study

Polycyclic aromatic hydrocarbons (PAHs) are considered to be rapidly biotransformed by organisms, whereas poly‐chlorinated biphenyls (PCBs) are strongly bioaccumulated. In the present study, the estuarine copepod Eurytemora affinis was exposed in a continuous flow‐through system to dissolved PAH (500 ng/L) and PCB (300 ng/L) mixtures for 86 h, whereas control groups were placed in a continuous flow‐through system with clean water. Both PCB and PAH body residues were measured and compared in exposed and in nonexposed copepods to assess the uptake and the elimination of these two contaminant classes in this copepod species. After the exposure, exposed copepods exhibited concentration factors, based on a dry‐weight basis, of 25, 750, and 1,200, respectively, for total PCBs and PAHs. The lower concentrations of PAHs in the nonexposed versus exposed copepods in contrast to small differences for PCBs suggest a higher rate of metabolism of PAHs compared with PCBs and could explain the differences observed in the accumulation. Furthermore, uptake as well as elimination of both PCBs and PAHs were compound selective in E. affinis. Therefore, higher‐molecular‐weight PCBs and PAHs were preferentially accumulated, while lower‐molecular‐weight compounds were preferentially eliminated. These results suggest the importance of copepods in the biogeochemical cycles of hydrophobic organic contaminants in estuarine ecosystems.
Prevention of sudden death in young athletes: a milestone in the history of sports cardiology

The field of sports cardiology has a long history within the European Society of Cardiology (ESC), being a topic of the first Working Group (WG1: Exercise physiology, physiopathology and stress testing). It was founded in 1982, the first chairmen being Bruno Caru from Italy and Henry Detry from Belgium, with the strong support of former ESC president Henry Denolin. With Italian colleagues, A. Venerando and V. Rulli, WG1 organized a meeting on sports cardiology for the first time in Fiuggi Terme (Italy) in 1984. From 1994, WG1 also included the WG of Rehabilitation, and kept an increasing interest in sports cardiology within the symposia organized in the annual spring meetings.
Soluble NKG2D ligands in the ovarian cancer microenvironment are associated with an adverse clinical outcome and decreased memory effector T cells independent of NKG2D downregulation

ABSTRACT The immune receptor NKG2D is predominantly expressed on NK cells and T cell subsets and confers anti-tumor activity. According to the current paradigm, immune surveillance is counteracted by soluble ligands shed into the microenvironment, which down-regulate NKG2D receptor expression. Here, we analyzed the clinical significance of the soluble NKG2D ligands sMICA and sULBP2 in the malignancy-associated ascites of ovarian cancer. We show that high levels of sMICA and sULBP2 in ascites were associated with a poor prognosis. Ascites inhibited the activation of normal NK cells, which, in contrast to the prevailing notion, was not associated with decreased NKG2D expression. Of note, an inverse correlation of soluble NKG2D ligands with effector memory T cells and a direct correlation with pro-tumorigenic CD163+CD206+ macrophages was observed. Thus, the role of soluble NKG2D ligands within the ovarian cancer microenvironment is more complex than anticipated and does not exclusively function via NKG2D downregulation.
Bayesian Analysis of Nonlinear Reproductive Dispersion Mixed Models for Longitudinal Data with Nonignorable Missing Covariates

This article proposes a Bayesian approach, which can simultaneously obtain the Bayesian estimates of unknown parameters and random effects, to analyze nonlinear reproductive dispersion mixed models (NRDMMs) for longitudinal data with nonignorable missing covariates and responses. The logistic regression model is employed to model the missing data mechanisms for missing covariates and responses. A hybrid sampling procedure combining the Gibber sampler and the Metropolis-Hastings algorithm is presented to draw observations from the conditional distributions. Because missing data mechanism is not testable, we develop the logarithm of the pseudo-marginal likelihood, deviance information criterion, the Bayes factor, and the pseudo-Bayes factor to compare several competing missing data mechanism models in the current considered NRDMMs with nonignorable missing covaraites and responses. Three simulation studies and a real example taken from the paediatric AIDS clinical trial group ACTG are used to illustrate the proposed methodologies. Empirical results show that our proposed methods are effective in selecting missing data mechanism models.
The effects of dexmedetomidine on neuromuscular blockade in human volunteers.

UNLABELLED The neuromuscular effects of dexmedetomidine in humans are unknown. We evaluated the effect of dexmedetomidine on neuromuscular block and hemodynamics during propofol/alfentanil anesthesia. During propofol/alfentanil anesthesia, the rocuronium infusion rate was adjusted in 10 volunteers to maintain a stable first response (T1) in the train-of-four sequence at 50% +/- 3% of the pre-rocuronium value. Dexmedetomidine was then administered by computer-controlled infusion, targeting a plasma dexmedetomidine concentration of 0.6 ng/mL for 45 min. The evoked mechanical responses of the adductor pollicis responses (T1 response and T4/T1 ratio), systolic blood pressure (SBP), heart rate (HR), and transmitted light through a fingertip were measured during the dexmedetomidine infusion and compared with predexmedetomidine values using repeated-measures analysis of variance and Dunnett's test. Plasma dexmedetomidine levels ranged from 0.68 to 1.24 ng/mL. T1 values decreased during the infusion, from 51% +/- 2% to 44% +/- 9% (P < 0.0001). T4/T1 values did not change during the infusion. Plasma rocuronium concentrations increased during the infusion (P = 0.02). Dexmedetomidine increased SBP (P < 0.001) and decreased HR (P < 0.001) (5-min median values) during the infusion compared with values before the infusion. Dexmedetomidine increased the transmitted light through the fingertip by up to 41% +/- 8% during the dexmedetomidine infusion (P < 0.001). We demonstrated that dexmedetomidine (0.98 +/- 0.01 microg/kg) increased the plasma rocuronium concentration, decreased T1, increased SBP, and decreased finger blood flow during propofol/alfentanil anesthesia. We conclude that dexmedetomidine-induced vasoconstriction may alter the pharmacokinetics of rocuronium. IMPLICATIONS We studied the effect of an alpha2-agonist (dexmedetomidine) on rocuronium-induced neuromuscular block during propofol/alfentanil anesthesia. We found that the rocuronium concentration increased and the T1 response decreased during the dexmedetomidine administration. Although these effects were statistically significant, it is unlikely that they are of clinical significance.
Direct torque control based multi-level inverter and artificial neural networks of wind energy conversion system

In this paper, we propose a new strategy for Direct Torque Neural Network Control, compatible with a voltage inverter three level and exploit artificial intelligence tools namely: neural networks. In addition, the use of multi-level inverter and the artificial techniques contribute to improved performance of the control of the wind energy conversion system. In fact, the use of (multilevel converter) associated with Torque Neural Network Control can help in reducing harmonics, torque ripple and have a high level of output voltage. This article aims to study and apply control technology Torque Neural Network Control associate with a three-level inverter to control the operation of a wind energy conversion system in optimal conditions. The detailed principle of operation of the wind energy conversion chain and the simulation results of the strategy proposed Torque Neural Network Control are also discussed.
Peer Review Social Network (PeRSoN) in Open Source Projects

SUMMARY Software peer review is regarded as one of the most important approaches to preserving software quality. Due to the distributed collaborations in Open Source Software (OSS) development, the review techniques and processes conducted in OSS environment di ﬀ er from the traditional review method that based on formal face-to-face meetings. Unlike other related works, this study investigates peer review processes of OSS projects from the social perspective: communication and interaction in peer review by using social network analysis (SNA). Moreover, the relationship between peer review contributors and their activities is studied. We propose an approach to evaluating contributors’ activeness and social relationship using SNA named Peer Review Social Network (PeRSoN). We evaluate our approach by empirical case study, 326,286 review comments and 1,745 contributors from three representative industrial OSS projects have been extracted and analyzed. The results indicate that the social network structure inﬂuences the realistic activeness of contributors signiﬁ-cantly. Based on the results, we suggest our approach can support project leaders in assigning review tasks, appointing reviewers and other activities to improve current software processes.
Thermoregulatory responses of the newborn pig during experimentally induced hypothermia and rewarming

Exposure to a temperature of 14 degrees C was used to induce a progressive hypothermia in fourteen conscious newborn piglets. Heat production, body (rectal) and skin (between the shoulders) temperatures and shivering intensity assessed as the electromyographic activity (EMG) of longissimus thoracis muscle were measured until body temperature reached 30 degrees C and during a recovery period of 2 h at an ambient temperature of 24 degrees C (n = 7) or 34 degrees C (n = 7). During body cooling, heat production increased up to 9.67 +/− 1.28 W (kg BW)‐1, but started to decrease below a body temperature threshold of 34.4 +/− 0.7 degrees C. EMG activity increased (P < 0.023) curvilinearly during body cooling; the main increase occurred between body temperatures of 38 and 33 degrees C (+142%, P < 0.001), and changes in EMG activity between 33 and 30 degrees C were not significant (+18%, P > 0.1). A marked increase in circulating levels of glucose (+312%, P < 0.001), glucagon (+76%, P < 0.05), adrenaline (+172%, P < 0.05) and noradrenaline (+113%, P < 0.05) occurred during body cooling. Insulin levels were not detectable at 2 h of life and increased during body cooling. During 2 h of rewarming at 24 degrees C, heat production and EMG activity remained elevated, changes in carbohydrate metabolism were not completely reversed and the final body temperature was only 35.6 +/− 0.9 degrees C. Rewarming of the piglets was faster at 34 degrees C. There was a net influx of heat into the animals and heat production and shivering activity decreased when body temperature reached 33.9 +/− 0.5 degrees C; the final body temperature was 37.5 +/− 0.2 degrees C. Circulating levels of lactate, glucagon and catecholamines returned to control levels. These results show that in conscious piglets exposed to a constant cold temperature there is an inverse relationship between EMG activity and body temperature during moderate hypothermia and that the thermoregulatory response and carbohydrate metabolism of the piglet are seriously impaired below a body temperature of 34 degrees C.
Fault detection using probabilistic prediction and data fusion on a bulk good system

Industrial companies worldwide want to keep a steady performance of their processes. In order to ensure this, a company usually implements a continuous condition monitoring for their machines. Ideally, the company analyzes the resulting data and obtains an insight on the failure causes of the machines. Unfortunately, the data itself cannot always discover the hidden causes for a fault in the machine, due either to the big amount of data or its complexity. This paper applies probabilistic prediction and data fusion techniques for fault detection on a bulk good system. The data acquisition from the bulk good system is implemented using the OPC Unified Architecture (OPC-UA) Machine-to-Machine Communication Protocol. OPC-UA collects data from the automation platform, and stores it in batches. Each batch contains all system features. Firstly, the system data is analyzed by means of a centralized approach. For that purpose, the probabilistic methods Naïve Bayes and Full Bayes are implemented. Furthermore, a decentralized approach is implemented using a two-step method. The first step gathers the health status of the main components by means of a local analysis. The second step fuses the results of each component, in order to obtain an overall status. The results show that the data fusion approach improves the performance of the fault detection algorithm.
Notch-Induced E2A Degradation Requires CHIP and Hsc70 as Novel Facilitators of Ubiquitination

ABSTRACT E2A transcription factors, E12 and E47, are important regulators of lymphocyte development. Notch signaling pathways have been shown to regulate E2A function by accelerating the degradation of E2A proteins through a mitogen-activated protein kinase-dependent and ubiquitin-mediated pathway. To further understand the mechanism underlying E2A ubiquitination and degradation, we conducted a yeast two-hybrid screen and identified the carboxyl terminus of Hsc70-interacting protein (CHIP) as an E47 binding protein. Here, we show that CHIP associates with E2A proteins in vivo and that overexpression of CHIP induces E47 degradation in a phosphorylation-dependent manner. Conversely, knocking down CHIP with small interfering RNA alleviates Notch-induced E47 degradation. CHIP binds E47 through the E protein homology domains 2 and 3 (EHD2 and EHD3). This interaction between CHIP and E47 is independent of the U-box domain with E3 ubiquitin ligase activity but requires the chaperone binding tetratricopeptide repeats domain. The ability of CHIP to induce E47 ubiquitination and degradation correlates with its ability to bind E47. We propose that CHIP, together with its partner Hsc70, forms a preubiquitination complex (PUC) with E47 and Skp2, thus facilitating the interaction between E47 and Skp2. CHIP also associates with Cul1, which introduces PUC to the SCF E3 ligase complex, responsible for E47 ubiquitination. Therefore, CHIP plays a crucial role in the ubiquitination and degradation of E2A proteins.
Determination of design parameters for a short-axis 10 MW HTS wind generator

This paper makes a preparation for a short-axis 10 MW HTS wind generator design by determining some uncertain design parameters through simulation and analysis. Simulation models are built based on Ansoft Maxwell to compare the change of efficiency, generator weight, HTS tapes consumption, and magnetic field distribution with these uncertain parameters. The optimal design parameters are therefore obtained.
Acceptance and Usability of Interactive Infographics in Online Newspapers

Interactive infographics are a powerful tool to represent and communicate complex information. In datadriven journalism journalists use interactive infographics to explain new insights and facts while telling complex stories on the basis of retrieved data. However, readers of online news are still unexperienced while using interactive infographics. The results of a user survey among readers of online newspapers show how readers use and interact with interactive infographics in online newspapers. To improve the acceptance among users and to identify success factors of their utilization the results of a usability study of interactive infographics are presented.
Therapeutic potential of mesenchymal stromal cells in a mouse breast cancer metastasis model.

BACKGROUND AIMS Mesenchymal stromal cells (MSC) have been studied intensively in regenerative medicine. However, their therapeutic potential against tumor formation and cancer metastasis is still unclear. The effects of transplantation of MSCs in early-stage of carcinogenesis, should be evaluated. METHODS MSC isolated from human umbilical cord blood (UCB) and adipose tissue (AD) were transplanted in a mouse cancer metastasis model. The effects of MSC on tumor growth and metastasis were analyzed. The effects of transplantation of MSC into the mouse model at very early stage carcinogenesis were also evaluated. RESULTS Human MSC reduced lung metastasis and inhibited the growth of human breast cancer cells by inducing apoptosis. In addition, transplantation of both UCB and AD MSC into a cancer model with no detectable clinical symptoms did not appear to promote tumor growth or metastasis. CONCLUSIONS We evaluated the effect of MSC derived from human UCB and AD tissue in a tumor model. Our findings may help to elucidate the interaction between cancer cells and MSC, as well as the application of MSC to clinical trials.