Anti-tumoral effect of the non-nucleoside DNMT inhibitor RG108 in human prostate cancer cells

Background: Current therapeutic strategies for advanced prostate cancer (PCa) are largely ineffective. Because aberrant DNA methylation associated with inappropriate gene-silencing is a common feature of PCa, DNA methylation inhibitors might constitute an alternative therapy. In this study we aimed to evaluate the anti-cancer properties of RG108, a novel non-nucleoside inhibitor of DNA methyltransferases (DNMT), in PCa cell lines. Methods: The anti-tumoral impact of RG108 in LNCaP, 22Rv1, DU145 and PC-3 cell lines was assessed through standard cell viability, apoptosis and cell cycle assays. Likewise, DNMT activity, DNMT1 expression and global levels of DNA methylation were evaluated in the same cell lines. The effectiveness of DNA demethylation was further assessed through the determination of promoter methylation and transcript levels of GSTP1, APC and RAR-β2, by quantitative methylation-specific PCR and RT-PCR, respectively. Results: RG108 led to a significant dose and time dependent growth inhibition and apoptosis induction in LNCaP, 22Rv1 and DU145. LNCaP and 22Rv1 also displayed decreased DNMT activity, DNMT1 expression and global DNA methylation. Interestingly, chronic treatment with RG108 significantly decreased GSTP1, APC and RAR-β2 promoter hypermethylation levels, although mRNA re-expression was only attained GSTP1 and APC. Conclusions: RG108 is an effective tumor growth suppressor in most PCa cell lines tested. This effect is likely mediated by reversion of aberrant DNA methylation affecting cancer related-genes epigenetically silenced in PCa. However, additional mechanism might underlie the anti-tumor effects of RG108. In vivo studies are now mandatory to confirm these promising results and evaluate the potential of this compound for PCa therapy.

Non pre-emptive scheduling of messages on SMTV token-passing networks

Fieldbus communication networks aim to interconnect sensors, actuators and controllers within distributed computer-controlled systems. Therefore, they constitute the foundation upon which real-time applications are to be implemented. A specific class of fieldbus communication networks is based on a simplified version of token-passing protocols, where each station may transfer, at most, a single message per token visit (SMTV). In this paper, we establish an analogy between non-preemptive task scheduling in single processors and the scheduling of messages on SMTV token-passing networks. Moreover, we clearly show that concepts such as blocking and interference in non-preemptive task scheduling have their counterparts in the scheduling of messages on SMTV token-passing networks. Based on this task/message scheduling analogy, we provide pre-run-time schedulability conditions for supporting real-time messages with SMTV token-passing networks. We provide both utilisation-based and response time tests to perform the pre-run-time schedulability analysis of real-time messages on SMTV token-passing networks, considering RM/DM (rate monotonic/deadline monotonic) and EDF (earliest deadline first) priority assignment schemes

Preemption delay analysis for floating non-preemptive region scheduling

In real-time systems, there are two distinct trends for scheduling task sets on unicore systems: non-preemptive and preemptive scheduling. Non-preemptive scheduling is obviously not subject to any preemption delay but its schedulability may be quite poor, whereas fully preemptive scheduling is subject to preemption delay, but benefits from a higher flexibility in the scheduling decisions. The time-delay involved by task preemptions is a major source of pessimism in the analysis of the task Worst-Case Execution Time (WCET) in real-time systems. Preemptive scheduling policies including non-preemptive regions are a hybrid solution between non-preemptive and fully preemptive scheduling paradigms, which enables to conjugate both world's benefits. In this paper, we exploit the connection between the progression of a task in its operations, and the knowledge of the preemption delays as a function of its progression. The pessimism in the preemption delay estimation is then reduced in comparison to state of the art methods, due to the increase in information available in the analysis.

The utilization bound of non-preemptive rate-monotonic scheduling in controller area networks is 25%

Consider a distributed computer system comprising many computer nodes, each interconnected with a controller area network (CAN) bus. We prove that if priorities to message streams are assigned using rate-monotonic (RM) and if the requested capacity of the CAN bus does not exceed 25% then all deadlines are met.

Non invasive ventilation during exercise in COPD patients: a systematic review with meta-analysis

COPD is a major cause of morbidity and mortality worldwide, representing a major public health problem due to the high health and economic resource consumption. Pulmonary rehabilitation is a standard care recommendation for these patients, in order to control the symptoms and optimize the functional capacity, reducing health care costs associated with exacerbations and activity limitations and participation. However, in patients with severe COPD exercise performance can be difficult, due to extreme dyspnea, decreased muscle strength and fatigue. In addition, hypoxemia and dyspnea during efforts and daily activities may occur, limiting their quality of life. Thus, NIV have been used as adjunct to exercise, in order to improve exercise capacity in these patients. However, there is no consensus for this technique recommendation. Our objective was to verify whether the use of NIV during exercise is effective than exercise without NIV in dyspnea, walked distance, blood gases and health status in COPD patients, through a systematic review and meta-analysis.

Non-adherence to telemedicine interventions for drug users: systematic review

OBJECTIVE To estimate rates of non-adherence to telemedicine strategies aimed at treating drug addiction. METHODS A systematic review was conducted of randomized controlled trials investigating different telemedicine treatment methods for drug addiction. The following databases were consulted between May 18, 2012 and June 21, 2012: PubMed, PsycINFO, SciELO, Wiley (The Cochrane Library), Embase, Clinical trials and Google Scholar. The Grading of Recommendations Assessment, Development and Evaluation was used to evaluate the quality of the studies. The criteria evaluated were: appropriate sequence of data generation, allocation concealment, blinding, description of losses and exclusions and analysis by intention to treat. There were 274 studies selected, of which 20 were analyzed. RESULTS Non-adherence rates varied between 15.0% and 70.0%. The interventions evaluated were of at least three months duration and, although they all used telemedicine as support, treatment methods differed. Regarding the quality of the studies, the values also varied from very poor to high quality. High quality studies showed better adherence rates, as did those using more than one technique of intervention and a limited treatment time. Mono-user studies showed better adherence rates than poly-user studies. CONCLUSIONS Rates of non-adherence to treatment involving telemedicine on the part of users of psycho-active substances differed considerably, depending on the country, the intervention method, follow-up time and substances used. Using more than one technique of intervention, short duration of treatment and the type of substance used by patients appear to facilitate adherence.

Visualizing non-linear control system performance by means of multidimensional scaling

This paper addresses the use of multidimensional scaling in the evaluation of controller performance. Several nonlinear systems are analyzed based on the closed loop time response under the action of a reference step input signal. Three alternative performance indices, based on the time response, Fourier analysis, and mutual information, are tested. The numerical experiments demonstrate the feasibility of the proposed methodology and motivate its extension for other performance measures and new classes of nonlinearities.

Non-uniform microstrip antenna array for RX DSRC communications

The urgent need to mitigate traffic problems such as accidents, road hazards, pollution and traffic jam have strongly driven the development of vehicular communications. DSRC (Dedicated Short Range Communications) is the technology of choice in vehicular communications, enabling real time information exchange among vehicles V2V (Vehicle-to-Vehicle) and between vehicles and infrastructure V2I (Vehicle-Infrastructure). This paper presents a receiving antenna for a single lane DSRC control unit. The antenna is a non-uniform array with five microstrip patches. The obtained beam width, bandwidth and circular polarization quality, among other characteristics, are compatible with the DSRC standards, making this antenna suitable for this application. © 2014 IEEE.

The impact of different power dividers used in a non-uniform planar antenna array

Wireless communications are widely used for various applications, requiring antennas with different features. Often, to achieve the desired radiation pattern, is necessary to employ antenna arrays, using non-uniform excitation on its elements. Power dividers can be used and the best known are the T-junction and the Wilkinson power divider, whose main advantage is the isolation between output ports. In this paper the impact of this isolation on the overall performance of a circularly polarized planar antenna array using non-uniform excitation is investigated. Results show a huge decrease of the array bandwidths either in terms of return loss or in polarization, without resistors. © 2014 IEEE.

Interlaminar fracture characterization of a carbon-epoxy composite in pure mode II

The interlaminar fracture toughness in pure mode II (GIIc) of a Carbon-Fibre Reinforced Plastic (CFRP) composite is characterized experimentally and numerically in this work, using the End-Notched Flexure (ENF) fracture characterization test. The value of GIIc was extracted by a new data reduction scheme avoiding the crack length measurement, named Compliance-Based Beam Method (CBBM). This method eliminates the crack measurement errors, which can be non-negligible, and reflect on the accuracy of the fracture energy calculations. Moreover, it accounts for the Fracture Process Zone (FPZ) effects. A numerical study using the Finite Element Method (FEM) and a triangular cohesive damage model, implemented within interface finite elements and based on the indirect use of Fracture Mechanics, was performed to evaluate the suitability of the CBBM to obtain GIIc. This was performed comparing the input values of GIIc in the numerical models with the ones resulting from the application of the CBBM to the numerical load-displacement (P-) curve. In this numerical study, the Compliance Calibration Method (CCM) was also used to extract GIIc, for comparison purposes.

A shared-disk parallel cluster file system

Dissertação apresentada para obtenção do Grau de Doutor em Informática Pela Universidade Nova de Lisboa, Faculdade de Ciências e Tecnologia

Validity and reliability of the Questionnaire for Compliance with Standard Precaution

ABSTRACT OBJECTIVE : To evaluate the validity and reliability of the Questionnaire for Compliance with Standard Precaution for nurses. METHODS : This methodological study was conducted with 121 nurses from health care facilities in Sao Paulo's countryside, who were represented by two high-complexity and by three average-complexity health care facilities. Internal consistency was calculated using Cronbach's alpha and stability was calculated by the intraclass correlation coefficient, through test-retest. Convergent, discriminant, and known-groups construct validity techniques were conducted. RESULTS : The questionnaire was found to be reliable (Cronbach's alpha: 0.80; intraclass correlation coefficient: (0.97) In regards to the convergent and discriminant construct validity, strong correlation was found between compliance to standard precautions, the perception of a safe environment, and the smaller perception of obstacles to follow such precautions (r = 0.614 and r = 0.537, respectively). The nurses who were trained on the standard precautions and worked on the health care facilities of higher complexity were shown to comply more (p = 0.028 and p = 0.006, respectively). CONCLUSIONS : The Brazilian version of the Questionnaire for Compliance with Standard Precaution was shown to be valid and reliable. Further investigation must be conducted with nurse samples that are more representative of the Brazilian reality. The use of the questionnaire may support the creation of educational measures considering the possible gaps that can be identified, focusing on the workers' health and on the patients' safety.

Evidence for non-coaxiality of ferrimagnetic and paramagnetic fabrics, developed during magma flow and cooling in a thick mafic dyke

A detailed analysis of fabrics of the chilled margin of a thick dolerite dyke (Foum Zguid dyke, Southern Morocco) was performed in order to better understand the development of sub-fabrics during dyke emplacement and cooling. AMS data were complemented with measurements of paramagnetic and ferrimagnetic fabrics (measured with high field torque magnetometer), neutron texture and microstructural analyses. The ferrimagnetic and AMS fabrics are similar, indicating that the ferrimagnetic minerals dominate the AMS signal. The paramagnetic fabric is different from the previous ones. Based on the crystallization timing of the different mineralogical phases, the paramagnetic fabric appears related to the upward flow, while the ferrimagnetic fabric rather reflects the late-stage of dyke emplacement and cooling stresses. (C) 2014 Elsevier B.V. All rights reserved.

Wrong sign and symmetric limits and non-decoupling in 2HDMs

We analyse the possibility that, in two Higgs doublet models, one or more of the Higgs couplings to fermions or to gauge bosons change sign, relative to the respective Higgs Standard Model couplings. Possible sign changes in the coupling of a neutral scalar to charged ones are also discussed. These wrong signs can have important physical consequences, manifesting themselves in Higgs production via gluon fusion or Higgs decay into two gluons or into two photons. We consider all possible wrong sign scenarios, and also the symmetric limit, in all possible Yukawa implementations of the two Higgs doublet model, in two different possibilities: the observed Higgs boson is the lightest CP-even scalar, or the heaviest one. We also analyse thoroughly the impact of the currently available LHC data on such scenarios. With all 8 TeV data analysed, all wrong sign scenarios are allowed in all Yukawa types, even at the 1 sigma level. However, we will show that B-physics constraints are crucial in excluding the possibility of wrong sign scenarios in the case where tan beta is below 1. We will also discuss the future prospects for probing the wrong sign scenarios at the next LHC run. Finally we will present a scenario where the alignment limit could be excluded due to non-decoupling in the case where the heavy CP-even Higgs is the one discovered at the LHC.

Equilibrium distributions of discrete non-autonomous graphs

We introduce the notions of equilibrium distribution and time of convergence in discrete non-autonomous graphs. Under some conditions we give an estimate to the convergence time to the equilibrium distribution using the second largest eigenvalue of some matrices associated with the system.