Matrix-assisted laser desorption ionization time-of-flight mass spectrometry for rapid identification of mold and yeast cultures of Penicillium marneffei

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Elizabethkingia anophelis bacteremia is associated with clinically significant infections and high mortality

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Metabolomic Profiling of Plasma from Melioidosis Patients Using UHPLC-QTOF MS Reveals Novel Biomarkers for Diagnosis

© 2016 by the authors; licensee MDPI, Basel, Switzerland.To identify potential biomarkers for improving diagnosis of melioidosis, we compared plasma metabolome profiles of melioidosis patients compared to patients with other bacteremia and controls without active infection, using ultra-high-performance liquid chromatography-electrospray ionization-quadruple time-of-flight mass spectrometry. Principal component analysis (PCA) showed that the metabolomic profiles of melioidosis patients are distinguishable from bacteremia patients and controls. Using multivariate and univariate analysis, 12 significant metabolites from four lipid classes, acylcarnitine (n = 6), lysophosphatidylethanolamine (LysoPE) (n = 3), sphingomyelins (SM) (n = 2) and phosphatidylcholine (PC) (n = 1), with significantly higher levels in melioidosis patients than bacteremia patients and controls, were identified. Ten of the 12 metabolites showed area-under-receiver operating characteristic curve (AUC) >0.80 when compared both between melioidosis and bacteremia patients, and between melioidosis patients and controls. SM(d18:2/16:0) possessed the largest AUC when compared, both between melioidosis and bacteremia patients (AUC 0.998, sensitivity 100% and specificity 91.7%), and between melioidosis patients and controls (AUC 1.000, sensitivity 96.7% and specificity 100%). Our results indicate that metabolome profiling might serve as a promising approach for diagnosis of melioidosis using patient plasma, with SM(d18:2/16:0) representing a potential biomarker. Since the 12 metabolites were related to various pathways for energy and lipid metabolism, further studies may reveal their possible role in the pathogenesis and host response in melioidosis.published_or_final_versio

The Formation and Evolution of the First Massive Black Holes

The first massive astrophysical black holes likely formed at high redshifts (z>10) at the centers of low mass (~10^6 Msun) dark matter concentrations. These black holes grow by mergers and gas accretion, evolve into the population of bright quasars observed at lower redshifts, and eventually leave the supermassive black hole remnants that are ubiquitous at the centers of galaxies in the nearby universe. The astrophysical processes responsible for the formation of the earliest seed black holes are poorly understood. The purpose of this review is threefold: (1) to describe theoretical expectations for the formation and growth of the earliest black holes within the general paradigm of hierarchical cold dark matter cosmologies, (2) to summarize several relevant recent observations that have implications for the formation of the earliest black holes, and (3) to look into the future and assess the power of forthcoming observations to probe the physics of the first active galactic nuclei.Comment: 39 pages, review for "Supermassive Black Holes in the Distant Universe", Ed. A. J. Barger, Kluwer Academic Publisher

Vitamin D supplementation and breast cancer prevention : a systematic review and meta-analysis of randomized clinical trials

In recent years, the scientific evidence linking vitamin D status or supplementation to breast cancer has grown notably. To investigate the role of vitamin D supplementation on breast cancer incidence, we conducted a systematic review and meta-analysis of randomized controlled trials comparing vitamin D with placebo or no treatment. We used OVID to search MEDLINE (R), EMBASE and CENTRAL until April 2012. We screened the reference lists of included studies and used the “Related Article” feature in PubMed to identify additional articles. No language restrictions were applied. Two reviewers independently extracted data on methodological quality, participants, intervention, comparison and outcomes. Risk Ratios and 95% Confident Intervals for breast cancer were pooled using a random-effects model. Heterogeneity was assessed using the I2 test. In sensitivity analysis, we assessed the impact of vitamin D dosage and mode of administration on treatment effects. Only two randomized controlled trials fulfilled the pre-set inclusion criteria. The pooled analysis included 5372 postmenopausal women. Overall, Risk Ratios and 95% Confident Intervals were 1.11 and 0.74–1.68. We found no evidence of heterogeneity. Neither vitamin D dosage nor mode of administration significantly affected breast cancer risk. However, treatment efficacy was somewhat greater when vitamin D was administered at the highest dosage and in combination with calcium (Risk Ratio 0.58, 95% Confident Interval 0.23–1.47 and Risk Ratio 0.93, 95% Confident Interval 0.54–1.60, respectively). In conclusions, vitamin D use seems not to be associated with a reduced risk of breast cancer development in postmenopausal women. However, the available evidence is still limited and inadequate to draw firm conclusions. Study protocol code: FARM8L2B5L

Characteristics of biochemical markers and quality parameters using whole wheat flours in Korean wheat cultivars and lines

Tese de doutoramento em Ciências e Tecnologias da Informação, apresentada ao Departamento de Engenharia Informática da Faculdade de Ciências e Tecnologia da Universidade de CoimbraO espectro rádio tem vindo a ser regulado de um modo estático. Ou seja, este encontra-se essencialmente dividido em bandas de frequência licenciadas, com utilização restringida a um número limitado de utilizadores autorizados, e em algumas bandas de frequência não licenciadas para utilização livre. Devido à falta de flexibilidade resultante desta abordagem, partes significativas do espectro rádio encontram-se subutilizadas. Em simultâneo, outras bandas de frequência estão a ficar cada vez mais saturadas, nomeadamente as não licenciadas em áreas densamente povoadas. O Rádio Cognitivo é um paradigma recente cujo objetivo é melhorar o nível de eficiência na utilização do espectro rádio. Os seus princípios gerais consistem em permitir que dispositivos sem fios não licenciados (os denominados Utilizadores Secundários) possam aceder às bandas de frequência licenciadas desde que estes não interferiram de forma prejudicial com os utilizadores licenciados (os denominados Utilizadores Primários). A abordagem preponderante na área de Rádio Cognitivo consiste em ter utilizadores secundários com capacidade para, de um modo dinâmico, detetar e aceder a oportunidades espectrais, ou seja, bandas de frequência que não estão a ser acedidas pelos respetivos utilizadores primários num determinado momento numa determinada localização. Neste contexto, os utilizadores secundários devem ser capazes de analisar o espectro rádio com precisão e, de preferência, possuírem mecanismos de aprendizagem baseados em observação local e experiência passada. Apesar da área de Rádio Cognitivo ter implicações na totalidade das camadas das pilhas protocolares de comunicação, os seus problemas fundamentais localizam-se nos níveis físico (PHY) e de controlo de acesso ao meio (MAC). Em particular, os protocolos de controlo de acesso ao meio desempenham um papel fundamental no âmbito de operações de controlo de acesso ao espectro rádio e de suporte à cooperação entre utilizadores secundários. Os utilizadores primários, quanto a eles, devem manter-se abstraídos das operações de Rádio Cognitivo e, em consequência, não estarem sujeitos a qualquer tipo de alteração em cenários de Rádio Cognitivo. Esta tese apresenta cinco contribuições, essencialmente relacionadas com o nível do controlo de acesso ao meio, com o objetivo de incrementar os níveis de proteção dos utilizadores primários e de desempenho dos utilizadores secundários em redes de Rádio Cognitivo distribuídas, especialmente quando os utilizadores secundários não têm antecipadamente acesso a qualquer tipo de informação, tal como a localização de utilizadores primários. Neste tipo de cenário, não existe qualquer entidade central responsável por recolher e processar dados de origem diversa ou tomar decisões de acesso ao espectro rádio. Ou seja, as soluções propostas adequam-se a utilizadores secundários que operam de um modo autónomo e cooperativo. Estes tomam as suas decisões baseando-se, essencialmente, em observações locais, em eventuais resultados de aprendizagem e em dados trocados entre si. A primeira contribuição desta tese consiste numa descrição da área de Rádio Cognitivo através de um estado da arte detalhado. A segunda contribuição resulta na definição de um protocolo de controlo de acesso ao meio apoiado num mecanismo inovador, designado COSBET (Cooperative Sense-Before-Transmit), que oferece um nível superior de proteção dos utilizadores primários em cenários de Rádio Cognitivo distribuídos sujeitos ao problema do utilizador primário oculto. Este tipo de anomalia ocorre quando um utilizador secundário é incapaz de detetar as atividades de um determinado utilizador primário apesar de poder provocar interferências na respetiva área de abrangência. Tal como já foi referido, na área de Rádio Cognitivo, é considerado desejável os utilizadores secundários terem capacidades de aprendizagem baseadas em observação local e experiência passada. No entanto, em cenários distribuídos, o problema do utilizador primário oculto afeta negativamente a qualidade dos resultados de aprendizagem obtidos e, em consequência, o nível efetivamente alcançado em termos de proteção dos utilizadores primários. Sendo assim, esta tese também analisa esta questão e propõe uma solução destinada a tratá-la, estando esta terceira contribuição baseada num conceito chave designado FIBASC (Filtering Based on Suspicious Channels). A troca de informação de controlo em redes de Rádio Cognitivo distribuídas é frequentemente suportada por um canal partilhado e acessível à globalidade dos utilizadores secundários. Este é o designado canal de controlo comum (CCC), sendo igualmente esta a abordagem seguida pelo protocolo COSBET-MAC proposto. No entanto, os CCC estão sujeitos a problemas de saturação. A ocorrência deste tipo de problema impede os utilizadores secundários de tirarem pleno proveito das potencialidades oferecidas pelo Rádio Cognitivo, acabando por limitar os níveis de desempenho de comunicação alcançáveis. Sendo assim, nesta tese também analisamos esta questão e propomos uma solução destinada a abordá-la, correspondendo esta à nossa quarta contribuição. A solução proposta, designada CORHYS (Cognitive Radio Hybrid Signalling), baseia-se num esquema de sinalização híbrido que recorre simultaneamente a um CCC e aos canais de dados que vão sendo alocados de forma dinâmica. A quinta e última contribuição desta tese consiste na definição de uma estratégia adicional, igualmente localizada no nível do controlo de acesso ao meio, destinada a melhorar o desempenho dos utilizadores secundários em cenários de Rádio Cognitivo distribuídos em que se recorre a um CCC. Fazem parte das suas linhas orientadoras a otimização da reutilização espacial do espectro rádio e a redução do tráfego de controlo gerado entre utilizadores secundários. As soluções de Rádio Cognitivo propostas no âmbito desta tese foram avaliadas em ambiente de simulação, sendo esta uma prática comum, nomeadamente devido a limitações de tempo e de outros tipos de recursos. Para o efeito, recorreu-se ao OMNET++ (Objective Modular Network Testbed in C++), um simulador baseado em eventos discretos e de código aberto. A totalidade das contribuições da presente tese podem ser aplicadas em conjunto. A integração destas deu origem a uma solução única e otimizada de controlo de acesso ao meio destinada a cenários de Rádio Cognitivo distribuídos. Esta aborda as duas principais preocupações existentes em cenários de Rádio Cognitivo: proteger os utilizadores primários de qualquer tipo de interferência prejudicial; e melhorar o desempenho de comunicação dos utilizadores secundários. Tanto quanto sabemos, as várias soluções propostas e o nível de completude que a utilização conjunta destas permite não são oferecidos por qualquer outra proposta de controlo de acesso ao meio existente para cenários de Rádio Cognitivo distribuídos. As contribuições desta tese também apontam direções que podem ser seguidas no âmbito de outros protocolos de controlo de acesso ao meio, especialmente aqueles que se destinam a redes de Rádio Cognitivo distribuídas.The radio spectrum has been statically regulated, i.e., essentially partitioned into licensed frequency bands, which are accessed exclusively by authorized users, and unlicensed frequency bands that can be freely accessed. Due to this inflexible policy, large portions of the entire radio spectrum remain unused independently of time and location in the world, while some frequency bands suffer from increasing levels of saturation, particularly the unlicensed ones in densely populated areas. Cognitive Radio (CR) is a recent paradigm that aims at improving efficiency regarding spectrum utilization. Its principles consist in allowing unlicensed wireless devices (i.e., secondary users) to access licensed frequency bands provided that the respective incumbent users (i.e., primary users) do not suffer any harmful interference. The most preponderant CR approach consists in having a secondary user (SU) dynamically locating and accessing spectrum opportunities, i.e., frequency bands that are not being accessed by any primary user (PU) at a given time and location. Consequently, sensing the spectrum and learning through local observation and past experience, which enables proactive spectrum decision, are key CR issues. Despite CR has implications in all the layers of the communication protocol stack, its fundamentals are mainly related to the physical (PHY) and medium access control (MAC) levels. In fact, CR MAC protocols are at the heart of spectrum access control and cooperation between SUs. PUs are expected to be unware of CR operations and, consequently, should not suffer any modification under CR scenarios. This thesis provides five contributions, essentially related to the MAC level, with the aim of improving the protection of PUs and the communication performance of SUs in cooperative distributed CR networks, particularly when there is no access to any a priori known information, such as the locations of primary transmitters. In this type of scenario, there are no central entities that collect and fuse data, or take spectrum decisions. That is, the proposed solutions fit into totally autonomous and cooperating SUs, i.e., SUs that take their own decisions based on local observation, on learning outcomes if any is available, and on data they exchange with each other. The first contribution of this thesis consists in a description of the CR area through an indepth state of the art. The second contribution lies in the definition of a CR MAC protocol that follows a novel approach, named Cooperative Sense-Before-Transmit (COSBET), which provides a higher protection of PUs in distributed CR scenarios that suffer from the hidden PU problem. This issue occurs when a SU cannot sense the activities of a given PU despite it can cause harmful interference to its coverage area. As already mentioned, CR considers that the SUs might have learning capabilities based on local observation and past experience. However, in distributed scenarios, the hidden PU problem affects the accuracy of learning and, therefore, the effectiveness of PU protection. For that reason, in this thesis we also discuss this issue and propose a novel solution that addresses it. This solution is based on a key concept named FIBASC (Filtering Based on Suspicious Channels). Utilizing a common control channel (CCC), i.e., a channel that is available to all the SUs in a CR network, for signalling purposes is a frequent practice concerning existing distributed CR MAC solutions. It is also the solution adopted by COSBET-MAC. However, a CCC is susceptible to saturation and can, therefore, become a performance bottleneck that inhibits the SUs from taking full advantage of CR potentialities. Consequently, the fourth contribution of this thesis consists in analysing this issue and addressing it through a novel solution, which we named CORHYS (Cognitive Radio Hybrid Signalling). CORHYS is based on a hybrid signalling approach that performs signalling over the CCC and over the allocated data channels simultaneously. The fifth and last contribution of this thesis consists in a MAC-level strategy that aims at further improving the performance of SUs in distributed CR scenarios that are based on a CCC. The key guidelines for this strategy are optimizing the spatial reuse of the radio spectrum and reducing control traffic. The CR solutions that resulted from this thesis were evaluated through simulation, which is a common practice, particularly due to time and other resource restrictions. For this purpose, we used OMNET++ (Objective Modular Network Testbed in C++), an open source discrete event simulator. The contributions of this thesis can be applied jointly and were successfully integrated with each other, which resulted in an optimized CR MAC solution that addresses the two main concerns in distributed CR scenarios: protecting the PUs from harmful interference; and improving the communication performance of the SUs. To the best of our knowledge, the proposed solutions and the level of completeness that they jointly achieve are not found in any other existing distributed CR MAC proposal. We also note that they define directions that can be followed by other CR MAC protocols, particularly those that target distributed CR networks

Exome-wide association analysis reveals novel coding sequence variants associated with lipid traits in Chinese

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AdaSpline-Net for Improved Short-Term Solar Irradiance Forecasting

Neural networks utilizing backpropagation are a powerful tool for solar irradiance forecasting, which is vital for climate research and energy market operations. This study addresses the challenge of modeling complex, nonlinear relationships between weather parameters by introducing an innovative adaptive B-spline activation function. The piecewise polynomial approach proposed in this work, integrated into the neural network framework and optimized using the Adaptive Moment Estimation (Adam) algorithm, allows for effective parameter tuning after each epoch, resulting in enhanced forecasting accuracy. Unlike traditional activation functions, which suffer from issues like the "dying ReLU" problem, the adaptive B-spline function provides smooth, flexible mappings with continuous gradients, allowing it to capture intricate data patterns effectively. This adaptability makes it particularly suitable for high-precision environmental applications. Validation using real-world datasets from Singapore and Hawaii shows that the adaptive B-spline significantly outperforms conventional activation functions, delivering up to a 10% improvement in forecasting accuracy for both training and testing datasets. Furthermore, its robustness across various neural network architectures demonstrates its adaptability and compatibility with backpropagation. This research highlights the potential of optimized B-spline activation functions to improve the accuracy and dependability of neural network-based forecasting models

Normalized periprostatic fat MRI measurements can predict prostate cancer aggressiveness in men undergoing radical prostatectomy for clinically localised disease

Periprostatic and pelvic fat have been shown to influence prostate cancer behaviour through the secretion of chemokines and growth factors, acting in a paracrine mode. We have measured periprostatic fat volume (PFV) with normalisation to prostate gland volume on pelvic magnetic resonance imaging (MRI) and have correlated this with grade (Gleason score; GS) and pathological staging (pT) of prostate cancer (PCa) following radical prostatectomy (RP). PFV was determined using a segmentation technique on contiguous T1-weighted axial MRI slices from the level of the prostate base to the apex. The abdominal fat area (AFA) and subcutaneous fat thickness (SFT) were measured using T1-weighted axial slices at the level of the umbilicus and the upper border of the symphysis pubis, respectively. PFV was normalised to prostate volume (PV) to account for variations in PV (NPFV=PFV/PV). Patients were stratified into three risk groups according to post-operative GS: ≤6, 7(3+4), and ≥7(4+3). NPFV was significantly different between the groups (p=0.001) and positively correlated with post-operative GS (ρ=0.294, p<0.001). There was a difference in NPFV between those with upgrading of GS from 6 post prostatectomy (2.43±0.98; n=26) compared to those who continued to be low grade (1.99±0.82; n=17); however, this did not reach statistical significance (p=0.11)