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

Sliding charge density wave in manganites

The so-called stripe phase of the manganites is an important example of the complex behaviour of metal oxides, and has long been interpreted as the localisation of charge at atomic sites. Here, we demonstrate via resistance measurements on La_{0.50}Ca_{0.50}MnO_3 that this state is in fact a prototypical charge density wave (CDW) which undergoes collective transport. Dramatic resistance hysteresis effects and broadband noise properties are observed, both of which are typical of sliding CDW systems. Moreover, the high levels of disorder typical of manganites result in behaviour similar to that of well-known disordered CDW materials. Our discovery that the manganite superstructure is a CDW shows that unusual transport and structural properties do not require exotic physics, but can emerge when a well-understood phase (the CDW) coexists with disorder.Comment: 13 pages; 4 figure

The fidelity of dynamic signaling by noisy biomolecular networks

This is the final version of the article. Available from Public Library of Science via the DOI in this record.Cells live in changing, dynamic environments. To understand cellular decision-making, we must therefore understand how fluctuating inputs are processed by noisy biomolecular networks. Here we present a general methodology for analyzing the fidelity with which different statistics of a fluctuating input are represented, or encoded, in the output of a signaling system over time. We identify two orthogonal sources of error that corrupt perfect representation of the signal: dynamical error, which occurs when the network responds on average to other features of the input trajectory as well as to the signal of interest, and mechanistic error, which occurs because biochemical reactions comprising the signaling mechanism are stochastic. Trade-offs between these two errors can determine the system's fidelity. By developing mathematical approaches to derive dynamics conditional on input trajectories we can show, for example, that increased biochemical noise (mechanistic error) can improve fidelity and that both negative and positive feedback degrade fidelity, for standard models of genetic autoregulation. For a group of cells, the fidelity of the collective output exceeds that of an individual cell and negative feedback then typically becomes beneficial. We can also predict the dynamic signal for which a given system has highest fidelity and, conversely, how to modify the network design to maximize fidelity for a given dynamic signal. Our approach is general, has applications to both systems and synthetic biology, and will help underpin studies of cellular behavior in natural, dynamic environments.We acknowledge support from a Medical Research Council and Engineering and Physical Sciences Council funded Fellowship in Biomedical Informatics (CGB) and a Scottish Universities Life Sciences Alliance chair in Systems Biology (PSS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

The protein corona determines the cytotoxicity of nanodiamonds: implications of corona formation and its remodelling on nanodiamond applications in biomedical imaging and drug delivery

The use of nanodiamonds for biomedical and consumer applications is growing rapidly. As their use becomes more widespread, so too do concerns around their cytotoxicity. The cytotoxicity of nanodiamonds correlates with their cellular internalisation and circulation time in the body. Both internalisation and circulation time are influenced by the formation of a protein corona on the nanodiamond surface. However, a precise understanding of both how the corona forms and evolves and its influence on cytotoxicity is lacking. Here, we investigated protein corona formation and evolution in response to two classes of nanodiamonds, pristine and aminated, and two types of proteins, bovine serum albumin and fibronectin. Specifically, we found that a corona made of bovine serum albumin (BSA), which represents the most abundant protein in blood plasma, reduced nanodiamond agglomeration. Fibronectin (FN9-10), the second most abundant protein found in the plasma, exhibited a significantly higher nanodiamond binding affinity than BSA, irrespective of the nanodiamond surface charge. Finally, nanodiamonds with a BSA corona displayed less cytotoxicity towards nonphagocytic liver cells. However, regardless of the type of corona (FN9-10 or BSA), both classes of nanodiamonds induced substantial phagocytic cell death. Our results emphasise that a precise understanding of the corona composition is fundamental to determining the fate of nanoparticles in the body

Measuring every particle's size from three-dimensional imaging experiments

Often experimentalists study colloidal suspensions that are nominally monodisperse. In reality these samples have a polydispersity of 4-10%. At the level of an individual particle, the consequences of this polydispersity are unknown as it is difficult to measure an individual particle size from microscopy. We propose a general method to estimate individual particle radii within a moderately concentrated colloidal suspension observed with confocal microscopy. We confirm the validity of our method by numerical simulations of four major systems: random close packing, colloidal gels, nominally monodisperse dense samples, and nominally binary dense samples. We then apply our method to experimental data, and demonstrate the utility of this method with results from four case studies. In the first, we demonstrate that we can recover the full particle size distribution {\it in situ}. In the second, we show that accounting for particle size leads to more accurate structural information in a random close packed sample. In the third, we show that crystal nucleation occurs in locally monodisperse regions. In the fourth, we show that particle mobility in a dense sample is correlated to the local volume fraction.Comment: 7 pages, 5 figure

Rapid reduction versus abrupt quitting for smokers who want to stop soon: a randomised controlled non-inferiority trial

Background: The standard way to stop smoking is to stop abruptly on a quit day with no prior reduction in consumption of cigarettes. Many smokers feel that reduction is natural and if reduction programmes were offered, many more might take up treatment. Few trials of reduction versus abrupt cessation have been completed. Most are small, do not use pharmacotherapy, and do not meet the standards necessary to obtain a marketing authorisation for a pharmacotherapy.\ud Design/Methods: We will conduct a non-inferiority andomised trial of rapid reduction versus standard abrupt cessation among smokers who want to stop smoking. In the reduction arm,participants will be advised to reduce smoking consumption by half in the first week and to 25% of baseline in the second, leading up to a quit day at which participants will stop smoking completely.This will be assisted by nicotine patches and an acute form of nicotine replacement therapy. In the abrupt arm participants will use nicotine patches only, whilst smoking as normal, for two weeks prior to a quit day, at which they will also stop smoking completely. Smokers in either arm will have standard withdrawal orientated behavioural support programme with a combination of nicotine patches and acute nicotine replacement therapy post-cessation.\ud Outcomes/Follow-up: The primary outcome of interest will be prolonged abstinence from smoking, with secondary trial outcomes of point prevalence, urges to smoke and withdrawal\ud symptoms. Follow up will take place at 4 weeks, 8 weeks and 6 months post-quit day

Estimating the Total Number of Susceptibility Variants Underlying Complex Diseases from Genome-Wide Association Studies

Recently genome-wide association studies (GWAS) have identified numerous susceptibility variants for complex diseases. In this study we proposed several approaches to estimate the total number of variants underlying these diseases. We assume that the variance explained by genetic markers (Vg) follow an exponential distribution, which is justified by previous studies on theories of adaptation. Our aim is to fit the observed distribution of Vg from GWAS to its theoretical distribution. The number of variants is obtained by the heritability divided by the estimated mean of the exponential distribution. In practice, due to limited sample sizes, there is insufficient power to detect variants with small effects. Therefore the power was taken into account in fitting. Besides considering the most significant variants, we also tried to relax the significance threshold, allowing more markers to be fitted. The effects of false positive variants were removed by considering the local false discovery rates. In addition, we developed an alternative approach by directly fitting the z-statistics from GWAS to its theoretical distribution. In all cases, the “winner's curse” effect was corrected analytically. Confidence intervals were also derived. Simulations were performed to compare and verify the performance of different estimators (which incorporates various means of winner's curse correction) and the coverage of the proposed analytic confidence intervals. Our methodology only requires summary statistics and is able to handle both binary and continuous traits. Finally we applied the methods to a few real disease examples (lipid traits, type 2 diabetes and Crohn's disease) and estimated that hundreds to nearly a thousand variants underlie these traits

Regulation of Energy Stores and Feeding by Neuronal and Peripheral CREB Activity in Drosophila

The cAMP-responsive transcription factor CREB functions in adipose tissue and liver to regulate glycogen and lipid metabolism in mammals. While Drosophila has a homolog of mammalian CREB, dCREB2, its role in energy metabolism is not fully understood. Using tissue-specific expression of a dominant-negative form of CREB (DN-CREB), we have examined the effect of blocking CREB activity in neurons and in the fat body, the primary energy storage depot with functions of adipose tissue and the liver in flies, on energy balance, stress resistance and feeding behavior. We found that disruption of CREB function in neurons reduced glycogen and lipid stores and increased sensitivity to starvation. Expression of DN-CREB in the fat body also reduced glycogen levels, while it did not affect starvation sensitivity, presumably due to increased lipid levels in these flies. Interestingly, blocking CREB activity in the fat body increased food intake. These flies did not show a significant change in overall body size, suggesting that disruption of CREB activity in the fat body caused an obese-like phenotype. Using a transgenic CRE-luciferase reporter, we further demonstrated that disruption of the adipokinetic hormone receptor, which is functionally related to mammalian glucagon and β-adrenergic signaling, in the fat body reduced CRE-mediated transcription in flies. This study demonstrates that CREB activity in either neuronal or peripheral tissues regulates energy balance in Drosophila, and that the key signaling pathway regulating CREB activity in peripheral tissue is evolutionarily conserved

Nitroxyl (HNO) Stimulates Soluble Guanylyl Cyclase to Suppress Cardiomyocyte Hypertrophy and Superoxide Generation

Background: New therapeutic targets for cardiac hypertrophy, an independent risk factor for heart failure and death, are essential. HNO is a novel redox sibling of NON attracting considerable attention for the treatment of cardiovascular disorders, eliciting cGMP-dependent vasodilatation yet cGMP-independent positive inotropy. The impact of HNO on cardiac hypertrophy (which is negatively regulated by cGMP) however has not been investigated. Methods: Neonatal rat cardiomyocytes were incubated with angiotensin II (Ang II) in the presence and absence of the HNO donor Angeli’s salt (sodium trioxodinitrate) or B-type natriuretic peptide, BNP (all 1 mmol/L). Hypertrophic responses and its triggers, as well as cGMP signaling, were determined. Results: We now demonstrate that Angeli’s salt inhibits Ang II-induced hypertrophic responses in cardiomyocytes, including increases in cardiomyocyte size, de novo protein synthesis and b-myosin heavy chain expression. Angeli’s salt also suppresses Ang II induction of key triggers of the cardiomyocyte hypertrophic response, including NADPH oxidase (on both Nox2 expression and superoxide generation), as well as p38 mitogen-activated protein kinase (p38MAPK). The antihypertrophic, superoxide-suppressing and cGMP-elevating effects of Angeli’s salt were mimicked by BNP. We also demonstrate that the effects of Angeli’s salt are specifically mediated by HNO (with no role for NON or nitrite), with subsequent activation of cardiomyocyte soluble guanylyl cyclase (sGC) and cGMP signaling (on both cGMP-dependen