Implications of Intercellular Signaling for Radiation Therapy: A Theoretical Dose-Planning Study

Purpose
Recent in vitro results have shown significant contributions to cell killing from signaling effects at doses that are typically used in radiation therapy. This study investigates whether these in vitro observations can be reconciled with in vivo knowledge and how signaling may have an impact on future developments in radiation therapy.
Methods and Materials
Prostate cancer treatment plans were generated for a series of 10 patients using 3-dimensional conformal therapy, intensity modulated radiation therapy (IMRT), and volumetric modulated arc therapy techniques. These plans were evaluated using mathematical models of survival following modulated radiation exposures that were developed from in vitro observations and incorporate the effects of intercellular signaling. The impact on dose-volume histograms and mean doses were evaluated by converting these survival levels into "signaling-adjusted doses" for comparison.
Results
Inclusion of intercellular communication leads to significant differences between the signalling-adjusted and physical doses across a large volume. Organs in low-dose regions near target volumes see the largest increases, with mean signaling-adjusted bladder doses increasing from 23 to 33 Gy in IMRT plans. By contrast, in high-dose regions, there is a small decrease in signaling-adjusted dose due to reduced contributions from neighboring cells, with planning target volume mean doses falling from 74 to 71 Gy in IMRT. Overall, however, the dose distributions remain broadly similar, and comparisons between the treatment modalities are largely unchanged whether physical or signaling-adjusted dose is compared. Conclusions Although incorporating cellular signaling significantly affects cell killing in low-dose regions and suggests a different interpretation for many phenomena, their effect in high-dose regions for typical planning techniques is comparatively small. This indicates that the significant signaling effects observed in vitro are not contradicted by comparison with clinical observations. Future investigations are needed to validate these effects in vivo and to quantify their ranges and potential impact on more advanced radiation therapy techniques.

Causal Models of Clinically Significant Behaviors in Angelman, Cornelia de Lange, Prader-Willi and Smith-Magenis Syndromes

The operant learning theory account of behaviors of clinical significance in people with intellectual disability (ID) has dominated the field for nearly 50 years. However, in the last two decades, there has been a substantial increase in published research that describes the behavioral phenotypes of genetic disorders and shows that behaviors such as self-injury and aggression are more common in some syndromes than might be expected given group characteristics. These cross-syndrome differences in prevalence warrant explanation, not least because this observation challenges an exclusively operant learning theory account. To explore this possible conflict between theoretical account and empirical observation, we describe the genetic cause and physical, social, cognitive and behavioral phenotypes of four disorders associated with ID (Angleman, Cornelia de Lange, Prader-Willi and Smith-Magenis syndromes) and focus on the behaviors of clinical significance in each syndrome. For each syndrome we then describe a model of the interactions between physical characteristics, cognitive and motivational endophenotypes and environmental factors (including operant reinforcement) to account for the resultant behavioral phenotype. In each syndrome it is possible to identify pathways from gene to physical phenotype to cognitive or motivational endophenotype to behavior to environment and back to behavior. We identify the implications of these models for responsive and early intervention and the challenges for research in this area. We identify a pressing need for meaningful dialog between different disciplines to construct better informed models that can incorporate all relevant and robust empirical evidence.

The Applicability of Two Strengths-based Systemic Psychotherapy Models for Young People Following Type 1 Trauma

This paper will consider the inter-relationship of a number of overlapping disciplinary theoretical concepts relevant to a strengths-based orientation, including well-being, salutogenesis, sense of coherence, quality of life and resilience. Psychological trauma will be referenced and the current evidence base for interventions with children and young people outlined and critiqued. The relational impact of trauma on family relationships is emphasised, providing a rationale for systemic psychotherapeutic interventions as part of a holistic approach to managing the effects of trauma. The congruence between second-order systemic psychotherapy models and a strengths-based philosophy is noted, with particular reference to solution-focused brief therapy and narrative therapy, and illustrated; via a description of the process of helping someone move from a victim position to a survivor identity using solution-focused brief therapy, and through a case example applying a narrative therapy approach to a teenage boy who suffered a serious assault. The benefits of a strength-based approach to psychological trauma for the clients and therapists will be summarised and a number of potential pitfalls articulated.

Electron impact excitation of Mg VIII: Collision strengths, transition probabilities and theoretical EUV and soft X-ray line intensities for Mg VIII

Context: Mg VIII emission lines are observed in a range of astronomical objects such as the Sun, other cool stars and in the coronal line region of Seyfert galaxies. Under coronal conditions Mg VIII emits strongly in the extreme ultraviolet (EUV) and soft X-ray spectral regions which makes it an ideal ion for plasma diagnostics.

Aims. Two theoretical atomic models, consisting of 125 fine structure levels, are developed for the Mg VIII ion. The 125 levels arise from the 2s(2)2p, 2s(2)p2, 2p(3), 2s(2)3s, 2s(2)3p, 2s(2)3d, 2s2p3s, 2s2p3p, 2s2p3d, 2p(2)3s, 2p(2)3p and 2p(2)3d configurations. Electron impact excitation collision strengths and radiative transition probabilities are calculated for both Mg VIII models, compared with existing data, and the best model selected to generate a set of theoretical emission line intensities. The EUV lines, covering 312-790 angstrom, are compared with existing solar spectra (SERTS-89 and SUMER), while the soft X-ray transitions (69-97 angstrom) are examined for potential density diagnostic line ratios and also compared with the limited available solar and stellar observational data.

Methods. The R-matrix codes Breit-Pauli RMATRXI and RMATRXII are utilised, along with the PSTGF code, to calculate the collision strengths for two Mg VIII models. Collision strengths are averaged over a Maxwellian distribution to produce the corresponding effective collision strengths for use in astrophysical applications. Transition probabilities are also calculated using the CIV3 atomic structure code. The best data are then incorporated into the modelling code CLOUDY and line intensities generated for a range of electron temperatures and densities appropriate to solar and stellar coronal plasmas.

Results. The present effective collision strengths are compared with two previous calculations. Good levels of agreement are found with the most recent, but there are large differences with the other for forbidden transitions. The resulting line intensities compare favourably with the observed values from the SERTS-89 and SUMER spectra. Theoretical soft X-ray emission lines are presented and several density diagnostic line ratios examined, which are in reasonable agreement with the limited observational data available.

Aggressiveness as a component of fighting ability in pigs using a game-theoretical framework

Understanding animal contests has benefited greatly from employing the concept of fighting ability, termed resource-holding potential (RHP), with body size/weight typically used as a proxy. However, victory does not always go to the larger/heavier contestant and the existing RHP approach thereby fails to accurately predict contest outcome. Aggressiveness, typically studied as a personality trait, might explain part of this discrepancy. We investigated whether aggressiveness forms a component of RHP, examining effects on contest outcome, duration and phases, plus physiological measures of costs (lactate and glucose). Furthermore, using the correct theoretical framework, we provide the first study to investigate whether individuals gather and use information on aggressiveness as part of an assessment strategy. Pigs, Sus scrofa, were assessed for aggressiveness in resident-intruder tests whereby attack latency reflects aggressiveness. Contests were then staged between size-matched animals diverging in aggressiveness. Individuals with a short attack latency in the resident-intruder test almost always initiated the first bite and fight in the subsequent contest. However, aggressiveness had no direct effect on contest outcome, whereas bite initiation did lead to winning in contests without an escalated fight. This indirect effect suggests that aggressiveness is not a component of RHP, but rather reflects a signal of intent. Winner and loser aggressiveness did not affect contest duration or its separate phases, suggesting aggressiveness is not part of an assessment strategy. A greater asymmetry in aggressiveness prolonged contest duration and the duration of displaying, which is in a direction contrary to assessment models based on morphological traits. Blood lactate and glucose increased with contest duration and peaked during escalated fights, highlighting the utility of physiological measures as proxies for fight cost. Integrating personality traits into the study of contest behaviour, as illustrated here, will enhance our understanding of the subtleties of agonistic interactions.

Hydraulics of stepped chutes: experimental-numerical-theoretical study

O estudo de escoamentos turbulentos em descarregadores em degraus tem sido um desafio para os investigadores. A macro-rugosidade do leito, a ondulação da superfície livre, a intermitência da localização da secção inicial de entrada de ar e o escoamento bi-fásico a jusante da secção inicial de entrada de ar fazem com que a caracterização do escoamento deslizante sobre turbilhões em descarregadores em degraus não seja simples. Actualmente, é possível combinar técnicas de medição fiáveis com simulações numéricas e análise teórica. Nesta dissertação, o estudo experimental baseia-se em resultados experimentais obtidos em duas instalações experimentais: a instalação A, do Laboratório Nacional de Engenharia Civil (LNEC), dotada de um descarregador em degraus com declive de 1V:0.75H e a instalação B, do Instituto Superior Técnico (IST), dotada de um descarregador em degraus com declive de 1V:2H. Uma sonda de ar, um tubo de Pitot modificado e vários hidrómetros permitiram o estudo do escoamento deslizante sobre turbilhões mono- e bifásico ao longo do descarregador em degraus da instalação A. Na bacia de dissipação de energia, a observação visual do escoamento foi auxiliada pelas leituras efectuadas em tomadas de pressão localizadas na soleira da bacia e pelas leituras da altura do escoamento efectuadas em réguas graduadas localizadas nas paredes da bacia. Na instalação B foram utilizados um tubo de Pitot e vários hidrómetros para estudar a região não arejada do escoamento deslizante sobre turbilhões no descarregador em degraus. O estudo numérico é baseado em simulações numéricas da região não arejada do escoamento deslizante sobre turbilhões sobre descarregadores em degraus com o código comercial de CFD FLOW-3D® de modo a reproduzir as condições ensaiadas experimentalmente. As simulações beneficiaram da técnica de blocos múltiplos (multi-block) num sistema de coordenadas cartesianas, da determinação da superfície livre pelo método TruVOF e da utilização de dois modelos de turbulência: os modelos k- e RNG k-. Por último, o estudo teórico consistiu em desenvolver um modelo simplificado 1D para determinar as características hidráulicas principais do trecho não arejado do escoamento deslizante sobre turbilhões em descarregadores em degraus. O modelo foi desenvolvido a partir das equações de Navier-Stokes, conjuntamente com resultados experimentais e numéricos. Os resultados apresentados nesta dissertação contribuem para o conhecimento do escoamento deslizante sobre turbilhões em descarregadores em degraus, nomeadamente na região não arejada, na secção inicial de entrada de ar e na região arejada. A hidráulica dos dissipadores de energia a jusante de descarregadores em degraus, em particular das bacias tipo III do USBR, é também objecto de estudo. Em relação à região não arejada do escoamento em descarregadores com declive acentuado, e com base em resultados experimentais e numéricos, são propostas expressões para estimar o desenvolvimento da altura equivalente de água, da espessura da camada limite, da concentração média de ar, do coeficiente de energia cinética, da dissipação de energia, do factor de resistência e do coeficiente n da fórmula de Manning. São ainda propostas expressões adimensionais para a energia cinética turbulenta e sua dissipação. Para declives moderados, são propostas expressões para estimar o desenvolvimento da altura equivalente de água, do coeficiente de energia cinética e da energia específica residual. São ainda apresentados valores do expoente 1/N da expressão adimensional da distribuição de velocidades, quer para descarregadores com declive acentuado quer com declive moderado. Em conformidade com outros estudos centrados em escoamentos de parede e com derivações teóricas, para a região não arejada do escoamento em descarregadores em degraus de acentuado declive, observa-se que o factor de resistência depende da macro-rugosidade criada pelos degraus e da geometria da secção transversal e que o coeficiente n da fórmula de Manning aumenta com a rugosidade. A descrição estatística da turbulência do escoamento é igualmente explorada, contribuindo para o conhecimento da estrutura do escoamento. Observou-se que para números de Reynolds rugoso não superiores a 6.8x104 a energia cinética turbulência e a sua dissipação cumprem leis de semelhança. Estas expressões adimensionais estão de acordo com os resultados obtidos por outros autores para escoamentos completamente desenvolvidos em canais abertos e no escoamento em rios com leito de gravilha. Em acréscimo, a taxa de dissipação de energia, quer para descarregadores de declive acentuado quer de moderado declive, é baixa. Por último, observa-se que os valores da média temporal da concentração de ar entre 0 e 1 medidos na região não arejada do escoamento dizem respeito não só ao ar capturado entre ondas de água, na zona de ondulação da superfície livre, mas também ao ar emulsionado no escoamento, i.e., sob a forma de bolhas de ar, quando perto da secção média inicial de entrada de ar, devido à diferença entre localizações instantânea e média temporal. Foram revistas metodologias e fórmulas para estimar a localização da secção inicial de entrada de ar e apresentadas expressões para estimar a concentração média de ar e a altura equivalente de água nessa secção. Relativamente à região de escoamento arejado em descarregadores em degraus com declive acentuado, os resultados experimentais apresentados nesta dissertação permitiram estimar a influência da definição da superfície livre nos parâmetros hidráulicos da região do escoamento arejado e estimar a máxima elevação do escoamento nesta região do escoamento. Com base nos resultados experimentais obtidos na bacia de dissipação de energia do tipo III do USBR localizada a jusante do descarregador em degraus da instalação A, observou-se que os perfis da altura piezométrica e da altura do escoamento tendem a seguir o perfil recomendado pelo USBR para bacias tipo III. A excepção ocorre à entrada da bacia, onde as alturas piezométricas apresentadas nesta dissertação excedem largamente as apresentadas pelo USBR. É ainda observado que, tal como entre as bacias tipo I e tipo III do USBR, o ressalto hidráulico estabiliza muito mais rapidamente numa bacia tipo III a jusante de um descarregador em degraus do que uma bacia tipo I a jusante do mesmo descarregador em degraus. Finalmente, observa-se que os blocos de amortecimento a colocar no descarregador não têm influência visível nos resultados da altura piezométrica nem da altura do escoamento ao longo da bacia. Relativamente às simulações numéricas do escoamento não arejado, a proximidade entre resultados experimentais e numéricos permite validar o modelo teórico e a integração numérica usados no FLOW-3D®. As simulações desenvolvidas também mostraram que o modelo de turbulência k- permite representar as características do escoamento não arejado em descarregadores em degraus, uma vez que não foram observadas diferenças significativas entre as simulações com este modelo e com o modelo RNG k-. Finalmente, observou-se que o modelo de entrada de ar usado no FLOW-3D® é válido para estimar a localização da secção inicial de entrada de ar. Por último, a proximidade entre os resultados obtidos da aplicação do modelo teórico desenvolvido no âmbito desta dissertação e os resultados experimentais indica que as hipóteses e simplificações consideradas no desenvolvimento do modelo são adequadas.

Phase transitions and nonlinear phenomena in neuronal network models

Communication and cooperation between billions of neurons underlie the power of the brain. How do complex functions of the brain arise from its cellular constituents? How do groups of neurons self-organize into patterns of activity? These are crucial questions in neuroscience. In order to answer them, it is necessary to have solid theoretical understanding of how single neurons communicate at the microscopic level, and how cooperative activity emerges. In this thesis we aim to understand how complex collective phenomena can arise in a simple model of neuronal networks. We use a model with balanced excitation and inhibition and complex network architecture, and we develop analytical and numerical methods for describing its neuronal dynamics. We study how interaction between neurons generates various collective phenomena, such as spontaneous appearance of network oscillations and seizures, and early warnings of these transitions in neuronal networks. Within our model, we show that phase transitions separate various dynamical regimes, and we investigate the corresponding bifurcations and critical phenomena. It permits us to suggest a qualitative explanation of the Berger effect, and to investigate phenomena such as avalanches, band-pass filter, and stochastic resonance. The role of modular structure in the detection of weak signals is also discussed. Moreover, we find nonlinear excitations that can describe paroxysmal spikes observed in electroencephalograms from epileptic brains. It allows us to propose a method to predict epileptic seizures. Memory and learning are key functions of the brain. There are evidences that these processes result from dynamical changes in the structure of the brain. At the microscopic level, synaptic connections are plastic and are modified according to the dynamics of neurons. Thus, we generalize our cortical model to take into account synaptic plasticity and we show that the repertoire of dynamical regimes becomes richer. In particular, we find mixed-mode oscillations and a chaotic regime in neuronal network dynamics.

A framework for extracting and representing project knowledge contexts using topic models and dynamic knowledge maps

There is still a lack of effective paradigms and tools for analysing and discovering the contents and relationships of project knowledge contexts in the field of project management. In this paper, a new framework for extracting and representing project knowledge contexts using topic models and dynamic knowledge maps under big data environments is proposed and developed. The conceptual paradigm, theoretical underpinning, extended topic model, and illustration examples of the ontology model for project knowledge maps are presented, with further research work envisaged.

Dermic diffusion and stratum corneum: a state of the art review of mathematical models

Transdermal biotechnologies are an ever increasing field of interest, due to the medical and pharmaceutical applications that they underlie. There are several mathematical models at use that permit a more inclusive vision of pure experimental data and even allow practical extrapolation for new dermal diffusion methodologies. However, they grasp a complex variety of theories and assumptions that allocate their use for specific situations. Models based on Fick's First Law found better use in contexts where scaled particle theory Models would be extensive in time-span but the reciprocal is also true, as context of transdermal diffusion of particular active compounds changes. This article reviews extensively the various theoretical methodologies for studying dermic diffusion in the rate limiting dermic barrier, the stratum corneum, and systematizes its characteristics, their proper context of application, advantages and limitations, as well as future perspectives.

Models and tools for value systems analysis in collaborative environments

Dissertation to obtain the degree of Doctor in Electrical and Computer Engineering, specialization of Collaborative Networks

Knowledge Society and Geography: A Theoretical Approach

The transition process between information and knowledge is faster and so the inputs that influence social and political practises. The dissemination of information is now determinant in terms of territorial competitiveness and both public and private sector take large benefits when the data-information- knowledge value chain repeats itself trough space and time. Mankind depends nowadays on the creation and diffusion of good and reliable information. Speed is also important and the greater the speed, the faster the opportunities for global markets. Information must be an input for knowledge and obviously for decision. So, the power of information is unquestionable. This paper focuses on concepts like information, knowledge and other, more geographical and tries to explain how territories change from real to virtual. Knowledge society appears on an evolutional context in which information dissemination is wider and technological potential overwrites traditional notions of Geography. To understand the mutations over the territories, the causes and the consequences emerges the Geography of the Knowledge Society, a new discipline inside Geography with a special concern about modern society and socio-economical developing models.

Participatory Surveillance and Mathematical Models in Epidemiologic Research: Successes and Challenges

Theoretical epidemiology aims to understand the dynamics of diseases in populations and communities. Biological and behavioral processes are abstracted into mathematical formulations which aim to reproduce epidemiological observations. In this thesis a new system for the self-reporting of syndromic data — Influenzanet — is introduced and assessed. The system is currently being extended to address greater challenges of monitoring the health and well-being of tropical communities.(...)

Mobile E-commerce business model – A value web based approach to business models in mobile gaming industry

Tämän tutkimuksen tavoitteena oli tutkia langattomien internet palveluiden arvoverkkoa ja liiketoimintamalleja. Tutkimus oli luonteeltaan kvalitatiivinen ja siinä käytettiin strategiana konstruktiivista case-tutkimusta. Esimerkkipalveluna oli Treasure Hunters matkapuhelinpeli. Tutkimus muodostui teoreettisesta ja empiirisestä osasta. Teoriaosassa liitettiin innovaatio, liiketoimintamallit ja arvoverkko käsitteellisesti toisiinsa, sekä luotiin perusta liiketoimintamallien kehittämiselle. Empiirisessä osassa keskityttiin ensin liiketoimintamallien luomiseen kehitettyjen innovaatioiden pohjalta. Lopuksi pyrittiin määrittämään arvoverkko palvelun toteuttamiseksi. Tutkimusmenetelminä käytettiin innovaatiosessiota, haastatteluja ja lomakekyselyä. Tulosten pohjalta muodostettiin useita liiketoimintakonsepteja sekä kuvaus arvoverkon perusmallista langattomille peleille. Loppupäätelmänä todettiin että langattomat palvelut vaativat toteutuakseen useista toimijoista koostuvan arvoverkon.

Privacy-friendly Business Models for Location-Based Mobile Services

This paper presents a theoretical model to analyze the privacy issues around location based mobile business models. We report the results of an exploratory field experiment in Switzerland that assessed the factors driving user payoff in mobile business. We found that (1) the personal data disclosed has a negative effect on user payoff; (2) the amount of personalization available has a direct and positive effect, as well as a moderating effect on user payoff; (3) the amount of control over user's personal data has a direct and positive effect, as well as a moderating effect on user payoff. The results suggest that privacy protection could be the main value proposition in the B2C mobile market. From our theoretical model we derive a set of guidelines to design a privacy-friendly business model pattern for third-party services. We discuss four examples to show the mobile platform can play a key role in the implementation of these new business models.

The Effects of Body Posture on Emotion Perception: A Developmental and Theoretical Analysis

Previously, studies investigating emotional face perception - regardless of whether they involved adults or children - presented participants with static photos of faces in isolation. In the natural world, faces are rarely encountered in isolation. In the few studies that have presented faces in context, the perception of emotional facial expressions is altered when paired with an incongruent context. For both adults and 8- year-old children, reaction times increase and accuracy decreases when facial expressions are presented in an incongruent context depicting a similar emotion (e.g., sad face on a fear body) compared to when presented in a congruent context (e.g., sad face on a sad body; Meeren, van Heijnsbergen, & de Gelder, 2005; Mondloch, 2012). This effect is called a congruency effect and does not exist for dissimilar emotions (e.g., happy and sad; Mondloch, 2012). Two models characterize similarity between emotional expressions differently; the emotional seed model bases similarity on physical features, whereas the dimensional model bases similarity on underlying dimensions of valence an . arousal. Study 1 investigated the emergence of an adult-like pattern of congruency effects in pre-school aged children. Using a child-friendly sorting task, we identified the youngest age at which children could accurately sort isolated facial expressions and body postures and then measured whether an incongruent context disrupted the perception of emotional facial expressions. Six-year-old children showed congruency effects for sad/fear but 4-year-old children did not for sad/happy. This pattern of congruency effects is consistent with both models and indicates that an adult-like pattern exists at the youngest age children can reliably sort emotional expressions in isolation. In Study 2, we compared the two models to determine their predictive abilities. The two models make different predictions about the size of congruency effects for three emotions: sad, anger, and fear. The emotional seed model predicts larger congruency effects when sad is paired with either anger or fear compared to when anger and fear are paired with each other. The dimensional model predicts larger congruency effects when anger and fear are paired together compared to when either is paired with sad. In both a speeded and unspeeded task the results failed to support either model, but the pattern of results indicated fearful bodies have a special effect. Fearful bodies reduced accuracy, increased reaction times more than any other posture, and shifted the pattern of errors. To determine whether the results were specific to bodies, we ran the reverse task to determine if faces could disrupt the perception of body postures. This experiment did not produce congruency effects, meaning faces do not influence the perception of body postures. In the final experiment, participants performed a flanker task to determine whether the effect of fearful bodies was specific to faces or whether fearful bodies would also produce a larger effect in an unrelated task in which faces were absent. Reaction times did not differ across trials, meaning fearful bodies' large effect is specific to situations with faces. Collectively, these studies provide novel insights, both developmentally and theoretically, into how emotional faces are perceived in context.