The relevance of individuals' values to clinical situations is increasingly recognised in political and clinical contexts. Enhancing an individual's capacity to live consistently with their values is assumed to facilitate mental well-being and quality of life (QoL). However, little research has empirically investigated whether this focus is appropriate. This collection of studies will examine the relationship between values, well-being and QoL. "Valued living" is a core aim of Acceptance and Commitment Therapy (ACT) but it has received little empirical attention. The values identified within ACT may not be equally applicable to all clinical populations. Encouraging value-consistent action is often assumed to be inappropriate to offender populations. Schwartz‟s universal model of human values is introduced to inform understanding of the relationship between values and well-being and whether mentally disordered offenders (MDOs) have similar values to a non-psychologically distressed comparison group. Method Study 1 investigated the relationship between values, quality of life (QoL), psychological distress and psychological inflexibility (cognitive fusion and experiential avoidance) amongst a sample from the non-clinical sample (N = 109) using an online survey. Study 2 compared a subsample from study 1 with MDOs detained in medium security (N = 15) on the same measures. Study 3 explored participants‟ beliefs about the origin and maintenance of meaningful values. Responses were coded according to ACT literature and analysed using content analysis. Results Amongst the non-clinical population, QoL was positively correlated with „valued living‟, and negatively correlated with psychological inflexibility and distress. Psychological distress and psychological inflexibility correlated positively with the Openness to Change value domain and conservatism correlated negatively with psychological distress. No other relationships were observed between psychological flexibility or distress and value domain in the non-clinical population. MDOs had higher rates of psychological distress and lower psychological flexibility and QoL than the non-distressed population; they also attributed less importance to the self-transcendence value domain and more to self-enhancement. Benevolence was ranked significantly lower by the MDO sample. Other large effect sizes were detected reflecting differences between the samples, but they were not statistically significant. Intrinsic reinforcement was considered an important factor that maintained values as meaningful to all participants. Self-report data suggests that there are similarities and differences to how each sample conceptualises values. Discussion A clinical focus on values appears to be justified. The addition of Schwartz‟s model provided insight into the values of MDOs. The clinical and theoretical implications of the results are discussed as are the strengths and limitations of the study.

Dehydrins are intrinsically disordered plant stress-proteins. Repetitively in their sequence are some highly conserved stretches of 7-17 residues, the so called K-, S-, Y- and lysine rich segments. This thesis aims to give insight into the possible role dehydrins have in the stressed plant cell with main focus on membrane interaction and protection. The work includes four recombinant dehydrins from the plant Arabidopsis thaliana: Cor47 (SK3), Lti29 (SK3), Lti30 (K6) and Rab18 (Y2SK2). Initially, we mimicked crowded cellular environment in vitro to verify that dehydrins are truly disordered proteins. Thereafter, the proposal that the compulsory K-segment determines membrane binding was tested. Experiments show that only Lti30 and Rab18 bind, whereas Cor47 and Lti29 does not. As Lti30 and Rab18 binds they assembles vesicles into clusters in vitro, a feature used to characterize the interaction. From this it was shown that membrane binding of Lti30 is electrostatic and determined by global as well as local charges. Protonation of histidine pairs flanking the K-segments works as an on/off-binding switch. By NMR studies it was shown that the K-segments form a dynamic α-helix upon binding, so called disorder-to-order behaviour. Also, dehydrins electrostatic interaction with lipids can be further tuned by posttranslational phosphorylation or coordination of calcium and zinc ions. Finally, specific binding of Rab18 to inositol lipids, mainly PI(4,5)P2, is reported. The interaction is mainly coordinated by two arginines neighboring one of the K-segments. In conclusion, the K-segments are indeed involved in the binding of dehydrins to membrane but only in combination with extensions (Lti30) or modified (Rab18). / <p>At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 4: Manuscript. Paper 5: Manuscript.</p>

The purpose of the current study was to further our understanding of the subjective experience of middle-age African American women who are HIV+ and on highly active antiretroviral therapy, particularly how self-reported lipodystrophy (LD), levels of body dissatisfaction, body image quality of life, and engagement in disordered eating behaviors are related. Multiple regression, MANOVA, MANCOVA, ANOVA, and chi-square were utilized to test hypotheses. Results revealed that HIV+ and HIV- women did not differ significantly on their levels of body dissatisfaction or drive for thinness. When HIV+ women were examined in more detail a pattern emerged: women who self-reported fat hypertrophy had significantly higher levels of body dissatisfaction, bingeing, but not purging, and dietary restriction and fear of weight gain compared to women who did not self-report LD. About 75% of the sample was overweight or obese, and when BMI was controlled for, these differences persisted for body dissatisfaction and disordered eating behaviors for fat hypertrophy, but not fat atrophy. Overall, the findings indicate that the type of LD, specifically hypertrophy, is more related to body dissatisfaction and disordered eating behaviors, than LD in general. Clinical implications and limitations of these findings are discussed.

Eating disorders and substance use disorders both exhibit a clear sex-difference in prevalence. Eating disorders are more common in females while substance use disorders are more common in males. Previous research has also established a strong association between these two disorders, especially within females. Much less research has examined comorbity in males. The etiology and reasons for these sex-differences and for the comorbidity of eating and substance use disorders remain unclear. The present report aimed to examine disordered eating (DE), substance use (SU), and their comorbidity further, in both sexes, using disorder eating attitudes and behaviors and substance use rather than diagnoses. DE was examined with the Drive for Thinness, Bulimia, and Body Dissatisfaction subscales of the Eating Disorder Inventory-II. Nicotine, alcohol, and illicit drug use was also assessed. Male and female twin pairs from The Swedish Twin study of CHild and Adolescent Development will be used which includes 1,480 twin pairs assessed at three age points; 13-14, 16-17, and 19-20. A twin design was utilized to examine important aspects of the genetic and environmental risk factors for DE, SU, and their comorbidity within three distinct studies. In Study I multivariate twin designs were used and revealed that an underlying common factor was responsible for the three facets of DE in both sexes at age 16-17. Sex-differences were exhibited within these genetic influences such that only 50% of the genetic risk for the DE factor is shared between the sexes. Total heritabilities for the three subscales were higher for females. In Study II a longitudinal, multivariate twin design was used and revealed that an underlying common factor was responsible for SU at all three assessment ages. In general, genetic effects became more substance specific, and common shared environmental effects decreased across the age groups. In Study III, the genetic and environmental covariance between the DE and SU common factors at age 16-17 was examined. The covariance between DE and SU was partly mediated through familial factors, and these factors impacted covariance similarly in the sexes. Genetic and shared environmental factors each accounted for approximately 50% of covariance.

Background: It is posited that attachment difficulties in infancy may result in reduced mentalisation capacity (understanding self and others’ subjective thoughts/mental processes), leading to potentially deleterious psychopathological outcomes such as eating disorders. The exact nature of the relationship between mentalisation and eating disorders/disordered eating is unclear however. Objectives: A systemic review examined whether those with Anorexia Nervosa (AN) experience mentalisation deficits compared to those without EDs. An empirical study, examining the link between mentalisation and disordered eating (DE) in an adolescent sample, was conducted to assess whether borderline trait features mediated the relationship between the two constructs. Method: A systematic search of 6 databases was conducted, and articles were assessed against predetermined inclusion/exclusion criteria. Included articles were assessed against 14 quality criteria and study findings were reported. For the empirical study, 162 participants aged 12-18 completed a questionnaire pack including mentalisation, borderline traits, impulsivity, emotion dysregulation and depression scales, and sociodemographic questions. Results: Results from 10 articles indicated those with AN may experience subtle mentalisation deficits, particularly in recognising negative emotions in others. Mentalisation ability may also vary according to interpersonal context. Mediation analyses found mentalisation ability exerted a significant effect on DE indirectly through borderline trait features, and partially through emotion dysregulation, but not impulsivity. Conclusion: More robust empirical studies are required in order to assess the relationship between mentalisation and AN. Findings regarding the link between mentalisation, borderline traits and DE may further aid psychological assessment/treatment. Therapies where the main focus is improving mentalisation capacity may be useful.

Estudamos o efeito do campo aleatório sobre um modelo de vidro de spin com interações de p spins de alcance infinito e distribuição de probabilidade gaussiana. O caso p = 2 corresponde ao modelo de Sherrington-Kirkpatrick na presença de um campo aleatório. O caso p \'SETA\' \'INFINITO\' corresponde ao REM (Random Energy Model) de Derrida na presença de um campo aleatório. Além da interação de p spins, consideramos a presença de interações uniformes ferro ou antiferromagnéticas de alcance infinito. Tanto no caso ferro quanto antiferromagnético, empregamos dois procedimentos para tratar o problema: o método de réplicas no ensemble canônico e o método da contagem de estados no ensemble microcanônico. No método de réplicas resolvemos o problema para qualquer valor de p tanto sem quebra da simetria de permutação entre réplicas, quanto com um passo de quebra de simetria de Parisi. Deste modo, recuperamos resultados conhecidos para alguns modelos já estudados na literatura. Em seguida, tomamos o limite p \'SETA\' \'INFINITO\' que fornece uma solução completa para o problema do REM na presença de um campo aleatório. No método da contagem de estados, aplicável apenas no limite p \'SETA\' \'INFINITO\', mostramos que podemos estender a solução de Derrida mesmo na presença de um campo aleatório. Isso nos permitiu fazer a contagem de estados evitando assim o problema da \"catástrofe da entropia negativa\" presenta na solução réplica simétrica. Além disso, mostramos que qualquer sistema que seja solúvel sem a interação aleatória de p spins continua solúvel na presença dessa interação no limite p \'SETA\' \'INFINITO\'. Portanto, concluímos que a interação aleatória de p spins é somente adicionar um carácter vidro de spin ao sistema. Obtivemos expressões gerais válidas para qualquer distribuição do campo aleatório, embora a análise numérica tenha sido restrita às distribuições duplo-delta e gaussiana. Estudamos a influência do campo aleatório sobre os diagramas de fases e, em particular, mostramos que podem surgir pontos tricríticos no caso de uma distribuição duplo-delta. / We studied the effect of a random field on spin-glass models with infinite-ranged p spin interactions with a Gaussian probability distribution. The case p = 2 corresponds to the Sherrington-Kirkpatrick model in the presence of a random field. The case p \'SETA\' \'INFINITO\' corresponds to the REM (Random Energy Model) introduced by Derrida in the presence of a random field. Besides the p-spin interactions we also included uniform infinite-ranged ferromagnetic and antiferromagnetic interactions. Both in the case of ferromagnetic and antiferromagnetic interactions we employed two different approaches: The replica method in the canonical ensemble and the method of counting of the states in the microcanonical ensemble. In the replica method we solved the problem for arbitrary p both in the case of replica symmetry and in the first step of Parisi\'s replica-symmetry breaking scheme. This allowed us to rederive results for some models already known in the Literature. Next we took the limit p \'SETA\' \'INFINITO\' which yielded a complete solution to the REM in a random field. In the method of counting of the states, which is effective only in the limit p \'SETA\' \'INFINITO\', we showed that we can extend the Derrida\'s solution even in the presence of a random field. This allowed us to do the counting of the states avoiding the so called negative-entropy catastrophe present in the replica-symmetric solution. We also showed that any solvable model without random p-spin interactions is also solvable in the presence of such interactions in the limit p \'SETA\' \'INFINITO\'. Therefore, we conclude that the p-spin random interactions only add a spin-glass character to the system. We have obtained general expressions valid for any random-field distributions, although we limited the numerical analysis to double-delta and Gaussian distributions. We studied the effects of the random field on the phase diagrams, and in particular, we showed the possibility of tricritical point in the case of double-delta distributions.

Neste trabalho investigamos as propriedade estatísticas de um modelo de coevolução de N espécies, sob a perspectiva da dinâmica de replicadores. As interações entre pares de espécies são dadas por variáveis aleatórias independentes, fixas no tempo. As interações são também simétricas, de modo que a dinâmica maximiza uma função de Lyapunov (o funcional adaptabilidade). Isto permite usar as técnicas da mecânica estatística de sistemas desordenados para determinar analiticamente as propriedades estatísticas dos estados estacionários, particularmente a diversidade de espécies (total de espécies coexistindo em um sistema ecológico). As auto-interações são iguais a um parâmetro de controle que mede a competição entre indivíduos de uma mesma espécie (competição intraespecífica). A cada espécie associamos um conjunto de p traços ou características, representados por variáveis binárias aleatórias distribuídas com igual probabilidade. As forças de interação são dadas por funções não lineares da regra de Hebb. Estas são funções moduladoras do número de elementos complementares entre os conjuntos de traços de um dado par de espécies. Estudamos analítica e numericamente o caso em que p é proporcional ao total de espécies na comunidade, via método de réplicas. A análise é possível devido ao resultado de Sompolinsky: funções não lineares da regra de Hebb são equivalentes, no limite de p extensivo, a regra de Hebb somada a um ruído gaussiano estático, cuja variância depende da forma da função moduladora. A competição intraespecífica, o total de traços, a presença de espécies altamente complementares e finalmente o peso dos termos de competição interespecífica (elementos não diagonais da matriz de acoplamentos) são as principais influências sobre o comportamento das grandezas termodinâmicas no equilíbrio, principalmente a diversidade. Os resultados analíticos concordam com a solução numérica da equação de replicadores, no regime em que as soluções de réplicas simétricas são estáveis. / We investigate the statistical properties of a coevolution model of N species using the replicator dynamics framework. The pairwise species interactions are given by independent quenched random variables. They are also symmetric, so that the dynamics maximizes a quadratic Lyapunov function (the fitness functional). This allows the use of tools of statistical mechanics of disordered systems to analyze the statistical properties of the equilibrium states, especially the ecosystem diversity (total number of coexisting species in an ecological system). The self-interactions are equal to a control parameter measuring the intraspecies competition. We associate to each species a set of p traits and represent them by independent random variables, equally distributed. The strength of the pairwise interactions is given by nonlinear functions of the Hebb rule. These are modulating functions of the number of complementary elements in the sets of traits of a given species pair. We study analytically and numerically the limit of extensive p, using the replica trick. The analytical approach is possible due to a result derived by Sompolinsky: in the limit of extensive p, nonlinear functions of the Hebb rule are equivalent to the Hebb rule plus a Gaussian static noise, whose variance is dependent on the form of the modulating function. The intraspecies competition, the total number of traits, the presence of highly complementary species pairs and the contribution of the nondiagonal elements of the interaction matrix are the main influences over the behavior of the equilibrium properties, principally the diversity. Our analytical results agree with the numerical solutions of the replicator equation in the regime of stable replica symmetric solutions.

Research into the relationship between the structure and function of proteins has been ongoing now for several decades. More recently, there has been an explosion in the investigation of the dynamic properties of proteins, and how their dynamic propensity relates to their function. This new direction in protein research requires new techniques to analyse protein dynamics, since most traditional techniques are biased towards a fixed tertiary structure. Mass spectrometry (MS) is emerging as a powerful tool to probe protein dynamics since it can provide information on interconverting conformations and has no preference towards the folded state. Furthermore, its low sample consumption, rapid data acquisition and low data processing positions MS as an attractive tool in protein structure research. The hybrid technique of ion mobility-mass spectrometry provides further insight into the range of conformations adopted by proteins and protein complexes, by providing information on the size in terms of rotationally averaged collision cross section. The work presented in this thesis considers proteins with a range of structural characteristics. We use ion mobility mass spectrometry to investigate proteins of different extents of disorder, protein complexes with dynamic entities and a system that undergoes structural rearrangement upon ligand binding. First, a framework of mass spectrometry experiments is described which allows identification of the extent of structure and disorder within proteins. This framework is tested on a range of different systems throughout the thesis. Differences in the gas-phase properties of two conformationally dynamic proteins which behave similarly in solution are investigated and from this research we postulate a new ionisation mechanism for partially folded proteins. The dynamic propensity of C-terminal p27 is investigated and compared to two permutants which allows us to delineate how the location of charged residues in a primary sequence affects the structure of a protein. We monitor the 'folding-upon-binding' behaviour of p27 upon association with its binding partners, and how this differs with the order of charged residues in the linear sequence. Finally, we describe the structural rearrangement of Fdc1 upon the binding of its cofactor; a prenylated FMN molecule. This thesis demonstrates the suitability of ion mobility-mass spectrometry for the investigation of dynamic properties of proteins and protein complexes.

For half a century, the central tenet of protein science has been grounded on the idea that the three-dimensional structure of a protein underlies its function. However, increasing evidence of natively unstructured but functional proteins is accumulating. Termed as intrinsically disordered proteins (IDPs), they populate a number of different conformations in isolation. Interestingly, as part of their function, some IDPs become fully or partly structured upon interaction with their binding partners. This process, known as coupled folding and binding raises the question what comes first - folding of the IDP or binding to its partner protein followed by folding. This thesis focuses on understanding the role of disorder in protein- protein interactions using biophysical characterization. Over-representation of IDPs in complex network and signalling pathways emphasizes the importance of disorder. Conformational flexibility in IDPs facilitates post-translational modifications, which provides a neat way to modulate the residual structure. This can alter affinity of IDPs to their partners and it is speculated that bound like structures of IDPs speed association. The impact of phosphorylation was explored in the KID/KIX system: phosphorylation modulates only the dissociation kinetics increasing the lifetime of the bound complex, which may be important in signalling processes. Further, phi-value analysis applied to investigate the mechanism of interaction reveals that non-native interactions play a key role in this reaction, before the IDP consolidates its final structure in the bound complex. Promiscuous interaction of IDPs with their partners often results in complexes with differing affinities. Members of BCL-2 family were explored, and the results indicate that IDPs bind to the same partner protein with marginal variation in the association rates, but significant differences in dissociation rates are observed. Thus, it seems that in such homologous but competing network of proteins, disorder facilitates complexes with differing affinities by modulating dissociation rate, again altering the lifetime of the bound complex. The work presented here demonstrates that disorder plays a role in altering complex lifetimes. Perhaps being disordered permits a level of plasticity to IDPs to adapt the rates at which they bind/unbind to many target proteins. This may be why disorder is conserved and abundant in proteins involved in intricate signalling networks.

abstract: The rigidity of a material is the property that enables it to preserve its structure when deformed. In a rigid body, no internal motion is possible since the degrees of freedom of the system are limited to translations and rotations only. In the macroscopic scale, the rigidity and response of a material to external load can be studied using continuum elasticity theory. But when it comes to the microscopic scale, a simple yet powerful approach is to model the structure of the material and its interparticle interactions as a ball$-$and$-$spring network. This model allows a full description of rigidity in terms of the vibrational modes and the balance between degrees of freedom and constraints in the system. In the present work, we aim to establish a microscopic description of rigidity in \emph{disordered} networks. The studied networks can be designed to have a specific number of degrees of freedom and/or elastic properties. We first look into the rigidity transition in three types of networks including randomly diluted triangular networks, stress diluted triangular networks and jammed networks. It appears that the rigidity and linear response of these three types of systems are significantly different. In particular, jammed networks display higher levels of self-organization and a non-zero bulk modulus near the transition point. This is a unique set of properties that have not been observed in any other types of disordered networks. We incorporate these properties into a new definition of jamming that requires a network to hold one extra constraint in excess of isostaticity and have a finite non-zero bulk modulus. We then follow this definition by using a tuning by pruning algorithm to build spring networks that have both these properties and show that they behave exactly like jammed networks. We finally step into designing new disordered materials with desired elastic properties and show how disordered auxetic materials with a fully convex geometry can be produced. / Dissertation/Thesis / Doctoral Dissertation Physics 2018