Modeling and simulation of fibrinogen and its adsorption behavior

In this thesis different approaches for the modeling and simulation of the blood protein fibrinogen are presented. The approaches are meant to systematically connect the multiple time and length scales involved in the dynamics of fibrinogen in solution and at inorganic surfaces. The first part of the thesis will cover simulations of fibrinogen on an all atom level. Simulations of the fibrinogen protomer and dimer are performed in explicit solvent to characterize the dynamics of fibrinogen in solution. These simulations reveal an unexpectedly large and fast bending motion that is facilitated by molecular hinges located in the coiled-coil region of fibrinogen. This behavior is characterized by a bending and a dihedral angle and the distribution of these angles is measured. As a consequence of the atomistic detail of the simulations it is possible to illuminate small scale behavior in the binding pockets of fibrinogen that hints at a previously unknown allosteric effect. In a second step atomistic simulations of the fibrinogen protomer are performed at graphite and mica surfaces to investigate initial adsorption stages. These simulations highlight the different adsorption mechanisms at the hydrophobic graphite surface and the charged, hydrophilic mica surface. It is found that the initial adsorption happens in a preferred orientation on mica. Many effects of practical interest involve aggregates of many fibrinogen molecules. To investigate such systems, time and length scales need to be simulated that are not attainable in atomistic simulations. It is therefore necessary to develop lower resolution models of fibrinogen. This is done in the second part of the thesis. First a systematically coarse grained model is derived and parametrized based on the atomistic simulations of the first part. In this model the fibrinogen molecule is represented by 45 beads instead of nearly 31,000 atoms. The intra-molecular interactions of the beads are modeled as a heterogeneous elastic network while inter-molecular interactions are assumed to be a combination of electrostatic and van der Waals interaction. A method is presented that determines the charges assigned to beads by matching the electrostatic potential in the atomistic simulation. Lastly a phenomenological model is developed that represents fibrinogen by five beads connected by rigid rods with two hinges. This model only captures the large scale dynamics in the atomistic simulations but can shed light on experimental observations of fibrinogen conformations at inorganic surfaces.

Dynamical Casimir effect and the structure of vacuum in quantum field theory

Some of the most interesting phenomena that arise from the developments of the modern physics are surely vacuum fluctuations. They appear in different branches of physics, such as Quantum Field Theory, Cosmology, Condensed Matter Physics, Atomic and Molecular Physics, and also in Mathematical Physics. One of the most important of these vacuum fluctuations, sometimes called "zero-point energy", as well as one of the easiest quantum effect to detect, is the so-called Casimir effect. The purposes of this thesis are: - To propose a simple retarded approach for dynamical Casimir effect, thus a description of this vacuum effect when we have moving boundaries. - To describe the behaviour of the force acting on a boundary, due to its self-interaction with the vacuum.

Two-dimensional linear-combination model fitting of magnetic resonance spectra to define the macromolecule baseline using FiTAID, a Fitting Tool for Arrays of Interrelated Datasets

To propose the determination of the macromolecular baseline (MMBL) in clinical 1H MR spectra based on T(1) and T(2) differentiation using 2D fitting in FiTAID, a general Fitting Tool for Arrays of Interrelated Datasets.

Kaon and D meson masses with N_f = 2+1+1 twisted mass lattice QCD

We discuss the computation of the kaon and D meson masses in the N_f = 2+1+1 twisted mass lattice QCD setup, where explicit heavy flavor and parity breaking occurs at finite lattice spacing. We present three methods suitable in this context and verify their consistency.

Single- and double-electron transfer reactions of ground and metastable state Ar2+ ions

Electron transfer cross sections have been measured for reactions of Ar2+ ions with Ar, N2, O2, CO2, CH4 and C2H6. Time-of-flight techniques have been used to measure both fast neutral Ar0 and fast Ar+ products from single- and double-electron transfer processes involving Ar2+ ions with 4.0 to 7.0 keV impact energies. Incident Ar2+ ions have produced by controlled electron impact ionisation of argon atoms. Reactions have been examined as a function of ionising electron energy and cross sections determined for ground state Ar2+(3P) ions. Charge transfer cross sections have been determined to be in the range of 3*10-16 cm2 for the systems examined. Double-electron transfer cross sections are the same order of magnitude as those measured for the corresponding single-electron transfer reactions. The state distribution of the reactant ion beam has been estimated and electron transfer cross sections obtained for single- and double-electron transfer reactions of metastable Ar2+ions. The magnitudes of electron transfer cross sections in individual systems are similar for both ground and metastable state Ar2+ reactions.

Entrainment and Unit Velocity: Surprises in an Accelerated Exclusion Process

We introduce a class of distance-dependent interactions in an accelerated exclusion process inspired by the observation of transcribing RNA polymerase speeding up when “pushed” by a trailing one. On a ring, the accelerated exclusion process steady state displays a discontinuous transition, from being homogeneous (with augmented currents) to phase segregated. In the latter state, the holes appear loosely bound and move together, much like a train. Surprisingly, the current-density relation is simply J=1-ρ, signifying that the “hole train” travels with unit velocity.

Entrainment and Unit Velocity: Surprises in an Accelerated Exclusion Process

We introduce a class of distance-dependent interactions in an accelerated exclusion process inspired by the observation of transcribing RNA polymerase speeding up when “pushed” by a trailing one. On a ring, the accelerated exclusion process steady state displays a discontinuous transition, from being homogeneous (with augmented currents) to phase segregated. In the latter state, the holes appear loosely bound and move together, much like a train. Surprisingly, the current-density relation is simply J=1-ρ, signifying that the “hole train” travels with unit velocity.

General and specific components of depression and anxiety in an adolescent population

Background Depressive and anxiety symptoms often co-occur resulting in a debate about common and distinct features of depression and anxiety. Methods An exploratory factor analysis (EFA) and a bifactor modelling approach were used to separate a general distress continuum from more specific sub-domains of depression and anxiety in an adolescent community sample (n = 1159, age 14). The Mood and Feelings Questionnaire and the Revised Children's Manifest Anxiety Scale were used. Results A three-factor confirmatory factor analysis is reported which identified a) mood and social-cognitive symptoms of depression, b) worrying symptoms, and c) somatic and information-processing symptoms as distinct yet closely related constructs. Subsequent bifactor modelling supported a general distress factor which accounted for the communality of the depression and anxiety items. Specific factors for hopelessness-suicidal thoughts and restlessness-fatigue indicated distinct psychopathological constructs which account for unique information over and above the general distress factor. The general distress factor and the hopelessness-suicidal factor were more severe in females but the restlessness-fatigue factor worse in males. Measurement precision of the general distress factor was higher and spanned a wider range of the population than any of the three first-order factors. Conclusions The general distress factor provides the most reliable target for epidemiological analysis but specific factors may help to refine valid phenotype dimensions for aetiological research and assist in prognostic modelling of future psychiatric episodes.

Opportunistic and systematic screening for chlamydia: a study of consultations by young adults in general practice

BACKGROUND: Opportunistic screening for genital chlamydia infection is being introduced in England, but evidence for the effectiveness of this approach is lacking. There are insufficient data about young peoples' use of primary care services to determine the potential coverage of opportunistic screening in comparison with a systematic population-based approach. AIM: To estimate use of primary care services by young men and women; to compare potential coverage of opportunistic chlamydia screening with a systematic postal approach. DESIGN OF STUDY: Population based cross-sectional study. SETTING: Twenty-seven general practices around Bristol and Birmingham. METHOD: A random sample of patients aged 16-24 years were posted a chlamydia screening pack. We collected details of face-to-face consultations from general practice records. Survival and person-time methods were used to estimate the cumulative probability of attending general practice in 1 year and the coverage achieved by opportunistic and systematic postal chlamydia screening. RESULTS: Of 12 973 eligible patients, an estimated 60.4% (95% confidence interval [CI] = 58.3 to 62.5%) of men and 75.3% (73.7 to 76.9%) of women aged 16-24 years attended their practice at least once in a 1-year period. During this period, an estimated 21.3% of patients would not attend their general practice but would be reached by postal screening, 9.2% would not receive a postal invitation but would attend their practice, and 11.8% would be missed by both methods. CONCLUSIONS: Opportunistic and population-based approaches to chlamydia screening would both fail to contact a substantial minority of the target group, if used alone. A pragmatic approach combining both strategies might achieve higher coverage.

Charge and spin transport in nanoscale junction from first principles

Recently nanoscale junctions consisting of 0-D nanostructures (single molecule) or 1-D nanostructures (semiconducting nanowire) sandwiched between two metal electrodes are successfully fabricated and characterized. What lacks in the recent developments is the understanding of the mechanism behind the observed phenomena at the level of atoms and electrons. For example, the origin of observed switching effect in a semiconducting nanowire due to the influence of an external gate bias is not yet understood at the electronic structure level. On the same context, different experimental groups have reported different signs in tunneling magneto-resistance for the same organic spin valve structure, which has baffled researchers working in this field. In this thesis, we present the answers to some of these subtle questions by investigating the charge and spin transport in different nanoscale junctions. A parameter-free, single particle Green’s function approach in conjunction with a posteriori density functional theory (DFT) involving a hybrid orbital dependent functional is used to calculate the tunneling current in the coherent transport limit. The effect of spin polarization is explicitly incorporated to investigate spin transport in a nanoscale junction. Through the electron transport studies in PbS nanowire junction, a new orbital controlled mechanism behind the switching of the current is proposed. It can explain the switching behavior, not only in PbS nanowire, but in other lead-chalcogenide nanowires as well. Beside this, the electronic structure properties of this nanowire are studied using periodic DFT. The quantum confinement effect was investigated by calculating the bandgap of PbS nanowires with different diameters. Subsequently, we explain an observed semiconducting to metallic phase transition of this nanowire by calculating the bandgap of the nanowire under uniform radial strain. The compressive radial strain on the nanowire was found to be responsible for the metallic to semiconducting phase transition. Apart from studying one dimensional nanostructure, we also present transport properties in zero dimensional single molecular junctions. We proposed a new codoping approach in a single molecular carborane junction, where a cation and an anion are simultaneously doped to find the role of a single atom in the device. The main purpose was to build a molecular junction where a single atom can dictate the flow of electrons in a circuit. Recent observations of both positive and negative sign in tunneling magnetoresistance (TMR) the using same organic spin-valve structure hasmystified researchers. From our spin dependent transport studies in a prototypical organic molecular tunneling device, we found that a 3% change in metal-molecule interfacial distance can alter the sign of TMR. Changing the interfacial distance by 3%, the number of participating eigenstates as well as their orbital characteristic changes for anti-parallel configuration of the magnetization at the two electrodes, leading to the sign reversal of the TMR. Apart from this, the magnetic proximity effect under applied bias is investigated quantitatively, which can be used to understand the observed unexpectedmagnetismin carbon basedmaterials when they are in close proximity with magnetic substrates.

CHANGE FOR GOOD? AN ASSESSMENT OF THE DISCONNECT BETWEEN PERCEIVED BENEFITS BY ENGOS AND USER SATISFACTION OF SOLAR BOTTLE LIGHTS IN INFORMAL SETTLEMENTS OF DHAKA CITY, BANGLADESH

A major challenge for a developing country such as Bangladesh is to supply basic services to its most marginalized populations, which includes both rural and urban dwellers. The government struggles to provide basic necessities such as water and electricity. In marginalized urban communities in Bangladesh, in particular informal settlements, meeting basic needs is even direr. Most informal settlements are built to respond to a rapid immigration to urban centers, and are thought of as ‘temporary structures’, though many structures have been there for decades. In addition, as the settlements are often squatting on private land, access to formalized services such as electricity or water is largely absent. In some cases, electricity and water connections are brought in - but through informal and non-government sanctioned ways -- these hookups are deemed ‘illegal’ by the state. My research will focus on recent efforts to help ameliorate issues associated with lack of basic services in informal settlements in Bangladesh – in this case lack of light. When the government fails to meet the needs of the general population, different non-government organizations tend to step in to intervene. A new emphasis on solar bottle systems in informal urban settlement areas to help address some energy needs (specifically day-time lighting). One such example is the solar bottle light in Bangladesh, a project introduced by the organization ‘Change’. There has been mixed reactions on this technology among the users. This is where my research intervenes. I have used quantitative method to investigate user satisfactions for the solar bottle lights among the residents of the informal settlements to address the overarching question, is there a disconnect between the perceived benefits of the ENGO and the user satisfaction of the residents of the informal settlements of Dhaka City? This paper uses survey responses to investigate level of user satisfaction and the contributing factors.