Mesoscale Modelling of Cytoplasmic Dynein using Fluctuating Finite Element Analysis

At the forefront of biological experimentation and simulation technology is the attempt to understand the biological mesoscale, the regime in which thermal fluctuations are still vital for function but atomic resolution may no longer be required. There is a wealth of low-resolution biomolecular structural data of macromolecules available for study, and experimental developments are allowing these biomolecules to be visualised to near-atomic resolution without the need for crystallisation. It is clear that a new form of simulation is required to take advantage of this structural data in order to better understand the dynamics of proteins at the biological mesoscale, and their relationship to dynamics at both the microscale and the macroscale. The work presented in this thesis concerns the development of Fluctuating Finite Element Analysis (FFEA), a mesoscale simulation technique that treats globular macromolecules as visco-elastic continuum objects subject to an additional thermal stress, satisfying our definition of the mesoscale. I have further developed the constitutive continuum model to better represent biological macromolecules, and designed a new solution procedure in order to both increase the computational efficiency of the algorithm and to remove superfluous dynamical information. I also introduce a completely new kinetic framework that couples to the underlying simulation protocol, enabling us to simulate discrete biological events, such as conformational changes, within a continuous dynamical simulation. I apply FFEA to the molecular motor cytoplasmic dynein, a mesoscopic system exhibiting dynamical features that are beyond the scope of standard molecular dynamics simulations, but well within the mesoscopic regime FFEA was designed for. I determine the physical parameters that an FFEA model of dynein requires for consistency with both experimental and high-resolution molecular dynamics simulations. Finally, I consider the diffusional properties of dynein with respect to its microtubule track, with the aim of understanding the potential mechanisms that enable the motor to be processive

IGR J18483-0311: a new intermediate supergiant fast X-ray transient

IGR J18483-0311 is a high-mass X-ray binary recently discovered by INTEGRAL. Its periodic fast X-ray transient activity and its position in the Corbet diagram - although ambiguous - led to the conclusion that the source was a likely Be/X-ray binary (BeXB), even if a supergiant fast X-ray transient (SFXT) nature could not be excluded. We aimed at identifying the companion star of IGR J18483-0311 to discriminate between the BeXB and the SFXT nature of the source. Optical and near-infrared photometry, as well as near-infrared spectroscopy of the companion star were performed to identify its spectral type. We also assembled and fitted its broad-band spectral energy distribution to derive its physical parameters. We show that the companion star of IGR J18483-0311 is an early-B supergiant, likely a B0.5Ia, and that its distance is about 3-4 kpc. The early-B supergiant nature of its companion star, as well as its fast X-ray transient activity point towards an SFXT nature of IGR J18483-0311. Nevertheless, the long duration and the periodicity of its outbursts, as well as its high level of quiescence, are consistent with IGR J18483-0311 being an intermediate SFXT, in between classical supergiant X-ray binaries (SGXBs) characterised by small and circular orbits, and classical SFXTs with large and eccentric orbits.Comment: 5 pages, 2 figures, 3 tables, accepted in A&

Discovery of a young and massive stellar cluster: Spectrophotometric near-infrared study of Masgomas-1

Context: Recent near-infrared data have contributed to the discovery of new (obscured) massive stellar clusters and massive stellar populations in previously known clusters in our Galaxy. These discoveries lead us to view the Milky Way as an active star-forming machine. Aims: The main purpose of this work is to determine physically the main parameters (distance, size, total mass and age) of Masgomas-1, the first massive cluster discovered by our systematic search programme. Methods: Using near-infrared (J, H, and Ks) photometry we selected 23 OB-type and five red supergiant candidates for multi-object H- and K-spectroscopy and spectral classification. Results: Of the 28 spectroscopically observed stars, 17 were classified as OB-type, four as supergiants, one as an A-type dwarf star, and six as late-type giant stars. The presence of a supergiant population implies a massive nature of Masgomas-1, supported by our estimate of the cluster initial total mass of (1.94\pm0.28)\cdot10^4 M_{sun}, obtained after integrating of the cluster mass function. The distance estimate of 3.53 kpc locates the cluster closer than the Scutum--Centaurus base but still within that Galactic arm. The presence of an O9V star and red supergiants in the same population indicates that the cluster age is in the range of 8 to 10 Myr.Comment: 11 pages, 6 figures, 2 tables, A&A accepte

Impediments to Marketing African Natural products From Ghana: Preliminary Results

For most of the African countries agriculture still remains the mainstay of the economies supplying both food and incomes via marketable surpluses. However, many odds against agriculture such low productivity, poor prices, and drought among others make it unsustainable. Results thus far show that such dependence has contributed little to neither economic development nor growth. Still many of its people living on and from agriculture remain poor, and are susceptible to hunger and malnutrition. Additionally, their over reliance on a few traditional exports such coffee, tea, and cocoa etc., products whose world prices keep declining has not helped either. At most this is futile response to raising incomes of its people, let alone spur any meaningful development. Agricultural may still contribute to development, if the countries could diversify from traditional products to the untapped areas. The continent's rich botanical heritage offers an excellent opportunity to diversify away from traditional exports. The natural products have a greater appeal to consumers especially in the rich west. Thus, development of natural products as alternative or complimentary to the current mix of tradable products will positively impact the social and economic lives of many people, especially those in the rural areas. Additionally, diversification of the production systems to include natural plants provides a superior route to the creating viable agribusinesses in rural communities currently lacking. Natural products happen to have enormous advantages; First, indigenous African plants occur naturally and so are relatively easy to cultivate commercially. Second, natural plant production is labor intensive rather than capital intensive, and so minimizes capital investment while at the same time maximizing job-creation potential. Third, African communities have extensive knowledge of indigenous plants, creating a natural competitive advantage in this sector. ASNAPP (Agribusiness in Sustainable Natural African Plants Products) a non-profit organization formed in 1999 with funding from USAID (United States Agency for International Development) is helping create and develop successful African agribusinesses in the natural plant products sector. The organization focuses on the development of high-value natural plant products that enable African agribusinesses to compete in local, regional and international markets. These products include herbal teas, culinary herbs and spices, essential and press oils, as well as medicinal plants. Currently, ASNAPP operates in five countries, namely South Africa, Ghana, Rwanda, Senegal and Zambia, working with 25 agri-enterprises that represent more than 2000 small-scale natural plant suppliers. The prospects for natural products market is very bright, for example the global nutraceutical market alone is estimated to be worth $60 billion annually in sales of dietary and meal supplements, as well as specialty products. There is also increasing demand for organic and natural products such as herbal teas, essential oils, herbs and spices, phytomedicines and phytocosmetics. This growth has been supported by a global swing away from synthetic products to those that are natural, healthy, sustainably produced and fairly traded. In the context of world trade in natural products, African country's natural forests supply more herbs, medicinal plants and natural food ingredients. The Americans and Europeans are the major consumers of natural products in the global market. Products such as the herbal tea's, essential oils, cosmetic and spices have readily available markets. Natural product sales was estimated$34 billion in 2001, It is estimated that Global sales for organic and natural products will reach about $100 billion by 2008 at an annual growth rate of 20-30$316 million dollar business in 1996 to over $454 million in 2001(Alberta Essential Oils, 1996; Datamonitor, 2002). Indeed there is untapped potential ranging from raw products to processed ones, which could fetch even higher returns to the farmers. However, it is only a few large enterprises that are active in the sector, leaving rural communities who had in fact been the first to discover the health and nutritional properties of indigenous plants out in the cold. The ASNAPP Ghana program which commenced in 2000 is currently working on essential oils, lippia tea, grains of paradise, cryptolepis, kombo butter, shea butter and Artemisia, with the focus on the Eastern, Central, Ashanti, Volta, Greater Accra and Northern regions of Ghana. The natural products industry in Ghana is characterized by low input- low output; mostly operated by small-scale farmers (suppliers) with low levels of levels of formal education and agricultural production knowledge. In this respect the supply side problems may be summarized as regularity of the supplies, quality and timeliness. Organizationally, the scale of the operations may be a bottleneck one hand, on the other hand, information, capital; product quality and assurance mechanisms hinder successful commercialization. The domestic markets are largely at the low levels of commercialization; the operators have limited technical knowledge about natural products, and limited capital to expand their businesses and exploit the readily available foreign markets. Similarly, on the demand side, there may be lack of consumer information as to the range of products, where to find them and what remedies they offer. This paper has the objective of highlighting the marketing impediments facing the natural products market in the retail and wholesale portions of the chain in Ghana. Specifically, (i) profile the technical, financial, organizational, etc., constraints the traders face (domestically and externally), (ii) profile the natural product range and their functions (iii) suggest policy interventions. Preliminary results from the Ghana business survey show that seven out of ten of the businesses are retailer operated, whose two-thirds supply is dependent on the small-scale farmers. There results also show that virtually all the traders have not received any technical, financial or trade assistance from any organization. At most only 1 out of ten businesses have ventured into external trade. The preliminary results show tremendous potential, however a lot need to be done to tap on this potential. The analysis will be based on a survey that was carried out in Ghana to correct information on; product ranges; the supply chain (from production to the retail stores and potential for exports. The analysis will contribute toward inform policy of which marketing to be addressed and inform domestic and foreign consumers of the presence of such products. References: Alberta Agriculture, Food, and Rural Development, Herb/Spice Industry Fact Sheet. Compiled by Dennis Dey. AG-Ventures, Agdex 263/830-1, www.agric.gov.ab.ca, September 1996. Datamonitor, Nov 15, 2002. Marty T. S., and Patrick R., "Natural Product Sales Top$42 Billion" Natural Foods Merchandiser, 2004, volume XXV/number 6/ p. 1 Organic Natural health, 2001. http://www.health-report.co.uk/organic-cosmetics-usa- opportunity.htm#Organic/natural%20industry%20profileInternational Relations/Trade,

An Overview of Marketing of Ghana Natural Products

The study finds strong correlations between natural products business performance and the impeding factors. The impediments include access to finance and markets, lack of herbal market information especially relating to external markets. Additionally, there is lack of processing capacity, while at the same time most if not all the natural products business operators lack technical training relating to product handling. However, there is big potential for success, the top ten traded natural products, may be exploited initially, both domestically and for export market, given range of perceived use. The constraints identified require concerted efforts from all stakeholders to recognize the importance of this sub-sector in providing opportunities to successful development.Marketing,

Network Growth and Structural Characteristics of Globular Protein Hydrogels

Folded protein-based hydrogels are a novel class of biomaterials which combine the useful viscoelastic properties of individual proteins together with the prospect of rational design principles. Although the macroscopic properties of these materials have been well studied, there is a paucity of understanding of their mesoscopic formation mechanisms, especially given the differences in building blocks compared to biopolymer hydrogels. We present the results of a simulation study into the growth of polymeric networks of chemically cross-linked folded proteins that form the structural backbone of these hydrogels, observing how experimentally controllable parameters affect the resultant network growth and structural characteristics. We show that the initial volume fraction emerges as a dominant parameter at the network level but that the properties of the single protein remain important. We ultimately show that we can tune the properties of a monodisperse protein hydrogel network only within limits which are dictated primarily by implicit diffusion time scales

Relations Among Gender, Violence Exposure, and Mental Health: The National Survey of Adolescents

Using a nationally representative sample of 4,008 adolescents, this study examines gender differences in violence exposure, major depressive episode (MDE) and posttraumatic stress disorder (PTSD), and characteristics of violence incidents. It was hypothesized that there would be gender differences in the types of violence exposure reported as well as the prevalence of MDE and PTSD; and that gender would moderate the relationship between violence exposure and mental health outcomes. Results indicated significant gender differences in rates of violence exposure, PTSD and MDE. Additionally, gender was a moderating variable in the relation between sexual assault and PTSD, but not in the other violence exposure-mental health relations examined. It thus appears that the pathways for developing PTSD may be different for male and female victims of sexual abuse. Implications for interventions and future research are discussed

The stellar population of the star forming region G61.48+0.09

- Context: We present the results of a near-infrared photometric and spectroscopic study of the star forming region G61.48+0.09. - Aims: The purpose of this study is to characterize the stellar content of the cluster and to determine its distance, extinction, age and mass. - Methods: The stellar population was studied by using color-magnitude diagrams to select twenty promising cluster members, for which follow up spectroscopy was done. The observed spectra allowed a spectral classification of the stars. - Results: Two stars have emission lines, twelve are G-type stars, and six are late-O or early-B stars. - Conclusions: The cluster's extinction varies from A_{K_S} = 0.9 to A_{K_S} = 2.6, (or A_{V}~8 to A_{V}~23). G61.48+0.09 is a star forming region located at 2.5+/-0.4 Kpc. The cluster is younger than 10 Myr and has a minimum stellar mass of 1500+/-500 Solar masses. However, the actual total mass of the cluster remains undetermined, as we cannot see its whole stellar content.Comment: 20 pages, 10 figures. Accepted for publication in A&

Obscured clusters.I. GLIMPSE30 - Young Milky Way Star Cluster Hosting Wolf-Rayet Stars

Young massive clusters are perfect astrophysical laboratories for study of massive stars. Clusters with Wolf-Rayet (WR) stars are of special importance, since this enables us to study a coeval WR population at a uniform metallicity and known age. GLIMPSE30 (G30) is one of them. The cluster is situated near the Galactic plane (l=298.756deg, b=-0.408deg) and we aimed to determine its physical parameters and to investigate its high-mass stellar content and especially WR stars. Our analysis is based on SOFI/NTT JsHKs imaging and low resolution (R~2000) spectroscopy of the brightest cluster members in the K atmospheric window. For the age determination we applied isochrone fits for MS and Pre-MS stars. We derived stellar parameters of the WR stars candidates using a full nonLTE modeling of the observed spectra. Using a variety of techniques we found that G30 is very young cluster, with age t~4Myr. The cluster is located in Carina spiral arm, it is deeply embedded in dust and suffers reddening of Av~10.5+-1.1mag. The distance to the object is d=7.2+-0.9kpc. The mass of the cluster members down to 2.35Msol is ~1600Msol. Cluster's MF for the mass range of 5.6 to 31.6Msol shows a slope of Gamma=-1.01+-0.03. The total mass of the cluster obtained by this MF down to 1Msol is about 3x10^3Msol. The spectral analysis and the models allow us to conclude that in G30 are at least one Ofpe/WN and two WR stars. The WR stars are of WN6-7 hydrogen rich type with progenitor masses more than 60Msol. G30 is a new member of the exquisite family of young Galactic clusters, hosting WR stars. It is a factor of two to three less massive than some of the youngest super-massive star clusters like Arches, Quintuplet and Central cluster and is their smaller analog.Comment: 11 pages, 9 figures, accepted for publication in Astronomy & Astrophysic

Near-infrared spectroscopy in NGC 7538

The characterisation of the stellar population toward young high-mass star-forming regions allows to constrain fundamental cluster properties like distance and age. These are essential when using high-mass clusters as probes to conduct Galactic studies. NGC 7538 is a star-forming region with an embedded stellar population only unearthed in the near-infrared. We present the first near-infrared spectro-photometric study of the candidate high-mass stellar content in NGC 7538. We obtained H and K spectra of 21 sources with both the multi-object and long-slit modes of LIRIS at the WHT, and complement these data with sub-arcsecond JHKs photometry of the region using the imaging mode of the same instrument. We find a wide variety of objects within the studied stellar population of NGC 7538. Our results discriminate between a stellar population associated to the HII region, but not contained within its extent, and several pockets of more recent star formation. We report the detection of CO bandhead emission toward several sources as well as other features indicative of a young stellar nature. We infer a spectro-photometric distance of 2.7+-0.5 kpc, an age spread in the range 0.5-2.2 Myr and a total mass ~1.7x10^3 Msun for the older population.Comment: 11 pages, 8 figures, 1 table, accepted by A&