Lung function and structure in Cystic Fibrosis infants one year after diagnosis by newborn screening.

Identifying early signs of lung disease reliably in asymptomatic infants with Cystic Fibrosis (CF) diagnosed by newborn screening (NBS) is a challenge. Very little is known about the origin and progression of lung disease in these infants hence there is uncertainty on best interventions to protect the lungs of these infants from functional and structural decline. This collaborative observational study aims to assess lung function and structure in CF NBS infants. Lung function tests (LFT) were performed in contemporaneous healthy controls and CF infants at 3 months and a year of age. In addition, CF infants underwent chest computed tomography (CT) at 1 year under general anaesthesia within 2 weeks of the LFTs. At a year, CF NBS infants had impaired lung function compared to contemporaneous healthy controls. However the percentage of CF NBS infants demonstrating what was considered abnormal lung function had reduced at a year of age compared to those with abnormal result at 3 months. Although some improvements were observed at 1- year LFTs, this was not universal using the different techniques. Some measurements improved, others remained stable and certainly none deteriorated. In terms of CT structural changes in CF NBS infants, fewer abnormalities were detected in our cohort compared to other reported studies and changes seen were mild. There was poor correlation between lung function and structure in this group of CF infants. To accurately detect CF infants with impaired lung function or structural abnormalities using important physiological and clinical determinants would play an important role in the management of these infants. This study could inform power calculation for future interventional studies using relevant clinical trial endpoints related to lung function and structure

Design, Synthesis, Characterization and Biological Evaluation of Some Novel 3, 4-Dihydropyrimidin-2(1h)-One as Anti Tubercular Agents.

The present study the ongoing progress in protein crystallography and NMR, structure-based drug design is gaining increasing importance in the search for new drugs. Modeling starts from the 3D structure of a target protein in order to construct molecules which are complementary to a binding site, in their geometry as well as in the pattern of their physicochemical properties around the molecules The present study relates to the synthesis of various derivatives and subsequent screening for their anti-tubercular activity. Due to several toxic effects of isoniazid, attempts were made to eliminate the toxicophore and substituting with a group contributing to the anti-tubercular action. This work also aims the same motive and the compounds were synthesized according to the developed and valid synthetic route. DOCKING: Several chemical libraries containing various scaffolds will be sketched and docked against the 3D structure of DprE1. The compounds for the synthesis will be chosen based on the high GScore and their feasibility in synthetic chemistry. SYNTHESIS: Based upon the Docking parameters, the following compounds will be synthesized Synthesis of 4-(4-hydroxyphenyl)-6-(pyridin-4-yl)-3,4-dihydropyrimidin-2(1H)-one(MBS2) Synthesis of 4-(4-chlorophenyl)-6-(pyridin-4-yl)-3,4-dihydropyrimidin-2(1H)-one (MBS3) Synthesis of 4-[4-(dimethylamino)phenyl]-6-(pyridin-4-yl)-3,4-dihydropyrimidin-2(1H)-one (MBS 6): CHARACTERIZATION: The above compounds will be characterized by using Infrared Spectroscopy, Nuclear Magnetic Spectroscopy and Mass spectroscopy. BIOLOGICAL EVALUATION: The synthesized compounds will be screened for their anti-tubercular activity by various in-vitro methods. CONCLUSION: Decaprenylphosphoryl-b-d-ribose 2’-Epimerase 1(DprE1) a enzyme of Oxido Reductase family is a critical enzyme for the growth of Mycobacterium tuberculosis H37Rv. From the review of literature DprE1 was chosen for our study for drug design. A database of 100 molecules with high potential of inhibiting the target possessing PDB ID of 4FDO were carefully chosen by making changes into the lead molecule 3,4- Dihydro pyrimidinones. The 3D structure of hopeful molecules were docked against the 3D structure of 4FDO using the docking platform Glide® (Grid Based Ligand Docking with Energetics). Three compounds with good Glide score( lower Binding energy) were selected for laboratory synthesis. Reaction conditions were optimized. The Compounds were labeled as MBS 2, MBS3, MBS6 were synthesized with satisfactory yield by Biginelli reaction. The purity of the synthesized compounds were evaluated by melting point and TLC. Recrystallization was done. The characterization of the synthesized compounds were done by Infrared, Nuclear magnetic resonance and Mass spectroscopic methods. The synthesized compounds were subjected to computer aided drug design (CADD) tool,for toxicity risk assessment by OSIRIS property calculator. The results are color coded as green color which confirms the drug likeness. The final pure compounds were screened for Antimycobacterial activity by in vitro method called Microplate Alamar Blue Assay(MABA). The Minimum Inhibitory Concentration (MIC) of the synthesized compounds were at 50mcg/ml against the MIC of known TB drugs Pyrazinamide: 3.125mcg/ml, Ciprofloxacin: 3.125mcg/ml and Streptomycin 6.25mcg/ml. Our work concludes that our synthesized molecules are effective in inhibiting Decaprenylphosphoryl-b-d-ribose 2’-Epimerase 1(DprE1) which is important for the growth of Mycobacterium tuberculosis. Further structural improvement in the structure of the synthesized compounds will give new outlook to the development of promising molecules against the pathogen Mycobacterium tuberculosis

Digital creativity - an investigation into architectural design in the electronic age

A dissertation submitted to the University of Bedfordshire in partial fulfilment of the requirements for the degree of Master of Philosophy.This study explores approaches to architectural creativity and collaborative design in the contemporary digital design context. The thesis identifies key trends and developments in the historical and present-day evolution of the creative use of computers by architects in education and practice. It examines the current manifestations of digitally supported architectural design, and investigates the ways in which computers and electronic communication technologies are being utilised in the design process. In the context of, and informed by, this investigative survey the author evolves three key models or analogues for the application of computer based techniques in the creative design process. Each design analogue has been tested with the collaboration of undergraduate architecture students and their academic teaching staff through experimental pedagogic design projects, which have been used to evaluate their validity and effectiveness. The working principles developed through these projects have also been applied in a realworld context, through a live professional case study architectural project undertaken by the author in commercial architectural practice. The concluding section examines the current state of play in the relationship between theoretical ideas and the practice of architectural design using digital techniques, to assess the methodological validity of the design analogues in the educational and practice spheres, and to make recommendations for future areas of research

Knowledge transfer and the use of social networks in the biopharmaceutical industry : an investigation into the micro-foundations of external absorptive capacity

In order to grow, the pharmaceutical sector has had to heavily rely on both formal and informal innovation networks. However, many analysts consider that the industry has not achieved its growth potential and suggest that this is in part due to the inherent organisational barriers to knowledge transfer that exist in the pharmaceutical sector. This thesis provides a critical review of the knowledge transfer literature; with particular reference to absorptive capacity, social capital and external knowledge transfer meta-routines. The study takes a pragmatic critical realist approach, using a two stage critical incident technique to elucidate the micro-foundations of problem solving routines as a proxy for knowledge transfer. Thematic analysis on the resulting narratives identifies routinized patterns of information seeking behaviour, reveals the micro-foundations of template use and provides insights into how scientists recognise value in the knowledge that they find. The study answers calls to research the role of the individual in organisational routines; to uncover the micro-foundations of external absorptive capacity and to determine how value is recognised in new knowledge. A model is proposed that suggests that recognising the value of new knowledge is a construct that is influenced by factors which affect the perceived information quality, the relative subjectivity of the solution and the source’s social-identity. The value of knowledge is also further corroborated with the support of other materials or through a wider stakeholder involvement. The study has adopted a ‘strategy-as-practice’ approach and contributes to organisational practice by examining how informal external knowledge transfer through problem solving in a biopharmaceutical organisation is accomplished. These insights enable the author to suggest a number of managerial strategies by which pharmaceutical managers might recognise, optimise and facilitate the use of informal networks; whilst protecting their intellectual property and maintaining the potential for innovation

Urban green spaces enhance carbon sequestration and conserve biodiversity in cities of the Global South : case of Kumasi, Ghana

Urbanization has the propensity to alter ecosystems, enervate ecosystem function and possibly jeopardise human wellbeing. While adequate integration of nature into the city landscape can pragmatically ameliorate urban environmental challenges, particularly those related to climate change and ecosystem degradation, in the developing regions, especially in Africa, urban green spaces (UGS) are hardly planned for and their ecosystem services unquantified and hence misappropriated. This study analyses 1) the spatio-temporal dynamics and distributional equity, 2) carbon sequestration potential, and 3) biodiversity patterns of UGS in Kumasi metropolis, Ghana. Direct ecosystem assessment (inventory and survey) and remote sensing techniques were adopted in this study. The vegetation cover of Kumasi is about 33 % and is declining fourfold faster in recent years (2009 – 2014) than previously (986 – 2001). Per capita UGS area for 2009 and 2014 are significantly correlated with the socio-economic conditions of submetropolis. The green area stores about 3758.1 Gg C: equivalent to 270±22 t C/ha per UGS cover or 125.7 ± 8 t C/ha for the entire study area in both soil and vegetation. Exactly 176 tree species in 46 families of both native and exotic origins occur in the city. Carbon stocks and species richness differ significantly across UGS types. Natural forest, public parks, cemeteries and institutional compounds stored more carbon in vegetation whereas soil organic carbon storage was highest in the home gardens, farmlands, plantations, and grasslands. The outer fringes of the city support more species and carbon stocks than the core urban area. Species and trait diversity are important drivers of urban ecosystem productivity (carbon storage). UGS species richness correlated strongly with vegetation carbon storage in the city. UGS are carbon sinks and biodiversity reservoirs which can be relevant to climate change mitigation and adaptation as well as the overall wellbeing of urbanites. However, UGS cover is currently plummeting and is threatened by further urbanization processes including rise in population. Maintenance, expansion, and uniform distribution of green spaces in cities should be a priority for planners, national and local governments as well as traditional leaders. It is recommended that urban biodiversity and carbon stocks be integrated into national and regional biodiversity and carbon stock assessments in Africa.Durch Verstädterung besteht die Tendenz, dass Ökosysteme verändert werden, die Funktion von Ökosystemen geschwächt wird und möglicherweise das menschliche Wohlergehen gefährdet wird. Während eine angemessene Integration von Grünflächen in die Stadtlandschaft bei der Bewältigung der städtischen ökologischen Herausforderungen, besonders in Bezug auf Klimawandel und die Beeinträchtigung des Ökosystems, pragmatisch helfen kann, werden in Entwicklungsgebieten, vor allem in Afrika, kaum städtische Grünflächen (urban green spaces - UGS) geplant. Des Weiteren werden die von UGS geleisteten Ökosystemdienstleistungen zumeist nicht beziffert und demnach in globalen Analysen nicht erfasst. Diese Studie analysiert 1) die räumlich-zeitliche Dynamik und das Verteilungsmuster, 2) das Potential von Kohlenstoffbindung und 3) die biologische Vielfalt und Funktion von UGS im städtischen Großraum von Kumasi, Ghana. In dieser Studie wurden Methoden zur direkten Bewertung des Ökosystems und Fernerkundungstechniken verwandt. UGS in Kumasi umfassen z.Z. etwa 33 % des städtischen Großraum von Kumasi und diese Fläche schrumpfte in den letzten Jahren (2009 – 2014) viermal schneller als zuvor (1986 – 2001). Die pro Kopf Verteilung von UGS in Kumasi korreliert signifikant mit den dortigen sozioökonomischen Bedingungen. Die Grünflächen speichern etwa 3758,1 Gg Kohlenstoff; im Durchschnitt entspricht dies 270 ± 22 t Kohlenstoff / ha UGS oder 125,7 t Kohlenstoff / ha im gesamten Untersuchungsgebiet, sowohl in Form von Böden als auch Vegetation. Im Großraum Kumasi kommen 176 verschiedene Baumarten aus 46 heimischen und nicht-heimischen Familien vor. Kohlenstoffbestände und Artenvielfalt unterscheiden sich strak in Abhängigkeit des Typus von UGS. Reste natürlichen Waldbestandes, öffentliche Parks, Friedhöfe und Bäume auf dem Gelände von öffentlichen Institutionen speicherten mehr Kohlenstoff in der Vegetation, wobei der organische Kohlenstoffspeicher in privaten Gärten, auf Feldern, Plantagen und Grasflächen am höchsten war. Stadtrandgebiete haben eine höhere Biodiversität und speichern mehr Biomasse als der innenstädtische Bereich. Arten- und phenotypische Vielfalt haben einen grossen Einfluß auf die Funktion städtischer Ökosysteme. Das Ausmaß der Artenvielfalt in städtischen Grünflächen steht im engen Zusammenhang mit dem Kohlenstoffbestand in der städtischen Vegetation. Städtische Grünflächen sind wichtige Kohlenstoffspeicher und Quellen der biologischen Vielfalt, die für die Vermeidung von und Anpassung an Klimawandelfolgen und das allgemeine Wohlergehen von Städten sehr relevant sind. Allerdings gefährdet das rapide Bevölkerungswachstum und die zunehmende Urbaniserung die existierenden städtischem Grünflächen in Afrika. Instandhaltung, Erweiterung und auch eine verbesserte und gerechtere Verteilung von städtischen Grünflächen sollten für Städteplaner, Landesregierungen, Lokalverwaltungen und traditionelle Führer eine Priorität darstellen

ENERGY CONSUMPTION OF MOBILE PHONES

Battery consumption in mobile applications development is a very important aspect and has to be considered by all the developers in their applications. This study will present an analysis of different relevant concepts and parameters that may have an impact on energy consumption of Windows Phone applications. This operating system was chosen because limited research related thereto has been conducted, even though there are related studies for Android and iOS operating systems. Furthermore, another reason is the increasing number of Windows Phone users. The objective of this research is to categorise the energy consumption parameters (e.g. use of one thread or several threads for the same output). The result for each group of experiments will be analysed and a rule will be derived. The set of derived rules will serve as a guide for developers who intend to develop energy efficient Windows Phone applications. For each experiment, one application is created for each concept and the results are presented in two ways; a table and a chart. The table presents the duration of the experiment, the battery consumed in the experiment, the expected battery lifetime, and the energy consumption, while the charts display the energy distribution based on the main threads: UI thread, application thread, and network thread

A WEB-BASED ENVIRONMENTAL TOOLKIT TO SUPPORT SMES IN THE IMPLEMENTATION OF AN ENVIRONMENTAL MANAGEMENT SYSTEM

With small and medium sized-enterprises (SMEs) taking up the majority of the global businesses, it is important they act in an environmentally responsible manner. Environmental management systems (EMS) help companies evaluate and improve their environmental impact but they often require human, financial, and temporary resources that not all SMEs can afford. This research encompasses interviews with representatives of two small enterprises in Germany to provide insights into their understanding, and knowledge of an EMS and how they perceive their responsibility towards the environment. Furthermore, it presents a toolkit created especially for small and medium-sized enterprises. It serves as a simplified version of an EMS based on the ISO 14001 standard and is evaluated by target users and appropriate representatives. Some of the findings are: while open to the idea of improving their environmental impact, SMEs do not always feel it is their responsibility to do so; they seem to lack the means to fully implement an EMS. The developed toolkit is considered useful and usable and recommendations are drawn for its future enhancement