Computational Methods for Accelerated Discovery and Characterization of Genes in Emerging Model Organisms

Cilia are evolutionarily conserved, complex, microtubule-based structures that protrude from many eukaryotic cells. In humans, cilia can be found on almost all cell types. The effect of abnormal or absent cilia has been established as the common underlying cause of a recently emerging class of genetic diseases collectively referred to as ciliopathies. The function and structure of cilia are conserved across all organisms with cilia. One of the most influential model systems used to study ciliopathies has been the ciliated green alga Chlamydomonas reinhardtii, an organism for which there is a sequenced genome with relatively few experimentally validated whole-gene annotations but in which the ciliogenesis process can be reliably induced. Experimental methods have been successful in identifying a handful of highly specific cilia disease genes in the alga, but high-throughput, automated computational analyses harbor the greatest potential to reveal a more comprehensive ciliopathy disease gene list. However, ii in order for a genome to be informative for downstream computational analyses, it must first be accurately annotated. This dissertation focuses on accelerating the accurate annotation of the Chlamydomonas genome using whole-genome and whole-transcriptome methodologies to identify human ciliopathy genes. Towards this end, we first develop a genefinder training method for Chlamydomonas that does not require whole gene annotations and demonstrate that this traning method results in a more accurate genefinder than any other genefinder for this alga. Next, we develop a new automated protein characterization method that facilitates the transfer of information across different protein families by extending simple homology categorization to identify new cilia gene candidates. Finally we perform and analyze high-throughput whole-transcriptome sequencing of Chlamydomonas at various timepoints during ciliogenesis to identify ~300 novel human ciliopathy gene candidates. Together these three methodologies complement each other and the existing literature to better elucidate a more complete and informative cilia gene catalog

Using Material and Energy Flow Analysis to Estimate Future Energy Demand at the City Level

Cities undergoing rapid growth encounter tremendous challenges, not only in terms of providing services to meet demand, but also in ensuring that development occurs in a sustainable way. This research evaluates the potential contribution of the material and energy flow analysis framework to predicting future energy flows and corresponding CO2 emissions in Riyadh, Saudi Arabia. The research presents a generic material and energy flow analysis model and applies it to the housing stock in Riyadh to estimate future energy demand and to assess associated effects. As the country starts to adopt sustainability measures and plan its transition from a fossil fuel-based energy system towards a renewable-based energy system, an understanding of future energy flows will allow early recognition of potential environmental impacts and provide information to enable accurate predictions of future demand for resources

Synthesizing and Salvaging NAD+: Lessons Learned from Chlamydomonas reinhardtii

The essential coenzyme nicotinamide adenine dinucleotide (NAD+) plays important roles in metabolic reactions and cell regulation in all organisms. Bacteria, fungi, plants, and animals use different pathways to synthesize NAD+. Our molecular and genetic data demonstrate that in the unicellular green alga Chlamydomonas NAD+ is synthesized from aspartate (de novo synthesis), as in plants, or nicotinamide, as in mammals (salvage synthesis). The de novo pathway requires five different enzymes: L-aspartate oxidase (ASO), quinolinate synthetase (QS), quinolate phosphoribosyltransferase (QPT), nicotinate/nicotinamide mononucleotide adenylyltransferase (NMNAT), and NAD+ synthetase (NS). Sequence similarity searches, gene isolation and sequencing of mutant loci indicate that mutations in each enzyme result in a nicotinamide-requiring mutant phenotype in the previously isolated nic mutants. We rescued the mutant phenotype by the introduction of BAC DNA (nic2-1 and nic13-1) or plasmids with cloned genes (nic1-1 and nic15-1) into the mutants. NMNAT, which is also in the de novo pathway, and nicotinamide phosphoribosyltransferase (NAMPT) constitute the nicotinamide-dependent salvage pathway. A mutation in NAMPT (npt1-1) has no obvious growth defect and is not nicotinamide-dependent. However, double mutant strains with the npt1-1 mutation and any of the nic mutations are inviable. When the de novo pathway is inactive, the salvage pathway is essential to Chlamydomonas for the synthesis of NAD+. A homolog of the human SIRT6-like gene, SRT2, is upregulated in the NS mutant, which shows a longer vegetative life span than wild-type cells. Our results suggest that Chlamydomonas is an excellent model system to study NAD+ metabolism and cell longevity

An investigation into future performance and overheating risks in Passivhaus dwellings

In response to UK government policy mandating the construction of 'zero carbon' homes by 2016 there have been significant changes in the way dwellings are being designed and built. Recent years have seen a rapid uptake in the adoption of the German Passivhaus standard as a template for ultra-low energy and zero carbon buildings in the UK. Despite genuine motivations to mitigate climate change and fuel poverty there is a lack of research investigating the long-term performance of Passivhaus buildings in a rapidly changing UK climate. This paper sets out to investigate whether Passivhaus dwellings will be able to provide high standards of thermal comfort in the future or whether they are inherently vulnerable to overheating risks. Scenario modelling using probabilistic data derived from the UKCP09 weather generator (WG) in conjunction with dynamic simulation and global sensitivity analysis techniques are used to assess the future performance of a range of typical Passivhaus dwellings relative to an identical Fabric Energy Efficiency Standard (FEES) compliant dwelling over its notional future lifespan. The emphasis of this study is to understand what impact climate change will pose to overheating risks for Passivhaus dwellings relative to the de facto (i.e. FEES) alternative, and which design factors play a dominant role in contributing to this risk. The results show that optimization of a small number of design inputs, including glazing ratios and external shading devices, can play a significant role in mitigating future overheating risks. © 2013 Elsevier Ltd

Establishing domestic low energy consumption reference levels for Saudi Arabia and the wider Middle Eastern region

Saudi Arabia is renowned for its full reliance on fossil fuel energy and lack of an energy regulatory framework for its built environment. The paper focuses on the domestic sector and aims to: (a) establish levels of energy reduction, informed by leading standards (such as Passivhaus in Germany), that can be achieved taking into account the complex local socio-cultural context and environmental factors, and (b) propose a low energy reference definition with a view of encouraging energy retrofitting programs and enforcing domestic low carbon interventions. An energy simulation environment is employed to simulate and analyze energy consumption patterns of three proposed low carbon prototype houses that reflect current house typology and space layout in the country. The three proposed homes offer a reduction in energy consumption of up to 71.6%, compared with similar houses. Based on these findings, a domestic energy performance reference is proposed with energy consumption ranging between 77 kWh/m2 and 98 kWh/m2. Economic and environmental benefits are discussed as well as recommendations for enforcing low carbon design in the country and across the regio

CMS Pixel Telescope Addition to T-980 Bent Crystal Collimation Experiment at the Tevatron

An enhancement to the T-980 bent crystal collimation experiment at the Tevatron has been completed. The enhancement was the installation of a pixel telescope inside the vacuum-sealed beam pipe of the Tevatron. The telescope is comprised of six CMS PSI46 pixel plaquettes, arranged as three stations of horizontal and vertical planes, with the CAPTAN system for data acquisition and control. The purpose of the pixel telescope is to measure beam profiles produced by bent crystals under various conditions. The telescope electronics inside the beam pipe initially were not adequately shielded from the image current of the passing beams. A new shielding approach was devised and installed, which resolved the problem. The noise issues encountered and the mitigating techniques are presented herein, as well as some preliminary results from the telescope.Comment: 9 pp. 2nd International Conference on Technology and Instrumentation in Particle Physics 2011: TIPP 2011. 9-14 Jun 2011. Chicago, Illinoi

Well-defined donor-acceptor rod-coil diblock copolymers based on P3HT containing C-60: the morphology and role as a surfactant in bulk-heterojunction solar cells

The synthesis of well-defined rod-coil block copolymers consisting of P3HT donor and C-60 acceptor chromophores (P3HT-b-P(S(x)A(y))-C-60) in a molecular architecture is reported for use in bulk-heterojunction (BHJ) solar cells. In thin films of the resulting block copolymer, reproducible self-assembly into well-defined "nanofibrils'' is observed. This is the first example of a block copolymer containing a C-60 derivative that shows exclusively a nanofibrilar structure. We have investigated the potential utility of the block copolymer as a "surfactant'' for controlling the interface morphology of the P3HT: PCBM donor-acceptor phase domains within the composite. We find a substantial improvement in device performance when 5% of block copolymer are introduced to the P3HT: PCBM blend system, resulting in ca. 35% improved efficiency relative to the P3HT: PCBM solar cell fabricated without the "surfactant''.close13212

Towards the innovation of an integrated 'one-stop-shop' online services utility management: exploring customer' technology acceptance

The revolutions in internet online service delivery have transformed the way that people interact with technology, resulting in an exponential growth in the number of online users. The various consumer characteristics and ways of providing services online have had a dramatic change on user acceptance and perceived value of technological innovation. Therefore, user perception is a vital issue in investigating user intentions in adopting online services. The scope of this paper is to examine the perceptions of adopters and non-adopters of online utility management, in terms of their experience towards existing service delivery approaches and their expectations of future innovations as regards perceived characteristics. The user perceptions contribute to defining an initial roadmap for exploring the evolution of ‘utilities service management’ on the Internet and their approaches to online service delivery. It highlights the general need for a value-added and integrated utilities service management solution as well as the specific demand of internet users for the integrated online delivery of utilities services to serve their particular interests. This paper discusses several traditional approaches in related fields of electronic service delivery and shows how the current situation demands a shift towards an integrated utilities service management solution that considers the interests of all stakeholders

Adjustment for shape restoration and force control of cable arch stayed bridges

Cable arch stayed bridges are one type of tensile structures, and there are increasingly such structures constructed. Their performance relies on how they are designed. This type of structures can suffer big deflections under load, in this situation the displacements may need to be reduced. Sometimes, it may be necessary to control internal force of a specific cable so the cable force remains within the desired limit. More study need to be done to develop the techniques that are available for such adjustments. This paper deals with theoretical and experimental adjusting of two physical models, and the linear and nonlinear geometrical behavior of cable (arch) stayed bridges. It was concluded that the techniques of adjustment were practical and efficient to reduce, eliminate shape distortion, and control internal bar force of both structures. For structures that behave linearly, it is easier to get the target (displacement or force), but for non-linear structures one iteration of adjustments was not enough to get the displacement target. Through the techniques of the internal bar force adjustment, the amount of force can be reduced even to the zero, e.g. in case of replacing damaged members