Androgen-regulated metabolism and biosynthesis in prostate cancer

Metabolic changes are a well-described hallmark of cancer and are responses to changes in the activity of diverse oncogenes and tumour suppressors. For example, steroid hormone biosynthesis is intimately associated with changes in lipid metabolism and represents a therapeutic intervention point in the treatment of prostate cancer (PCa). Both prostate gland development and tumorigenesis rely on the activity of a steroid hormone receptor family member, the androgen receptor (AR). Recent studies have sought to define the biological effect of the AR on PCa by defining the whole-genome binding sites and gene networks that are regulated by the AR. These studies have provided the first systematic evidence that the AR influences metabolism and biosynthesis at key regulatory steps within pathways that have also been defined as points of influence for other oncogenes, including c-Myc, p53 and hypoxia-inducible factor 1α, in other cancers. The success of interfering with these pathways in a therapeutic setting will, however, hinge on our ability to manage the concomitant stress and survival responses induced by such treatments and to define appropriate therapeutic windows.

Protective role of glycerol against benzene stress: insights from the Pseudomonas putida proteome

Chemical activities of hydrophobic substances can determine the windows of environmental conditions over which microbial systems function and the metabolic inhibition of microorganisms by benzene and other hydrophobes can, paradoxically, be reduced by compounds that protect against cellular water stress (Bhaganna et al. in Microb Biotechnol 3:701-716, 2010; Cray et al. in Curr Opin Biotechnol 33:228-259, 2015a). We hypothesized that this protective effect operates at the macromolecule structure-function level and is facilitated, in part at least, by genome-mediated adaptations. Based on proteome profiling of the soil bacterium Pseudomonas putida, we present evidence that (1) benzene induces a chaotrope-stress response, whereas (2) cells cultured in media supplemented with benzene plus glycerol were protected against chaotrope stress. Chaotrope-stress response proteins, such as those involved in lipid and compatible-solute metabolism and removal of reactive oxygen species, were increased by up to 15-fold in benzene-stressed cells relative to those of control cultures (no benzene added). By contrast, cells grown in the presence of benzene + glycerol, even though the latter grew more slowly, exhibited only a weak chaotrope-stress response. These findings provide evidence to support the hypothesis that hydrophobic substances induce a chaotropicity-mediated water stress, that cells respond via genome-mediated adaptations, and that glycerol protects the cell's macromolecular systems. We discuss the possibility of using compatible solutes to mitigate hydrocarbon-induced stresses in lignocellulosic biofuel fermentations and for industrial and environmental applications.

Biocontrol agents promote growth of potato pathogens, depending on environmental conditions

There is a pressing need to understand and optimize biological control so as to avoid over-reliance on the synthetic chemical pesticides that can damage environmental and human health. This study focused on interactions between a novel biocontrol-strain, Bacillus sp. JC12GB43, and potato-pathogenic Phytophthora and Fusarium species. In assays carried out in vitro and on the potato tuber, the bacterium was capable of near-complete inhibition of pathogens. This Bacillus was sufficiently xerotolerant (water activity limit for growth = 0.928) to out-perform Phytophthora infestans (~0.960) and challenge Fusarium coeruleum (~0.847) and Fusarium sambucinum (~0.860) towards the lower limits of their growth windows. Under some conditions, however, strain JC12GB43 stimulated proliferation of the pathogens: for instance, Fusarium coeruleum growth-rate was increased under chaotropic conditions in vitro (132 mM urea) by >100% and on tubers (2-M glycerol) by up to 570%. Culture-based assays involving macromolecule-stabilizing (kosmotropic) compatible solutes provided proof-of-principle that the Bacillus may provide kosmotropic metabolites to the plant pathogen under conditions that destabilize macromolecular systems of the fungal cell. Whilst unprecedented, this finding is consistent with earlier reports that fungi can utilize metabolites derived from bacterial cells. Unless the antimicrobial activities of candidate biocontrol strains are assayed over a full range of field-relevant parameters, biocontrol agents may promote plant pathogen infections and thereby reduce crop yields. These findings indicate that biocontrol activity, therefore, ought to be regarded as a mode-of-behaviour (dependent on prevailing conditions) rather than an inherent property of a bacterial strain.

YSOVAR: Mid-infrared Variability in the Star-forming Region Lynds 1688

The emission from young stellar objects (YSOs) in the mid-infrared (mid-IR) is dominated by the inner rim of their circumstellar disks. We present IR data from the Young Stellar Object VARiability (YSOVAR) survey of ~800 objects in the direction of the Lynds 1688 (L1688) star-forming region over four visibility windows spanning 1.6 yr using the Spitzer Space Telescope in its warm mission phase. Among all light curves, 57 sources are cluster members identified based on their spectral energy distribution and X-ray emission. Almost all cluster members show significant variability. The amplitude of the variability is larger in more embedded YSOs. Ten out of 57 cluster members have periodic variations in the light curves with periods typically between three and seven days, but even for those sources, significant variability in addition to the periodic signal can be seen. No period is stable over 1.6 yr. Nonperiodic light curves often still show a preferred timescale of variability that is longer for more embedded sources. About half of all sources exhibit redder colors in a fainter state. This is compatible with time-variable absorption toward the YSO. The other half becomes bluer when fainter. These colors can only be explained with significant changes in the structure of the inner disk. No relation between mid-IR variability and stellar effective temperature or X-ray spectrum is found.

Geochronological database and classification system for age uncertainties in Neotropical pollen records.

The newly updated inventory of palaeoecological research in Latin America offers an important overview of sites available for multi-proxy and multi-site purposes. From the collected literature supporting this inventory, we collected all available age model metadata to create a chronological database of 5116 control points (e.g. 14C, tephra, fission track, OSL, 210Pb) from 1097 pollen records. Based on this literature review, we present a summary of chronological dating and reporting in the Neotropics. Difficulties and recommendations for chronology reporting are discussed. Furthermore, for 234 pollen records in northwest South America, a classification system for age uncertainties is implemented based on chronologies generated with updated calibration curves. With these outcomes age models are produced for those sites without an existing chronology, alternative age models are provided for researchers interested in comparing the effects of different calibration curves and age–depth modelling software, and the importance of uncertainty assessments of chronologies is highlighted. Sample resolution and temporal uncertainty of ages are discussed for different time windows, focusing on events relevant for research on centennial- to millennial-scale climate variability. All age models and developed R scripts are publicly available through figshare, including a manual to use the scripts.

The Exclusive Brethren ‘Doctrine of Separation’: An Anthropology of Theology

Why do the Exclusive Brethren attend church ten times a week? Why do they shun excommunicated members, including immediate family? Why do they refuse to eat with outsiders? Why will they employ outsiders in their businesses, but never be employed by them? Why do they reject modern media as “pipelines of filth”? Why do they refuse to vote, while simultaneously campaigning for Conservative Party candidates? Why do they only live in detached houses, and build churches entirely without windows? How, in other words, do the Exclusive Brethren try to live good lives? And what can we learn anthropologically from these models of ‘the good’, and from the objections they provoke? Drawing inspiration from Keane’s (2014) suggestion that ‘we shouldn’t decide in advance what ethics will look like’, this paper seeks to critically contribute to new scholarship within the anthropology of morality and detachment by constructing, in a very literal sense, an anthropology of theology via an analysis of the Exclusive Brethren ‘doctrine of separation’.

Pre- and post-settlement processes regulating recruitment of the shore crab Carcinus maenas

O sucesso do recrutamento em espécies com ciclos de vida complexos, i.e. com duas ou mais fases de desenvolvimento, depende do fornecimento de larvas aos locais apropriados do assentamento (mecanismos de pré-assentamento) e na consequente sobrevivência destas larvas até aos estágios bentónicos iniciais (mecanismos de pós-assentamento). O estudo dos principais processos físicos que controlam a variabilidade intra-anual do recrutamento do caranguejo Carcinus maenas foi possível com à obtenção em séries diárias da abundância de megalopas no plâncton e do seu assentamento em substratos artificiais de assentamento, e de parâmetros físicos relacionados com a amplitude de maré e o upwelling, durante os meses da época reprodutiva deste caranguejo. Os nossos resultados demonstraram um padrão cíclico de fornecimento de megalopas de C. maenas aos estuários na costa ocidental de Portugal, relacionado com a amplitude de maré e favorecido pelos ventos de sul. O assentamento de megalopas nos substratos artificiais de assentamento mostrou-se desacoplado do fornecimento nos dois estuários. Os dados obtidos sugerem que as megalopas são transportadas para a costa após a acção de ventos de downwelling, e o fornecimento para os estuários ocorre por transporte selectivo por corrente de maré. A utilização de substratos artificiais para medir densidades de juvenis de Carcinus maenas deve ser ponderada, uma vez que se verificou que em habitats estruturalmente menos complexos os juvenis utilizam os colectores como refúgio; em habitats mais complexos, os juvenis preferiram refugiar-se nas ervas marinhas existentes. No entanto, a estimativa de abundâncias diárias medidas nos colectores permitiu a descrição das abundâncias dos vários estádios de desenvolvimento juvenis, bem como as respectivas taxas de crescimento. As capacidades locomotoras de diferentes classes de tamanho de juvenis de C. maenas foram estimadas mediante o cálculo de um índice de locomoção. Os nossos resultados sugerem que os juvenis mais pequenos estão relativamente protegidos em habitats com vegetação densa, provavelmente porque este tipo de habitats inibe os movimentos dos juvenis de maiores dimensões. Foram também encontradas evidências da existência de segregação temporal na actividade locomotora das diferentes classes de juvenis, que funcionará como um mecanismo que permite reduzir o canibalismo e, consequentemente, aumentar a capacidade de suporte dos habitats juvenis. Foi realizado um estudo sobre o canibalismo nos juvenis de C. maenas na Ria de Aveiro, in situ e utilizando densidades reais. Verificou-se que as presas mais pequenas eram as mais vulneráveis, sendo os juvenis de maiores dimensões os predadores mais eficazes. Por outro lado, as taxas de canibalismo foram menores em habitats com elevadas densidades de refúgio (Zostera noltii). A estimativa das taxas diárias de mortalidade devidas ao canibalismo são aproximadamente metade das taxas diárias de mortalidade devidas aos processos de pré-assentamento, indicando que esta população de C. maenas será regulada pelo fornecimento larvar, i.e., será uma população regulada essencialmente por mecanismos préassentamento.

Optimization models for a short sea fuel oil distribution problem

O transporte marítimo e o principal meio de transporte de mercadorias em todo o mundo. Combustíveis e produtos petrolíferos representam grande parte das mercadorias transportadas por via marítima. Sendo Cabo Verde um arquipelago o transporte por mar desempenha um papel de grande relevância na economia do país. Consideramos o problema da distribuicao de combustíveis em Cabo Verde, onde uma companhia e responsavel por coordenar a distribuicao de produtos petrolíferos com a gestão dos respetivos níveis armazenados em cada porto, de modo a satisfazer a procura dos varios produtos. O objetivo consiste em determinar políticas de distribuicão de combustíveis que minimizam o custo total de distribuiçao (transporte e operacões) enquanto os n íveis de armazenamento sao mantidos nos n íveis desejados. Por conveniencia, de acordo com o planeamento temporal, o prob¬lema e divido em dois sub-problemas interligados. Um de curto prazo e outro de medio prazo. Para o problema de curto prazo sao discutidos modelos matemáticos de programacao inteira mista, que consideram simultaneamente uma medicao temporal cont ínua e uma discreta de modo a modelar multiplas janelas temporais e taxas de consumo que variam diariamente. Os modelos sao fortalecidos com a inclusão de desigualdades validas. O problema e então resolvido usando um "software" comercial. Para o problema de medio prazo sao inicialmente discutidos e comparados varios modelos de programacao inteira mista para um horizonte temporal curto assumindo agora uma taxa de consumo constante, e sao introduzidas novas desigualdades validas. Com base no modelo escolhido sao compara¬das estrategias heurísticas que combinam três heur ísticas bem conhecidas: "Rolling Horizon", "Feasibility Pump" e "Local Branching", de modo a gerar boas soluçoes admissíveis para planeamentos com horizontes temporais de varios meses. Finalmente, de modo a lidar com situaçoes imprevistas, mas impor¬tantes no transporte marítimo, como as mas condicões meteorológicas e congestionamento dos portos, apresentamos um modelo estocastico para um problema de curto prazo, onde os tempos de viagens e os tempos de espera nos portos sao aleatórios. O problema e formulado como um modelo em duas etapas, onde na primeira etapa sao tomadas as decisões relativas as rotas do navio e quantidades a carregar e descarregar e na segunda etapa (designada por sub-problema) sao consideradas as decisoes (com recurso) relativas ao escalonamento das operacões. O problema e resolvido por um metodo de decomposto que usa um algoritmo eficiente para separar as desigualdades violadas no sub-problema.

Development of a single photon counting computed tomography system using MPGDs

The development of computed tomography systems with energy resolving detectors is a current challenge in medical physics and biomedical engineering. A computed tomography system of this kind allows getting complementary informations relatively to conventional systems, that can help the medical diagnosis, being of great interest in medicine. The work described in this thesis is related to the development of a computed tomography system using micropattern gaseous detectors, which allow storing, simultaneously, information about the interaction position and the energy of each single photon that interacts with the detector. This kind of detectors has other advantages concerning the cost and characteristics of operation when compared with solid state detectors. Tomographic acquisitions were performed using a MicroHole & Strip Plate based detector, which allowed reconstructing cross-sectional images using energy windows, applying the energy weighting technique and performing multi-slice and tri-dimensional reconstructions. The contrast-to-noise ratio was improved by 31% by applying the energy weighting technique, comparing with the corresponding image obtained with the current medical systems. A prototype of a computed tomography with flexibility to change the detector was developed, making it possible to apply different detectors based on Thick-COBRA. Several images acquired with these detectors are presented and demonstrate their applicability in X-ray imaging. When operating in NeCH4, the detector allowed a charge gain of 8 104, an energy resolution of 20% (full width at half maximum at 8 keV), a count rate of 1 106 Hz/mm2, a very stable operation (gain fluctuations below 5%) and a spacial resolution of 1.2 mm for an energy photon of 3.6 keV. Operating the detector in pure Kr allowed increasing the detection efficiency and achieving a charge gain of 2 104, an energy resolution of 32% (full width at half maximum at 22 keV), a count rate of 1 105 Hz/mm2, very stable operation and a spatial resolution of 500 m. The software already existing in the group was improved and tools to correct geometric misalignments of the system were also developed. The reconstructions obtained after geometrical correction are free of artefacts due to the referred misalignments.

The estimation and improvement of the selectivity in crustacean and fish trawls

Tese de dout., Ciências e Tecnologias das Pescas, Faculdade de Ciências do Mar e do Ambiente, Univ. do Algarve, 2003

Development of a Piggybac based direct reprogramming system for derivation of integration free induced pluripotent stem cells

Induced pluripotent stem cells (iPSc) have great potential for applications in regenerative medicine, disease modeling and basic research. Several methods have been developed for their derivation. The original method of Takahashi and Yamanaka involved the use of retroviral vectors which result in insertional mutagenesis, presence in the genome of potential oncogenes and effects of residual transgene expression on differentiation bias of each particular iPSc line. Other methods have been developed, using different viral vectors (adenovirus and Sendai virus), transient plasmid transfection, mRNA transduction, protein transduction and use of small molecules. However, these methods suffer from low efficiencies; can be extremely labor intensive, or both. An additional method makes use of the piggybac transposon, which has the advantage of inserting its payload into the host genome and being perfectly excised upon re-expression of the transposon transposase. Briefly, a policistronic cassette expressing Oct4, Sox2, Klf4 and C-Myc flanked by piggybac terminal repeats is delivered to the cells along with a plasmid transiently expressing piggybac transposase. Once reprogramming occurs, the cells are re-transfected with transposase and subclones free of tranposon integrations screened for. The procedure is therefore very labor intensive, requiring multiple manipulations and successive rounds of cloning and screening. The original method for reprogramming with the the PiggyBac transposon was created by Woltjen et al in 2009 (schematized here) and describes a process with which it is possible to obtain insert-free iPSc. Insert-free iPSc enables the establishment of better cellular models of iPS and adds a new level of security to the use of these cells in regenerative medicine. Due to the fact that it was based on several low efficiency steps, the overall efficiency of the method is very low (<1%). Moreover, the stochastic transfection, integration, excision and the inexistence of an active way of selection leaves this method in need of extensive characterization and screening of the final clones. In this work we aime to develop a non-integrative iPSc derivation system in which integration and excision of the transgenes can be controlled by simple media manipulations, avoiding labor intensive and potentially mutagenic procedures. To reach our goal we developed a two vector system which is simultaneously delivered to original population of fibroblasts. The first vector, Remo I, carries the reprogramming cassette and GFP under the regulation of a constitutive promoter (CAG). The second vector, Eneas, carries the piggybac transposase associated with an estrogen receptor fragment (ERT2), regulated in a TET-OFF fashion, and its equivalent reverse trans-activator associated with a positive-negative selection cassette under a constitutive promoter. We tested its functionality in HEK 293T cells. The protocol is divided in two the following steps: 1) Obtaining acceptable transfection efficiency into human fibroblasts. 2) Testing the functionality of the construct 3) Determining the ideal concentration of DOX for repressing mPB-ERT2 expression 4) Determining the ideal concentration of TM for transposition into the genome 5) Determining the ideal Windows of no DOX/TM pulse for transposition into the genome 6) 3, 4 and 5) for transposition out of the genome 7) Determination of the ideal concentration of GCV for negative selection We successfully demonstrated that ENEAS behaved as expected in terms of DOX regulation of the expression of mPB-ERT2. We also demonstrated that by delivering the plasmid into 293T HEK cells and manipulating the levels of DOX and TM in the medium, we could obtain puromycin resistant lines. The number of puromycin resistant colonies obtained was significantly higher when DOX as absent, suggesting that the colonies resulted from transposition events. Presence of TM added an extra layer of regulation, albeit weaker. Our PCR analysis, while not a clean as would be desired, suggested that transposition was indeed occurring, although a background level of random integration could not be ruled out. Finally, our attempt to determine whether we could use GVC to select clones that had successfully mobilized PB out of the genome was unsuccessful. Unexpectedly, 293T HEK cells that had been transfected with ENEAS and selected for puromycin resistance were insensitive to GCV.

The intra-industry effects of going concern withdrawn audit reports

Dissertação de mestrado, Finanças Empresariais, Faculdade de Economia, Universidade do Algarve, 2014

Route planning in wireless sensor networks for data gathering purposes

Dissertação de Mestrado, Engenharia Informática, Faculdade de Ciências e Tecnologia, Universidade do Algarve, 2015

Hotel Valuation Software, Version 4.0

[Updated August 2016] The Hotel Valuation Software, freely available from Cornell’s Center for Hospitality Research, has been updated to reflect the many changes in the 11th Edition of the Uniform System of Accounts for the Lodging Industry (USALI). Version 4.0 of the Hotel Valuation Software provides numerous enhancements over the original tool from 2011. In addition to a significant increase in functionality and an update to reflect the 11th edition of the USALI, Version 4.0 takes advantage of the power of the latest release of Microsoft Excel®. Note that Version 4.0 works only on a PC running Microsoft Windows, it does not work on a Mac running OS X. Users desiring an OS X compatible version should click here (Labeled as Version 2.5). 酒店评估软件手册和三个程序（点击这里 ) Users desiring a Mandarin version of the Hotel Valuation Software should click here The Hotel Valuation Software remains the only non-proprietary computer software designed specifically to assist in the preparation of market studies, forecasts of income and expense, and valuations for lodging property. The software provides an accurate, consistent, and cost-effective way for hospitality professionals to forecast occupancy, revenues and expenses and to perform hotel valuations. Version 4.0 of the Hotel Valuation Software includes the following upgrades – a complete update to reflect the 11th edition of the USALI – the most significant change to the chart of accounts in a generation, an average daily rate forecasting tool, a much more sophisticated valuation module, and an optional valuation tool useful in periods of limited capital liquidity. Using established methodology, the Hotel Valuation Software is a sophisticated tool for lodging professionals. The tool consists of three separate software programs written as Microsoft Excel files and a software users' guide. The tool is provided through the generosity of HVS and the School of Hotel Administration. The three software modules are: Room Night Analysis and Average Daily Rate: Enables the analyst to evaluate the various competitive factors such as occupancy, average room rate, and market segmentation for competitive hotels in a local market. Calculates the area-wide occupancy and average room rate, as well as the competitive market mix. Produce a forecast of occupancy and average daily rate for existing and proposed hotels in a local market. The program incorporates such factors as competitive occupancies, market segmentation, unaccommodated demand, latent demand, growth of demand, and the relative competitiveness of each property in the local market. The program outputs include ten-year projections of occupancy and average daily rate. Fixed and Variable Revenue and Expense Analysis: The key to any market study and valuation is a supportable forecast of revenues and expenses. Hotel revenue and expenses are comprised of many different components that display certain fixed and variable relationships to each other. This program enables the analyst to input comparable financial operating data and forecast a complete 11-year income and expense statement by defining a small set of inputs: The expected future occupancy levels for the subject hotel Base year operating data for the subject hotel Fixed and variable relationships for revenues and expenses Expected inflation rates for revenues and expenses Hotel Capitalization Software: A discounted cash flow valuation model utilizing the mortgage-equity technique forms the basis for this program. Values are produced using three distinct underwriting criteria: A loan-to-value ratio, in which the size of the mortgage is based on property value. A debt coverage ratio (also known as a debt-service coverage ratio), in which the size of the mortgage is based on property level cash flow, mortgage interest rate, and mortgage amortization. A debt yield, in which the size of the mortgage is based on property level cash flow. By entering the terms of typical lodging financing, along with a forecast of revenue and expense, the program determines the value that provides the stated returns to the mortgage and equity components. The program allows for a variable holding period from four to ten years The program includes an optional model useful during periods of capital market illiquidity that assumes a property refinancing during the holding period

e-poltergeist

E-poltergeist takes over the user’s internet browser, automatically initiating Web searches without their permission. Web-based artwork which explores issues of user control when confronted with complex technological systems, questioning the limits of digital interactive arts as consensual reciprocal systems. e-poltergeist was a major web commission that marked an early stage of research in a larger enquiry by Craighead and Thomson into the relationship between live virtual data, global communications networks and instruction-based art, exploring how such systems can be re-contextualised within gallery environments. e-poltergeist presented the 'viewer' with a singular narrative by using live internet search-engine data that aimed to create a perpetual and virtually unstoppable cycle of search engine results, banner ads and moving windows as an interruption into the normal use of an internet browser. The work also addressed the ‘de-personalisation’ of internet use by sending a series of messages from the live search engine data that seemed to address the user directly: 'Is anyone there?'; 'Can anyone hear me?', 'Please help me!'; 'Nobody cares!' e-poltergeist makes a significant contribution to the taxonomy of new media art by dealing with the way that new media art can re-address notions of existing traditions in art such as appropriation and manipulation, instruction-based art and conceptual art. e-poltergeist was commissioned ($12,000) for 010101: Art in Technological Times, a landmark international exhibition presented by the San Francisco Museum of Modern Art, which bought together leading international practitioners working with emergent technologies, including Tatsuo Miyajima, Janet Cardiff, Brian Eno. Peer recognition of the project in the form of reviews include: Curating New Media. Gateshead: Baltic Centre for Contemporary Art. Cook, Sarah, Beryl Graham and Sarah Martin ISBN: 1093655064; The Wire; http://www.wired.com/culture/lifestyle/news/2000/12/40464 (review by Reena Jana); Leonardo (review Barbara Lee Williams and Sonya Rapoport) http://www.leonardo.info/reviews/feb2001/ex_010101_willrapop.html All the work is developed jointly and equally between Craighead and her collaborator, Jon Thomson, Slade School of Fine Art.