833 research outputs found

    Optimal design of an aeroelastic wing structure with seamless control surfaces

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    This article presents an investigation into the concept and optimal design of a lightweight seamless aeroelastic wing (SAW) structure for small air vehicles. Attention has been first focused on the design of a hingeless flexible trailing edge (TE) control surface. Two innovative design features have been created in the SAW TE section: an open sliding TE and a curved beam and disc actuation mechanism. This type of actuated TE section allows for the SAW having a camber change in a desirable shape and minimum control power demand. This design concept has been simulated numerically and demonstrated by a test model. For a small air vehicle of large sweep back wing, it is noted that significant structural weight saving can be achieved. However, further weight saving is mainly restricted by the aeroelastic stability and minimum number of carbon/epoxy plies in a symmetric layup rather than the structural strength. Therefore, subsequent effort was made to optimize the primary wing box structure. The results show that an initial structural weight can be reduced significantly under the strength criterion. The resulting reduction of the wing box stiffness and aeroelastic stability and control effectiveness can be improved by applying the aeroelastic tailoring. Because of the large swept angle and resulting lightweight and highly flexible SAW, geometrical non-linearity and large bending-torsion aeroelastic coupling have been considered in the analysis

    Study of some aspects of managerial communication

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    This research is concerned with factors which improve or inhibit effective communication between managers in organisations.An appraisal of the literature is carried out and a framework of the main variables affecting effective communication is suggested. This framework is tested within seven operating companies and the results discussed. Of particular interest is the finding that an individual manager's career achievement is related to the accuracy with which he communicates with his superior. The study also isolates factors affecting this accuracy and shows for example that when subordinates trust their superiors more accurate communication results, while strong desires for promotion reduce accuracy. These secondary variables are then examined to indicate how individual managers and organisations as a whole might improve their communicating effectiveness.Finally suggestions are made to develop the methods used in the present study and to point out areas which seem worthy of future research

    Friend or foe? The current epidemiologic evidence on selenium and human cancer risk.

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    Scientific opinion on the relationship between selenium and the risk of cancer has undergone radical change over the years, with selenium first viewed as a possible carcinogen in the 1940s then as a possible cancer preventive agent in the 1960s-2000s. More recently, randomized controlled trials have found no effect on cancer risk but suggest possible low-dose dermatologic and endocrine toxicity, and animal studies indicate both carcinogenic and cancer-preventive effects. A growing body of evidence from human and laboratory studies indicates dramatically different biological effects of the various inorganic and organic chemical forms of selenium, which may explain apparent inconsistencies across studies. These chemical form-specific effects also have important implications for exposure and health risk assessment. Overall, available epidemiologic evidence suggests no cancer preventive effect of increased selenium intake in healthy individuals and possible increased risk of other diseases and disorders

    Stable conditional expression and effect of C/EBPβ-LIP in adipocytes using the pSLIK system

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    Murine 3T3-L1 adipocytes are widely used as a cellular model of obesity. However, whereas transfection of 3T3-L1 preadipocytes is straightforward, ectopic gene expression in mature 3T3-L1 adipocytes has proved challenging. Here, we used the pSLIK vector system to generate stable doxycycline-inducible expression of the liver-enriched inhibitor protein isoform of CCAAT/enhancer binding protein (C/EBP) {beta} (C/EBP{beta}-LIP) in fully differentiated 3T3-L1 adipocytes. Because overexpression of C/EBP{beta}-LIP impairs adipocyte differentiation, the C/EBP{beta}-LIP construct was first integrated in 3T3-L1 preadipocytes but expression was induced only when adipocytes were fully differentiated. Increased C/EBP{beta}-LIP in mature adipocytes down-regulated C/EBP{beta} target genes including 11{beta}-hydroxysteroid dehydrogenase type 1, phosphoenolpyruvate carboxykinase and fatty acid binding protein 4, but had no effect on asparagine synthetase, demonstrating that transcriptional down-regulation by C/EBP{beta}-LIP in 3T3-L1 adipocytes is not a general effect. Importantly, these genes were modulated in a similar manner in adipose tissue of mice with genetically increased C/EBP{beta}-LIP levels. The use of the pSLIK system to conditionally express transgenes in 3T3-L1 cells could be a valuable tool to dissect adipocyte physiology

    Multivariate frailty models for multi-type recurrent event data and its application to cancer prevention trial

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    Multi-type recurrent event data arise in many situations when two or more different event types may occur repeatedly over an observation period. For example, in a randomized controlled clinical trial to study the efficacy of nutritional supplements for skin cancer prevention, there can be two types of skin cancer events occur repeatedly over time. The research objectives of analyzing such data often include characterizing the event rate of different event types, estimating the treatment effects on each event process, and understanding the correlation structure among different event types. In this paper, we propose the use of a proportional intensity model with multivariate random effects to model such data. The proposed model can take into account the dependence among different event types within a subject as well as the treatment effects. Maximum likelihood estimates of the regression coefficients, variance-covariance components, and the nonparametric baseline intensity function are obtained via a Monte Carlo Expectation-Maximization (MCEM) algorithm. The expectation step of the algorithm involves the calculation of the conditional expectations of the random effects by using the Metropolis-Hastings sampling. Our proposed method can easily handle recurrent event data that have more than two types of events. Simulation studies were used to validate the performance of the proposed method, followed by an application to the skin cancer prevention data.</p

    Gene drive: past, present and future roads to vertebrate biocontrol

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    Scientists have long sought a technology to humanely control populations of damaging invasive pests in a species-specific manner. Gene drive technology could see this become a reality. This review charts the twists and turns on the road to developing gene drives in vertebrates. We focus on rodents, as these will likely be the first targets, and trace the journey from the early understanding of selfish genetic elements to engineering gene drives in mice; before discussing future research focuses and the crucial role that public perception and governance will play in the application of this technology. The realisation of robust gene drive strategies in vertebrate pests has the potential to revolutionise biocontrol

    Calorie Labelling on Menus: Are There Adverse Outcomes Related to Eating Disturbances?

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    Obesity is a serious health concern in Canada. Thirty-seven percent of the population are overweight and approximately 25% are obese. Increased energy intake from eating outside the home has contributed to the rise in obesity. Approximately one quarter of all Canadians consume food in a quick-service restaurant on a given day. Although not all food consumed outside the home is of poor nutritional quality, restaurants generally offer foods that have larger portions, and are higher in calories and fat. Menu labelling has the potential to promote healthier eating by informing consumers about the calorie content of meals. Currently, there is little or no research on possible unintended effects of displaying calorie information at restaurants and quick-service establishments. In particular, it is unclear how such information would affect individuals with clinical eating disorders, or those with eating disturbances. In the current study, 325 female undergraduate students over the age of 16 took part in a 10-minute paper-based survey after meal consumption in a cafeteria on the University of Waterloo campus. The study employed a pre-post design, with data collection occurring in paired and unpaired samples one month before calorie information was added to menu boards, and one week after. In the 299 participants with usable data the prevalence of eating disturbances (EAT-26 > 20) was 10.4%. Calorie consumption decreased from baseline (mean=678.2 kcal) to follow-up (mean=602.3 kcal; p=0.049). There were no statistically significant changes in any of the other outcomes from baseline to follow-up, including body image satisfaction, anxiety, mood, and frequency of engaging in unhealthy behaviours. Additionally, there were no interactions between eating disturbance level and time, which suggests that calorie labels did not differentially affect those in this high-risk population. Overall, no adverse outcomes related to eating disturbances were associated with the implementation of calorie labels in this at-risk population. The results have potential implications for menu labelling regulations

    Pyrimidine biosynthesis is not an essential function for trypanosoma brucei bloodstream forms

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    &lt;p&gt;Background: African trypanosomes are capable of both pyrimidine biosynthesis and salvage of preformed pyrimidines from the host, but it is unknown whether either process is essential to the parasite.&lt;/p&gt; &lt;p&gt;Methodology/Principal Findings: Pyrimidine requirements for growth were investigated using strictly pyrimidine-free media, with or without single added pyrimidine sources. Growth rates of wild-type bloodstream form Trypanosoma brucei brucei were unchanged in pyrimidine-free medium. The essentiality of the de novo pyrimidine biosynthesis pathway was studied by knocking out the PYR6-5 locus that produces a fusion product of orotate phosphoribosyltransferase (OPRT) and Orotidine Monophosphate Decarboxylase (OMPDCase). The pyrimidine auxotroph was dependent on a suitable extracellular pyrimidine source. Pyrimidine starvation was rapidly lethal and non-reversible, causing incomplete DNA content in new cells. The phenotype could be rescued by addition of uracil; supplementation with uridine, 2′deoxyuridine, and cytidine allowed a diminished growth rate and density. PYR6-5−/− trypanosomes were more sensitive to pyrimidine antimetabolites and displayed increased uracil transport rates and uridine phosphorylase activity. Pyrimidine auxotrophs were able to infect mice although the infection developed much more slowly than infection with the parental, prototrophic trypanosome line.&lt;/p&gt; &lt;p&gt;Conclusions/Significance: Pyrimidine salvage was not an essential function for bloodstream T. b. brucei. However, trypanosomes lacking de novo pyrimidine biosynthesis are completely dependent on an extracellular pyrimidine source, strongly preferring uracil, and display reduced infectivity. As T. brucei are able to salvage sufficient pyrimidines from the host environment, the pyrimidine biosynthesis pathway is not a viable drug target, although any interruption of pyrimidine supply was lethal.&lt;/p&gt

    Efficient TALEN-mediated gene knockout in livestock

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    Transcription activator-like effector nucleases (TALENs) are programmable nucleases that join FokI endonuclease with the modular DNA-binding domain of TALEs. Although zinc-finger nucleases enable a variety of genome modifications, their application to genetic engineering of livestock has been slowed by technical limitations of embryo-injection, culture of primary cells, and difficulty in producing reliable reagents with a limited budget. In contrast, we found that TALENs could easily be manufactured and that over half (23/36, 64%) demonstrate high activity in primary cells. Cytoplasmic injections of TALEN mRNAs into livestock zygotes were capable of inducing gene KO in up to 75% of embryos analyzed, a portion of which harbored biallelic modification. We also developed a simple transposon coselection strategy for TALEN-mediated gene modification in primary fibroblasts that enabled both enrichment for modified cells and efficient isolation of modified colonies. Coselection after treatment with a single TALEN-pair enabled isolation of colonies with mono- and biallelic modification in up to 54% and 17% of colonies, respectively. Coselection after treatment with two TALEN-pairs directed against the same chromosome enabled the isolation of colonies harboring large chromosomal deletions and inversions (10% and 4% of colonies, respectively). TALEN-modified Ossabaw swine fetal fibroblasts were effective nuclear donors for cloning, resulting in the creation of miniature swine containing mono- and biallelic mutations of the LDL receptor gene as models of familial hypercholesterolemia. TALENs thus appear to represent a highly facile platform for the modification of livestock genomes for both biomedical and agricultural applications
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