308 research outputs found
Optimal design of an aeroelastic wing structure with seamless control surfaces
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
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.
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
Pyrimidine biosynthesis is not an essential function for trypanosoma brucei bloodstream forms
<p>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.</p>
<p>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.</p>
<p>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.</p>
Efficient TALEN-mediated gene knockout in livestock
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
Cytokinesis in bloodstream stage Trypanosoma brucei requires a family of katanins and spastin
Microtubule severing enzymes regulate microtubule dynamics in a wide range of organisms and are implicated in important cell cycle processes such as mitotic spindle assembly and disassembly, chromosome movement and cytokinesis. Here we explore the function of several microtubule severing enzyme homologues, the katanins (KAT80, KAT60a, KAT60b and KAT60c), spastin (SPA) and fidgetin (FID) in the bloodstream stage of the African trypanosome parasite, Trypanosoma brucei. The trypanosome cytoskeleton is microtubule based and remains assembled throughout the cell cycle, necessitating its remodelling during cytokinesis. Using RNA interference to deplete individual proteins, we show that the trypanosome katanin and spastin homologues are non-redundant and essential for bloodstream form proliferation. Further, cell cycle analysis revealed that these proteins play essential but discrete roles in cytokinesis. The KAT60 proteins each appear to be important during the early stages of cytokinesis, while downregulation of KAT80 specifically inhibited furrow ingression and SPA depletion prevented completion of abscission. In contrast, RNA interference of FID did not result in any discernible effects. We propose that the stable microtubule cytoskeleton of T. brucei necessitates the coordinated action of a family of katanins and spastin to bring about the cytoskeletal remodelling necessary to complete cell divisio
A novel piggybac transposon inducible expression system identifies a role for akt signalling in primordial germ cell migration
In this work, we describe a single piggyBac transposon system containing both a tet-activator and a doxycycline-inducible expression cassette. We demonstrate that a gene product can be conditionally expressed from the integrated transposon and a second gene can be simultaneously targeted by a short hairpin RNA contained within the transposon, both in vivo and in mammalian and avian cell lines. We applied this system to stably modify chicken primordial germ cell (PGC) lines in vitro and induce a reporter gene at specific developmental stages after injection of the transposon-modified germ cells into chicken embryos. We used this vector to express a constitutively-active AKT molecule during PGC migration to the forming gonad. We found that PGC migration was retarded and cells could not colonise the forming gonad. Correct levels of AKT activation are thus essential for germ cell migration during early embryonic development
Absolute Oral Bioavailability of Creatine Monohydrate in Rats: Debunking a Myth
Creatine is an ergogenic compound used by athletes to enhance performance. Supplementation with creatine monohydrate (CM) has been suggested for musculoskeletal and neurological disorders. Until now, little is known about its pharmacokinetic profile. Our objective was to determine the oral bioavailability of CM and the influence of dose on oral absorption. Rats were dosed orally with low dose (10 mg/kg) or high dose (70 mg/kg
Optimum design and testing of a postbuckled stiffened panel
The efficient, industrially used, linear elastic
preliminary design software VICONOPT is employed
to design a stiffened panel with a post-buckled
reserve of strength. The initial buckling mode is a
local skin mode in longitudinal compression with
allowance being made for the effects of an initial
overall imperfection. The resulting panel has been
analyzed using the non-linear FE package ABAQUS
and four laboratory specimens have been tested to
failure. The similarity of the experimental failure with
the VICONOPT and ABAQUS predictions suggests
that VICONOPT can give a satisfactory preliminary
design. While neither model matches completely the
boundary conditions found in a real aircraft
compression panel, it is suggested that the
VICONOPT model may be a better representation
than either the ABAQUS model or the experimental
tests
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