Mycobacterium tuberculosis DinG Is a Structure-specific Helicase That Unwinds G4 DNA IMPLICATIONS FOR TARGETING G4 DNA AS A NOVEL THERAPEUTIC APPROACH

The significance of G-quadruplexes and the helicases that resolve G4 structures in prokaryotes is poorly understood. The Mycobacterium tuberculosis genome is GC-rich and contains >10,000 sequences that have the potential to form G4 structures. In Escherichia coli, RecQ helicase unwinds G4 structures. However, RecQ is absent in M. tuberculosis, and the helicase that participates in G4 resolution in M. tuberculosis is obscure. Here, we show that M. tuberculosis DinG (MtDinG) exhibits high affinity for ssDNA and ssDNA translocation with a 5' -> 3' polarity. Interestingly, MtDinG unwinds overhangs, flap structures, and forked duplexes but fails to unwind linear duplex DNA. Our data with DNase I footprinting provide mechanistic insights and suggest that MtDinG is a 5' -> 3' polarity helicase. Notably, in contrast to E. coli DinG, MtDinG catalyzes unwinding of replication fork and Holliday junction structures. Strikingly, we find that MtDinG resolves intermolecular G4 structures. These data suggest that MtDinG is a multifunctional structure-specific helicase that unwinds model structures of DNA replication, repair, and recombination as well as G4 structures. We finally demonstrate that promoter sequences of M. tuberculosis PE_PGRS2, mce1R, and moeB1 genes contain G4 structures, implying that G4 structures may regulate gene expression in M. tuberculosis. We discuss these data and implicate targeting G4 structures and DinG helicase in M. tuberculosis could be a novel therapeutic strategy for culminating the infection with this pathogen.

Flexibility in flapping foil suppresses meandering of induced jet in absence of free stream

Thrust-generating flapping foils are known to produce jets inclined to the free stream at high Strouhal numbers St = fA/U-infinity, where f is the frequency and A is the amplitude of flapping and U-infinity is the free-stream velocity. Our experiments, in the limiting case of St —> infinity (zero free-stream speed), show that a purely oscillatory pitching motion of a chordwise flexible foil produces a coherent jet composed of a reverse Benard-Karman vortex street along the centreline, albeit over a specific range of effective flap stiffnesses. We obtain flexibility by attaching a thin flap to the trailing edge of a rigid NACA0015 foil; length of flap is 0.79 c where c is rigid foil chord length. It is the time-varying deflections of the flexible flap that suppress the meandering found in the jets produced by a pitching rigid foil for zero free-stream condition. Recent experiments (Marais et al., J. Fluid Mech., vol. 710, 2012, p. 659) have also shown that the flexibility increases the St at which non-deflected jets are obtained. Analysing the near-wake vortex dynamics from flow visualization and particle image velocimetry (PIV) measurements, we identify the mechanisms by which flexibility suppresses jet deflection and meandering. A convenient characterization of flap deformation, caused by fluid-flap interaction, is through a non-dimensional effective stiffness', EI* = 8 EI/(rho V-TEmax(2) s(f) c(f)(3)/2), representing the inverse of the flap deflection due to the fluid-dynamic loading; here, EI is the bending stiffness of flap, rho is fluid density, V-TEmax is the maximum velocity of rigid foil trailing edge, s(f) is span and c(f) is chord length of the flexible flap. By varying the amplitude and frequency of pitching, we obtain a variation in EI* over nearly two orders of magnitude and show that only moderate EI*. (0.1 less than or similar to EI * less than or similar to 1 generates a sustained, coherent, orderly jet. Relatively `stiff' flaps (EI* greater than or similar to 1), including the extreme case of no flap, produce meandering jets, whereas highly `flexible' flaps (EI* less than or similar to 0.1) produce spread-out jets. Obtained from the measured mean velocity fields, we present values of thrust coefficients for the cases for which orderly jets are observed.

Robust design of multiple trailing edge flaps for helicopter vibration reduction: A multi-objective bat algorithm approach

The objective of this study is to determine an optimal trailing edge flap configuration and flap location to achieve minimum hub vibration levels and flap actuation power simultaneously. An aeroelastic analysis of a soft in-plane four-bladed rotor is performed in conjunction with optimal control. A second-order polynomial response surface based on an orthogonal array (OA) with 3-level design describes both the objectives adequately. Two new orthogonal arrays called MGB2P-OA and MGB4P-OA are proposed to generate nonlinear response surfaces with all interaction terms for two and four parameters, respectively. A multi-objective bat algorithm (MOBA) approach is used to obtain the optimal design point for the mutually conflicting objectives. MOBA is a recently developed nature-inspired metaheuristic optimization algorithm that is based on the echolocation behaviour of bats. It is found that MOBA inspired Pareto optimal trailing edge flap design reduces vibration levels by 73% and flap actuation power by 27% in comparison with the baseline design.

Effect of mass loading on ionic polymer metal composite actuators and sensors

Ionic polymer metal composites (IPMC) actuator for flapping insect scale wing is advantageous due to its low mass, high deflection and simple actuation mechanism. Some of the factors that affect the actuation of IPMC are the amount of hydration in the polymer membrane and the environmental conditions such as temperature, humidity etc. In structural design, the attachment of wing on the IPMC actuators is an important concern as the attached wing increases the mass of actuators thereby affecting the parameters like displacement, stiffness and resonant frequencies. Such IPMC actuators have to produce sufficient actuation force and frequency to lift and flap the attached wing. Therefore, it is relevant to study the influence of attachment of wing on the actuator parameters (displacement, resonant frequency, block force and stiffness) and performance of the actuators. This paper is divided into two parts; the first part deals with the modeling of the IPMC actuators for its effect on the level of water uptake and temperature using energy based method. The modeling method adapted is validated with the experimental procedure used to actuate the IPMC. The second part deals with the experimental analysis of IPMC actuation at dry, wet and in water conditions. The effect of end mass loading on the performance of 20 Hz, high frequency actuator (HFA) and 8.7 Hz, low frequency IPMC actuators (LFA) and sensors is studied. The IPMC actuators are attached with IPMC flapping wing at its free end and performance analysis on the attached wing is also carried out.

Alterações estruturais da matriz extracelular do prepúcio humano causadas pelo tabagismo

Os autores têm como objetivo, investigar a matriz extra celular, musculatura lisa e densidade vascular do prepúcio de pacientes tabagistas. Espécimes de prepúcio foram obtidas de 20 jovens adultos (média de idade= 27.2) submetidos a postectomia. Dentre os pacientes analisados, um grupo (n=10) possui história prévia de tabagismo (3 to 13 maços/ano, média = 5.8 3.2), e outro grupo (n=10) formam o grupo controle, não fumantes. A coloração de Tricrômico Masson foi utilizada para quantificar tecido conectivo, musculatura lisa e vasos. A coloração Resorcina-fucsina de Weigert foi utilizada para estabelecer as fibras do sistema elástico e a coloração, Vermelho de Picrosirius para o estudo do colágeno. O estudo estereológico foi realizado utilizando o software Image J, para determinar as densidades volumétricas. Para a análise bioquímica o colágeno total foi determinado em μg de hidroxiprolina por MG de tecido seco. O estudo estatístico foi realizado lançando mão do t-teste (p<0,05). Fibras do sistema elástico de fumantes apresentaram-se aumentadas em 42.5% quando comparado ao grupo controle (p=0,002). Em contraste, musculatura lisa (p=0,42) e densidade vascular (p=0,16) não mostraram nenhuma diferença estatística. Foi realizado uma análise quantitativa utilizando Vermelho de Picrosirius sob luz polarizada, que evidenciou a presença de colágeno tipo I e III, sem diferença estatisticamente significativa. A concentração total do colágeno não mostrou diferença entre tabagistas e o grupo controle. (73.1μg/mg 8.0 vs. 69.2μg/mg 5.9, respectivamente, p=0,23). Tabagismo está associado a um significante aumento de fibras do sistema elástico do tecido prepucial. Estes resultados podem, possivelmente, explicar os altos índices de falha na uretroplastia peniana, com uso de flap de prepúcio em fumantes

Participação do propranolol no reparo tecidual de lesões isquêmicas cutâneas em ratos

Receptores adrenérgicos são amplamente expressos em diferentes tecidos, incluindo na pele. Recentemente foi descoberto que bloqueadores dos receptores β-adrenérgicos são capazes de modular o processo de reparo tecidual. O propranolol é um β-bloqueador não seletivo largamente utilizado na prática clínica para o tratamento de doenças cardiovasculares, parecendo apresentar propriedades antioxidantes. O objetivo desse estudo foi avaliar a resposta de diferentes doses de propranolol durante a lesão isquêmica cutânea em roedores. Ratos Wistar foram tratados com propranolol nas concentrações de 3 e 6 mg/kg. O grupo controle recebeu apenas o veículo e o grupo controle positivo recebeu vitamina E (50 mg/kg/dia). A administração do propranolol iniciou-se no dia da lesão, sendo realizada diariamente até o sacrifício. Incisões bilaterais foram feitas no dorso de cada animal. O flap foi suturado e foram realizadas lesões excisionais totais entre as lesões incisionais. A contração das lesões foi avaliada e os cortes histológicos foram corados com hematoxilina e eosina e vermelho de picrosirius. Foram utilizadas também as seguintes técnicas: Dopplerfluxometria, análises bioquímicas, análise estereológica e expressão de PECAM-1. O grupo tratado com 3 mg de propranolol apresentou uma maior redução na área total da lesão quando comparado ao grupo controle. Da mesma forma, este grupo apresentou um aumento na densidade de vasos sanguíneos, uma maior expressão de PECAM-1 e aumento na perfusão sanguínea na pele isquêmica e no sítio da lesão quando comparado ao grupo controle. Não observamos efeito antioxidante do propranolol neste modelo. Em resumo, nós sugerimos que o propranolol quando administrado na dose de 3 mg/kg/dia foi capaz de modular a angiogênese e melhorar o fechamento da lesão em modelo de roedores

The Fish Funnel: A Trawl Modification to Reduce Fish Escapement

In the Gulf of Mexico there is a need to assess the potential of underutilized fish resource stocks before a commercial fishery develops. Standard sampling trawls used in the Gulf are ineffective for sampling the resource, so larger, high opening, bottom trawls have been introduced. The larger trawls are more effective, but most of the faster swimming fish species are able to escape these nets, especially during haul back. To reduce fish escapement, webbing panels, attached inside the trawls ahead of the cod ends, were tested. Initial tests were conducted with two single panel designs--a fish flap and a "floppa." Neither design reduced fish escapement. The floppa distorted the trawl webbing and actually increased fish escapement. A multi-panel conical funnel design (the fish funnel) was tested and found to increase fish retention by trapping the fish after they passed through it. When used in combination with a technique known as pulsing the trawl, the fish funnel substantially increased trawl catch rates with no indication of fish escapement.

A new species of western Atlantic lizardfish (Teleostei: Synodontidae: Synodus) and resurrection of Synodus bondi Fowler, 1939, as a valid species from the Caribbean with redescriptions of S. bondi, S. foetens (Linnaeus, 1766), and S. intermedius (Agassiz, 1829)

Western Atlantic synodontid species were studied as part of an ongoing effort to reanalyze Caribbean shorefish diversity. A neighbor-joining tree constructed from cytochrome c oxidase I (COI) data revealed 2 highly divergent genetic lineages within both Synodus intermedius (Agassiz, 1829) (Sand Diver) and S. foetens (Linnaeus, 1766) (Inshore Lizardfish). A new species, Synodus macrostigmus, is described for one of the S. intermedius lineages. Synodus macrostigmus and S. intermedius differ in number of lateral-line scales, caudal pigmentation, size of the scapular blotch, and shape of the anterior-nostril flap. Synodus macrostigmus and S. intermedius have overlapping geographic and depth distributions, but S. macrostigmus generally inhabits deeper water (>28 m) than does S. intermedius and is known only from coastal waters of the southeastern United States and the Gulf of Mexico, in contrast to those areas and the Caribbean for S. intermedius. Synodus bondi Fowler, 1939, is resurrected from the synonymy of S. foetens for one of the S. foetens genetic lineages. The 2 species differ in length and shape of the snout, number of anal-fin rays, and shape of the anterior-nostril flap. Synodus bondi and S. foetens co-occur in the central Caribbean, but S. bondi otherwise has a more southerly distribution than does S. foetens. Redescriptions are provided for S. intermedius, S. foetens, and S. bondi. Neotypes are designated for S. intermedius and S. foetens. A revised key to Synodus species in the western Atlantic is presented.

Reproductive biology of the blue swimmer crab (Portunus pelagicus, Decapoda: Portunidae) in five bodies of water on the west coast of Australia

Portunus pelagicus was collected at regular intervals from two marine embayments and two estuaries on the lower west coast of Australia and from a large embayment located approximately 800 km farther north. The samples were used to obtain data on the reproductive biology of this species in three very different environments. Unlike females, the males show a loosening of the attachment of the abdominal flap to the cephalothorax at a prepubertal rather than a pubertal molt. Males become gonadally mature (spermatophores and seminal fluid present in the medial region of the vas deferentia) at a very similar carapace width (CW) to that at which they achieve morphometric maturity, as reflected by a change in the relative size of the largest cheliped. Logistic curves, derived from the prevalence of mature male P. pelagicus, generally had wider confidence limits with morphometric than with gonadal data. This presumably reflects the fact that the morphometric (allometric) method of classifying a male P. pelagicus as mature employs probabilities and is thus indirect, whereas gonadal structure allows a mature male to be readily identified. However, the very close correspondence between the CW50’s derived for P. pelagicus by the two methods implies that either method can be used for management purposes. Portunus pelagicus attained maturity at a significantly greater size in the large embayment than in the four more southern bodies of water, where water temperatures were lower and the densities of crabs and fishing pressure were greater. As a result of the emigration of mature female P. pelagicus from estuaries, the CW50’s derived by using the prevalence of mature females in estuaries represent overestimates for those populations as a whole. Estimates of the number of egg batches produced in a spawning season ranged from one in small crabs to three in large crabs. These data, together with the batch fecundities of different size crabs, indicate that the estimated number of eggs produced by P. pelagicus during the spawning season ranges from about 78,000 in small crabs (CW=80 mm) to about 1,000,000 in large crabs (CW=180 mm).

Design of a pitching and surging point absorber.

The linear dynamics, operation, and engineering aspects of P.S. FROG, a point absorber wave energy conversion buoy, are summarized. The device consists of a floating flap or paddle facing the waves and reacting against them through an interior moving mass in an enlarged section at the bottom of the buoy.

Development of blade profiles for low pressure turbine applications

This paper describes a program of work, largely experimental, which was undertaken with the objective of developing an improved blade profile for the low-pressure turbine in aero-engine applications. Preliminary experiments were conducted using a novel technique. An existing cascade of datum blades was modified to enable the pressure distribution on the suction surface of one of the blades to be altered. Various means, such as shaped inserts, an adjustable flap at the trailing edge, and changing stagger were employed to change the geometry of the passage. These experiments provided boundary layer and lift data for a wide range of suction surface pressure distributions. The data was then used as a guide for the development of new blade profiles. The new blade profiles were then investigated in a low-speed cascade that included a set of moving bars upstream of the cascade of blades to simulate the effect of the incoming wakes from the previous blade row in a multistage turbine environment.

The low Reynolds number aerodynamics of leading edge flaps

Within the low Reynolds number regime at which birds and small air vehicles operate (Re=15,000-500,000), flow is beset with laminar separation bubbles and bubble burst which can lead to loss of lift and early onset of stall. Recent video footage of an eagle's wings in flight reveals an inconspicuous wing feature: the sudden deployment of a row of feathers from the lower surface of the wing to create a leading edge flap. An understanding of the aerodynamic function of this flap has been developed through a series of low speed wind tunnel tests performed on an Eppler E423 aerofoil. Experiments took place at Reynolds numbers ranging from 40000 to 140000 and angles of attack up to 30°. In the lower range of tested Reynolds numbers, application of the flap was found to substantially enhance aerofoil performance by augmenting the lift and limiting the drag at certain incidences. The leading edge flap was determined to act as a transition device at low Reynolds numbers, preventing the formation of separation bubbles and consequently decreasing the speed at which stall occurs during landing and manoeuvring.

Heliconema savala n.sp. (Nematoda:Physalopteridae) from marine fish Lepturacanthus savala (Cuvier) (Trichiuridae) and Psettodes erumei (Schneider) new host (Pisces:Pettodidae) of Physalopterid Nematode, Bulbocephalus inglisi Rasheed, 1966 in Pakistan

Helicnonema savala, n.sp. obtained from the marine fish, Lepturacanthus savala in Sindh coast is distinguished from members of the genus processing in the male 10 tessellated longtitudinal ridges and a spicule ratio 1:15. Females have vulvular flap. Heliconema savala is a morphologically most closely related to Heliconema heliconema. The marine fish, Psettodes erumei is recorded as a new host of Bulbocephalus inglisi.

The influence of geometry on jet plume development

Our recent efforts of using large-eddy simulation (LES) type methods to study complex and realistic geometry single stream and co-flow nozzle jets and acoustics are summarized in this paper. For the LES, since the solver being used tends towards having dissipative qualities, the subgrid scale (SGS) model is omitted, giving a numerical type LES (NLES). To overcome near wall streak resolution problems a near wall RANS (Reynolds averaged Navier-Stokes) model is smoothly blended in the LES making a hybrid RANS-NLES approach. Several complex nozzle geometries including the serrated (chevron) nozzle, realistic co-axial nozzles with eccentricity, pylon and wing-flap are discussed. The hybrid RANS-NLES simulations show encouraging predictions for the chevron jets. The chevrons are known to increase the high frequency noise at high polar angles, but decrease the low frequency noise at lower angles. The deflection effect of the potential core has an important mechanism of noise reduction. As for co-axial nozzles, the eccentricity, the pylon and the deployed wing-flap are shown to influence the flow development, especially the former to the length of potential core and the latter two having a significant impact on peak turbulence levels and spreading rates. The studies suggest that complex and real geometry effects are influential and should be taken into count when moving towards real engine simulations. © 2012 Elsevier Ltd. All rights reserved.

On the effects of turbulence modelling in design optimisation for high-lift devices

Aerodynamic shape optimisation is being increasingly utilised as a design tool in the aerospace industry. In order to provide accurate results, design optimisation methods rely on the accuracy of the underlying CFD methods applied to obtain aerodynamic forces for a given configuration. Previous studies of the authors have highlighted that the variation of the order of accuracy of the CFD solver with a fixed turbulence model affects the resulting optimised airfoil shape for a single element airfoil. The accuracy of the underlying CFD model is even more relevant in the context of high-lift configurations where an accurate prediction of flow is challenging due to the complex flow physics involving transition and flow separation phenomena. This paper explores the effect of the fidelity of CFD results for a range of turbulence models within the context of the computational design of aircraft configurations. The NLR7301 multi-element airfoil (main wing and flap) is selected as the baseline configuration, because of the wealth of experimental an computational results available for this configuration. An initial validation study is conducted in order to establish optimal mesh parameters. A bi-objective shape optimisation problem is then formulated, by trying to reveal the trade-off between lift and drag coefficients at high angles of attack. Optimisation of the airfoil shape is performed with Spalart-Allmaras, k - ω SST and k - o realisable models. The results indicate that there is consistent and complementary impact to the optimum level achieved from all the three different turbulence models considered in the presented case study. Without identifying particular superiority of any of the turbu- lence models, we can say though that each of them expressed favourable influence towards different optimality routes. These observations lead to the exploration of new avenues for future research. © 2012 AIAA.