Experimental analysis of composite single-lap joints using digital image correlation and comparison with theoretical models

The demand for energy efficient, low weight structures has boosted the use of composite structures assembled using increased quantities of structural adhesives. Bonded structures may be subjected to severe working environments such as high temperature and moisture due to which the adhesive gets degraded over a period of time. This reduces the strength of a joint and leads to premature failure. Measurement of strains in the adhesive bondline at any point of time during service may be beneficial as an assessment can be made on the integrity of a joint and necessary preventive actions may be taken before failure. This paper presents an experimental approach of measuring peel and shear strains in the adhesive bondline of composite single-lap joints using digital image correlation. Different sets of composite adhesive joints with varied bond quality were prepared and subjected to tensile load during which digital images were taken and processed using digital image correlation software. The measured peel strain at the joint edge showed a rapid increase with the initiation of a crack till failure of the joint. The measured strains were used to compute the corresponding stresses assuming a plane strain condition and the results were compared with stresses predicted using theoretical models, namely linear and nonlinear adhesive beam models. A similar trend in stress distribution was observed. Further comparison of peel and shear strains also exhibited similar trend for both healthy and degraded joints. Maximum peel stress failure criterion was used to predict the failure load of a composite adhesive joint and a comparison was made between predicted and actual failure loads. The predicted failure loads from theoretical models were found to be higher than the actual failure load for all the joints.

Capturability of augmented proportional navigation (APN) guidance with nonlinear engagement dynamics

Proportional Navigation (PN) and its variants are widely used guidance philosophies. However, in the presence of target maneuver, PN guidance law is effective only for a restrictive set of initial geometries. To account for target maneuvers, the concept of Augmented Proportional Navigation (APN) guidance law was introduced and analyzed in a linearized interceptor-target engagement framework presented in literature. However, there is no work in the literature, that addresses the capturability performance of the APN guidance law in a nonlinear engagement framework. This paper presents such an analysis and obtains the conditions for capturability. It also shows that a shorter time of interception is obtained when APN is formulated in the nonlinear framework as proposed in this paper. Simulation results are given to support the theoretical findings.

Mitochondria-Targeting Oxidovanadium(IV) Complex as a Near-IR Light Photocytotoxic Agent

Oxidovanadium(IV) complexes VO(L-1)(phen)]Cl (1) and VO(L-2)(L-3)]Cl (2), in which HL1 is 2-{(benzimidazol-2-yl)methylimino]-methyl}phenol (sal-ambmz), HL2 is 2-({1-(anthracen-9-yl)methyl]-benzimidazol-2-yl}methylimino)-met hyl]phenol (sal-an-ambmz), phen is 1,10-phenanthroline and L-3 is dipyrido3,2-a:2,3-c]phenazine (dppz) conjugated to a Gly-Gly-OMe dipeptide moiety, were prepared, characterized, and their DNA binding, photoinduced DNA-cleavage, and photocytotoxic properties were studied. Fluorescence microscopy studies were performed by using complex 2 in HeLa and HaCaT cells. Complex 1, structurally characterized by X-ray crystallography, has a vanadyl group in VO2N4 core with the VO2+ moiety bonded to N,N-donor phen and a N,N,O-donor Schiff base. Complex 2, having an anthracenyl fluorophore, showed fluorescence emission bands at 397, 419, and 443nm. The complexes are redox-active exhibiting the V(IV)/V(III) redox couple near -0.85V versus SCE in DMF 0.1M tetrabutylammonium perchlorate (TBAP). Complex 2, having a dipeptide moiety, showed specific binding towards poly(dAdT)(2) sequence. The dppz-Gly-Gly-OMe complex showed significant DNA photocleavage activity in red light of 705nm through a hydroxyl radical ((OH)-O-.) pathway. Complex 2 showed photocytotoxicity in HaCaT and HeLa cells in visible light (400-700nm) and red light (620-700nm), however, the complex was less toxic in the dark. Fluorescence microscopy revealed the localization of complex 2 primarily in mitochondria. Apoptosis was found to occur inside mitochondria (intrinsic pathway) caused by ROS generation.

Carbohydrate-appended photocytotoxic (imidazophenanthroline)-oxovanadium(IV) complexes for cellular targeting and imaging

Oxovanadium(IV) complexes VO(aip)(L)](ClO4)(2) (L = phtpy, 1; stpy, 2) and VO(pyip)(L)](ClO4)(2) (L = phtpy, 3; stpy, 4), where aip is 2-(9-anthryl)-1H-imidazo4,5-f]1,10] phenanthroline, pyip is 2-(1-pyrenyl)-1Himidazo4,5-f]1,10] phenanthroline, phtpy is (4'-phenyl)-2,2': 6',2 `'-terpyridine and stpy is (2,2': 6', 2 `'-terpyridin-4'-oxy) ethyl-beta-D-glucopyranoside, were prepared, characterized and their DNA binding and photocleavage activity, cellular uptake and photocytotoxicity in visible light were studied. The complexes are avid binders to calf thymus DNA (K-b similar to 10(5) mol(-1)). They efficiently cleave pUC19 DNA in red light of 705 nm via the formation of HO center dot species. The glucose appended complexes 2 and 4 showed higher photocytotoxicity in HeLa and Hep G2 cells over the normal HEK 293T cells. No such preference was observed for the phtpy complexes 1 and 3. No significant difference in IC50 values was observed for the HEK 293T cells. Cell cycle analysis showed that the glucose appended complexes 2 and 4 are more photocytotoxic in cancer cells than in normal cells. Fluorescence microscopy was done to study the cellular localization of complex 4 having a pendant pyrenyl group.

Image deconvolution research: its scope and importance in live cell microscopy

Fluorescence microscopy has become an indispensable tool in cell biology research due its exceptional specificity and ability to visualize subcellular structures with high contrast. It has highest impact when applied in 4D mode, i.e. when applied to record 3D image information as a function of time, since it allows the study of dynamic cellular processes in their native environment. The main issue in 4D fluorescence microscopy is that the phototoxic effect of fluorescence excitation gets accumulated during 4D image acquisition to the extent that normal cell functions are altered. Hence to avoid the alteration of normal cell functioning, it is required to minimize the excitation dose used for individual 2D images constituting a 4D image. Consequently, the noise level becomes very high degrading the resolution. According to the current status of technology, there is a minimum required excitation dose to ensure a resolution that is adequate for biological investigations. This minimum is sufficient to damage light-sensitive cells such as yeast if 4D imaging is performed for an extended period of time, for example, imaging for a complete cell cycle. Nevertheless, our recently developed deconvolution method resolves this conflict forming an enabling technology for visualization of dynamical processes of light-sensitive cells for durations longer than ever without perturbing normal cell functioning. The main goal of this article is to emphasize that there are still possibilities for enabling newer kinds of experiment in cell biology research involving even longer 4D imaging, by only improving deconvolution methods without any new optical technologies.

Sparse Recovery Methods Hold Promise for Diffuse Optical Tomographic Image Reconstruction

The sparse recovery methods utilize the l(p)-normbased regularization in the estimation problem with 0 <= p <= 1. These methods have a better utility when the number of independent measurements are limited in nature, which is a typical case for diffuse optical tomographic image reconstruction problem. These sparse recovery methods, along with an approximation to utilize the l(0)-norm, have been deployed for the reconstruction of diffuse optical images. Their performancewas compared systematically using both numerical and gelatin phantom cases to show that these methods hold promise in improving the reconstructed image quality.

Targeting the dopamine receptor in schizophrenia: investigational drugs in Phase III trials

Introduction: Antipsychotic drugs date back to the 1950s and chlorpromazine. Soon after, it was established that blockade of dopamine and, in particular, the D-2 receptor was central to this effect. Dopamine continues to represent a critical line of investigation, although much of the work now focuses on its potential in other symptom domains. Areas covered: A search was carried out for investigational drugs using the key words `dopamine', `schizophrenia' and `Phase III' in an American clinical trial registry (clinicaltrials.gov), published articles using the National Library of Medicine's PubMed database, and supplemented results with a manual search of cross-references and conference abstracts. Drugs were excluded that were already FDA approved. Expert opinion: There remains interest, albeit diminished, in developing better antipsychotic compounds. The greatest enthusiasm currently centres on dopamine's role in negative and cognitive symptom domains. With theories conceptualising hypodopaminergic activity as underlying these deficits, considerable effort is focused on drug strategies that will enhance dopamine activity. Finally, a small body of research is investigating dopaminergic compounds vis-a-vis side-effect treatments. In domains beyond psychosis, however, dopamine arguably is not seen as so central, reflected in considerable research following other lines of investigation.

Carbohydrate-Appended Tumor Targeting Iron(III) Complexes Showing Photocytotoxicity in Red Light

Glucose-appended photocytotoxic iron(III) complexes of a tridentate Schiff base phenolate ligand Fe(bpyag) (L)] (NO3) (1-3), where bpyag is N,N-bis(2- pyridylmethyl)-2-aminoethyl-beta-D-glucopyranoside and H2L is 3-(2-hydroxyphenylimino)-1-phenylbutan-1-one (H(2)phap) in 1, 3-(2-hydroxyphenylimino)-9-anthrylbutan-1-one (H(2)anap) 2, and 3- (2-hydroxyphenylimino)-1-pyrenylbutan-1-one (H(2)pyap) in 3, were synthesized and characterized. The complex Fe(dpma)(anapn(NO3) (4), having bis-(2-pyridylmethyl)benzylamine (dpma), in which the glucose moiety of bpyag is substituted by a phenyl group, was used as a control, and the complex Fe(dpma)(anap)](PF6) (4a) was structurally characterized by X-ray crystallography. The structure shows a FeN4O2 core in a distorted octahedral geometry. The high-spin iron(III) complexes with magnetic moment value of similar to 5.9 mu(B) showed a low-energy phenolate-to-Fe(III) charge-transfer (CT) absorption band as a shoulder near 500 nm with a tail extending to 700 nm and an irreversible Fe(III)-Fe(II) redox couple near -0.6 V versus saturated calomel electrode. The complexes are avid binders to calf thymus DNA and showed photocleavage of supercoiled pUC19 DNA in red (647 nm) and green (532 nm) light. Complexes 2 and 3 displayed significant photocytotoxicity in red light, with an IC50 value of similar to 20 mu M in HeLa and HaCaT cells, and no significant toxicity in dark. The cell death is via an apoptotic pathway, by generation of reactive oxygen species. Preferential internalization of the carbohydrate-appended complexes 2 and 3 was evidenced in HeLa cells as compared to the control complex 4. A 5-fold increase in the cellular uptake was observed for the active complexes in HeLa cells. The photophysical properties of the complexes are rationalized from the density functional theory calculations.

Mitochondria targeting Photocytotoxic Oxidovanadium( IV) Complexes of Curcumin and ( Acridinyl) dipyridophenazine in Visible Light

Oxidovanadium(IV) complexes, VO(acac)(L)Cl] (1), VO(cur)(L)Cl] (2), and VO(scur)(L)Cl] (3) {acac = acetylacetonate, cur = curcumin monoanion, scur = diglucosylcurcumin monoanion, L = 11-(9-acridinyl)dipyrido3, 2-a:2',3'-c]phenazine (acdppz)}, were prepared and characterized. The complexes are non-electrolytic in DMF and 1:1 electrolytic in aqueous DMF. The one-electron paramagnetic complexes showed a d-d band near 725 nm in aqueous DMF and green emission near 520 nm in aqueous DMSO. The complexes exhibited an irreversible V-IV/V-III redox response near -0.85 V versus SCE in aqueous DMF. The complexes showed good binding strengths to calf thymus DNA (K-b: 3.1x10(5)-9.6x10(5) M-1) and efficient pUC19 DNA photocleavage activity in red light of 705 and 785 nm by singlet oxygen (O-1(2)) pathway. Complexes 1 and 2 exhibited significant photocytotoxicity (IC50: 0.1-1.0 M) in visible light (400-700 nm) with low dark toxicity (IC50: >20 M) in HeLa and HaCaT cells. Complex 3 was cytotoxic in both light and dark. DNA ladder formation experiments indicated cell death via apoptotic pathway. Confocal microscopy done with 1 and 2 revealed primarily cytosolic localization of the complexes with significant presence of the complex in the mitochondria as evidenced from the imaging data using mitotracker red.

Advances in the molecular design of potential anticancer agents via targeting of human telomeric DNA

Telomerases are an attractive drug target to develop new generation drugs against cancer. A telomere appears from the chromosomal termini and protects it from double-stranded DNA degradation. A short telomere promotes genomic instability, like end-to-end fusion and regulates the over-expression of the telomere repairing enzyme, telomerase. The telomerase maintains the telomere length, which may lead to genetically abnormal situations, leading to cancer. Thus, the design and synthesis of an efficient telomerase inhibitor is a viable strategy toward anticancer drugs development. Accordingly, small molecule induced stabilization of the G-quadruplex structure, formed by the human telomeric DNA, is an area of contemporary scientific art. Several such compounds efficiently stabilize the G-quadruplex forms of nucleic acids, which often leads to telomerase inhibition. This Feature article presents the discovery and development of the telomere structure, function and evolution in telomere targeted anticancer drug design and incorporates the recent advances in this area, in addition to discussing the advantages and disadvantages in the methods, and prospects for the future.

Multi-Temporal Satellite Image Analysis Using Gene Expression Programming

This paper discusses an approach for river mapping and flood evaluation to aid multi-temporal time series analysis of satellite images utilizing pixel spectral information for image classification and region-based segmentation to extract water covered region. Analysis of Moderate Resolution Imaging Spectroradiometer (MODIS) satellite images is applied in two stages: before flood and during flood. For these images the extraction of water region utilizes spectral information for image classification and spatial information for image segmentation. Multi-temporal MODIS images from ``normal'' (non-flood) and flood time-periods are processed in two steps. In the first step, image classifiers such as artificial neural networks and gene expression programming to separate the image pixels into water and non-water groups based on their spectral features. The classified image is then segmented using spatial features of the water pixels to remove the misclassified water region. From the results obtained, we evaluate the performance of the method and conclude that the use of image classification and region-based segmentation is an accurate and reliable for the extraction of water-covered region.

Studies and Evaluation of EIT Image Reconstruction in EIDORS with Simulated Boundary Data

Simulated boundary potential data for Electrical Impedance Tomography (EIT) are generated by a MATLAB based EIT data generator and the resistivity reconstruction is evaluated with Electrical Impedance Tomography and Diffuse Optical Tomography Reconstruction Software (EIDORS). Circular domains containing subdomains as inhomogeneity are defined in MATLAB-based EIT data generator and the boundary data are calculated by a constant current simulation with opposite current injection (OCI) method. The resistivity images reconstructed for different boundary data sets and images are analyzed with image parameters to evaluate the reconstruction.

Targeting Mycobacterium tuberculosis nucleoid-associated protein HU with structure-based inhibitors

The nucleoid-associated protein HU plays an important role in maintenance of chromosomal architecture and in global regulation of DNA transactions in bacteria. Although HU is essential for growth in Mycobacterium tuberculosis (Mtb), there have been no reported attempts to perturb HU function with small molecules. Here we report the crystal structure of the N-terminal domain of HU from Mtb. We identify a core region within the HU-DNA interface that can be targeted using stilbene derivatives. These small molecules specifically inhibit HU-DNA binding, disrupt nucleoid architecture and reduce Mtb growth. The stilbene inhibitors induce gene expression changes in Mtb that resemble those induced by HU deficiency. Our results indicate that HU is a potential target for the development of therapies against tuberculosis.

Solar thermal power system augmented with LHP

The present work reports the study of the bubble formation dynamics in the compensation chamber (CC) of the evaporator in Loop Heat Pipes. A series of experiments were conducted at different heat loads and bubbles in the CC were visualized. Bubbles diameter, frequency and velocity were measured and correlated against heat loads. Temperatures were measured at various locations and heat transfer coefficient was calculated. Performance of the LHP evaporator was evaluated at different heat loads. (C) 2013 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license

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.