Derivation of the stress concentrations at holes in orthotropic plates using thermoelastic stress analysis

An experimental study of the stress distribution around holes in orthotropic composite laminates has been conducted using thermoelastic stress analysis (TSA). Quantitative thermoelastic studies of stress concentrations in metallic plates is a straightforward matter, all that is required is the ratio of the response from the hole and a far-field reading. For orthotropic materials the situation is more complex as the response is not simply proportional to the sum of the principal stresses. In general the thermoelastic response of an orthotropic laminate is a function of the stresses in the principal surface material directions and the associated coefficient of thermal expansion. The approach in this paper is to obtain ‘stress factors’ at the hole and identify the maxima in the plot. Specimens manufactured from a variety of different laminate lay-ups (unidirectional (UD), cross-ply (CP), angle-ply (AP) and quasi-isotropic (QI)) are considered. In all these cases the principal stress directions at the hole are not coincident with the principal material directions and it is a challenging proposition to derive meaningful stress data from these configurations. To validate the approach the experimental data are compared to analytical models. To better understand the nature of the response finite element models are produced that mimic the thermoelastic response

Identification of the source of the thermoelastic response from orthotropic laminated composites

In previous work, a series of theoretical considerations have been made aimed at identifying the source and assessing prominent factors influencing the thermoelastic response from laminated composites. In this paper four different methods of interpreting the data are investigated and the theoretical thermoelastic response is compared to experimental data to identify the source of the thermoelastic response

Intense violet–blue emission and paramagnetism of nanocrystalline Gd3+ doped ZnO ceramics

Nanocrystalline Zn1-xGdxO (x = 0, 0.02, 0.04, 0.06, and 0.08) ceramics were synthesized by ball milling and subsequent solid-state reaction. The transmission electron microscopy (TEM) micrograph of as synthesized samples revealed the formation of crystallites with an average diameter of 60 nm, and the selected area electron diffraction (SAED) pattern confirmed the formation of wurtzite structure. A red shift in the band gap was observed with increasing Gd3+ concentration. The photoluminescence of nanocrystalline Gd3+ doped ZnO exhibited a strong violet–blue emission. Concentration dependence of the emission intensity of Gd3+ in ZnO was studied, and the critical concentration was found to be 4 mol% of Gd3+. The Gd3+ doped ZnO exhibited paramagnetic behavior at room temperature, and the magnetic moment increased with Gd3+ concentration

Discovery of FNDR-20123, a histone deacetylase inhibitor for the treatment of Plasmodium falciparum malaria

BACKGROUND: Emergence of anti-malarial drug resistance and perpetual increase in malaria incidence necessitates the development of novel anti-malarials. Histone deacetylases (HDAC) has been shown to be a promising target for malaria, despite this, there are no HDAC inhibitors in clinical trials for malaria treatment. This can be attributed to the poor pharmacokinetics, bioavailability and selectivity of the HDAC inhibitors. METHODS: A collection of HDAC inhibitors were screened for anti-malarial activity, and the best candidate was profiled in parasite-killing kinetics, growth inhibition of sensitive and multi-drug resistant (MDR) strains and against gametocytes. Absorption, distribution, metabolism and excretion pharmacokinetics (ADME-PK) parameters of FNDR-20123 were determined, and in vivo efficacy was studied in a mouse model for Plasmodium falciparum infection. RESULTS: A compound library of HDAC inhibitors (180 in number) was screened for anti-malarial activity, of which FNDR-20123 was the most potent candidate. The compound had been shown to inhibit Plasmodium HDAC with IC50 of 31 nM and human HDAC with IC50 of 3 nM. The IC50 obtained for P. falciparum in asexual blood-stage assay was 42 nM. When compared to atovaquone and pyrimethamine, the killing profiles of FNDR-20123 were better than atovaquone and comparable to pyrimethamine. The IC50 values for the growth inhibition of sensitive and MDR strains were similar, indicating that there is no cross-resistance and a low risk of resistance development. The selected compound was also active against gametocytes, indicating a potential for transmission control: IC50 values being 190 nM for male and > 5 microM for female gametocytes. FNDR-20123 is a stable candidate in human/mouse/rat liver microsomes (> 75% remaining post 2-h incubation), exhibits low plasma protein binding (57% in humans) with no human Ether-a-go-go-Related Gene (hERG) liability (> 100 microM), and does not inhibit any of the cytochrome P450 (CYP) isoforms tested (IC50 > 25 microM). It also shows negligible cytotoxicity to HepG-2 and THP-1 cell lines. The oral pharmacokinetics in rats at 100 mg/kg body weight shows good exposures (Cmax = 1.1 microM) and half-life (T1/2 = 5.5 h). Furthermore, a 14-day toxicokinetic study at 100 mg/kg daily dose did not show any abnormality in body weight or gross organ pathology. FNDR-20123 is also able to reduce parasitaemia significantly in a mouse model for P. falciparum infection when dosed orally and subcutaneously. CONCLUSION: FNDR-20123 may be a suitable candidate for the treatment of malaria, which can be further developed

Hepatoprotective potential of Azima tetracantha and Tribulus terrestris on ferrous sulfate-induced toxicity in rat

The present study is to evaluate the antihepatotoxic effect of hydroalcoholic extract of leaf powder of Azima tetracantha and the fruit powder of Tribulus terrestris. Ferrous sulfate was used to induce hepatotoxicity and Silymarin was used as a standard drug. The level of biochemical parameters such as protein, albumin, globulin, HDL, vitamin E, superoxide dismutase and catalase were observed to be decreased and the level of glucose, LDL, VLDL, bilirubin, cholesterol, triglycerides, alkaline phosphatase and TBARS were increased in hepatotoxicity-induced rats. Retrieval of liver parameters to normal level was obtained after the oral administration of herbal drugs. Histopathological studies revealed diminished hepatocellular injury in the herbal drugs treated rats. As a conclusion hydro alcoholic extract of leaf powder of A. tetracantha and fruit powder of T. terrestris were possesses significant hepatoprotective activity

Consequences of a telomerase-related fitness defect and chromosome substitution technology in yeast synIX strains

We describe the complete synthesis, assembly, debugging, and characterization of a synthetic 404,963 bp chromosome, synIX (synthetic chromosome IX). Combined chromosome construction methods were used to synthesize and integrate its left arm (synIXL) into a strain containing previously described synIXR. We identified and resolved a bug affecting expression of EST3, a crucial gene for telomerase function, producing a synIX strain with near wild-type fitness. To facilitate future synthetic chromosome consolidation and increase flexibility of chromosome transfer between distinct strains, we combined chromoduction, a method to transfer a whole chromosome between two strains, with conditional centromere destabilization to substitute a chromosome of interest for its native counterpart. Both steps of this chromosome substitution method were efficient. We observed that wild-type II tended to co-transfer with synIX and was co-destabilized with wild-type IX, suggesting a potential gene dosage compensation relationship between these chromosomes. </p

The impacts of urban air pollution on Malaysian traffic police: A framework for evaluation of real-time monitoring system on its usability

The respiratory health of Malaysian Traffic Police has been compromised by working in heavy traffic and congested junctions with bad air for long hours. A wireless outdoor individual exposure device is vital to track their exposure, however, the efficacy of the system remains uncertain. While existing techniques exist to examine the efficacy of such system, there is a lack of methodology for engaging multiple assessment methods to evaluate the degree of user experience. This paper aims to propose a methodological framework tool for a quantitative evaluation of the wireless outdoor individual exposure indicator system prototype. A systematic search was conducted in major electronic databases (MEDLINE, Web of Science, Google), grey literature sources and all relevant data in the field. A three-stage framework consisting of simulation real-time monitoring, in-field testing, and usability testing is assembled. The three-stage framework proposed serves as a generic approach for evaluating the prototype with the purpose of tracking individual outdoor exposure. The method is capable of describing the complete evaluation process, from the accuracy and performance of the sensor to the extent of the end-user experience. Using the three-stage approach, future researchers may be able to create a monitoring system that is relevant to their needs

The wheat Sr22, Sr33, Sr35 and Sr45 genes confer resistance against stem rust in barley

In the last 20 years, stem rust caused by the fungus Puccinia graminis f. sp. tritici (Pgt), has re-emerged as a major threat to wheat and barley production in Africa and Europe. In contrast to wheat with 60 designated stem rust (Sr) resistance genes, barley’s genetic variation for stem rust resistance is very narrow with only ten resistance genes genetically identified. Of these, only one complex locus consisting of three genes is effective against TTKSK, a widely virulent Pgt race of the Ug99 tribe which emerged in Uganda in 1999 and has since spread to much of East Africa and parts of the Middle East. The objective of this study was to assess the functionality, in barley, of cloned wheat Sr genes effective against race TTKSK. Sr22, Sr33, Sr35 and Sr45 were transformed into barley cv. Golden Promise using Agrobacterium-mediated transformation. All four genes were found to confer effective stem rust resistance. The barley transgenics remained susceptible to the barley leaf rust pathogen Puccinia hordei, indicating that the resistance conferred by these wheat Sr genes was specific for Pgt. Furthermore, these transgenic plants did not display significant adverse agronomic effects in the absence of disease. Cloned Sr genes from wheat are therefore a potential source of resistance against wheat stem rust in barley

Resistance gene cloning from a wild crop relative by sequence capture and association genetics

Disease resistance (R) genes from wild relatives could be used to engineer broad-spectrum resistance in domesticated crops. We combined association genetics with R gene enrichment sequencing (AgRenSeq) to exploit pan-genome variation in wild diploid wheat and rapidly clone four stem rust resistance genes. AgRenSeq enables R gene cloning in any crop that has a diverse germplasm panel