A compendium of molecules involved in vector-pathogen interactions pertaining to malaria

Malaria is a vector-borne disease causing extensive morbidity, debility and mortality. Development of resistance to drugs among parasites and to conventional insecticides among vector-mosquitoes necessitates innovative measures to combat this disease. Identification of molecules involved in the maintenance of complex developmental cycles of the parasites within the vector and the host can provide attractive targets to intervene in the disease transmission. In the last decade, several efforts have been made in identifying such molecules involved in mosquito-parasite interactions and, subsequently, validating their role in the development of parasites within the vector. In this study, a list of mosquito proteins, which facilitate or inhibit the development of malaria parasites in the midgut, haemolymph and salivary glands of mosquitoes, is compiled. A total of 94 molecules have been reported and validated for their role in the development of malaria parasites inside the vector. This compendium of molecules will serve as a centralized resource to biomedical researchers investigating vector-pathogen interactions and malaria transmission. © 2013 Sreenivasamurthy et al.; licensee BioMed Central Ltd

Structural and Functional Diversity of Acidic Scorpion Potassium Channel Toxins

Background: Although the basic scorpion K + channel toxins (KTxs) are well-known pharmacological tools and potential drug candidates, characterization the acidic KTxs still has the great significance for their potential selectivity towards different K + channel subtypes. Unfortunately, research on the acidic KTxs has been ignored for several years and progressed slowly. Principal Findings: Here, we describe the identification of nine new acidic KTxs by cDNA cloning and bioinformatic analyses. Seven of these toxins belong to three new a-KTx subfamilies (a-KTx28, a-KTx29, and a-KTx30), and two are new members of the known k-KTx2 subfamily. ImKTx104 containing three disulfide bridges, the first member of the a-KTx28 subfamily, has a low sequence homology with other known KTxs, and its NMR structure suggests ImKTx104 adopts a modified cystine-stabilized a-helix-loop-b-sheet (CS-a/b) fold motif that has no apparent a-helixs and b-sheets, but still stabilized by three disulfide bridges. These newly described acidic KTxs exhibit differential pharmacological effects on potassium channels. Acidic scorpion toxin ImKTx104 was the first peptide inhibitor found to affect KCNQ1 channel, which is insensitive to the basic KTxs and is strongly associated with human cardiac abnormalities. ImKTx104 selectively inhibited KCNQ1 channel with a Kd of 11.69 mM, but was less effective against the basic KTxs-sensitive potassium channels. In addition to the ImKTx104 toxin, HeTx204 peptide, containing a cystine-stabilized a-helix-loop-helix (CS-a/a) fold scaffold motif

Comparative evolutionary genetics of deleterious load in sorghum and maize

Sorghum and maize share a close evolutionary history that can be explored through comparative genomics1,2. To perform a large-scale comparison of the genomic variation between these two species, we analysed ~13 million variants identi- fied from whole-genome resequencing of 499 sorghum lines together with 25 million variants previously identified in 1,218 maize lines. Deleterious mutations in both species were prev- alent in pericentromeric regions, enriched in non-syntenic genes and present at low allele frequencies. A comparison of deleterious burden between sorghum and maize revealed that sorghum, in contrast to maize, departed from the domestication-cost hypothesis that predicts a higher deleterious burden among domesticates compared with wild lines. Additionally, sorghum and maize population genetic summary statistics were used to predict a gene deleterious index with an accuracy greater than 0.5. This research represents a key step towards understanding the evolutionary dynamics of deleterious variants in sorghum and provides a comparative genomics framework to start prioritizing these variants for removal through genome editing and breeding

Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes

BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to -0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P = 0.98). There were no significant between-group differences in rates of acute pancreatitis (P = 0.07) or pancreatic cancer (P = 0.32). CONCLUSIONS: Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events

Degradation Of H.V. Generator Insulation Under Mechanical, Electrical And Thermal Stresses

The paper presents the results of ageing experiments under combined electrical, mechanical (vibration) and thermal stresses on epoxy bonded mica insulation. Actual 11 KV machine coils designed for use in 1 MW rotating machines are used as the specimens. Both diagnostic and destructive tests were carried out to assess the amount of ageing. It was observed that the incremental loss tangent and partial discharge energy per cycle increase monotonically with time of ageing and that the dielectric strength fell monotonically. Thus indicating a high degree of correlation between these properties

On the High Frequency Dielectric Behavior of Castor Oil

The low frequency dielectric behavior of castor oil (a vegetable oil) has been analyzed quite exhaustively in the context of its application as impregnant in capacitors. For the sake of completeness and in order to understand the relaxation phenomena in this liquid dielectric, this high frequency dielectric study was undertaken. In order to compare its properties with a liquid dielectric used in similar application and whose high frequency behavior has been quite well analyzed, Arochlor 1476 was studied. It is observed that both liquids have distributed relaxation times. The distribution parameters together with the two distinct relaxation times have been calculated by measuring the average relaxation time. It has been found that the distinct relaxation times thus calculated represent the dielectric behavior quite satisfactorily. The average dipole moments, dipole radii and thermal activation energies for dipole relaxation have also been evaluated

Certain aspects of breakdown in mineral oils used in UHV transformers under transient voltages

This paper deals with several aspects of breakdown in mineral oils used in UHV power transformers and gives a fairly detailed exposition of the process involved, the factors affecting the breakdown and a new statistical method of acquisition and analysis of breakdown data. Some information regarding structure property correlations are also included

Polymer Nanocomposites as Insulation for HV DC Cables – Investigations on the Thermal Breakdown

With the advent of nano-particle fillers in insulating materials, the insulating materials of superior quality have come to fore. In the recent past, nanocomposite LDPE/XLPE (Low Density Polyethylene/Cross Linked Polyethelene) power cable dielectrics have been synthesized. A preliminary evaluation of these new class of materials seem to show that, addition of small amounts of sub-micron inorganic fillers improved the dielectric properties of the composite, in particular, the volume resistivity, and the dc breakdown strength. The thermal behaviour, for example, the stability of composites against decomposition and ensuing electrical failure, do not seem to have been addressed. In a conventional XLPE insulated cable, the average thermal breakdown strength and maximum temperature at the onset of breakdown were seen to be markedly lower than the corresponding intrinsic breakdown strength and decomposition temperature. In the present paper, the Authors have presented and demonstrated the methods of estimating the limiting thermal breakdown voltages on a few nanocomposite materials used as power cable insulation. Experimental data on the volume resistivity reported in recent literature has been used in the series of computations. Nanocomposites of LDPE doped with small amounts of nano-particles of MgO, are chosen. The results show a considerable improvement in the thermal maximum voltage and other related parameters

Mobil Informationsvisualisering : Rekommendationer för att skapa bättre gränssnitt för informationsvisualiserings på mobila enheter

An increasing use of smartphones and other mobile devices puts pressure on user interfaces to work as well on small touch-screens as on desktop computers, and information visualisation interfaces are no exception. Even though there has been a demand for research on mobile information visualisation for many years, relatively little has been accomplished in this area, and the research that has been conducted is often narrow and oriented toward to a certain design. Therefore, this paper aims to give more general recommendations regarding the design of information visualisation interfaces for mobile devices. A qualitative user study was conducted to find weaknesses and strengths in existing information visualisation interfaces when interacted with on a smartphone. For this study, five prototypes were made by which different visualisations and interaction methods were tested by the participants of the study. The participants were given tasks based on the Visual Information Seeking Mantra, which focuses on four types of interaction with information visualisations (overview, zoom, filter and details-on-demand). The results indicate that the interaction with a visualisation is more important than visualisation itself to achieve a useful and efficient information visualisation interface. Other aspects to consider is to have an adequate zoom function, to not have interactive objects that are too small and to avoid over-cluttering. The latter aspect can be solved by either taking advantage of gestures or using more layers in the interface. However, what visualisations and interaction methods that work best is heavily dependent on the data and purpose of the visualisationEn ökande användning av smartphones och andra mobila enheter sätter press på användargränssnitt att fungera lika bra på små pekskärmar som på stationära datorer, och gränssnitt för informationsvisualisering är inget undantag. Trots att det har funnits en efterfrågan på forskning om mobil informationsvisualisering under många år har relativt lite uppnåtts inom detta område, samt att den forskning som har utförts ofta är smal och inriktad mot en viss design. Därför är syftet för denna forskningsartikel att ge mer allmänna rekommendationer om utformningen av gränssnitt för informationsvisualisering på mobila enheter. En kvalitativ användarstudie genomfördes för att hitta svagheter och styrkor i befintliga gränssnitt vid interaktion med en smartphone. För denna studie gjordes fem prototyper genom vilka olika visualiseringar och interaktionsmetoder testades av deltagarna i studien. Deltagarna fick uppgifter baserade på et mantra kallat ”the Visual Information Seeking Mantra”, som fokuserar på fyra typer av interaktion med informationsvisualiseringar. Resultaten indikerar att interaktionen med en visualisering är viktigare än själva visualiseringen för att uppnå ett användbart och effektivt informationsvisualiseringsgränssnitt. Andra aspekter att tänka på är att ha en effektiv zoomfunktion, att inte ha interaktiva objekt som är för små och att undvika att ha för många objekt på ett litet område. Den senare aspekten kan lösas genom att antingen dra fördel av gester eller använda fler lager i gränssnittet. Vilka visualiseringar och interaktionsmetoder som fungerar bäst är dock starkt beroende av data och syftet med visualiseringen