Allelic forms of the knob associated histidine-rich protein gene of Plasmodium falciparum

AbstractThe knob associated histidine-rich protein (KAHRP) gene was cloned and sequenced from two Indian isolates of Plasmodium falciparum, Pf3-92 and Pf29-92. These isolates showed major sequence differences in the C-terminal repeat domain of KAHRP. However, the biologically important domains such as spectrin-actin binding region remained highly conserved. The PCR amplification of a variable C-terminal repeat domain from the clinical isolates of P. falciparum, from Rajasthan epidemic, showed the presence of multiple alleles of KAHRP gene. The presence of multiple alleles indicates the existence of several P. falciparum strains in India. This should be taken into account for future malaria control strategies such as molecular therapy and vaccines

Multispectral Classification With Bias-Tunable Quantum Dots-in-a-Well Focal Plane Arrays

Mid-wave and long-wave infrared (IR) quantum-dots-in-a-well (DWELL) focal plane arrays (FPAs) are promising technology for multispectral (MS) imaging and sensing. The DWELL structure design provides the detector with a unique property that allows the spectral response of the detector to be continuously, albeit coarsely, tuned with the applied bias. In this paper, a MS classification capability of the DWELL FPA is demonstrated. The approach is based upon: 1) imaging an object repeatedly using a sequence of bias voltages in the tuning range of the FPA and then 2) applying a classification algorithm to the totality of readouts, over multiple biases, at each pixel to identify the “class” of the material. The approach is validated for two classification problems: separation among different combinations of three IR filters and discrimination between rocks. This work is the first demonstration of the MS classification capability of the DWELL FPA

Demonstration of a Bias Tunable Quantum Dots-in-a-well Focal Plane Array

Infrared detectors based on quantum wells and quantum dots have attracted a lot of attention in the past few years. Our previous research has reported on the development of the first generation of quantum dots-in-a-well (DWELL) focal plane arrays, which are based on InAs quantum dots embedded in an InGaAs well having GaAs barriers. This focal plane array has successfully generated a two-color imagery in the mid-wave infrared (i.e. 3–5 μm) and the long-wave infrared (i.e. 8–12 μm) at a fixed bias voltage. Recently, the DWELL device has been further modified by embedding InAs quantum dots in InGaAs and GaAs double wells with AlGaAs barriers, leading to a less strained InAs/InGaAs/GaAs/AlGaAs heterostructure. This is expected to improve the operating temperature while maintaining a low dark current level. This paper examines 320 × 256 double DWELL based focal plane arrays that have been fabricated and hybridized with an Indigo 9705 read-out integrated circuit using Indium-bump (flip-chip) technology. The spectral tunability is quantified by examining images and determining the transmittance ratio (equivalent to the photocurrent ratio) between mid-wave and long-way infrared filter targets. Calculations were performed for a bias range from 0.3 to 1.0 V. The results demonstrate that the mid-wave transmittance dominates at these low bias voltages, and the transmittance ratio continuously varies over different applied biases. Additionally, radiometric characterization, including array uniformity and measured noise equivalent temperature difference for the double DWELL devices is computed and compared to the same results from the original first generation DWELL. Finally, higher temperature operation is explored. Overall, the double DWELL devices had lower noise equivalent temperature difference and higher uniformity, and worked at higher temperature (70 K and 80 K) than the first generation DWELL device

Demonstration of Bias-Controlled Algorithmic Tuning of Quantum Dots in a Well (DWELL) MidIR Detectors

The quantum-confined Stark effect in intersublevel transitions present in quantum-dots-in-a-well (DWELL) detectors gives rise to a midIR spectral response that is dependent upon the detector\u27s operational bias. The spectral responses resulting from different biases exhibit spectral shifts, albeit with significant spectral overlap. A postprocessing algorithm was developed by Sakoglu that exploited this bias-dependent spectral diversity to predict the continuous and arbitrary tunability of the DWELL detector within certain limits. This paper focuses on the experimental demonstration of the DWELL-based spectral tuning algorithm. It is shown experimentally that it is possible to reconstruct the spectral content of a target electronically without using any dispersive optical elements for tuning, thereby demonstrating a DWELL-based algorithmic spectrometer. The effects of dark current, detector temperature, and bias selection on the tuning capability are also investigated experimentally

Therapeutic efficacy of artemether-lumefantrine in uncomplicated falciparum malaria in India

<p>Abstract</p> <p>Background</p> <p>Artemisinin-based combination therapy (ACT) is the treatment of choice for uncomplicated falciparum malaria. Artemether-lumefantrine (AL), a fixed dose co-formulation, has recently been approved for marketing in India, although it is not included in the National Drug Policy for treatment of malaria. Efficacy of short course regimen (4 × 4 tablets of 20 mg artemether plus 120 mg lumefantrine over 48 h) was demonstrated in India in the year 2000. However, low cure rates in Thailand and better plasma lumefantrine concentration profile with a six-dose regimen over three days, led to the recommendation of higher dose globally. This is the first report on the therapeutic efficacy of the six-dose regimen of AL in Indian uncomplicated falciparum malaria patients. The data generated will help in keeping the alternative ACT ready for use in the National Programme as and when required.</p> <p>Methods</p> <p>One hundred and twenty four subjects between two and fifty-five years of age living in two highly endemic areas of the country (Assam and Orissa) were enrolled for single arm, open label prospective study. The standard six-dose regimen of AL was administered over three days and was followed-up with clinical and parasitological evaluations over 28 days. Molecular markers <it>msp</it>-<it>1 </it>and <it>msp</it>-2 were used to differentiate the recrudescence and reinfection among the study subjects. In addition, polymorphism in <it>pfmdr</it>1 was also carried out in the samples obtained from patients before and after the treatment.</p> <p>Results</p> <p>The PCR corrected cure rates were high at both the sites viz. 100% (n = 53) in Assam and 98.6% (n = 71) in Orissa. The only treatment failure case on D7 was a malnourished child. The drug was well tolerated with no adverse events. Patients had pre-treatment carriage of wild type codons at positions 86 (41.7%, n = 91) and 184 (91.3%, n = 91) of <it>pfmdr1 </it>gene.</p> <p>Conclusion</p> <p>AL is safe and effective drug for the treatment of acute uncomplicated falciparum malaria in India. The polymorphism in <it>pfmdr</it>1 gene is not co-related with clinical outcome. However, treatment failure can also occur due to incomplete absorption of the drug as is suspected in one case of failure at D7 in the study. AL can be a viable alternative of artesunate plus sulphadoxine/pyrimethamine (AS + SP), however, the drug should be used rationally and efficacy needs to be monitored periodically.</p

Plasmodium vivax Tryptophan-Rich Antigen PvTRAg33.5 Contains Alpha Helical Structure and Multidomain Architecture

Tryptophan-rich proteins from several malarial parasites have been identified where they play an important role in host-parasite interaction. Structural characterization of these proteins is needed to develop them as therapeutic targets. Here, we describe a novel Plasmodium vivax tryptophan-rich protein named PvTRAg33.5. It is expressed by blood stage(s) of the parasite and its gene contains two exons. The exon 1 encodes for a 23 amino acids long putative signal peptide which is likely to be cleaved off whereas the exon 2 encodes for the mature protein of 252 amino acids. The mature protein contains B-cell epitopes which were recognized by the human immune system during P.vivax infection. The PvTRAg33.5 contains 24 (9.5%) tryptophan residues and six motifs whose patterns were similar among tryptophan-rich proteins. The modeled structure of the PvTRAg33.5 consists of a multidomain architecture which is stabilized by the presence of large number of tryptophan residues. The recombinant PvTRAg33.5 showed predominantly α helical structure and alpha helix to beta sheet transition at pH below 4.5. Protein acquires an irreversible non-native state at temperature more than 50°C at neutral pH. Its secondary and tertiary structures remain stable in the presence of 35% alcohol but these structures are destabilized at higher alcohol concentrations due to the disturbance of hydrophobic interactions between tryptophanyl residues. These structural changes in the protein might occur during its translocation to interact with other proteins at its final destination for biological function such as erythrocyte invasion

Protective Gene Expression Changes Elicited by an Inherited Defect in Photoreceptor Structure

Inherited defects in retinal photoreceptor structure impair visual transduction, disrupt relationship with the retinal pigment epithelium (RPE), and compromise cell viability. A variety of progressive retinal degenerative diseases can result, and knowledge of disease etiology remains incomplete. To investigate pathogenic mechanisms in such instances, we have characterized rod photoreceptor and retinal gene expression changes in response to a defined insult to photoreceptor structure, using the retinal degeneration slow (rds) mouse model. Global gene expression profiling was performed on flow-sorted rds and wild-type rod photoreceptors immediately prior and subsequent to times at which OSs are normally elaborated. Dysregulated genes were identified via microarray hybridization, and selected candidates were validated using quantitative PCR analyses. Both the array and qPCR data revealed that gene expression changes were generally modest and dispersed amongst a variety of known functional networks. Although genes showing major (>5-fold) differential expression were identified in a few instances, nearly all displayed transient temporal profiles, returning to WT levels by postnatal day (P) 21. These observations suggest that major defects in photoreceptor cell structure may induce early homeostatic responses, which function in a protective manner to promote cell viability. We identified a single key gene, Egr1, that was dysregulated in a sustained fashion in rds rod photoreceptors and retina. Egr1 upregulation was associated with microglial activation and migration into the outer retina at times subsequent to the major peak of photoreceptor cell death. Interestingly, this response was accompanied by neurotrophic factor upregulation. We hypothesize that activation of Egr1 and neurotrophic factors may represent a protective immune mechanism which contributes to the characteristically slow retinal degeneration of the rds mouse model

Measurement of the top quark forward-backward production asymmetry and the anomalous chromoelectric and chromomagnetic moments in pp collisions at √s = 13 TeV

Abstract The parton-level top quark (t) forward-backward asymmetry and the anomalous chromoelectric (d̂ t) and chromomagnetic (μ̂ t) moments have been measured using LHC pp collisions at a center-of-mass energy of 13 TeV, collected in the CMS detector in a data sample corresponding to an integrated luminosity of 35.9 fb−1. The linearized variable AFB(1) is used to approximate the asymmetry. Candidate t t ¯ events decaying to a muon or electron and jets in final states with low and high Lorentz boosts are selected and reconstructed using a fit of the kinematic distributions of the decay products to those expected for t t ¯ final states. The values found for the parameters are AFB(1)=0.048−0.087+0.095(stat)−0.029+0.020(syst),μ̂t=−0.024−0.009+0.013(stat)−0.011+0.016(syst), and a limit is placed on the magnitude of | d̂ t| &lt; 0.03 at 95% confidence level. [Figure not available: see fulltext.

Measurement of t(t)over-bar normalised multi-differential cross sections in pp collisions at root s=13 TeV, and simultaneous determination of the strong coupling strength, top quark pole mass, and parton distribution functions

Peer reviewe