Antigenic repertoire of Plasmodium vivax transmission-blocking vaccine candidates from the Indian subcontinent

<p>Abstract</p> <p>Background</p> <p>Genetic polymorphism is an inevitable component of a multistage infectious organism, such as the malaria parasite. By means of genetic polymorphism, parasite opts particular polymorph and reveals survival advantage. <it>Pvs25 </it>and <it>pvs28 </it>are sexual stage antigen genes, expressed at the ookinete stage inside the mosquito gut, and considered as potential transmission-blocking vaccine candidates. This study presents sequence variations in two important transmission blocking antigen genes <it>pvs25 and pvs28 </it>in the field isolates of <it>P. vivax </it>from the Indian subcontinent.</p> <p>Methods</p> <p>One hundred microscopically diagnosed <it>P. vivax </it>isolates were collected from five geographical regions of India. <it>Pvs25 and pvs28 </it>genes were PCR amplified and sequenced to assess sequence variation among field isolates.</p> <p>Results</p> <p>A total of 26 amino acid substitutions were observed in Pvs25 (10) and Pvs28 (16) among field isolates of <it>P. vivax</it>. Tandem repeat polymorphism observed in <it>pvs28 </it>shows 3-6 tandem repeats in the field isolates. Seven and eight novel amino acid substitutions were observed in Pvs25 and Pvs28, respectively in Indian isolates. Comparison of amino acid substitutions suggests that majority of substitutions observed in global isolates were also present in Indian subcontinent. A single haplotype was observed to be major haplotype among isolates of Delhi, Nadiad, Chennai and Panna except in isolates of Kamrup. Further, population comparison analyses suggest that <it>P. vivax </it>isolates inhabiting in north-eastern region (Kamrup) were distantly related with the isolates from remaining parts of the country. Majority of the amino acid substitutions observed in Indian isolates were more identical to the substitutions reported from isolates of Thailand and Bangladesh.</p> <p>Conclusion</p> <p>Study uncovered many new amino acid substitutions as well as a predominance of single haplotype in Indian subcontinent except in north-eastern region of the country. The amino acid substitutions data generated in this study from different geographical regions of the Indian subcontinent could be helpful in designing a more effective anti-malarial transmission-blocking vaccine.</p

Molecular epidemiology of Plasmodium vivax anti-folate resistance in India

<p>Abstract</p> <p>Background</p> <p>Sulphadoxine and pyrimethamine are anti-folate drugs that show synergistic anti-malarial effect. Point mutations in <it>dihydrofolate reductase </it>(<it>dhfr</it>) and <it>dihydropteorate synthatase </it>(<it>dhps</it>) cause anti-folate drug resistance phenotype in human malaria parasites. This study presents pattern of point mutations in <it>dhfr/dhps </it>genes among Indian sub-continent.</p> <p>Methods</p> <p>Microscopically diagnosed one hundred <it>Plasmodium vivax </it>field isolates were collected from five widely separated geographical regions of India. <it>Dhfr </it>and <it>dhps </it>genes were PCR amplified and sequenced. Previously published mutations data were collected and analyzed using Chi square test to identify geographical cluster of mutant/wild type genotypes.</p> <p>Results</p> <p>Sequence analysis revealed single (S58R), double (S58R/S117N) and quadruple (F57L/S58R/T61M/S117T/) point mutations at <it>dhfr </it>and single (A383G) to double (A383G/A553G) mutations at <it>dhps </it>in <it>P. vivax </it>field isolates. In addition, three new mutations were also observed at <it>dhfr</it>. Both, <it>dhfr </it>and <it>dhps </it>genes revealed tandem repeat variations in field isolates. <it>Dhps </it>revealed very low mutation frequency (14.0%) compared to <it>dhfr </it>(50.70%). Comparative analysis revealed a progressive increase in frequency of quadruple mutant <it>dhfr </it>genotype (p < 0.001) within five years in north-eastern state (Kamrup, Assam). Frequency of <it>dhfr </it>genotypes revealed three distinct geographical clusters of wild (northern India), double mutant (southern India), and quadruple mutant (north-eastern and island regions of India) on the Indian sub-continent.</p> <p>Conclusion</p> <p>Study suggests that SP may be susceptible to <it>P. vivax </it>in India, except Andaman and north-eastern state. The distinction of geographical regions with sensitive and resistant parasite phenotypes would be highly useful for designing and administering national anti-malarial drug policy.</p

Modern Control Approaches for a Wind Energy Conversion System based on a Permanent Magnet Synchronous Generator (PMSG) Fed by a Matrix Converter

This “paper proposes a super-twisting adaptive Control Approaches for a Wind Energy Conversion System Based on a Permanent Magnet Synchronous Generator (PMSG) Fed by a matrix sliding mode for tracking the maximum power point of wind energy conversion systems using permanent magnet synchronous generators (PMSGs). As the adaptive control algorithm employed retains the robustness properties of classical wind energy conversion system control methods when perturbations and parameter uncertainties are present, it can be considered an effective solution; at the same time, it reduces chattering by adjusting gain and generating second-order adaptive control methods. The Egyptian power system (EPS), a three-zone interconnected microgrid (MG), and a single machine linked to the grid are only a few examples of the power systems for which this article introduces the concept of direct adaptive control (SMIB).The goal of our work is to maximize the captured power by solving a multi-input multi-output tracking control problem. In the presence of variations in stator resistance, stator inductance, and magnetic flux linkage, simulation results are presented using real wind speed data and discussed for the proposed controller and four other sliding mode control solutions for the same problem. The proposed controller achieves the best trade-off between tracking performance and chattering reduction among the five considered solutions: compared to a standard sliding mode control algorithm, it reduces chattering by two to five orders of magnitude, and steadystate errors on PMSG rotor velocity by one order of magnitude”. The purpose of this article is to examine wind turbine control system techniques and controller trends related to permanent magnet synchronous generators. The article presents an overview of the most popular control strategies for PMSG wind power conversion systems. There are several kinds of nonlinear sliding modes, such as direct power, backstepping, and predictive currents. To determine the performance of each control under variable wind conditions, a description of each control is presented, followed by a simulation performed in MATLAB /Simulink. This simulation evaluates the performance of each control in terms of reference tracking, response times, stability, and signal quality. Finally, this work was concluded with a comparison of the four controls to gain a better understanding of their effects. “Moreover, it reduces the above-mentioned steady-state error by four orders of magnitude compared to a previously-proposed linear quadratic regulator based integral sliding mode control law.  A dynamic model is simulated under both variable step and random wind speeds using the DEV-C++ software, and the results are plotted using MATLAB. The obtained results demonstrate the robustness of the proposed controller in spite of the presence of different uncertainties when compared to the classical direct torque control technique

Designing a Mobile Crowdsourcing System for Campus Safety

Safety on college campuses remains a dire issue. Current reporting methods are still cumbersome and include no enhancing social aspect. Given the unique opportunity that universities are required to publish their safety report logs, we conducted a preliminary data analysis of a university's safety report log. The analysis allowed us to detect relevant trends in reporting behavior, specifically pertaining to where, when, and how soon the community would report safety incidents. Motivated by these findings and by literature promoting interactive reporting systems, we designed a novel mobile app which aims to enable the spread of crowdsourced public safety information. This app allows for immediate mass sharing of self-reported safety incidents, as well as the opportunity for witness reporting. Feedback from a paper prototype interview study indicated that these qualities would facilitate increased interactivity among its user community, and ultimately promote awareness of campus safety.ye

Smart Atlas for Supporting the Interpretation of probe-based Confocal Laser Endomicroscopy (pCLE) of Biliary Strictures: First Classification Results of a Computer-Aided Diagnosis Software based on Image Recognition

International audiencepCLE enables microscopic imaging of biliary strictures, in vivo and in real time, during an ERCP procedure. Results of a multicentric study (Meining et al., GIE 2011) have shown that pCLE allows endoscopists to diferentiate benign from malignant strictures in real time with high sensitivity and NPV. A computer-aided diagnosis software called Smart Atlas has been developed to assist endoscopists with the interpretation of pCLE sequences. This study aims at evaluating the performance of this software for the diferentiation of benign and malignant strictures

Smart Atlas for Supporting the Interpretation of needle-based Confocal Laser Endomicroscopy (nCLE) of Pancreatic Cysts: First Classification Results of a Computer-Aided Diagnosis Software based on Image Recognition

International audiencenCLE enables microscopic imaging of pancreatic cysts, in vivo and in real time, during an EUS-FNA procedure. Diferentiating branch duct-type Intraductal Papillary Mucinous Neoplasm (IPMN) and Serous Cystadenoma (SCA) of the pancreas can be difcult, especially in case of a solitary lesion without clear communication with the pancreatic duct. Recent studies (Konda et al., Endoscopy 2013; Napoléon et al., DDW 2013) have identifed reliable nCLE descriptive features (superfcial vascular network in SCA; fngerlike projections in IPMN), allowing endoscopists to discriminate between SCA and IPMN. In parallel, a computer-aided diagnosis software called Smart Atlas has been developed to assist endoscopists with the interpretation of nCLE video sequences. This study aims at evaluating the performance of this software for the diferentiation of SCA and IPMN cases

Smart Atlas for Supporting the Interpretation of probe-based Confocal Laser Endomicroscopy (pCLE) of Gastric Lesions: First Classification Results of a Computer-Aided Diagnosis Software based on Image Recognition

International audiencepCLE enables microscopic imaging of gastrointestinal mucosal lesions, in vivo and in real time, during an endoscopy procedure. Recent studies have demonstrated that pCLE enables accurate diagnosis of superfcial gastric neoplasia. In parallel, a computer-aided diagnosis software called Smart Atlas has been developed to assist endoscopists with the interpretation of pCLE sequences. This study aims at evaluating the performance of this software for the classifcation of gastric lesions into four pathological classes: healthy stomach, gastric intestinal metaplasia (GIM), dysplasia, and cancer

Postbiotic production: harnessing the power of microbial metabolites for health applications

Postbiotics, which are bioactive substances derived from the metabolic processes of beneficial microbes, have received considerable attention in the field of microbiome science in recent years, presenting a promising path for exploration and innovation. This comprehensive analysis looks into the multidimensional terrain of postbiotic production, including an extensive examination of diverse postbiotic classes, revealing their sophisticated mechanisms of action and highlighting future applications that might significantly affect human health. The authors thoroughly investigate the various mechanisms that support postbiotic production, ranging from conventional fermentation procedures to cutting-edge enzyme conversion and synthetic biology approaches. The review, as an acknowledgment of the field’s developing nature, not only highlights current achievements but also navigates through the problems inherent in postbiotic production. In order to successfully include postbiotics in therapeutic interventions and the production of functional food ingredients, emphasis is given to critical elements, including improving yields, bolstering stability, and assuring safety. The knowledge presented herein sheds light on the expanding field of postbiotics and their potential to revolutionize the development of novel therapeutics and functional food ingredients

Evaluation of serum glycoprotein biomarker candidates for detection of esophageal adenocarcinoma and surveillance of Barrett’s esophagus

Esophageal adenocarcinoma (EAC) is thought to develop from asymptomatic Barrett’s esophagus (BE) with a low annual rate of conversion. Current endoscopy surveillance for BE patients is probably not cost-effective. Previously, we discovered serum glycoprotein biomarker candidates which could discriminate BE patients from EAC. Here, we aimed to validate candidate serum glycoprotein biomarkers in independent cohorts, and to develop a biomarker candidate panel for BE surveillance. Serum glycoprotein biomarker candidates were measured in 301 serum samples collected from Australia (4 states) and USA (1 clinic) using previously established lectin magnetic bead array (LeMBA) coupled multiple reaction monitoring mass spectrometry (MRM-MS) tier 3 assay. The area under receiver operating characteristic curve (AUROC) was calculated as a measure of discrimination, and multivariate recursive partitioning was used to formulate a multimarker panel for BE surveillance. Complement C9 (C9), gelsolin (GSN), serum paraoxonase/arylesterase 1 (PON1) and serum paraoxonase/lactonase 3 (PON3) were validated as diagnostic glycoprotein biomarkers in lectin pull-down samples for EAC across both cohorts. A panel of 10 serum glycoprotein biomarker candidates discriminated BE patients not requiring intervention [BE+/- low grade dysplasia] from those requiring intervention [BE with high grade dysplasia (BE-HGD) or EAC] with an AUROC value of 0.93. Tissue expression of C9 was found to be induced in BE, dysplastic BE and EAC. In longitudinal samples from subjects that have progressed towards EAC, levels of serum C9 were significantly (P\u3c0.05) increased with disease progression in EPHA (erythroagglutinin from Phaseolus vulgaris) and NPL (Narcissus pseudonarcissus lectin) pull-down samples. The results confirm alteration of complement pathway glycoproteins during BE-EAC pathogenesis. Further prospective clinical validation of the confirmed biomarker candidates in a large cohort is warranted, prior to development of a first-line BE surveillance blood test

EUS-Guided Needle-Based Confocal Laser Endomicroscopy: A Novel Technique With Emerging Applications

E ndoscopic ultrasound (EUS) has assumed an important role in the evaluation of the gastrointestinal tract in the past few decades. EUS has evolved from a purely diagnostic imaging modality to an interventional procedure that provides a minimally invasive alternative to interventional radiologic and surgical techniques. In EUS, a high-frequency ultrasound transducer is placed into the tip of the endoscope to provide high-quality images of the gastrointestinal tract and nearby structures. 1 Linear echoendoscopes have an advantage over radial instruments in that a fine-needle aspiration (FNA) needle can be guided through the endoscope during real-time EUS monitoring and visualization