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The increased resistance of human malaria parasite Plasmodium falciparum (Pf) to currently used drugs necessities the development of novel anti-malarials. Here, we examine the potential of erythritol, a sugar substitute for therapeutic intervention. Erythritol is a permeant of Plasmodium falciparum aquaglyceroporin (PfAQP) which is a multifunctional channel responsible for maintaining hydro-homeostasis. We show that erythritol effectively inhibited growth and progression of asexual blood stage malaria parasite, and effect invasion and egress processes. It also inhibited the liver stage (sporozoites) and transmission stage parasite (gametocytes) development. Interestingly, erythritol inhibited in vivo growth of malaria parasite in mouse experimental model. It was more effective in inhibiting parasite growth both in vivo and in vitro when tested together with a known anti-malarial 'artesunate'. Additionally, erythritol showed cytokine-modulating effect which suggests its direct effect on the host immune system. Ammonia detection assay demonstrated that erythritol uptake effects the amount of ammonia release across the parasite. Our functional complementation assays suggest that PfAQP expression in yeast mutant restores its growth in hyperosmotic conditions but showed reduced growth in the presence of erythritol. Osmotic lysis assay suggests that erythritol creates osmotic stress for killing the parasite. Overall, our data bestow erythritol as a promising lead compound with an attractive antimalarial profile and could possibly be combined with known drugs without losing its efficacy. We propose the use of erythritol based sweet candies for protection against malaria specially in children living in the endemic area.

Constant emergence of drug-resistant Plasmodium falciparum warrants urgent need for effective and inexpensive drugs. Herein, phthalimide (Pht) analogs possessing the bioactive scaffolds, benzimidazole and 1,2,3-triazole, were evaluated for in vitro and in vivo anti-plasmodial activity without any apparent hemolysis, or cytotoxicity. Analogs 4(a-e) inhibited the growth of 3D7 and RKL-9 strains at submicromolar concentrations. Defects were observed during parasite egress from or invasion of the red blood cells. Mitochondrial membrane depolarization was measured as one of the causes of cell death. Phts 4(a-e) in combination with artemisinin exhibited two-to three-fold increased efficacy. Biophysical and biochemical analysis suggest that Pht analogs mediate plasmodial growth inhibition by interacting with tubulin protein of the parasite. Lastly, Phts 4(a-e) significantly decreased parasitemia and extended host survival in murine model Plasmodium berghei ANKA infection. Combined, the data indicate that Pht analogs should be further explored, which could offer novel value to the antimalarial drug development pipeline.

CO2-O2 based underground coal gasification (UCG) is a promising technology for exploiting deep coal seams using a greenhouse gasification agent. High molecular weight hydrocarbons, aromatics, tar etc. in the form of volatile matters in a coal seam possess a significant calorific value. During UCG, these components get evolved as vapours and leave the coal seam without undergoing significant cracking and reforming reactions. As a consequence, a substantial amount of tar is produced along with syngas stream. Alternatively, a novel result of the present study shows that tar-CO2 based dry reforming reactions are catalysed by the pyrolysed carbon zones in the borehole at low temperatures and, these reactions enhanced the calorific value of syngas under a CO2 reactive atmosphere. In continuation of our earlier studies, a detailed experimental study is carried out under single and two stage gasification methods using a typical high ash (42% ash) Indian coal and a low ash (4% ash) North East Indian coal. The effect of feed gas flow rate, molar feed ratio and inherent ash content of the coals on the product gas composition is studied. The results show that two stage gasification of high ash coal produces a medium calorific syngas in the order of 189 kJ/mol, which is equivalent to the heating value of a steam-O2 based UCG syngas. Further, the present study shows that a syngas with a high calorific value of 265 kJ/mol can be produced using the low ash coal under two stage gasification mode. Also, the single stage gasification of low ash coal shows the feasibility of producing a syngas with a medium calorific value of 250 kJ/mol.

CO2-air is a potential gasifying-oxidizing medium for two stage mode of underground coal gasification (UCG). The existing literature deficits the UCG studies on the use of CO2-air as a gasifying medium especially for high ash Indian coals. Thus, the present study investigated the viability of utilizing the CO2-air as a gasifying medium for high ash Indian coals using a laboratory scale borehole gasification set-up in a two-stage gasification mode of operation. A typical Indian coal having 42% ash and a North East Indian coal having 4% ash are used for the borehole gasification experiments. The effect of the process parameters such as the molar ratio of O2/air and the molar ratio of CO2/oxidizing agent on the product gas composition is evaluated. The results show that the gasification of low ash coal and high ash coal produced product gas with a calorific value as high as 260 kJ/mol and 214 kJ/mol, respectively. CO2-air based gasification necessitates the presence of oxygen in the feed gas with O2/air ratio of 0.1 and 1 for the low and the high ash coal, respectively. Repeatability experiments show 7% and 14% error in the calorific values of syngas for low and high ash coals, respectively.

Oxidizing/gasifying agents play an essential role in the economy of underground coal gasification (UCG). The selection of feed gases to UCG depends on the prevailing conditions and inherent properties of a coal seam. Steam based UCG operation would lead to transportation and operational difficulty for efficient gasification. Alternatively, CO2 gas is a potential gasifying medium for coal gasification and this option would ensure the reutilization of waste CO2 gas in a UCG operation. Thus, in the present study, borehole coal combustion and gasification experiments are carried out to simulate CO2 enhanced UCG system using a low ash coal originating from the Northeast region of India. UCG experiments are simulated in a laboratory scale using CO2/O2 gases and the results are compared with pure oxygen and oxygen enriched air based UCG operation. The composition and calorific value of syngas are analysed for various gasifying agents. The CO2/O2 borehole experimental studies show that a CO enriched product gas (∼40 vol.%) can be generated under dried coal seam conditions. Thermo-gravimetric analysis (TGA) studies show that the rate of pyrolysis is higher under a CO2 atmosphere as compared to N2 atmosphere. Further, the TGA results show that the generated CO2 pyrolysis products led to substantial char gasification even at low temperatures. The reactivity of tar with CO2 enhanced the calorific value of the product gas due to dry reforming reactions. Also, the presence of suitable inorganic species in the coal progressed the CO2 gasification through ash catalysis.

O 2 /CO 2 based underground coal gasification (UCG) is a promising clean coal technology for the exploitation of deep underground coal resources with a minimal difficulty of the operation. However, the generated syngas of the underground is enriched with carbon monoxide and it should be converted into a clean gas on the above ground for the end use. In the present study, a clean mode of power generation is proposed using the CO enriched UCG syngas. Firstly, the UCG gas is reformed into pure hydrogen using chemical looping reforming (CLR) method. Secondly, the pure hydrogen obtained from CLR process is used suitably to generate electric power in a proton exchange membrane fuel cell (PEMFC) system. Hence, carbon energy is converted into hydrogen energy through the CLR technique and this clean gas is efficiently transformed into electrical energy using the PEMFC system. A net efficiency for converting CO enriched gas into H 2 through conventional system using water gas shifting reactors is evaluated and compared with the CLR system. An energy analysis of O 2 /CO 2 based UCG integrated with CLR-PEMFC shows 43.6% net efficiency with carbon capture and storage (CCS).

A long working hours is a common issue in a software industry. This research study was carried out to investigate the impact of working environment on job satisfaction of software professionals in software industry. Work environment, results that are affected by job satisfaction on employee’s performance are investigated in this paper. It was indicated that how software professionals were getting experience and satisfaction from the work environment. The well-designed pretested questionnaire was used for data collection. The total sample size engaged for research study was taken to be 100. Among 100 employees, 65 were male and 35 were females. The convenience sampling method was employed for the study and analysis of data were completed by means of the statistical tools correlation and regression. The regression analysis confirmed that the work environment dimension influences only 21.8% to job satisfaction of software professionals at Wipro Technologies, Greater Noida, India. So based on the findings of this study, the study concluded that work environment has got substantial influence over job satisfaction of software professional at Wipro Technologies, Greater Noida, India.

The use of injectable hydrogels is currently restricted by the challenge of achieving fast gelation, good mechanical strength, and cytocompatibility. Polymeric self-assembly is a potent tool for generating functional materials that combine multiple characteristics and can react to external factors. In this study, we have developed fiber-reinforced composite hydrogels that exhibits significantly enhanced mechanical strength, reduced gelling time, and excellent cytocompatibility. The practicability of developing a chitosan-based thermogelling solution using hydroxyapatite and polyelectrolyte complex (PEC) self-assembled fibers were evaluated. The effect of βGP concentration on gelation time was studied by varying the concentration of βGP added to the chitosan solution. Various combinations were tested to create a suitable hydrogel environment for cell encapsulation, growth, and proliferation at physiological pH and temperature. Determination of Young modulus revealed that PEC fibers reinforced hydrogel was three times stiffer than chitosan-βGP gels. The gelation time was reduced to 3 min, and the hydrogels had porous structures and gels at physiological pH, temperature, and showed >80% viability for MTT assay to MG63 cells. Moreover, confocal imaging of PEC fiber reinforced hydrogels showed noticeable viability and proliferation. The molecular interactions between gelling agents, polyelectrolytes, and hydroxyapatite were studied using FTIR. We investigated interfacial bonding between PEC fibers with βGP, NaHCO3, and HAp. The combination of hydroxyapatite and polymer self-assembly technique improved the efficiency of injectable hydrogels that are helpful in minimally invasive applications.

Cell cycle progression requires a series of highly coordinated events that ultimately lead to faithful segregation of chromosomes. Aurora B is an essential mitotic kinase, which is involved in regulation of microtubule-kinetochore attachments and cytokinesis. Inhibition of Aurora B results in stabilization of p53 and induction of p53-target genes such as p21 to inhibit proliferation. We have previously demonstrated that induction of p21 by p53 after inhibition of Aurora B is dependent on the p38 MAPK, which promotes transcriptional elongation of p21 by RNA Pol II. In this study, we show that a subset of p53-target genes are induced in a p38-dependent manner upon inhibition of Aurora B. We also demonstrate that inhibition of Aurora B results in down-regulation of E2F-mediated transcription and that the cell cycle arrest after Aurora B inhibition depends on p53 and pRB tumor suppressor pathways. In addition, we report that activation of p21 after inhibition of Aurora B is correlated with increased chromosome missegregation and aneuploidy but not with binucleation or tetraploidy. We provide evidence that p21 is activated in aneuploid cells by reactive oxygen species (ROS) and p38 MAPK. Finally, we demonstrate that certain drugs that act on aneuploid cells synergize with inhibitors of Aurora B to inhibit colony formation and oncogenic transformation. These findings provide an important link between aneuploidy and the stress pathways activated by Aurora B inhibition and also support the use of Aurora B inhibitors in combination therapy for treatment of cancer.