Identifying new targets in leukemogenesis using computational approaches

AbstractThere is a need to identify novel targets in Acute Lymphoblastic Leukemia (ALL), a hematopoietic cancer affecting children, to improve our understanding of disease biology and that can be used for developing new therapeutics. Hence, the aim of our study was to find new genes as targets using in silico studies; for this we retrieved the top 10% overexpressed genes from Oncomine public domain microarray expression database; 530 overexpressed genes were short-listed from Oncomine database. Then, using prioritization tools such as ENDEAVOUR, DIR and TOPPGene online tools, we found fifty-four genes common to the three prioritization tools which formed our candidate leukemogenic genes for this study. As per the protocol we selected thirty training genes from PubMed. The prioritized and training genes were then used to construct STRING functional association network, which was further analyzed using cytoHubba hub analysis tool to investigate new genes which could form drug targets in leukemia. Analysis of the STRING protein network built from these prioritized and training genes led to identification of two hub genes, SMAD2 and CDK9, which were not implicated in leukemogenesis earlier. Filtering out from several hundred genes in the network we also found MEN1, HDAC1 and LCK genes, which re-emphasized the important role of these genes in leukemogenesis. This is the first report on these five additional signature genes in leukemogenesis. We propose these as new targets for developing novel therapeutics and also as biomarkers in leukemogenesis, which could be important for prognosis and diagnosis

An Innovative High Thermal Conductivity Fuel Design

Thermal conductivity of the fuel in today's Light Water Reactors, Uranium dioxide, can be improved by incorporating a uniformly distributed heat conducting network of a higher conductivity material, Silicon Carbide. The higher thermal conductivity of SiC along with its other prominent reactor-grade properties makes it a potential material to address some of the related issues when used in UO2 [97% TD]. This ongoing research, in collaboration with the University of Florida, aims to investigate the feasibility and develop a formal methodology of producing the resultant composite oxide fuel. Calculations of effective thermal conductivity of the new fuel as a function of %SiC for certain percentages and as a function of temperature are presented as a preliminary approach. The effective thermal conductivities are obtained at different temperatures from 600K to 1600K. The corresponding polynomial equations for the temperature-dependent thermal conductivities are given based on the simulation results. Heat transfer mechanism in this fuel is explained using a finite volume approach and validated against existing empirical models. FLUENT 6.1.22 was used for thermal conductivity calculations and to estimate reduction in centerline temperatures achievable within such a fuel rod. Later, computer codes COMBINE-PC and VENTURE-PC were deployed to estimate the fuel enrichment required, to maintain the same burnup levels, corresponding to a volume percent addition of SiC

Experimental Investigation and Numerical Optimization of Dual Evaporator Refrigerator

Improving energy efficiency and reducing the cost of the appliance simultaneously is a continuing challenge for refrigerator manufacturers. While conventional system configuration is based on a single evaporator vapor compression cycle, there are several other system configurations that can offer benefits over it. For example, a dual evaporator (one evaporator for freshfood and one for freezer) offers several benefits such as increased efficiency, isolation of odors, and higher humidity levels in the freshfood compartment. Engineers typically use extensive experimentation to optimize the system. This approach takes significant time and resources. Although optimization studies exists for a conventional single evaporator cycle, studies for dual evaporator cycle optimization are limited. Most manufacturers do not explore complex architecture due to time consuming, labor intensive and expensive development procedures. This study presents experimental results obtained from a prototype dual evaporator refrigerator. Further, this study presents a physics-based model and a multi-objective optimization methodology that demonstrates how engineers can optimize a refrigeration system by considering multiple objectives simultaneously. The study presents example optimization results for simultaneously minimizing cost and maximizing performance within a specified design space. Optimization of the novel design uses a genetic algorithm-based optimizer in conjunction with a response surface based metamodel. Using optimization techniques, we can arrive at lowest cost design relatively quickly as shown in the analysis. More work needs to be done to validate optimized solutions as well as alternate methods to improve temperature control

Removal of organic matter from wastewater reverse osmosis concentrate using granular activated carbon and anion exchange resin adsorbent columns in sequence.

Reverse osmosis concentrate (ROC) generated as a waste stream during reverse osmosis treatment of reclaimed wastewater, presents significant disposal challenges. This is because it causes environmental pollution when it is disposed to lands and natural water bodies. A long-term dynamic adsorption experiment was conducted by passing ROC from a wastewater reclamation plant, firstly through a granular activated carbon (GAC) column, and subsequently through an anion exchange resin (Purolite) column, for the removal of two major ROC pollutants, namely dissolved organic carbon (DOC) and microorganic pollutants (MOP). GAC removed most of the smaller-sized low molecular weight neutrals and building block fractions as well as the hydrophobic fraction of DOC with much less removal by the subsequent Purolite column. In contrast, the humics fraction was less well removed by the GAC column; however, Purolite column removed all that was remaining of this fraction. This study demonstrated that combining adsorbents having different affinities towards a variety of DOC fractions constitute an effective method of taking advantage of their different properties and achieving larger DOC removals. Almost 100% of all 17 MOPs were removed by the GAC column, even after 2880 bed volumes of continuous use. This contrasted with the DOC fractions' removal which was much lower

ESAT6-Induced IFNγ and CXCL9 Can Differentiate Severity of Tuberculosis

BACKGROUND: Protective responses against Mycobacterium tuberculosis are dependent on appropriate T cell and macrophage activation. Mycobacterial antigen six kDa early secreted antigenic target (ESAT6) and culture filtrate protein 10 (CFP10) can detect M. tuberculosis specific IFNgamma responses. However, most studies have been performed in non-endemic regions and to study pulmonary tuberculosis (PTB). We have studied ESAT6 and CFP10 induced cytokine and chemokines responses in PTB and extrapulmonary (EPul) TB. METHODOLOGY: IFNgamma, IL10, CXCL9 and CCL2 responses were determined using an ex vivo whole blood assay system in PTB (n = 30) and EPulTB patients with limited (LNTB, n = 24) or severe (SevTB, n = 22) disease, and in healthy endemic controls (ECs). Responses to bacterial LPS were also determined. PRINCIPAL FINDINGS: ESAT6- and CFP10-induced IFNgamma was comparable between ECs and TB patients. Both ESAT6- and CFP10-induced IFNgamma secretion was greater in LNTB than PTB. ESAT6-induced CXCL9 was greater in EPulTB as compared with PTB, with an increase in SevTB as compared with LNTB. CFP10-induced CCL2 was higher in PTB than LNTB patients. LPS-stimulated CXCL9 was greatest in SevTB and LPS-induced CCL2 was increased in PTB as compared with LNTB patients. A positive correlation between ESAT6-induced IFNgamma and CXCL9 was present in all TB patients, but IFNgamma and CCL2 was only correlated in LNTB. ESAT-induced CCL2 and CXCL9 were significantly associated in LNTB while correlation in response to LPS was only present in SevTB. CONCLUSIONS: ESAT6 induced IFNgamma and CXCL9 can differentiate between limited and severe TB infections

Comparative physicochemical and histo-anatomical study of vague traditional and magical herb Lavandula stoechas L. with Lavandula officinalis Chaix.

723-730Lavandula stoechas L. (Lamiaceae) is a medicinal plant of traditional Unani, Iranian and Tunisian systems of medicine. It has a unique attribute to expel out and remove all impurities and obstructions and reinvigorate the brain power, honored as broom of brain in classical Unani literatures. To establish clear identification between L. stoechas (LS) and L. officinalis (LO) standard operating parameters, TLC fingerprinting and physicochemical and histo-anatomical studies were done. LS exhibited significantly higher physical values for their standardization and quality parameters with respect to LO. Histoanatomical disquisition and chemo-microscopic studies of the drug revealed that presence of substantial and marked diagnostic feature to LS having large bract, brown colored flexible peduncle, presence of exorbitant number of uniseriate and multi seriate covering and uniseriate glandular trichomes leading to soft stem and peduncle. It has distinguished and well-developed phloem, centrally filled with parenchymatous cells, with camphoric stench along with bitter in taste while LO has lesser hairs, hard stem and peduncle, greenish color, presence of centrally hollow pith, indiscriminate bract, and flowers are without stalks with pleasant aroma. Seeds of LS are yellowish brown, frivolous weight and very small in size while LO have blackish seeds and are comparatively larger in size and weight

Enhanced solar light photocatalytic performance of Fe-ZnO in the presence of H2O2, S2O82−, and HSO5− for degradation of chlorpyrifos from agricultural wastes: Toxicities investigation

This study reported Fe doped zinc oxide (Fe-ZnO) synthesis to degrade chlorpyrifos (CPY), a highly toxic organophosphate pesticide and important sources of agricultural wastes. Fourier transform infrared, X-ray diffraction, scanning electron microscope, and energy-dispersive X-ray spectroscopic analyses showed successful formation of the Fe-ZnO with highly crystalline and amorphous nature. Water collected from agricultural wastes were treated with Fe-ZnO and the results showed 67% degradation of CPY by Fe-ZnO versus 39% by ZnO at 140 min treatment time. Detail mechanism involving reactive oxygen species production from solar light activated Fe-ZnO and their role in degradation of CPY was assessed. Use of H2O2, peroxydisulfate (S2O82−) and peroxymonosulfate (HSO5−) with Fe-ZnO under solar irradiation promoted removal of CPY. The peroxides yielded hydroxyl ([rad]OH) and sulfate radical ([Formula presented]) under solar irradiation mediated by Fe-ZnO. Effects of several parameters including concentration of pollutant and oxidants, pH, co-existing ions, and presence of natural organic matter on CPY degradation were studied. Among peroxides, HSO5− revealed to provide better performance. The prepared Fe-ZnO showed high reusability and greater mineralization of CPY. The GC-MS analysis showed degradation of CPY resulted into several transformation products (TPs). Toxicity analysis of CPY as well as its TPs was performed and the formation of non-toxic acetate imply greater capability of the treatment technology

Antinociceptive and Antioxidant Activity of Zanthoxylum budrunga

Different parts of the medicinal plant Zanthoxylum budrunga Wall enjoy a variety of uses in ethnobotanical practice in Bangladesh. In the present study, a number of phytochemical and pharmacological investigations were done on the ethanol extract of Z. budrunga seeds (ZBSE) to evaluate its antinociceptive and antioxidant potential. ZBSE was also subjected to HPLC analysis to detect the presence of some common antioxidants. In acetic acid induced writhing test in mice, ZBSE showed 65.28 and 74.30% inhibition of writhing at the doses of 250 and 500 mg/kg and the results were statistically significant (P<0.001). In hot-plate test, ZBSE raised the pain threshold significantly (P<0.001) throughout the entire observation period. In DPPH scavenging assay, the IC50 of ZBSE was observed at 82.60 μg/mL. The phenolic content was found to be 338.77 mg GAE/100 g of dried plant material. In reducing power assay, ZBSE showed a concentration dependent reducing ability. HPLC analysis indicated the presence of caffeic acid with a concentration of 75.45 mg/100 g ZBSE. Present investigation supported the use of Zanthoxylum budrunga seed in traditional medicine for pain management. Constituents including caffeic acid and other phenolics might have some role in the observed activity