No evidence that FLT3 status should be considered as an indicator for transplantation in acute myeloid leukemia (AML): an analysis of 1135 patients, excluding acute promyelocytic leukemia, from the UK MRC AML 10 and 12 trials

Fetal liver tyrosine kinase 3 (FLT3) internal tandem duplications (ITDs) are powerful adverse prognostic indicators for relapse in acute myelold leukemia (AML) but the most efficacious therapy for FLT3/ ITD+ patients is currently unknown. We evaluated outcome according to FLT3/ITD status in 1135 adult patients treated according to United Kingdom Medical Research Council (UK MRC) AML protocols: 141 received an autograft, and 170 received a matched sibling allograft in first complete remission (CR). An FLT3/ITD was detected in 25% of patients and was an independent predictor for relapse (P < .001). It remained prognostic for increased relapse in patients who received a transplant (odds ratio [OR] = 1.91; 95% confidence intervals [CIs] 1.13-3.21; P = .02), with no evidence of a difference in effect between patients who received an autograft (OR = 2.39; CIs = 1.24-4.62) and patients who received an allograft (OR = 1.31; CIs = 0.56-3.06) (test for interaction, P = .3) or between patients who did or did not receive a transplant (P = .4). These results were confirmed in an analysis of 186 patients randomized to receive or not receive an autograft in first CR and in a donor-versus-no donor analysis of 683 patients to assess the role of allograft (for latter, FLT3/ITD- OR = 0.70, CIs = 0.53-0.92; FLT3/ITD+ OR = 0.59, CIs = 0.40-0.87; test for interaction, P = .5). These results suggest that at present there is no strong evidence that FLT3 status should influence the decision to proceed to transplantation

Fuzzy and Position Particle Swarm Optimized Routing in VANET

In Intelligent Transport Systems, traffic management and providing stable routing paths between vehicles using vehicular ad hoc networks (VANET\u27s) is critical. Lots of research and several routing techniques providing a long path lifetime have been presented to resolve this issue. However, the routing algorithms suffer excessive overhead or collisions when solving complex optimization problems. In order to improve the routing efficiency and performance in the existing schemes, a Position Particle Swarm Optimization based on Fuzzy Logic (PPSO-FL) method is presented for VANET that provides a high-quality path for communication between nodes. The PPSO-FL has two main steps. The first step is selecting candidate nodes through collectively coordinated metrics using the fuzzy logic technique, improving packet delivery fraction, and minimizing end-to-end delay. The second step is the construction of an optimized routing model. The optimized routing model establishes an optimal route through the candidate nodes using position-based particle swarm optimization. The proposed work is simulated using an NS2 simulator. Simulation results demonstrate that the method outperforms the standard routing algorithms in packet delivery fraction, end-to-end delay and execution time for routing in VANET scenarios

Manipulating the Sleeping Beauty Mutase Operon in Engineered Escherichia Coli for Controlled Biosynthesis of 1-Propanol and Other Value-Added Chemicals

A great fraction of the world’s energy requirements are presently met through the unrestricted use of fossil-derived fuels. However, due to the anticipated demise of these energy sources and the environmental and socioeconomic concerns associated with their use, a recent paradigm shift is to displace conventional fuels with renewable energy sources. Although most resources in biofuels have been directed towards the implementation of bioethanol platforms, the advanced alcohol 1-propanol has recently received significant attention as a promising alternative biofuel. Compared to that of ethanol, 1-propanol has an energy density that is more comparable to gasoline and is far less hygroscopic and volatile. Nevertheless, no microorganism has been identified as a natural 1-propanol producer. Accordingly, in this thesis, we manipulated a novel metabolic pathway for the synthesis of 1-propanol in the genetically tractable bacterium Escherichia coli. E. coli strains capable of producing 1-propanol were engineered by extending the dissimilation of the tricarboxylic acid intermediate succinate to the C3 biogenic precursor propionyl-CoA. This was accomplished by activation of the dormant yet extant Sleeping beauty mutase operon genes (i.e. sbm-ygfD-ygfG). In our initial studies, we developed propanogenic E. coli strains by episomally expressing selection of key genes, i.e. (1) three native genes in the sleeping beauty mutase (Sbm) operon (2) the genes encoding bifunctional aldehyde/alcohol dehydrogenases (ADHs) from various microbial sources, and (3) the sucCD gene encoding succinyl-CoA synthetase from E. coli. Using these triple-plasmid expression systems in E. coli, production titers up to 150 mg/L of 1-propanol were obtained in laboratory shake-flask growths under strict anaerobic conditions using glucose as the major carbon source. Following the development of these plasmid-haboring propanogenic E. coli hosts, we systematically explored various biochemical, genetic and metabolic/physiological factors to potentially enhance 1-propanol production and productivity. It was found that 1-propanol production can be significantly improved in a bioreactor under anaerobic conditions by using glycerol as a carbon source using a single-plasmid system solely expressing the Sbm operon genes. This may in part be due to the high reductance degree of glycerol compared with the microbial cell biomass. Equally important, we also alleviated plasmid-induced metabolic burden by chromosomally activating the Sbm operon genes. This plasmid-free propanogenic strain allowed high-level coproduction of 1-propanol and ethanol (accounting for 85 % of dissimilated carbon) under anaerobic fed-batch cultivation using glycerol as the major carbon source. To expand the chemical diversity and utility of our plasmid-free propanogenic E. coli strains, we explored the possibility of producing other value-added chemicals of biotechnological relevance derived propionyl-CoA. We first examined the possibility of producing butanone, an important commodity ketone. To produce butanone, we developed a modular CoA-dependent chain elongation platform to fuse Sbm-derived propionyl-CoA and endogenous acetyl-CoA to form the C5 biogenic precursor 3-ketovaleryl-CoA. Next, 3-ketovaleryl-CoA was channeled into the clostridial acetone-formation pathway for thioester hydrolysis and subsequent decarboxylation. In also manipulating initial glycerol dissimilation in the engineered ketogenic E. coli strains, we achieved co-production of 1.3 g/L butanone and 2.9 g/L acetone under semi-aerobic batch cultivation with glycerol as the major carbon source. In our final study we investigated the feasibility of using our developed propanogenic strains for the production of the bio(co)polymer poly(3-hydroxybutyrate-co-3-hydroxyvalerate) using unrelated carbon sources glycerol or glucose. (i.e. without exogenous supplementation of propionate or valerate). P(3HB-co-3HV) producing propanogenic strains were developed by first fusing two acetyl-CoA moieties or acetyl-CoA and propionyl-CoA generate the C4 and C5 thioesters 3-hydoxybutyryl-CoA and 3-ketovaleryl-CoA, respectively via a CoA-dependent chain elongation platform. Next, the resulting C4 and C5 thioesters intermediates were channeled into a polyhydroxyalkanoate biosynthetic pathway for subsequent thioester reduction and polymerization. In modulating various carbon sources, aeration regimes, and host-gene deletions, copolymers with 3HV fractions ranging from ~3 mol% to ~19 mol% were obtained. Taken together, we have demonstrated that activating the Sbm operon not only transforms E. coli to be propanogenic, but also introduces an intracellular “flux competition” between the traditional C2-fermentative pathway (i.e. acetate and ethanol) and the novel C3-fermentative pathway (i.e. propionate and 1-propanol). Harnessing this flux and employing various modular chain elongation and pathway enzymes can open the avenue for the controlled production of various odd-chain organic acids, medium chain ketones, bio(co)polymers and other oleochemicals. Accordingly, the developed propanogenic E. coli strains and associated genetic and metabolic tools reported here expands the classes of chemicals that can be produced microbially via propionyl-CoA

Land policies in Delhi: their contribution to unauthorised land development

Government intervention in land markets through public land policies increasingly sought for a more balanced development, better income and wealth distribution, and to satisfy the basic human needs such as housing and essential services in developing countries. Delhi's large-scale land acquisition, development and disposal policy has aimed at orderly growth of planned development, and universal access to housing land through public expropriation, banking, development and delivery. But the policy has been widely criticised for failing to promote planned development and consequently creating large-scale illegal land developments and sales. The present research investigates the impact of Delhi's public land policy on the creation of informal land developments and unauthorised housing in Delhi. The analysis of data gathered from office records and exhaustive structured interviews yield substantial evidence that the large-scale land policy governing the public authority's delivery of land for housing, has indeed been a major contributor to the creation of unauthorised land development and sales. Through interviews with 300 households living on illegally developed land, 106 living on illegally resold (legally developed land), 28 who had illegally resold their plots, and 69 property agents, this study found that the large-scale public land policy has not provided adequate land for housing. The policy's inability to deliver timely and adequate quantities of affordable land in varying parcel sizes, and with flexible lease conditions, was a prime factor in encouraging a large number of households to opt for illegally developed or sold land. The responses of households indicate a substantial number sought illegally to obtain housing land, because the large-scale public land policy failed to offer them legal alternatives that were affordable, adequate in quantity, in the desired time and flexible in their lease conditions. The opportunities to obtain varying sizes of unauthorised plots, at cheaper prices, in the desired time, with flexible payments, and acceptable terms of construction and use have attracted a large number of middle and high income households. Equally, the policy of regularisation of some unauthorised developments has also encouraged investment in additional illegal development. This research also found that the public land policy's failure to deliver the right land to the right person at reasonable prices prompted unauthorised resales of legally developed plots, in effect, downward filtration of high income groups. The higher resale prices that these subsidised plots obtained, and the ability of some households to obtain an allocation of more than one plot encouraged a large number of households to illegally resell plots

Severely Plastic Deformed Magnesium Based Alloys

Magnesium can be replaced with materials which experience strain controlled fatigue in their respective applications. Still, there are infrequent predicaments with utilizing magnesium alloys, comprising lower strength, fatigue life, ductility, toughness, and creep resistant attributes correlate with aluminum alloys. Some recent studies have been affirming that through the severe plastic deformation process, particularly equal-channel angular pressing (ECAP) method promotes very significant ultra-grain refinement in bulk solids, which enhances the mechanical properties. ECAP with a 90° clockwise rotation around the billet axis between consecutive passes in route BC has improved the ductile characteristics with increased yield strength and rate of elongation which leads to a greater fatigue life because ultra-fine grain refinement can be able to resist the crack propagations. To attain the plasticity at higher temperature magnesium and its alloys are required to undergo extrusion operation before proceeding to the multiple pass ECAP at 200°C because the magnesium alloys exhibit a limited number of slip systems due to its hexagonal crystal structure

Determinants of Bacterial Contamination in Pools, Spas, and Wading Pools: Should Chlorine Standards Be Revised?

Using a retrospective case-control study, we compared poolside tests with bacteriological samples during three consecutive summers. A total of 844 matched samples were obtained. Increased chlorine levels were associated with lower rates of contamination. Alkalinity, pH, and TDS were not statistically associated with bacteriological failures. In swimming pools with \u3e 1 ppm of chlorine, 27/30 (90.0%) passed bacteriologic evaluation. In spas with \u3c 1.0 ppm of chlorine, only 12/28 (42.9%) passed. Of the spas with \u3e 3.0 ppm of chlorine, 170/176 (96.6%) passed. Of the wading pools with \u3c 1ppm of chlorine, only 12/25 (48.0%) passed. Of the wading pools with \u3e 2 ppm, 263/290 (90.7%) passed. Of available poolside tests, only chlorine levels are predictive of positive testing for fecal contamination. Higher levels of chlorine were associated with higher passing rates. Current standards for disinfection in spas and wading pools may need to be increased to help prevent contamination

Novel mutation in FOXC1 wing region causing Axenfeld-Rieger anomaly

Purpose: To determine the possible molecular genetic defect underlying Axenfeld-Rieger anomaly (ARA) and to identify the pathogenic mutation causing this anterior segment dysgenesis in an Indian pedigree. Methods: The FOXC1 gene was amplified from genomic DNA of members of an ARA-affected family and control subjects using four novel sets of primers. The amplicons were directly sequenced, and the sequences were analyzed to identify the disease-causing mutation. Results: A heterozygous novel missense mutation was identified in the coding region of the FOXC1 gene in all three patients in this family. Consistent with the autosomal dominant inheritance pattern, the mutation segregated with the disease phenotype and was fully penetrant. The mutation was found in the wing region of the highly conserved forkhead domain of the FOXC1 gene and resulted in a very severe phenotype leading to blindness. Conclusions: This is the first study to demonstrate that a mutation in the FOXC1 wing region can cause an anterior segment dysgenesis of the eye. This mutation resulted in blindness in the ARA-affected family, and the findings suggest that the FOXC1 wing region has a functional role in the normal development of the eye. Moreover, this is the first study from India to report the genetic etiology of Axenfeld-Rieger anomaly. Genotype-phenotype correlations of FOXC1 may help in establishing the disease prognosis and also in understanding the clinical and genetic heterogeneity associated with various anterior segment dysgenesis caused by this gene

Integration of renewable energy in microgrids coordinated with demand response resources: Economic evaluation of a biomass gasification plant by Homer Simulator

This paper deals with how demand response can contribute to the better integration of renewable energy resources such as wind power, solar, small hydro, biomass and CHP. In particular, an economic evaluation performed by means of the micro-power optimization model HOMER Energy has been done, considering a micro-grid supplied by a biomass gasification power plant, operating isolated to the grid and in comparison with other generation technologies. Different scenarios have been simulated considering variations in the power production of the gasified biomass generator and different solutions to guarantee the balance generation/consumption are analyzed, demonstrating as using demand response resources is much more profitable than producing this energy by other conventional technologies by using fossil fuels.Montuori, L.; Alcázar Ortega, M.; Álvarez Bel, CM.; Domijan, A. (2014). Integration of renewable energy in microgrids coordinated with demand response resources: Economic evaluation of a biomass gasification plant by Homer Simulator. Applied Energy. 132(1):15-22. doi:10.1016/j.apenergy.2014.06.075S1522132

Manipulating the sleeping beauty mutase operon for the production of 1-propanol in engineered Escherichia coli

Background: While most resources in biofuels were directed towards implementing bioethanol programs, 1-propanol has recently received attention as a promising alternative biofuel. Nevertheless, no microorganism has been identified as a natural 1-propanol producer. In this study, we manipulated a novel metabolic pathway for the synthesis of 1-propanol in the genetically tractable bacterium Escherichia coli. Results: E. coli strains capable of producing heterologous 1-propanol were engineered by extending the dissimilation of succinate via propionyl-CoA. This was accomplished by expressing a selection of key genes, i.e. (1) three native genes in the sleeping beauty mutase (Sbm) operon, i.e. sbm-ygfD-ygfG from E. coli, (2) the genes encoding bifunctional aldehyde/alcohol dehydrogenases (ADHs) from several microbial sources, and (3) the sucCD gene encoding succinyl-CoA synthetase from E. coli. Using the developed whole-cell biocatalyst under anaerobic conditions, production titers up to 150 mg/L of 1-propanol were obtained. In addition, several genetic and chemical effects on the production of 1-propanol were investigated, indicating that certain host-gene deletions could abolish 1-propanol production as well as that the expression of a putative protein kinase (encoded by ygfD/argK) was crucial for 1-propanol biosynthesis. Conclusions: The study has provided a novel route for 1-propanol production in E. coli, which is subjected to further improvement by identifying limiting conversion steps, shifting major carbon flux to the productive pathway, and optimizing gene expression and culture conditions.Natural Sciences and Engineering Research Council (NSERC); Canada Research Chair (CRC) program of Canad

Effects of pretreatments of Napier Grass with deionized water, sulfuric acid and sodium hydroxide on pyrolysis oil characteristics

The depletion of fossil fuel reserves has led to increasing interest in liquid bio-fuel from renewable biomass. Biomass is a complex organic material consisting of different degrees of cellulose, hemicellulose, lignin, extractives and minerals. Some of the mineral elements tend to retard conversions, yield and selectivity during pyrolysis processing. This study is focused on the extraction of mineral retardants from Napier grass using deionized water, dilute sodium hydroxide and sulfuric acid and subsequent pyrolysis in a fixed bed reactor. The raw biomass was characterized before and after each pretreatment following standard procedure. Pyrolysis study was conducted in a fixed bed reactor at 600 o�C, 30 �C/min and 30 mL/min N2 flow. Pyrolysis oil (bio-oil) collected was analyzed using standard analytic techniques. The bio-oil yield and characteristics from each pretreated sample were compared with oil from the non-pretreated sample. Bio-oil yield from the raw sample was 32.06 wt% compared to 38.71, 33.28 and 29.27 wt% oil yield recorded from the sample pretreated with sulfuric acid, deionized water and sodium hydroxide respectively. GC–MS analysis of the oil samples revealed that the oil from all the pretreated biomass had more value added chemicals and less ketones and aldehydes. Pretreatment with neutral solvent generated valuable leachate, showed significant impact on the ash extraction, pyrolysis oil yield, and its composition and therefore can be regarded as more appropriate for thermochemical conversion of Napier grass