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Chirality is a key factor in the safety and efficacy of many drug products and thus the production of single enantiomers of drug intermediates and drugs has become increasingly important in the pharmaceutical industry. There has been an increasing awareness of the enormous potential of microorganisms and enzymes derived there from for the transformation of synthetic chemicals with high chemo-, regio- and enatioselectivities. In this article, biocatalytic processes are described for the synthesis of chiral alcohols and unntural aminoacids for pharmaceuticals.

Biocatalytic processes to selectively hydrolyze the N-carbobenzyloxy (CBz) group from CBz-protected d - or l -amino acids have been developed. The substrate specificities of the CBz-deprotecting enzymes from Burkholderia phenazinium SC 16530, and Sphingomonas paucimobilis expressed into Escherichia coli SC 16501 were evaluated on CBz-protected amino acids and structurally related compounds. Modifications of various structural components and their effects on enzyme activity and enantioselectivity provided a greater understanding of the two CBz-deprotecting enzymes.

Environment is made up of natural factors like air, water and land. Each and every human activities supports directly/indirectly by natural factors. India is facing a problem of natural resource scarcity, especially of water in view of population growth and economic development. Due to growth of Population, advancement in agriculture, urbanization and industrialization has made surface water pollution a great problem and decreased the availability of drinking water. Many parts of the world face such a scarcity of water. Lakes are important feature of the Earth's landscape which are not only the source of precious water, but provide valuable habitats to plants and animals, moderate hydrological cycles, influence microclimate, enhance the aesthetic beauty of the landscape and extend many recreational opportunities to humankind .For issues, perspectives on pollution, restoration and management of Bellandur Lake Falls under Bangalore Metropolitan city is very essential to know their status but so far, there was no systematic environmental study carried out. Hence now the following studies are essential namely Characteristics, Status, Effects (on surrounding Groundwater, Soil, Humans health, Vegetables, Animals etc.,), resolving the issues of degradation, preparation of conceptual design for restoration and management.

Gasification of four Indian coals is carried out in a CO2 atmosphere, using a thermogravimetric analyzer (TGA) to determine the intrinsic kinetics over a temperature range of 800-1050 degrees C with different partial pressures of CO2. The applicability of three models, viz., the volumetric reaction model, the shrinking core model and the random pore model, is evaluated. Of these three models, the random pore model is found to be the most suitable for all the coals considered in the current study. The dependence of the reaction rate on the gas-phase partial pressures is explained by the Langmuir-Hinshelwood model, and the parameters for the inhibition due to CO and CO2 are determined by performing experiments at different partial pressures. In underground coal gasification, the reaction takes place on reasonably large sized coal particles, wherein diffusion effects are significant A one-dimensional reaction diffusion model is therefore developed in order to determine the diffusional resistance in the coal particle, and values of diffusivity are estimated.

Plants recruit microbial communities from the soil in which they germinate. Our understanding of the recruitment process and the factors affecting it is still limited for most microbial taxa. We analysed several factors potentially affecting root microbiome structure - the importance of geographic location of natural populations, the microbiome of native seeds as putative source of colonization and the effect of a plant's response to UVB exposure on root colonization of highly abundant species. The microbiome of Nicotiana attenuata seeds was determined by a culture-dependent and culture-independent approach, and the root microbiome of natural N. attenuata populations from five different locations was analysed using 454-pyrosequencing. To specifically address the influence of UVB light on root colonization by Deinococcus, a genus abundant and consistently present in N. attenuata roots, transgenic lines impaired in UVB perception (irUVR8) and response (irCHAL) were investigated in a microcosm experiment with/without UVB supplementation using a synthetic bacterial community. The seed microbiome analysis indicated that N. attenuata seeds are sterile. Alpha and beta diversities of native root bacterial communities differed significantly between soil and root, while location had only a significant effect on the fungal but not the bacterial root communities. With UVB supplementation, root colonization of Deinococcus increased in wild type, but decreased in irUVR8 and irCHAL plants compared to nontreated plants. Our results suggest that N. attenuata recruits a core root microbiome exclusively from soil, with fungal root colonization being less selective than bacterial colonization. Root colonization by Deinococcus depends on the plant's response to UVB.

Enzymes are widely used for peptide synthesis, both for coupling and for terminal activation and modification. Broad-specificity proteases of different mechanistic classes can be used for C-terminal activation and peptide coupling reactions, whereas enzymes that recognize specific sequences are increasingly used for selective modification and tagging. Protein engineering can tailor hydrolases for improved synthesis, better reaction medium tolerance, and desired substrate selectivity. This chapter highlights properties of natural and engineered peptidases, amidases, and peptide transferases for chemoenzymatic peptide synthesis and terminal modification, with an emphasis on basic principles and innovations leading to new applications.

The synthesis of optically active sulfoxides, compounds due to their unique properties, has been a main target for synthetic organic chemistry. Recent efforts in the field of biocatalysis have allowed the preparation of enantiopure sulfoxides starting from the corresponding sulfides while using relatively mild conditions. In fact, several different types of redox biocatalysts have been found that can catalyze enantio- and/or regioselective sulfoxidations. The most promising group of enzymes able to perform selective sulfoxidations is the flavin-containing monooxygenases (FMOs). Enzymes containing a flavin cofactor have already been widely studied and used in organic synthesis, especially in reduction and/or oxidation processes. This chapter highlights the recent efforts in the preparation of chiral sulfoxides catalyzed by different types of flavoenzymes, with special attention to the parameters that can improve their catalytic properties. Novel approaches that allow performing selective sulfoxidations in which modified flavin systems are used are also discussed.

Chirality is a key factor in the safety and efficacy of many drug products and thus producing single enantiomers of drug intermediates and drugs has become increasingly important in the pharmaceutical industry. There has been an increasing awareness of the enormous potential of microorganisms and enzymes derived from them for the transformation of synthetic chemicals with high chemo-, regio-, and enatioselectivities. In this article, biocatalytic processes are described for the synthesis of key chiral intermediates for development of pharmaceuticals and fine chemicals.

Chirality is a key factor for the safety and efficacy of many drug products. The production of single enantiomers of drug intermediates has become increasingly important in the pharmaceutical industry. There has been an enormous potential of microorganisms and enzymes derived from there for the transformation of synthetic chemicals with high chemo-, regio-, and enatioselectivities. Recent development in the area of directed evolution has led screen mutants under process conditions to increase activity and selectivity of biocatalysts, thus making the enzymatic process highly efficient and economically feasible. In this review, chemoenzymatic processes are described for the synthesis of chiral intermediates for the development of pharmaceuticals.

Background: Sacroiliac joints (SJ) involvement is a distinctive and charasteristic feature of Spondyloarthritis (SpA) and x-ray is the test routinely used to make a diagnosis. However, x-ray reveals late structural damage but cannot detect active inflammation. The objective of this study was to assess the validity of Doppler ultrasound in SJ. Methods: Prospective blinded and controlled study of SJ, in which three populations were compared. We studied 106 consecutive cases, who were divided into three groups: a) 53 patients diagnosed with SpA who had inflammatory lumbar and gluteal pain assessed by a rheumatologist; b) 26 patients diagnosed with SpA who didn't have SJ tenderness and had normal physical examination; c) control group of 27 subjects (healthy subjetcs or with mechanical lumbar pain). All patients included that were diagnosed with SpA met almost the European Spondyloarthropathy Study Group (ESSG) classification criteria. Physical examination of the SJ included: sacral sulcus tenderness, iliac gapping, iliac compression, midline sacral thrust test, Gaenslen's test, and Patrick s test were used as gold standard. Both SJ were examined with Doppler ultrasound (General Electric Logiq 9, Wauwatosa WI, USA) fitted with a 9-14 Mhz lineal probe. The ultrasonographer was blinded to clinical data. Doppler in SJ was assessed as positive when both Doppler colour and resistance index (RI)

Systematic laboratory scale experiments on coal blocks can provide significant insight into the underground coal gasification (UCG) process. Our earlier work has demonstrated the various features of the early UCG cavity shape and rate of growth through lab-scale experiments on coal combustion, wherein the feed gas is oxygen. In this paper, we study the feasibility of in situ gasification of coal in a similar laboratory scale reactor set-up, under conditions relevant for field practice of UCG, using an oxygen-steam mixture as the feed gas. By performing the gasification reaction in a cyclic manner, we have been able to obtain a product gas with hydrogen concentrations as high as 39% and a calorific value of 178 kJ/mol. The effect of various operating parameters such as feed temperature, feed steam to oxygen ratio, initial combustion time and so on, on the product gas composition is studied and the optimum operating conditions in order to achieve desired conversion to syngas, are determined. We also study the effect of various design and operating parameters on the evolution of the gasification cavity. Empirical correlations are proposed for the change in cavity volume and its dimensions in various directions. The results of the previous study on the combustion cavity evolution are compared with this gasification study. (C) 2011 Elsevier Ltd. All rights reserved.

Polypyrrole (PPy) was synthesized by chemical oxidative polymerization technique using monomer pyrrole and ammo-nium persulphate as an oxidant in a ratio of 1:1. Thin films of polypyrrole were prepared by dissolving polypyrrole in mcresol and cast using spin coating technique on glass substrates. Thin films of polypyrrole were characterized by X ray diffraction (XRD), Scanning electron microscopy (SEM), Fourier transform infra red spectroscopy (FTIR), UV visible spectroscopy and electrical resistivity by four probe method. The XRD spectra showed that the polypyrrole is amorphous in nature. SEM studies revealed a uniform granular structure of PPy. The FTIR spectra shows that the presence of all characteristics absorption peaks of polypyrrole that is, 890 cm?1 (=C–H out-of-plane vibration), 1040 cm?1 (=C–H in-plane vibration), 1170 cm?1 (N–C stretch bending) and 1410 cm?1 (pyrrole ring vibration). UV visible study shows PPy films exhibit absorption peak at 446 nm (2.77 eV). Room temperature electrical resistivity of PPy is in the critical regime of the metal –to –insulator (M-I) transition.

During underground coal gasification (UCG), a cavity is formed in the coal seam when coal is converted to gaseous products. This cavity grows three dimensionally in a nonlinear fashion as gasification proceeds. The cavity shape is determined by the flow field, which is a strong function of various parameters such as the position and orientation of the inlet nozzle and the temperature distribution and coal properties such as thermal conductivity. In addition to the complex flow patterns in the UCG cavity, several phenomena occur simultaneously. They include chemical reactions (both homogeneous and heterogeneous), water influx, thermomechanical failure of the coal, heat and mass transfer, and so on. Thus, enormous computational efforts are required to simulate the performance of UCG through a mathematical model. It is therefore necessary to simplify the modeling approach for relatively quick but reliable predictions for application in process design and optimization. The primary objective of this work is to understand the velocity distribution and quantify the nonideal flow patterns in a UCG cavity by performing residence time distribution (RTD) studies using computational fluid dynamics (CFD). The methodology of obtaining RTD by CFD is validated by means of of representative laboratory-scale tracer experiments. Based on the RTD studies, the actual UCG cavity at different times is modeled as a simplified network of ideal reactors, called compartments. The compartment model thus obtained could offer a computationally less expensive and easier option for determining UCG process performance at any given time, when used in a reactor-scale model including reactions. The network of ideal reactors can be easily simulated using a flowsheet simulator (e.g., Aspen Plus). We illustrate the proposed modeling approach by presenting selected simulation results for a single gas-phase second-order water gas shift reaction.

The (S)-amino acid, (S)-2-amino-3-(6-o-tolylpyridin-3-yl)propanoic acid (3), is a key intermediate needed for synthesis of an antidiabetic drug candidate. Three enzymatic routes to 3 were explored. (S)-Amino acid 3 could be prepared in 73% isolated yield with 99.9% ee from racemic amino acid 1 using (R)-amino acid oxidase from Trigonopsis variabilis expressed in Escherichia coli in combination with an (S)-aminotransferase using (S)-aspartate as amino donor. The (S)-aminotransferase was purified from a soil organism identified as Burkholderia sp. and cloned and expressed in E. coli. (S)-Amino acid 3 with 100% ee was also prepared in 68% solution yield and 54% isolated yield from 1 using recombinant (R)-amino acid oxidase from T. variabilis and an (S)-amino acid dehydrogenase from Sporosarcina ureae. The cofactor NADH required for the reductive amination reaction was regenerated using formate and formate dehydrogenase. The chemoenzymatic dynamic resolution of 1 by (R)-selective oxidation with Celite-immobil...

Cavity formation is an important phenomenon in the underground coal gasification (UCG) process. In the early stages of cavity formation, only the combustion reaction is performed in order to stabilize the temperature field. In the present work, we study the formation of the combustion cavity and the effect of various design and operating parameters such as the distance between the wells, feed flow rate and operation time, on its evolution. This paper presents details of laboratory-scale experiments that demonstrate the shape and size of the combustion cavity, and their dependence on various parameters. Empirical correlations for the cavity volume and dimensions in various directions are developed, which indicate the strong effects of mass transport. Results from computational fluid dynamics (CFD), which map the velocity profiles in the cavity, support the experimental observations.

A synthetic gene encoding a Streptomyces l -proline-3-hydroxylase was constructed and used to produce the hydroxylase protein in recombinant Escherichia coli. A fermentation process for growth of this recombinant E. coli for enzyme production was scaled-up to 250 L. A biotransformation process was developed using cell suspensions of the recombinant E. coli and subsequently scaled-up to 10 L for conversion of l -proline to cis-3-hydroxy- l -proline. A reaction yield of 85 M% and d.e. of 99.9% was obtained for cis-3-hydroxy- l -proline.

Calcineurin is an important signalling protein that regulates a number of molecular and cellular processes. Previously, we found that inhibition of calcineurin with cyclosporine reduced renal hypertrophy and blocked glomerular matrix expansion in the diabetic kidney. Isoforms of the catalytic subunit of calcineurin are reported to have tissue specific expression and functions. In particular, the β isoform has been implicated in cardiac and skeletal muscle hypertrophy. Therefore, we examined the role of calcineurin β in diabetic renal hypertrophy and glomerular matrix expansion. Type I diabetes was induced in wild-type and β(-/-) mice and then renal function, extracellular matrix expansion and hypertrophy were evaluated. The absence of β produced a significant decrease in total calcineurin activity in the inner medulla (IM) and reduced nuclear factor of activated T-cells (NFATc) activity. Loss of β did not alter diabetic renal dysfunction assessed by glomerular filtration rate, urine albumin excretion and blood urea nitrogen. Similarly, matrix expansion in the whole kidney and glomerulus was not different between diabetic wild-type and β(-/-) mice. In contrast, whole kidney and glomerular hypertrophy were significantly reduced in diabetic β(-/-) mice. Moreover, β(-/-) renal fibroblasts demonstrated impaired phosphorylation of Erk1/Erk2, c-Jun N-terminal kinases (JNK) and mammalian target of rapamycin (mTOR) following stimulation with transforming growth factor-β and did not undergo hypertrophy with 48 hrs culture in high glucose. In conclusion, loss of the β isoform of calcineurin is sufficient to reproduce beneficial aspects of cyclosporine on diabetic renal hypertrophy but not matrix expansion. Therefore, while multiple signals appear to regulate matrix, calcineurin β appears to be a central mechanism involved in organ hypertrophy.

Calcineurin is an important intracellular signaling molecule which can be inhibited by cyclosporin resulting in immune suppression and nephrotoxicity. Previously, we reported that homozygous loss of the α isoform of calcineurin impairs kidney development and function and mimics many features of cyclosporin nephrotoxicity. However, early lethality of null mice prevented further study of renal changes. Alternatively, we examined aged heterozygous (CnAα+/−) mice. In addition to renal dysfunction and inflammation, we find that CnAα+/− mice spontaneously develop tertiary lymphoid aggregates in the kidney, small intestine, liver, and lung. Lymphoid aggregates contain both T cells and B cells and exhibited organization suggestive of tertiary lymphoid organs (TLOs). Kidney function and TLO formation were highly correlated suggesting that this process may contribute to nephrotoxicity. Consistent with previous findings, transforming growth factor (TGF)-β is significantly increased in CnAα+/− mice. Neutralization of TGF-β attenuated TLO formation and improved kidney function. In conclusion, we report that haploinsufficiency of CnAα causes uregulation of TGF-β which contributes to chronic inflammation and formation of TLOs. While the process that leads to TLOs formation in transplant allografts is unknown, TLOs are associated with poor clinical prognosis. This study suggests that calcineurin inhibition itself may lead to TLO formation and that TGF-β may be a novel therapeutic target.