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Several Fold (several + fold)
Selected AbstractsIdentification of optimal poultry litter biorefinery location in Alabama through minimization of feedstock transportation costENVIRONMENTAL PROGRESS & SUSTAINABLE ENERGY, Issue 4 2008Burak Aksoy Abstract The estimated amount of poultry litter produced annually in Alabama is more than 1,250,000 tons. This large amount results in significant litter management challenges. Currently, poultry producers are facing many regulatory issues and challenges with respect to environmental impacts of litter management. Commercialization and implementation of environmentally benign biorefinery technologies have the potential to generate electric power (including on-site power) and heat as well as transportation fuels, hydrogen, valuable chemicals, and fertilizer from poultry litter economically while addressing environmental problems caused by traditional disposal practices. In this study, poultry litter generated annually in northern and southern Alabama was documented on the basis of published literature, and transportation cost of poultry litter is minimized for both north and south Alabama by the selection of the best large-scale biorefining facility location and optimal feedstock allocation using mathematical optimization techniques. The available portion of the existing poultry litter feedstock for a large scale biorefinery is found to be an important factor in determining transportation cost. Transportation cost increases several fold as the local feedstock availability for biorefining reduces from 100 to 50%. Optimum facility locations for both north and south Alabama were found within a 10 mile radius for three different poultry litter feedstock availabilities. © 2008 American Institute of Chemical Engineers Environ Prog, 2008 [source] Extra terminal residues have a profound effect on the folding and solubility of a Plasmodium falciparum sexual stage-specific protein over-expressed in Escherichia coliFEBS JOURNAL, Issue 21 2002Sushil Prasad Sati The presence of extra N- and C- terminal residues can play a major role in the stability, solubility and yield of recombinant proteins. Pfg27 is a 27K soluble protein that is essential for sexual development in Plasmodium falciparum. It was over-expressed using the pMAL-p2 vector as a fusion protein with the maltose binding protein. Six different constructs were made and each of the fusion proteins were expressed and purified. Our results show that the fusion proteins were labile and only partially soluble in five of the constructs resulting in very poor yields. Intriguingly, in the sixth construct, the yield of soluble fusion protein with an extended carboxyl terminus of 17 residues was several fold higher. Various constructs with either N-terminal or smaller C-terminal extensions failed to produce any soluble fusion protein. Furthermore, all five constructs produced Pfg27 that precipitated after protease cleavage from its fusion partner. The sixth construct, which produced soluble protein in high yields, also gave highly stable and soluble Pfg27 after cleavage of the fusion. These results indicate that extra amino acid residues at the termini of over-expressed proteins can have a significant effect on the folding of proteins expressed in E. coli. Our data suggest the potential for development of a novel methodology, which will entail construction of fusion proteins with maltose binding protein as a chaperone on the N-terminus and a C-terminal ,solubilization tag'. This system may allow large-scale production of those proteins that have a tendency to misfold during expression. [source] Thrombin induces cyclooxygenase-2 expression and prostaglandin E2 release via PAR1 activation and ERK1/2- and p38 MAPK-dependent pathway in murine macrophagesJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 5 2009Huey-Ming Lo Abstract Thrombin levels increase at sites of vascular injury and during acute coronary syndromes. It is also increased several fold by sepsis with a reciprocal decrease in the anti-thrombin III levels. In this study we investigate the effects of thrombin on the induction of cyclooxygenase-2 (COX-2) and prostaglandin (PG) production in macrophages. Thrombin-induced COX-2 protein and mRNA expression in RAW264.7 and primary cultured peritoneal macrophages. A serine proteinase, trypsin, also exerted a similar effect. The inducing effect by thrombin in macrophages was not affected by a lipopolysaccharide (LPS)-binding antibiotic, polymyxin B, excluding the possibility of LPS contamination. The increase of COX-2 expression by thrombin was functionally linked to release of PGE2 and PGI2 but not thromboxane A2 into macrophage culture medium. Thrombin-induced COX-2 expression and PGE2 production were significantly attenuated by PD98059 and SB202190 but not by SP600125, suggesting that ERK1/2 and p38 MAPK activation were involved in this process. This was supported by the observation that thrombin could directly activate ERK1/2 and p38 MAPK in macrophages. A further analysis indicated that the proteinase-activated receptor 1 (PAR1)-activating agonist induced effects similar to those induced by thrombin in macrophages and the PAR1 antagonist-SCH79797 could attenuate thrombin-induced COX-2 expression and PGE2 release. Taken together, we provided evidence demonstrating that thrombin can induce COX-2 mRNA and protein expression and PGE2 production in macrophages through PAR1 activation and ERK1/2 and p38 MAPK-dependent pathway. The results presented here may explain, at least in part, the possible contribution of thrombin and macrophages in these pathological conditions. J. Cell. Biochem. 108: 1143,1152, 2009. © 2009 Wiley-Liss, Inc. [source] Lipophilic cationic drugs increase the permeability of lysosomal membranes in a cell culture system,JOURNAL OF CELLULAR PHYSIOLOGY, Issue 1 2010Johannes Kornhuber Lysosomes accumulate many drugs several fold higher compared to their extracellular concentration. This mechanism is believed to be responsible for many pharmacological effects. So far, uptake and release kinetics are largely unknown and interactions between concomitantly administered drugs often provoke mutual interference. In this study, we addressed these questions in a cell culture model. The molecular mechanism for lysosomal uptake kinetics was analyzed by live cell fluorescence microscopy in SY5Y cells using four drugs (amantadine, amitriptyline, cinnarizine, flavoxate) with different physicochemical properties. Drugs with higher lipophilicity accumulated more extensively within lysosomes, whereas a higher pKa value was associated with a more rapid uptake. The drug-induced displacement of LysoTracker was neither caused by elevation of intra-lysosomal pH, nor by increased lysosomal volume. We extended our previously developed numerical single cell model by introducing a dynamic feedback mechanism. The empirical data were in good agreement with the results obtained from the numerical model. The experimental data and results from the numerical model lead to the conclusion that intra-lysosomal accumulation of lipophilic xenobiotics enhances lysosomal membrane permeability. Manipulation of lysosomal membrane permeability might be useful to overcome, for example, multi-drug resistance by altering subcellular drug distribution. J. Cell. Physiol. 224:152,164, 2010 © 2010 Wiley-Liss, Inc. [source] Application of torsion angle molecular dynamics for efficient sampling of protein conformationsJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 15 2005Jianhan Chen Abstract We investigate the application of torsion angle molecular dynamics (TAMD) to augment conformational sampling of peptides and proteins. Interesting conformational changes in proteins mainly involve torsional degrees of freedom. Carrying out molecular dynamics in torsion space does not only explicitly sample the most relevant degrees of freedom, but also allows larger integration time steps with elimination of the bond and angle degrees of freedom. However, the covalent geometry needs to be fixed during internal coordinate dynamics, which can introduce severe distortions to the underlying potential surface in the extensively parameterized modern Cartesian-based protein force fields. A "projection" approach (Katritch et al. J Comput Chem 2003, 24, 254,265) is extended to construct an accurate internal coordinate force field (ICFF) from a source Cartesian force field. Torsion crossterm corrections constructed from local molecular fragments, together with softened van der Waals and electrostatic interactions, are used to recover the potential surface and incorporate implicit bond and angle flexibility. MD simulations of dipeptide models demonstrate that full flexibility in both the backbone ,/, and side chain ,1 angles are virtually restored. The efficacy of TAMD in enhancing conformational sampling is then further examined by folding simulations of small peptides and refinement experiments of protein NMR structures. The results show that an increase of several fold in conformational sampling efficiency can be reliably achieved. The current study also reveals some complicated intrinsic properties of internal coordinate dynamics, beyond energy conservation, that can limit the maximum size of the integration time step and thus the achievable gain in sampling efficiency. © 2005 Wiley Periodicals, Inc. J Comput Chem 26: 1565,1578, 2005 [source] Absence of detectable measles virus genome sequence in blood of autistic children who have had their MMR vaccination during the routine childhood immunization schedule of UKJOURNAL OF MEDICAL VIROLOGY, Issue 5 2006M.A. Afzal Abstract Leukocyte preparations from children with documented evidence of MMR vaccination and confirmed diagnosis of autism were examined by several assays designed to target multiple regions of the measles virus genome sequence. No sample was found positive by any method. The assays applied were highly sensitive, specific and robust in nature, and were based on the amplification of measles virus RNA transcripts by real-time quantitative RT-PCR (QRT-PCR) as well as by conventional RT-PCR-nested PCR. The assays applied were potentially able to detect measles virus RNA down to single figure copy numbers per reaction. The amount of total nucleic acid extract of leukocytes subjected to various measles virus-specific investigations was several fold higher than minimally required of a sample where measles virus persistence is well documented. This study failed to substantiate reports of the persistence of measles virus in autistic children with development regression. J. Med. Virol. 78:623,630, 2006. © 2006 Wiley-Liss, Inc. [source] Stiffness, viscosity, and upper-limb inertia about the glenohumeral abduction axisJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 1 2000Li-Qun Zhang To evaluate the dynamic properties of the shoulder and understand how they are controlled by the central nervous system, glenohumeral-joint stiffness and viscosity and upper-limb inertia were quantified under various levels of muscle contraction in seven healthy human subjects. Through a cast attachment, the upper limb was perturbed in a precise pattern by a computer-controlled servomotor to manifest the dynamic properties of the joint. The recorded joint position and torque were used to estimate joint stiffness and viscosity and upper-limb inertia. With moderate muscle contraction, the stiffness and viscosity increased several fold. A stiffer shoulder joint associated with stronger muscle contraction made the shoulder more stable and protected it from potential injuries during strenuous tasks. Joint viscosity, especially the stronger viscous damping associated with more strenuous contraction, smoothed shoulder movement and stabilized the joint. From the control viewpoint, the glenohumeral joint responded to the central nervous system more quickly with increasing muscle contraction, which was useful during strenuous tasks. On the other hand, the central nervous system controlled stiffness and viscosity synchronously so that it dealt with only a nearly constant damping ratio of the joint over various levels of contraction, which simplified its task substantially. This approach quantified the dynamic and static properties of the shoulder under various levels of contraction more accurately and completely than a manual test, and it can potentially be used to evaluate changes in these properties caused by musculoskeletal injuries and their surgical treatments. [source] Differential expression of three members of the AMT1 gene family encoding putative high-affinity NH4+ transporters in roots of Oryza sativa subspecies indicaPLANT CELL & ENVIRONMENT, Issue 6 2003A. KUMAR ABSTRACT In order to investigate the molecular basis of high-affinity ammonium absorption by roots of rice plants (Oryza sativa subspecies indica) the expression patterns of three members of the AMT1 family of genes in rice seedling roots in response to altered nitrogen provision and diurnal changes in irradiance were examined. The 13NH4+ influx and transcript levels of OsAMT1.1 in roots decreased several fold within 48 h when plants acclimated to 10 µm external NH4+ for 3 weeks were transferred to 10 mm NH4+. Likewise when plants acclimated in 10 mm NH4+ were transferred to 10 µm NH4+, there was an equally rapid up-regulation of OsAMT1.1 and 13NH4+ influx in the roots. Changes in transcript abundance of OsAMT1.2 following these treatments were approximately 50% less than in OsAMT1.1, and changes of OsAMT1.3 expression were even less. By contrast, in response to the diurnal changes of irradiance, root transcript abundance of OsAMT1.3 and 15NH4+ influx increased approximately three-fold late in the photoperiod, whereas OsAMT1.1 and OsAMT1.2 exhibited only modest changes. The present results suggest that high-affinity NH4+ influx is differentially regulated at the transcriptional level through the expression of three members of the OsAMT1 family of genes in roots of rice seedlings in response to changes of N status and daily irradiance. In general, these findings are in agreement with earlier observations in Arabidopsis and tomato. [source] Rofecoxib is a potent inhibitor of cytochrome P450 1A2: studies with tizanidine and caffeine in healthy subjectsBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 3 2006Janne T. Backman Aims Case reports suggest an interaction between rofecoxib and the CYP1A2 substrate tizanidine. Our objectives were to explore the extent and mechanism of this possible interaction and to determine the CYP1A2 inhibitory potency of rofecoxib. Methods In a randomized, double-blind, two-phase cross-over study, nine healthy subjects took 25 mg rofecoxib or placebo daily for 4 days and, on day 4, each ingested 4 mg tizanidine. Plasma concentrations and the urinary excretion of tizanidine, its metabolites (M) and rofecoxib, and pharmacodynamic variables were measured up to 24 h. On day 3, a caffeine test was performed to estimate CYP1A2 activity. Results Rofecoxib increased the area under the plasma concentration,time curve (AUC0,,) of tizanidine by 13.6-fold [95% confidence interval (CI) 8.0, 15.6; P < 0.001), peak plasma concentration (Cmax) by 6.1-fold (4.8, 7.3; P < 0.001) and elimination half-life (t1/2) from 1.6 to 3.0 h (P < 0.001). Consequently, rofecoxib markedly increased the blood pressure-lowering and sedative effects of tizanidine (P < 0.05). Rofecoxib increased several fold the tizanidine/M-3 and tizanidine/M-4 ratios in plasma and urine and the tizanidine/M-5, tizanidine/M-9 and tizanidine/M-10 ratios in urine (P < 0.05). In addition, it increased the plasma caffeine/paraxanthine ratio by 2.4-fold (95% CI 1.4, 3.4; P = 0.008) and this ratio correlated with the tizanidine/metabolite ratios. Finally, the AUC0,25 of rofecoxib correlated with the placebo phase caffeine/paraxanthine ratio (r = 0.80, P = 0.01). Conclusions Rofecoxib is a potent inhibitor of CYP1A2 and it greatly increases the plasma concentrations and adverse effects of tizanidine. The findings suggest that rofecoxib itself is also metabolized by CYP1A2, raising concerns about interactions between rofecoxib and other CYP1A2 substrate and inhibitor drugs. [source] Antiviral prodrugs , the development of successful prodrug strategies for antiviral chemotherapyBRITISH JOURNAL OF PHARMACOLOGY, Issue 1 2006Erik De Clercq Following the discovery of the first effective antiviral compound (idoxuridine) in 1959, nucleoside analogues, especially acyclovir (ACV) for the treatment of herpesvirus infections, have dominated antiviral therapy for several decades. However, ACV and similar acyclic nucleosides suffer from low aqueous solubility and low bioavailability following oral administration. Derivatives of acyclic nucleosides, typically esters, were developed to overcome this problem and valaciclovir, the valine ester of ACV, was among the first of a new series of compounds that were readily metabolized upon oral administration to produce the antiviral nucleoside in vivo, thus increasing the bioavailility by several fold. Concurrently, famciclovir was developed as an oral formulation of penciclovir. These antiviral ,prodrugs' thus established a principle that has led to many successful drugs including both nucleoside and nucleotide analogues for the control of several virus infections, notably those caused by herpes-, retro- and hepatitisviruses. This review will chart the origins and development of the most important of the antiviral prodrugs to date. British Journal of Pharmacology (2006) 147, 1,11. doi:10.1038/sj.bjp.0706446 [source] Assessment of potential ecological disruption based on heavy metal toxicity, accumulation and distribution in media of the Lagos LagoonAFRICAN JOURNAL OF ECOLOGY, Issue 4 2007Otitoloju A. Adebayo Abstract Toxicity evaluations of heavy metals against three benthic animals, Tympanotonus fuscatus, Clibanarius africanus and Sesarma huzardi of the Lagos Lagoon were carried out under laboratory conditions. On the basis of the 96hLC50 values, Cd was found to be the most toxic metal tested followed by Cu, Zn and Pb, in a descending order of toxicity against T. fuscatus and S. huzardi; however, against C. africanus, Cu was the most toxic followed by Cd, Zn and Pb (least toxic). The determination of the metal concentrations in the water column and sediment of the Lagos Lagoon revealed that these media of the lagoon contained measurable concentrations of heavy metals but the levels were still several folds lower than the concentrations that will cause 50% mortality of exposed animals under laboratory conditions. The significance of the observed differences between the 96hLC50 values of the test metals, the concentration of heavy metals detected in tissues of field animals and ambient levels of the metals in the Lagos lagoon were discussed in relation to the protection of aquatic lives and potential public health risks. The need to verify the possibilities of synergistic interactions between the constituent metals when acting jointly against the exposed animals was recommended. Resume On a procédé en laboratoire à des évaluations de la toxicité des métaux lourds chez trois animaux benthiques, Tympanotonus fuscatus, Clibanarius africanus et Sesarma huzardi, du lagon de Lagos. Sur la base des valeurs de 96hLC50, on a trouvé que le Cd était le métal testé le plus toxique suivi par le Cu, le Zn et le Pb, en ordre de toxicité décroissant pour T. fuscatus et S. huzardi; cependant, pour C. africanus, le Cu était le plus toxique, suivi par Zn et Pb (le moins toxique). La détermination des concentrations de métaux dans l'eau et les sédiments du lagon de Lagos a révélé que ces milieux contenaient des concentrations mesurables de métaux lourds, mais que les niveaux étaient encore plusieurs fois plus bas que les concentrations qui causaient 50% de mortalité chez les animaux qui y étaient exposés en laboratoire. La signification des différences constatées entre les valeurs de 96hLC50 des métaux testés, la concentration des métaux lourds détectés dans les tissus des animaux du lagon et les niveaux observés dans le lagon ont été discutés en relation avec la protection de la vie aquatique et des risques potentiels pour la santé des personnes. On a recommandé de vérifier s'il est possible qu'il existe des interactions synergiques entre les métaux constituants lorsqu'ils agissent conjointement sur les animaux qui y sont exposés. [source] | ||||||||||||||||