904 resultados para Strains and stresses.
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本文主要研究了从造纸厂碱性土壤中筛选得到的,能够产生耐碱木聚糖酶的两株放线菌X24-14和X15-17。通过16 S rRNA基因序列分析并结合菌株的形态特征以及生理生化特性,初步认为菌株X15-17为拟诺卡氏菌属(Nocardiopsis)的一个潜在新种;菌株X24-14为纤维化纤维菌(Cellulosimicrobium cellulans)。 在此基础上探索了菌株X24-14和菌株X15-17所产木聚糖酶的基本酶学性质。研究发现,两株菌所产的木聚糖酶的耐碱性均较强: 1)菌株X24-14所产的木聚糖酶,在pH 4.2~9.4的范围内能维持较高的活力,pH 9.4条件下,仍能保持80%的酶活力;2)菌株X15-17所产的木聚糖酶在pH 4.0~9.0的范围内能维持较高的活力,pH 9.0条件下,仍能保持80%的酶活力;3)两株菌所产的木聚糖酶均具有较好的pH稳定性,在pH 2.0~11.0范围内稳定,pH 11.0、4 ℃条件下处理24 h仍具有75%的活力。 本文还重点研究了菌株X24-14在不同培养基成分及不同培养条件下的产酶情况,确定了其适宜的产酶条件。结果显示,菌株X24-14的最适碳源为麸皮;最适氮源为蛋白胨;最适产酶pH为pH 8.5。菌株X24-14适宜的产酶条件为:麸皮60 g/L,蛋白胨10 g/L,K2HPO4 7.0 g/L,pH 8.5,接种量为5%,37 ℃,200 r/min发酵培养108 h。 Two strains of actinomycetes, X24-14 and X15-17, which produced alkali-tolerant xylanase were screened from the soil samples collected from a pulp mill in china. Based on the morphological, physiochemical characteristics and 16S rRNA sequence, X24-14 was priminarily identified as cellulosimicrobium cellulans ; X15-17 was priminarily identified as a new species of Nocardiopsis. The investigation examined the enzyme activities which produced by X24-14 and X15-17 under different pH and different temperatures. The results showed that : 1)The xylanase from X24-14 had characteristic of alkali-tolerance: It remains 80% relative activity at pH ranges between pH 4.2 and pH 9.4 under 50℃. 2)The xylanase from X15-17 also showed characteristic of alkali-tolerance, it remains 80% relative activity at pH ranges between pH 4.0and pH 9.0 under 50℃. 3)The xylanase from the two strains showed alkali-stable characteristics. They were stable at pH ranges between pH 2.0 and pH 11.0, showing 75% of its maximal activity remaining under 24 hours of treatment at 4℃. We also studied the effect of different growth conditions: carbon source, nitrogen sources, inoculum size, and initial pH on the production of xylanase of strain X24-14. The results showed that :The optimal carbon source was wheat bran; The optima nitrogen source was peptone; The maximum xylanase activity was achieved in the medium containing 60 g/L wheat bran, 10 g/L peptone, 7 g/L K2HPO4, inoculum size 5% and pH 8.5, under 37℃ in 108 h.
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Background: Serine/threonine kinases (STKs) have been found in an increasing number of prokaryotes, showing important roles in signal transduction that supplement the well known role of two-component system. Cyanobacteria are photoautotrophic prokaryotes able to grow in a wide range of ecological environments, and their signal transduction systems are important in adaptation to the environment. Sequence information from several cyanobacterial genomes offers a unique opportunity to conduct a comprehensive comparative analysis of this kinase family. In this study, we extracted information regarding Ser/Thr kinases from 21 species of sequenced cyanobacteria and investigated their diversity, conservation, domain structure, and evolution. Results: 286 putative STK homologues were identified. STKs are absent in four Prochlorococcus strains and one marine Synechococcus strain and abundant in filamentous nitrogen-fixing cyanobacteria. Motifs and invariant amino acids typical in eukaryotic STKs were conserved well in these proteins, and six more cyanobacteria- or bacteria-specific conserved residues were found. These STK proteins were classified into three major families according to their domain structures. Fourteen types and a total of 131 additional domains were identified, some of which are reported to participate in the recognition of signals or substrates. Cyanobacterial STKs show rather complicated phylogenetic relationships that correspond poorly with phylogenies based on 16S rRNA and those based on additional domains. Conclusion: The number of STK genes in different cyanobacteria is the result of the genome size, ecophysiology, and physiological properties of the organism. Similar conserved motifs and amino acids indicate that cyanobacterial STKs make use of a similar catalytic mechanism as eukaryotic STKs. Gene gain-and-loss is significant during STK evolution, along with domain shuffling and insertion. This study has established an overall framework of sequence-structure-function interactions for the STK gene family, which may facilitate further studies of the role of STKs in various organisms.
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Background: Serine/threonine kinases (STKs) have been found in an increasing number of prokaryotes, showing important roles in signal transduction that supplement the well known role of two-component system. Cyanobacteria are photoautotrophic prokaryotes able to grow in a wide range of ecological environments, and their signal transduction systems are important in adaptation to the environment. Sequence information from several cyanobacterial genomes offers a unique opportunity to conduct a comprehensive comparative analysis of this kinase family. In this study, we extracted information regarding Ser/Thr kinases from 21 species of sequenced cyanobacteria and investigated their diversity, conservation, domain structure, and evolution. Results: 286 putative STK homologues were identified. STKs are absent in four Prochlorococcus strains and one marine Synechococcus strain and abundant in filamentous nitrogen-fixing cyanobacteria. Motifs and invariant amino acids typical in eukaryotic STKs were conserved well in these proteins, and six more cyanobacteria- or bacteria-specific conserved residues were found. These STK proteins were classified into three major families according to their domain structures. Fourteen types and a total of 131 additional domains were identified, some of which are reported to participate in the recognition of signals or substrates. Cyanobacterial STKs show rather complicated phylogenetic relationships that correspond poorly with phylogenies based on 16S rRNA and those based on additional domains. Conclusion: The number of STK genes in different cyanobacteria is the result of the genome size, ecophysiology, and physiological properties of the organism. Similar conserved motifs and amino acids indicate that cyanobacterial STKs make use of a similar catalytic mechanism as eukaryotic STKs. Gene gain-and-loss is significant during STK evolution, along with domain shuffling and insertion. This study has established an overall framework of sequence-structure-function interactions for the STK gene family, which may facilitate further studies of the role of STKs in various organisms.
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The Ultrahigh Pressure Metamorphic (UHPM) eclogite, which was resulted from deep subduction of crustal continent, is very significant due to its continental dynamic implications. Further more, this kind of rocks experienced great P-T, fluid and stresses changes during its forming and exhumation, causing mineral reactions occur intensively, which resulted in a lot of fantastic micro-texture. The micro-texture was preserved duo to a rapid exhumation of the eclogite. This PhD dissertation takes such micro-textures in 10 Donghai eclogite samples South Sulu UHPM terrene, as research object to reveal the transformation of the eclogite to amphibolite. Microscope and Scanning Electron Microscope were employed to observe the micro-texture. Basing on microprobe analysis of minerals, the ACF projections and iso-con analysis were used to uncover the mineral reactions during the transformation. Micro-texture observation (both of Microcopy and Electron Scanning Microscope), demonstrated: l.The peak mineral assemblage of the researched Donghai eclogites is garnet + omphacite + rutile (+ kyanite + aptite +coesite). 2.The transformation of the Donghai eclogite to amphibolite can be divided into two stages: The earlier one is Symplectization, resulting in the forming of diopside + albite (+magnetite) symplectite that occurred only along the boundary between two adjacent omphacite grains. Other minerals were not involved in such reaction. The latter stage is Fluid-Infiltration of the eclogite, which was caused by fluid-intrusion. The infiltration is demonstrated by amphibolization of the symplectite, decomposition of garnet and the forming of some hydrous minerals such as phengite and epidote, and resulted in an amphibole + plagioclase + phengite + epidote or ziosite assemblage. Basing on microprobe analysis of the minerals, ACF projections indicated: In the ACF diagrams, the two joint lines of peak Grt + Omp and Dio + Ab crossed at Omp projection-point, indicating that the garnet had not taken part in the forming reaction of the Dio + Ab symplectite, just like that had been pointed out by micro-texture observation. In the ACF diagrams, the hornblende + plagioclase + epidote + phengite quadrilateral intersected with Dio + Ab + Grt triangle, demonstrating that the hydrous mineral assemblage was formed by fluid infiltration through garnet, diopside and albite. Iso-con (mass-balance) analysis of the symplectization and infiltration reveals: 1.The symplectization of the omphacite has a very complex mass exchange: Some symplectite gained only silicon from its surroundings; and some one requires Ca, but provides Na to its surroundings; while other symplectite provides Ca, Mg and Fe to its surroundings. 2.The infiltration cause variable mass exchanges occurring among the garnet, diopside and albite: In some eclogite sample, no mass, except H2O, exchange occurred during the infiltration. Meanwhile, there was not any hydrous mineral except hornblende formed in the sample accordingly. In some samples, the mass exchange among the three minerals is complex: amphibolization of the diopside in a symplectite gained Al from garnet, and provided Si and Ca to its surrounding, resulting in a Si, Ca and Al-rich fluid. Correspondingly, there was a lot of phengite and ziosite occurred in the sample. In other samples, the amphibolization of a symplectite provided Fe and Mg besides Si and Ca to its surrounding while gained Al. In such kind of sample, epidote occurred within the hydrous mineral assemblage. Synthesizing the micro-texture observation, ACF analysis and iso-con analysis, we deduced the transformation procedure as following: 1. A symplectite after an omphacite was resulted by one, or two, or all of following mineral reactions together: Jd (Ca-Tsch) +SiO2=Ab (An) (1) 4NaA IS i.A+CaO=2NaAlS i308+Na20+CaAl2S 1208 (2) 2NaAlSi2OB (Jd in Omp)+CaMgSi;,0B(Dio in Omp)-2NaAlSi:,O"(Ab)+Ca0+Mg0 (3) 2(CaAl2Si0fi) (Ca-tsch in Omp)+CaFeSi2O6(Hed in 0mp)-H>2CaAl2Si208(An)+Ca0 + FeO (4) A CO2-rich fluid is suggested as cataclysm for the above reactions, which largely increased the mobility of Ca, Mg and Na resulted from reaction (2), (3) and (4). The immobile product Fe2* combined with rutile to form ilmenite, resulting in rutile + ilmenite symplectite. Or, the Fe was precipitated as hematite locally. A procedure of the fluid infiltration as following is suggested: I .A hydrous fluid intruded into the eclogite, and reacted first with garnet to form hornblende and extra Al, resulting in a hornblende film around the garnet grain and an Al-rich fluid. 2.The Al-rich fluid infiltrated through the symplectite, OH" and part of the Al in the fluid combined with Dio while some Si and Ca in the Dio were dissolved made the Dio transferred to amphibole. Meanwhile, plagioclase-type cation exchange occurred between the fluid and plagioclase in the symplectite, making the plagioclase have a higher An-content. 3.Above infiltration and cation exchange resulted in an Al, Si, Ca (and K, providing the primary hydrous fluid contain K)-rich fluid. 4.Under suitable conditions, the solute in the fluid precipitated to form phengite firstly. After the K element in the fluid was consumed up, ziosite or epidote was formed. If the fluid did not contain any K. element, only ziosite or epidote was precipitated. For those eclogites, where all omphacite had been replaced by symplectite before infiltration, neither element exchange occurred, nor did phengite or epidote form during the infiltration. At the last stage, the garnet was oxidized and breakdown: garnet + H2O = epidote + hornblende + hematite, due to more and more fluid intruding into the eclogite. At this time, all the peak minerals were replaced by amphibolite-phase ones, and the eclogite transformed to an amphibolite completely. Tentative pressure calculation indicates that the infiltration occurred at 3-6kbar (about 10-20km depth), where the deformation mechanics transformed from brittle to ductile yield. At such depth, the surface water can permeate the rocks through fault system, causing a rapid cooling.
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Cox, S.J. (2006) The mixing of bubbles in two-dimensional bidisperse foams under extensional shear. Journal of Non-Newtonian Fluid Mechanics . 137:39-45.
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Crohn’s disease (CD) is a chronic, relapsing inflammatory condition affecting the gastrointestinal tract of humans, of which there is currently no cure. The precise etiology of CD is unknown, although it has become widely accepted that it is a multifactorial disease which occurs as a result of an abnormal immune response to commensal enteric bacteria in a genetically susceptible host. Recent studies have shown that a new group of Escherichia coli, called Adherent Invasive Escherichia coli (AIEC) are present in the guts of CD patients at a higher frequency than in healthy subjects, suggesting that they may play a role in the initiation and/or maintenance of the inflammation associated with CD. Two phenotypes define an AIEC and differentiate them from other groups of E. coli. Firstly, AIEC can adhere to and invade epithelial cells; and secondly, they can replicate in macrophages. In this study, we use a strain of AIEC which has been isolated from the colonic mucosa of a CD patient, called HM605, to examine the relationship between AIEC and the macrophage. We show, using a systematic mutational approach, that while the Tricarboxylic acid (TCA) cycle, the glyoxylate pathway, the Entner-Doudoroff (ED) pathway, the Pentose Phosphate (PP) pathway and gluconeogenesis are dispensable for the intramacrophagic growth of HM605, glycolysis is an absolute requirement for the ability of this organism to replicate intracellularly. We also show that HM605 activates the inflammasome, a major driver of inflammation in mammals. Specifically, we show that macrophages infected with HM605 produce significantly higher levels of the pro-inflammatory cytokine IL-1β than macrophages infected with a non-AIEC strain, and we show by immunoblotting that this is due to cleavage of caspase-1. We also show that macrophages infected with HM605 exhibit significantly higher levels of pyroptosis, a form of inflammatory cell death, than macrophages infected with a non-AIEC strain. Therefore, AIEC strains are more pro-inflammatory than non-AIEC strains and this may have important consequences in terms of CD pathology. Moreover, we show that while inflammasome activation by HM605 is independent of intracellular bacterial replication, it is dependent on an active bacterial metabolism. Through the establishment of a genetic screen aimed at identifying mutants which activate the inflammasome to lower levels than the wild-type, we confirm our observation that bacterial metabolism is essential for successful inflammasome activation by HM605 and we also uncover new systems/structures that may be important for inflammasome activation, such as the BasS/BasR two-component system, a type VI secretion system and a K1 capsule. Finally, in this study, we also identify a putative small RNA in AIEC strain LF82, which may be involved in modulating the motility of this strain. Overall this works shows that, in the absence of specialised virulence factors, the ability of AIEC to metabolise within the host cell may be a key determinant of its pathogenesis.
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Mitochondria are responsible for producing the vast majority of cellular ATP, and are therefore critical to organismal health [1]. They contain thir own genomes (mtDNA) which encode 13 proteins that are all subunits of the mitochondrial respiratory chain (MRC) and are essential for oxidative phosphorylation [2]. mtDNA is present in multiple copies per cell, usually between 103 and 104 , though this number is reduced during certain developmental stages [3, 4]. The health of the mitochondrial genome is also important to the health of the organism, as mutations in mtDNA lead to human diseases that collectively affect approximately 1 in 4000 people [5, 6]. mtDNA is more susceptible than nuclear DNA (nucDNA) to damage by many environmental pollutants, for reasons including the absence of Nucleotide Excision Repair (NER) in the mitochondria [7]. NER is a highly functionally conserved DNA repair pathway that removes bulky, helix distorting lesions such as those caused by ultraviolet C (UVC) radiation and also many environmental toxicants, including benzo[a]pyrene (BaP) [8]. While these lesions cannot be repaired, they are slowly removed through a process that involves mitochondrial dynamics and autophagy [9, 10]. However, when present during development in C. elegans, this damage reduces mtDNA copy number and ATP levels [11]. We hypothesize that this damage, when present during development, will result in mitochondrial dysfunction and increase the potential for adverse outcomes later in life.
To test this hypothesis, 1st larval stage (L1) C. elegans are exposed to 3 doses of 7.5J/m2 ultraviolet C radiation 24 hours apart, leading to the accumulation of mtDNA damage [9, 11]. After exposure, many mitochondrial endpoints are assessed at multiple time points later in life. mtDNA and nucDNA damage levels and genome copy numbers are measured via QPCR and real-time PCR , respectively, every 2 day for 10 days. Steady state ATP levels are measured via luciferase expressing reporter strains and traditional ATP extraction methods. Oxygen consumption is measured using a Seahorse XFe24 extra cellular flux analyzer. Gene expression changes are measured via real time PCR and targeted metabolomics via LC-MS are used to investigate changes in organic acid, amino acid and acyl-carnitine levels. Lastly, nematode developmental delay is assessed as growth, and measured via imaging and COPAS biosort.
I have found that despite being removed, UVC induced mtDNA damage during development leads to persistent deficits in energy production later in life. mtDNA copy number is permanently reduced, as are ATP levels, though oxygen consumption is increased, indicating inefficient or uncoupled respiration. Metabolomic data and mutant sensitivity indicate a role for NADPH and oxidative stress in these results, and exposed nematodes are more sensitive to the mitochondrial poison rotenone later in life. These results fit with the developmental origin of health and disease hypothesis, and show the potential for environmental exposures to have lasting effects on mitochondrial function.
Lastly, we are currently working to investigate the potential for irreparable mtDNA lesions to drive mutagenesis in mtDNA. Mutations in mtDNA lead to a wide range of diseases, yet we currently do not understand the environmental component of what causes them. In vitro evidence suggests that UVC induced thymine dimers can be mutagenic [12]. We are using duplex sequencing of C. elegans mtDNA to determine mutation rates in nematodes exposed to our serial UVC protocol. Furthermore, by including mutant strains deficient in mitochondrial fission and mitophagy, we hope to determine if deficiencies in these processes will further increase mtDNA mutation rates, as they are implicated in human diseases.
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In recognition of the differences of scale between the welding pool and the heat affected zone along the welding line on one hand, and the overall size of the components being welded on the other, a local-global finite element approach was developed for the evaluation of distortions in laser welded shipbuilding parts. The approach involves the tandem use of a 'local' and a 'global' step. The local step involves a three-dimensional finite element model for the simulation of the laser welding process using the Sysweld finite element code, which takes into account thermal, metallurgical, and mechanical aspects. The simulation of the laser welding process was performed using a non-linear heat transfer analysis, based on a keyhole formation model, and a coupled transient thermomechanical analysis, which takes into account metallurgical transformations using the temperature dependent material properties and the continuous cooling transformation diagram. The size and shape of the keyhole used in the local finite element analysis was evaluated using a keyhole formation model and the Physica finite volume code. The global step involves the transfer of residual plastic strains and the stiffness of the weld obtained from the local model to the global analysis, which then provides the predicted distortions for the whole part. This newly developed methodology was applied to the evaluation of global distortions due to laser welding of stiffeners on a shipbuilding part. The approach has been proved reliable in comparison with experiments and of practical industrial use in terms of computing time and storage.
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Analysis of the bacterial population of soil surface samples from a creosote-contaminated site showed that up to 50% of the culturable micro-organisms detected were able to utilise a mixture of cresols. From fifty different microbial isolates fourteen that could utilise more than one cresol isomer were selected and identified by 16S rRNA analysis. Eight isolates were Rhodococcus strains and six were Pseudomonas strains. In general, the Rhodococcus strains exhibited a broader growth substrate range than the Pseudomonas strains. The distribution of various extradiol dioxygenase (edo) genes, previously associated with aromatic compound degradation in rhodococci, was determined for the Rhodococcus strains by PCR detection and Southern-blot hybridization. One strain, Rhodococcus sp. I1 exhibited the broadest growth substrate range and possessed five different edo genes. Gene disruption experiments indicated that two genes (edoC and edoD) were associated with isopropylbenzene and naphthalene catabolism respectively. The other Rhodococcus strains also possessed some of the edo genes and one (edoB) was present in all of the Rhodococcus strains analysed. None of the rhodococcal edo genes analysed were present in the Pseudomonas strains isolated from the site. It was concluded that individual strains of Rhodococcus possess a wide degradative ability and may be very important in the degradation of complex mixtures of substrates found in creosote.
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The impact of the alternative sigma factor sigma B (SigB) on pathogenesis of Staphylococcus aureus is not conclusively clarified. In this study, a central venous catheter (CVC) related model of multiorgan infection was used to investigate the role of SigB for the pathogenesis of S. aureus infections and biofilm formation in vivo. Analysis of two SigB-positive wild-type strains and their isogenic mutants revealed uniformly that the wild-type was significantly more virulent than the SigB-deficient mutant. The observed difference in virulence was apparently not linked to the capability of the strains to form biofilms in vivo since wild-type and mutant strains were able to produce biofilm layers inside of the catheter. The data strongly indicate that the alternative sigma factor SigB plays a role in CVC-associated infections caused by S. aureus.
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A split-EGFP bimolecular fluorescence complementation assay was used to visualise and locate three interacting pairs of proteins from the GAL genetic switch of the budding yeast, Saccharomyces cerevisiae. Both the Gal4p-Gal80p and Gal80p-Gal3p pairs were found to be located in the nucleus under inducing conditions. However, the Gal80p-Gal1p complex was located throughout the cell. These results support recent work establishing an initial interaction between Gal3p and Gal80p occurring in the nucleus. Labelling of all three protein pairs impaired the growth of the yeast strains and resulted in reduced galactokinase activity in cell extracts. The most likely cause of this impairment is decreased dissociation rates of the complexes, caused by the essentially irreversible reassembly of the EGFP fragments. This suggests that a fully functional GAL genetic switch requires dynamic interactions between the protein components. These results also highlight the need for caution in the interpretation of in vivo split-EGFP experiments.
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Initial sizing procedures for aircraft stiffened panels that include the influence of welding fabrication residual process effects are missing. Herein, experimental and Finite Element analyses are coupled to generate knowledge to formulate an accurate and computationally efficient sizing procedure which will enable designers to routinely consider panel fabrication, via welding, accounting for the complex distortions and stresses induced by this manufacturing process. Validating experimental results demonstrate the need to consider welding induced material property degradation, residual stresses and distortions, as these can reduce static strength performance. However, results from fuselage and wing trade-studies, using the validated sizing procedure, establish that these potential reductions in strength performance may be overcome through local geometric tailoring during initial sizing, negating any weight penalty for the majority of design scenarios.
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Objectives: There is great urgency for alternate sources of antibiotics to be identified. One relatively untapped source of novel bioproducts, including antimicrobials, is organisms derived from extreme environments. Halophiles (which require high salt concentrations) are one such group which is being increasingly explored for their biotechnological potential. The aim of this study was to identify halophilic environmental isolates which possessed in vitro and in vivo antimicrobial and antibiofilm activities. Methods: 73 halophilic bacteria and archaea were isolated from Kilroot salt mine in Northern Ireland. Culture extracts of each isolate were screened for antimicrobial and antibiofilm activity against numerous pathogenic bacteria, including Staphylococcus species and Pseudomonas aeruginosa, both model strains and clinical isolates. The methods used included disc diffusion assays of crude extracts, MIC screening, the MBEC assay, and an in vivo model based on the Greater Wax Moth (Galleria mellonella). Results: The assays indicated >50% of extracts displayed antimicrobial and antibiofilm activity against at least one pathogen, the majority being Staphylococcus species, but also E. coli and P. aeruginosa. Biofilms were either reduced or eradicated by halophile extracts when tested with the MBEC device. Further experiments demonstrated that these effects could be replicated in vivo, with extracts reducing the severity of infections and enhancing the survival of infected G. mellonella. Conclusions: The importance of extremophiles to pharmaceutical research should not be underestimated. While not yet fully characterised, based on the data obtained, the halophiles isolated during this study may provide a promising reservoir of novel antimicrobial and antibiofilm compounds.
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We have developed an instrument to study the behavior of the critical current density (J(c)) in superconducting wires and tapes as a function of field (mu(0)H), temperature (T), and axial applied strain (epsilon(a)). The apparatus is an improvement of similar devices that have been successfully used in our institute for over a decade. It encompasses specific advantages such as a simple sample layout, a well defined and homogeneous strain application, the possibility of investigating large compressive strains and the option of simple temperature variation, while improving the main drawback in our previous systems by increasing the investigated sample length by approximately a factor of 10. The increase in length is achieved via a design change from a straight beam section to an initially curved beam, placed perpendicular to the applied field axis in the limited diameter of a high field magnet bore. This article describes in detail the mechanical design of the device and its calibrations. Additionally initial J(c)(epsilon(a)) data, measured at liquid helium temperature, are presented for a bronze processed and for a powder-in-tube Nb3Sn superconducting wire. Comparisons are made with earlier characterizations, indicating consistent behavior of the instrument. The improved voltage resolution, resulting from the increased sample length, enables J(c) determinations at an electric field criterion E-c=10 muV/m, which is substantially lower than a criterion of E-c=100 muV/m which was possible in our previous systems. (C) 2004 American Institute of Physics.
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Purpose: To determine differences in overall tumor responses measured by volumetric assessment and bioluminescence imaging (BLI) following exposure to uniform and non-uniform radiation fields in an ectopic prostate tumor model.
Materials and methods: Bioluminescent human prostate tumor xenografts were established by subcutaneous implantation into male mice. Tumors were irradiated with uniform or non-uniform field configurations using conventional in vivo irradiation procedures performed using a 225 kVp generator with custom lead shielding. Tumor responses were measured using Vernier calipers and by BLI using an in vivo imaging system. Survival was defined as the time to quadroupling of pre-treatment tumor volume.
Results: The correlation between BLI and tumor volume measurements was found to be different for un-irradiated (R = 0.61), uniformly irradiated (R = 0.34) and partially irradiated (R = 0.30) tumors. Uniformly irradiated tumors resulted in an average tumor growth delay of 60 days with median survival of 75 days, compared to partially irradiated tumors which showed an average growth delay of 24 days and median survival of 38 days.
Conclusions: Correlation between BLI and tumor volume measurements is lower for partially irradiated tumors than those exposed to uniform dose distributions. The response of partially irradiated tumors suggests non-uniformity in response beyond physical dose distribution within the target volume. Dosimetric uncertainty associated with conventional in vivo irradiation procedures prohibits their ability to accurately determine tumor response to non-uniform radiation fields and stresses the need for image guided small animal radiation research platforms.