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Local Changes (local + change)
Selected AbstractsLearning from others: the scope and challenges for participatory disaster risk assessmentDISASTERS, Issue 4 2007Mark Pelling This paper develops a framework based on procedural, methodological and ideological elements of participatory vulnerability and risk assessment tools for placing individual approaches within the wide range of work that claims a participatory, local or community orientation. In so doing it draws on relevant experience from other areas of development practice from which the disasters field can learn. Participatory disaster risk assessments are examined for their potential to be empowering, to generate knowledge, to be scaled up, to be a vehicle for negotiating local change and as part of multiple-methods approaches to disaster risk identification and reduction. The paper is a response to an international workshop on Community Risk Assessment organised by ProVention Consortium and the Disaster Mitigation for Sustainable Livelihoods Programme, University of Cape Town. The workshop brought together practitioners and academics to review the challenges and opportunities for participatory methodologies in the field of disaster risk reduction. In conclusion the contribution made by participatory methodologies to global disaster risk reduction assessment and policy is discussed. [source] Seismotectonics of the Sinai subplate , the eastern Mediterranean regionGEOPHYSICAL JOURNAL INTERNATIONAL, Issue 1 2003Amos Salamon SUMMARY We define the Sinai subplate, from a seismotectonic perspective, as a distinct component in the plate tectonics of the eastern Mediterranean region. This is based on the tectonic characteristics of a comprehensive listing of all ML, 4 recorded seismicity in the region during the 20th century, on newly calculated and recalculated fault plane mechanisms of first P -wave arrivals and on published solutions based on waveform inversion of broad-band data. The low seismicity level and scarcity of strong events in the region required a thorough search for useful data and a careful examination of the reliability of the focal solutions. We gathered all available records of first P -wave onsets from the ISS and ISC Bulletins and the local seismic networks. Altogether, we were able to calculate 48 new focal mechanisms and 33 recalculated ones of events that occurred during the years 1940,1992. With the increasing number of teleseismic and regional broad-band stations in the later years, we added 37 solutions based on teleseismic and regional waveform inversions of events that occurred during 1977,2001. These mechanisms enabled us to examine the seismotectonic character of the Sinai subplate. The strike and rake directions of the calculated mechanisms usually reflect the geometry and the large-scale type of deformation observed along the boundaries of the Sinai subplate,the Dead Sea Transform, the Cypriot Arc convergent zone and the Suez Rift. Nevertheless, along each of these boundaries we found anomalous solutions that attest to the complexity of the deformation processes along plate margins. Earthquakes along the Dead Sea Transform exhibit mainly sinistral transtension and transpression, reflecting its leaky manner and local change in the transform geometry. The presence of other unexpected mechanisms near the transform, however, reflects the heterogeneous deformation it induces around. As expected, thrust mechanisms along the Cypriot Arc mirror its convergent nature and typical curved geometry. Transtension and transpressional solutions in the eastern segment of the arc reflect the sinistral shear motion between Anatolia and Sinai there. However, shear mechanisms found between Cyprus and the Eratosthenes Seamount pose a problem regarding its collision process. Most intriguing of all are ML, 4 thrust and shear solutions found in the Gulf of Suez. They are associated with predominantly normal mechanisms within a rift zone and therefore constitute a unique phenomenon, yet to be deciphered. [source] NURBS to Avoid Boundary Orientation Poses in Serial ManipulatorsJOURNAL OF FIELD ROBOTICS (FORMERLY JOURNAL OF ROBOTIC SYSTEMS), Issue 12 2003Andrzej J. Cebula A procedure to build NURBS motion interpolants to avoid boundary orientation poses for serial manipulator architectures is presented. As an example, the PUMA architecture was used. The procedure, which emerged from B-spline curves theory, enables a local change of the NURBS motion interpolant. The change may be introduced in any arbitrary neighborhood of the chosen boundary orientation pose. Therefore, when tracking a trajectory, one may change NURBS motion interpolant value at any time instant, leaving its remaining values untouched. Recommendation for further research pertains to exploiting the flexibility of NURBS applied to robot kinematics. © 2003 Wiley Periodicals, Inc. [source] Conformational changes induced by a single amino acid substitution in the trans -membrane domain of Vpu: Implications for HIV-1 susceptibility to channel blocking drugsPROTEIN SCIENCE, Issue 10 2007Sang Ho Park Abstract The channel-forming trans -membrane domain of Vpu (Vpu TM) from HIV-1 is known to enhance virion release from the infected cells and is a potential target for ion-channel blockers. The substitution of alanine at position 18 by a histidine (A18H) has been shown to render HIV-1 infections susceptible to rimantadine, a channel blocker of M2 protein from the influenza virus. In order to describe the influence of the mutation on the structure and rimantadine susceptibility of Vpu, we determined the structure of A18H Vpu TM, and compared it to those of wild-type Vpu TM and M2 TM. Both isotropic and orientationally dependent NMR frequencies of the backbone amide resonance of His18 were perturbed by rimantadine, and those of Ile15 and Trp22 were also affected, suggesting that His18 is the key residue for rimantadine binding and that residues located on the same face of the TM helix are also involved. A18H Vpu TM has an ideal, straight ,-helix spanning residues 6,27 with an average tilt angle of 41° in C14 phospholipid bicelles, indicating that the tilt angle is increased by 11° compared to that of wild-type Vpu TM. The longer helix formed by the A18H mutation has a larger tilt angle to compensate for the hydrophobic mismatch with the length of the phospholipids in the bilayer. These results demonstrate that the local change of the primary structure plays an important role in secondary and tertiary structures of Vpu TM in lipid bilayers and affects its ability to interact with channel blockers. [source] Lost in Translation: A Multi-Level Case Study of the Metamorphosis of Meanings and Action in Public Sector Organizational InnovationPUBLIC ADMINISTRATION, Issue 1 2006Catherine Pope This paper explores the early implementation of an organizational innovation in the UK National Health Service (NHS) , Treatment Centres (TCs) , designed to dramatically reduce waiting lists for elective care. The paper draws on case studies of 8 TCs (each at varying stages of their development) and aims to explore how meanings about TCs are created and evolve, and how these meanings impact upon the development of the organizational innovation. Research on organizational meanings needs to take greater account of the fact that modern organizations like the NHS are complex multi-level phenomena, comprising layers of interlacing networks. To understand the pace, direction and impact of organizational innovation and change we need to study the interconnections between meanings across different organizational levels. The data presented in this paper show how the apparently simple, relatively unformed, concept of a TC framed by central government is translated and transmuted by subsequent layers in the health service administration, and by players in local health economies, and, ultimately, in the TCs themselves, picking up new rationales, meanings and significance as it goes along. The developmental histories of TCs reveal a range of significant re-workings of macro policy with the result that there is considerable diversity and variation between local TC schemes. The picture is of important disconnections between meanings, that in many ways mirror Weick's (1976) 'loosely coupled systems'. The emergent meanings and the direction of micro-level development of TCs appear more strongly determined by interactions within the local TC environment, notably between what we identify as groups of 'idealists', 'pragmatists', 'opportunists' and 'sceptics' than by the framing (Goffman 1974) provided by macro and meso organizational levels. While this illustrates the limitations of top down and policy-driven attempts at change, and highlights the crucial importance of the front-line local 'micro-systems' (Donaldson and Mohr 2000) in the overall scheme of implementing organizational innovations, the space or headroom provided by frames at the macro and meso levels can enable local change, albeit at variable speed and with uncertain outcomes. [source] Structural and functional growth in self-reproducing cellular automata,COMPLEXITY, Issue 6 2006Eleonora Bilotta Abstract In this article, we analyze the dynamics of change in two-dimensional self-reproducers, identifying the processes that drive their evolution. We show that changes in self-reproducers structure and behavior depend on their genetic memory. This consists of distinct yet interlinked components determining their form and function. In some cases these components degrade gracefully, changing only slightly; in others the changes destroy the original structure and function of the self-reproducer. We sketch these processes at the genotype and the phenotype level,showing that they follow distinct trajectories within mutation space and quantifying the degree of change produced by different trajectories. We show that changes in structure and behavior depend on the interplay between the genotype and the phenotype. This determines universal structures, from which it is possible to construct a great number of self-reproducing systems, as we observe in biology. Creative processes of change produce divergent and/or convergent methods for the generation of self-reproducers. Divergence involves the creation of completely new information convergence involves local change and specialization of the structures concerned. © 2006 Wiley Periodicals, Inc. Complexity 11: 12,29, 2006 [source] Folding of the tectal cortex by local remodeling of neural differentiationDEVELOPMENTAL DYNAMICS, Issue 3 2004Tatsuo Mima Abstract The folding pattern of the brain cortex is a precisely regulated process, but the mechanism involved during development remains unclear. A proposed theory predicts that the initiation of cortical folding depends, at least partly, on nonuniform distribution of neuronal differentiation and neurite growth. We tested this theory experimentally, by remodeling the normal pattern of neuronal cell differentiation within the embryonic optic tectum. Multiple foci of activated fibroblast growth factor signaling were created in the tectal cortex to locally change the neural differentiation and axonal growth patterns. At these foci, tectal cells remained undifferentiated and their radial and tangential migration was suppressed. These local changes in the neuronal cell differentiation resulted in a conversion of the tectal cortex from smoothly extended into precociously folded. The results provide in vivo experimental evidence that microscopic changes in the neuronal cell differentiation pattern can induce or remodel the folding pattern of the brain cortex. Developmental Dynamics 229:475,479, 2004. © 2004 Wiley-Liss, Inc. [source] Satellite sleuthing: does remotely sensed land-cover change signal ecological degradation in a protected area?DIVERSITY AND DISTRIBUTIONS, Issue 2 2009T. A. Waite ABSTRACT Aim, We evaluate whether remotely sensed land-cover change within a newly protected area signalled human-driven ecological degradation. Vegetation density changed in a quarter of pixels during the first 13 years (1986,1999) following the sanctuary's formal enclosure, with many patches showing a decrease in density. We use on-the-ground data collected in 2006 in 132 random plots to explore whether these changes in vegetation density reliably signalled latent shifts in local diversity of woody plants and whether they could be attributed to illicit activities including fuel wood collection and livestock grazing. Location, Kumbhalgarh Wildlife Sanctuary, Rajasthan, India. Results, Species richness, species sharing, species assemblages, and incidence of invasive and useful species were statistically similar among plots in which vegetation density had decreased, increased or remained similar. Likewise, intensity of disturbance associated with human activities was similar across these plot types. Main conclusions, Our data provide no clear evidence that local changes in vegetation density signalled latent shifts in local diversity of woody plants. They also fail to reveal any clear association between local changes in vegetation density and human-related activities. Finding no evidence that land-cover change led to biotic erosion, we reflect on the utility of resource-use bans in protected areas, particularly those embedded within historically coupled human-nature systems. [source] Invasion impacts local species turnover in a successional systemECOLOGY LETTERS, Issue 9 2004Kathryn A. Yurkonis Abstract Exotic plant invasions are often associated with declines in diversity within invaded communities. However, few studies have examined the local community dynamics underlying these impacts. Changes in species richness associated with plant invasions must occur through local changes in extinction and/or colonization rates within the community. We used long-term, permanent plot data to evaluate the impacts of the exotic vine Lonicera japonica. Over time, species richness declined with increasing L. japonica cover. L. japonica reduced local colonization rates but had no effect on extinction rates. Furthermore, we detected significant reductions in the immigration of individual species as invasion severity increased, showing that some species are more susceptible to invasion than others. These findings suggest that declines in species richness associated with L. japonica invasion resulted from effects on local colonization rates only and not through the competitive displacement of established species. [source] Deep brain stimulation mechanisms: beyond the concept of local functional inhibitionEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2010Jean-Michel Deniau Abstract Deep brain electrical stimulation has become a recognized therapy in the treatment of a variety of motor disorders and has potentially promising applications in a wide range of neurological diseases including neuropsychiatry. Behavioural observation that electrical high-frequency stimulation of a given brain area induces an effect similar to a lesion suggested a mechanism of functional inhibition. In vitro and in vivo experiments as well as per operative recordings in patients have revealed a variety of effects involving local changes of neuronal excitability as well as widespread effects throughout the connected network resulting from activation of axons, including antidromic activation. Here we review current data regarding the local and network activity changes induced by high-frequency stimulation of the subthalamic nucleus and discuss this in the context of motor restoration in Parkinson's disease. Stressing the important functional consequences of axonal activation in deep brain stimulation mechanisms, we highlight the importance of developing anatomical knowledge concerning the fibre connections of the putative therapeutic targets. [source] In situ Investigation of Structural Changes during Deformation and Fracture of Polymers by Synchrotron SAXS and WAXS,ADVANCED ENGINEERING MATERIALS, Issue 6 2009Konrad Schneider By simultaneous mechanical characterisation and synchrotron wide-angle x-ray scattering (WAXS) and small-angle x-ray scattering (SAXS), it is possible to characterise on-line local changes in a polymer's structure with a rather-high time and space resolution, together with the mechanical properties. In this contribution, we discuss the experimental requirements for such investigations as well as three examples. The evolution of structural features during tensile deformation of a polyethylene copolymer, as depicted by WAXS (top) and SAXS (bottom) are shown in the figure. The deformation leads to a martensitic transformation from the orthorhombic to monoclinic system and the formation of nanocavities. [source] Histone modifications and chromatin dynamics: a focus on filamentous fungiFEMS MICROBIOLOGY REVIEWS, Issue 3 2008Gerald Brosch Abstract The readout of the genetic information of eukaryotic organisms is significantly regulated by modifications of DNA and chromatin proteins. Chromatin alterations induce genome-wide and local changes in gene expression and affect a variety of processes in response to internal and external signals during growth, differentiation, development, in metabolic processes, diseases, and abiotic and biotic stresses. This review aims at summarizing the roles of histone H1 and the acetylation and methylation of histones in filamentous fungi and links this knowledge to the huge body of data from other systems. Filamentous fungi show a wide range of morphologies and have developed a complex network of genes that enables them to use a great variety of substrates. This fact, together with the possibility of simple and quick genetic manipulation, highlights these organisms as model systems for the investigation of gene regulation. However, little is still known about regulation at the chromatin level in filamentous fungi. Understanding the role of chromatin in transcriptional regulation would be of utmost importance with respect to the impact of filamentous fungi in human diseases and agriculture. The synthesis of compounds (antibiotics, immunosuppressants, toxins, and compounds with adverse effects) is also likely to be regulated at the chromatin level. [source] Au@pNIPAM Thermosensitive Nanostructures: Control over Shell Cross-linking, Overall Dimensions, and Core GrowthADVANCED FUNCTIONAL MATERIALS, Issue 19 2009Rafael Contreras-Cáceres Abstract Thermoresponsive nanocomposites comprising a gold nanoparticle core and a poly(N -isopropylacrylamide) (pNIPAM) shell are synthesized by grafting the gold nanoparticle surface with polystyrene, which allows the coating of an inorganic core with an organic shell. Through careful control of the experimental conditions, the pNIPAM shell cross-linking density can be varied, and in turn its porosity and stiffness, as well as shell thickness from a few to a few hundred nanometers is tuned. The characterization of these core,shell systems is carried out by photon-correlation spectroscopy, transmission electron microscopy, and atomic force microscopy. Additionally, the porous pNIPAM shells are found to modulate the catalytic activity, which is demonstrated through the seeded growth of gold cores, either retaining the initial spherical shape or developing a branched morphology. The nanocomposites also present thermally modulated optical properties because of temperature-induced local changes of the refractive index surrounding the gold cores. [source] Functional magnetic resonance imagery (fMRI) in fibromyalgia and the response to milnacipranHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue S1 2009Yves MainguyArticle first published online: 28 MAY 200 Abstract Functional imaging has been used to study response to pain in fibromyalgia patients. Functional magnetic resonance imagery (fMRI) which tracks local changes in blood flow has a higher spatial and temporal resolution than other techniques such as positron emission tomography (PET) or single-photon emission tomography (SPECT). fMRI studies in fibromyalgia patients suggest that similar levels of subjective pain result in similar central nervous system (CNS) activation in both fibromyalgia patients and controls. For a similar stimulus, however, fibromyalgia patients have a greater subjective sensation of pain. This increased sensitivity is accompanied with a decreased activity in brain regions implicated in the descending pain inhibitory pathways. The hypothesis that increased sensitivity to pain is due to decreased activity of the descending inhibitory pathways is supported by results with milnacipran. Fibromyalgia patients treated with the serotonin and noradrenaline reuptake inhibitor, milnacipran, exhibited a reduction in pain sensitivity and a parallel increase in activity in brain regions implicated in the descending pain inhibitory pathways compared to placebo-treated patients. Copyright © 2009 John Wiley & Sons, Ltd. [source] Theory and numerics of geometrically non-linear open system mechanicsINTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN ENGINEERING, Issue 11 2003E. Kuhl Abstract The present contribution aims at deriving a general theoretical and numerical framework for open system thermodynamics. The balance equations for open systems differ from the classical balance equations by additional terms arising from possible local changes in mass. In contrast to existing formulations, these changes not only originate from additional mass sources or sinks but also from a possible in- or outflux of matter. Constitutive equations for the mass source and the mass flux are discussed for the particular model problem of bone remodelling in hard tissue mechanics. Particular emphasis is dedicated to the spatial discretization of the coupled system of the balance of mass and momentum. To this end we suggest a geometrically non-linear monolithic finite element based solution technique introducing the density and the deformation map as primary unknowns. It is supplemented by the consistent linearization of the governing equations. The resulting algorithm is validated qualitatively for classical examples from structural mechanics as well as for biomechanical applications with particular focus on the functional adaption of bones. It turns out that, owing to the additional incorporation of the mass flux, the proposed model is able to simulate size effects typically encountered in microstructural materials such as open-pored cellular solids, e.g. bones. Copyright © 2003 John Wiley & Sons, Ltd. [source] Simulation of seasonal precipitation and raindays over Greece: a statistical downscaling technique based on artificial neural networks (ANNs)INTERNATIONAL JOURNAL OF CLIMATOLOGY, Issue 7 2007K. Tolika Abstract A statistical downscaling technique based on artificial neural network (ANN) was employed for the estimation of local changes on seasonal (winter, spring) precipitation and raindays for selected stations over Greece. Empirical transfer functions were derived between large-scale predictors from the NCEP/NCAR reanalysis and local rainfall parameters. Two sets of predictors were used: (1) the circulation-based 500 hPa and (2) its combination along with surface specific humidity and raw precipitation data (nonconventional predictor). The simulated time series were evaluated against observational data and the downscaling model was found efficient in generating winter and spring precipitation and raindays. The temporal evolution of the estimated variables was well captured, for both seasons. Generally, the use of the nonconventional predictors are attributed to the improvement of the simulated results. Subsequently, the present day and future changes on precipitation conditions were examined using large-scale data from the atmospheric general circulation model HadAM3P to the statistical model. The downscaled climate change signal for both precipitation and raindays, partly for winter and especially for spring, is similar to the signal from the HadAM3P direct output: a decrease of the parameters is predicted over the study area. However, the amplitude of the changes was different. Copyright © 2006 Royal Meteorological Society [source] Theoretical studies on water,tetracaine interactionINTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY, Issue 5 2006R. C. Bernardi Abstract The action of local anesthetics (LA) is controversial. There is experimental evidence that the unprotonated form of LA penetrates the axon, while the charged form acts in the intracellular phase. To obtain some insight on the structure of the local anesthetics tetracaine and its pharmacological action, we made calculations using the density functional theory (DFT) method. After those calculations, we performed molecular dynamics (MD) simulations in a p, N, T ensemble, in an aqueous environment, on both unprotonated and protonated forms of the molecule. The radial distribution function was used to study water solvent effects, through the characterization of the affinity of tetracaine to water. The results indicate that the molecule has regions with different degree of hydrophobicity, and the N-terminal of the anesthetic was primarily affected by changes in the protonation state of the anesthetic. The pH-dependent activity of TTC should then be analyzed in view of local changes in different regions of the molecule, rather than in terms of general effects on the hydrophobicity of the molecule as a whole. © 2005 Wiley Periodicals, Inc. Int J Quantum Chem, 2006 [source] Influence of carbohydrates on stability of papain in aqueous tetrahydrofuran mixtureJOURNAL OF CHEMICAL TECHNOLOGY & BIOTECHNOLOGY, Issue 1 2009András Szabó Abstract BACKGROUND: The use of enzymes in organic solvents has extended the scale of their practical applications. Papain has been widely used in chemical syntheses because of its broad substrate specificity. The aim of the present study was to improve the stability of papain in aqueous tetrahydrofuran (THF) by using different saccharides. The effects of these carbohydrates on the structure of papain were followed by means of circular dichroism (CD) and fluorescence spectroscopic measurements. RESULTS: In contrast with most organic solvents, 60% (i.e. 600 mL L,1) THF practically inactivated the enzyme within 30 min. Sugars protected papain from THF-induced inactivation in the sequence D -ribose > D -fructose > D -glucose > D -saccharose > D -raffinose. Ribose at 1.6 mol L,1 proved the most effective stabiliser: in 60% THF in the presence of ribose, papain preserved about 55% of its initial activity after 2 h. Fluorescence and near-UV CD spectroscopic measurements revealed local changes in the papain conformation. With decrease in the free amino group content of the enzyme, protein-carbohydrate interactions (Schiff base formation) were detected. CONCLUSION: These results demonstrate that the catalytic activity and stability of papain may be increased in aqueous THF by using different carbohydrates, when a more compact structure of the enzyme is formed. Copyright © 2008 Society of Chemical Industry [source] Adjusted Scaling of FDG Positron Emission Tomography Images for Statistical Evaluation in Patients With Suspected Alzheimer's DiseaseJOURNAL OF NEUROIMAGING, Issue 4 2005Ralph Buchert PhD ABSTRACT Background and Purpose. Statistical parametric mapping (SPM) gained increasing acceptance for the voxel-based statistical evaluation of brain positron emission tomography (PET) with the glucose analog 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) in patients with suspected Alzheimer's disease (AD). To increase the sensitivity for detection of local changes, individual differences of total brain FDG uptake are usually compensated for by proportional scaling. However, in cases of extensive hypometabolic areas, proportional scaling overestimates scaled uptake. This may cause significant underestimation of the extent of hypometabolic areas by the statistical test. Methods. To detect this problem, the authors tested for hyper metabolism. In patients with no visual evidence of true focal hypermetabolism, significant clusters of hypermetabolism in the presence of extended hypometabolism were interpreted as false-positive findings, indicating relevant overestimation of scaled uptake. In this case, scaled uptake was reduced step by step until there were no more significant clusters of hypermetabolism. Results. In 22 consecutive patients with suspected AD, proportional scaling resulted in relevant overestimation of scaled uptake in 9 patients. Scaled uptake had to be reduced by 11.1%± 5.3% in these cases to eliminate the artifacts. Adjusted scaling resulted in extension of existing and appearance of new clusters of hypometabolism. Total volume of the additional voxels with significant hypometabolism depended linearly on the extent of the additional scaling and was 202 ± 118 mL on average. Conclusions. Adjusted scaling helps to identify characteristic metabolic patterns in patients with suspected AD. It is expected to increase specificity of FDGPET in this group of patients. [source] Bicuculline-induced brain activation in mice detected by functional magnetic resonance imagingMAGNETIC RESONANCE IN MEDICINE, Issue 2 2001Thomas Mueggler Abstract Dynamic measurements of local changes in relative cerebral blood volume (CBVrel) during a pharmacological stimulation paradigm were performed in mice. Using magnetite nanoparticles as an intravascular contrast agent, high-resolution CBVrel maps were obtained. Intravenous administration of the GABAA antagonist bicuculline prompted increases in local CBVrel as assessed by MRI with a high spatial resolution of 0.2 × 0.2 mm2 and a temporal resolution of 21 s. Signal changes occurred 20,30 s after the onset of drug infusion in the somatosensory and motor cortex, followed by other cortical and subcortical structures. The magnitudes of the CBVrel increases were 18% ± 4%, 46% ± 14%, and 67% ± 7%, as compared to prestimulation values for the cortex, and 9% ± 3%, 25% ± 4%, and 36% ± 7% for the caudate putamen for bicuculline doses of 0.6, 1.25, and 1.5 mg/kg, respectively. On-line monitoring of transcutaneous carbon dioxide tension PtcCO2 reflecting arterial PaCO2 did not show any alteration during the stimulation paradigm. One of five of the mice receiving the highest bicuculline dose, and three of seven receiving the intermediate dose displayed a different cortical response pattern. After a CBVrel increase of 40% lasting for approximately 1 min, significant CBVrelreductions by 80% have been observed. Subcortical structures did not display this behavior. The present study suggests that this noninvasive approach of functional MRI (fMRI) can be applied to study drug-induced brain activation by central nervous system (CNS) drugs in mice under normal and pathological situations. Magn Reson Med 46:292,298, 2001. © 2001 Wiley-Liss, Inc. [source] Physical attachment of fluorescent protein particles to atomic force microscopy probes in aqueous media: Implications for surface pH, fluorescence, and mechanical properties studiesMICROSCOPY RESEARCH AND TECHNIQUE, Issue 8 2010Susana Moreno-Flores Abstract Transfer of a fluorescently labeled protein particle from a surface to a microsized scanning probe has been induced by repetitive scanning in aqueous medium. The so-attached particle can in turn act as a probing tool to study particle,substrate and particle,particle interactions. Attachment of the fluorescent particle occurs at the apical region of an atomic force microscope (AFM) cantilever tip and it endures repetitive loading,unloading cycles against the sample surface. Fluorescence microscopy has been used to address the exact location of the attached particle in the cantilever and to identify the moment when the particle contacts the sample. Moreover, we have observed that fluorescence intensity at the contact point is lower when the probing particle contacts another fluorescent particle than when it contacts the nonfluorescent substrate. The change in fluorescence is attributed to local changes of pH and interparticle-quenching of fluorophores in the contact region. These findings are promising since they constitute a chemical-free way to attach bioparticles to AFM probes under fisiological conditions. The atomic force microscopy combined with fluorescence microscopy provides a straight forward method to study particle/particle and particle/substrate interactions, as well as to investigate mechanical properties of biocolloids. Microsc. Res. Tech. 73:746,751, 2010. © 2009 Wiley-Liss, Inc. [source] Photo-induced improvement of radiative efficiency and structural changes in GaAsN alloysPHYSICA STATUS SOLIDI (C) - CURRENT TOPICS IN SOLID STATE PHYSICS, Issue 6 2006H. Yaguchi Abstract We have investigated the excitation power density and nitrogen concentration dependence of the changes in the radiative efficiency of GaAsN alloys to examine the mechanism of the photo-induced improvement of radiative efficiency. With increasing excitation power density, the radiative efficiency increased more rapidly. The measure of the improvement Iafter/Ibefore superlinearly increased with increasing nitrogen concentration x up to ,1%. This suggests that the nonradiative recombination centers eliminated by photoexcitation are not defects formed by a single nitrogen atom but complexes formed by gathering of several nitrogen atoms. Micro Raman study revealed that the GaAs-like LO mode phonon peak intensity increased with photoexcitation time in a similar way to the increase in the radiative efficiency. Considering that this phenomenon is in a time scale of several seconds, the photo-induced structural changes correspond not to long range inter-diffusion but to local changes in atomic configuration which lead to the decrease in the density of nonradiative recombination centers. (© 2006 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Trend analysis of Indian summer monsoon rainfall at different spatial scalesATMOSPHERIC SCIENCE LETTERS, Issue 4 2009Subimal Ghosh Abstract The results obtained from a conventional trend analysis of the Indian summer monsoon rainfall over a larger region are contradicted when analysis is performed at a finer resolution because of spatial variability and heterogeneity in the rainfall pattern. The present study analyzes the trend of summer monsoon rainfall all over India at a finer spatial resolution (1° latitude × 1° longitude) to identify the places that have a significant trend in terms of both rainfall amount and occurrence. The results obtained from this study are compared with those of a recent study by Goswami et al. (2006), where trend analysis is performed over a larger region [Central India (CI); 10° latitude × 12° longitude; assumed to be homogeneous in that study]. The increasing trend of occurrence of heavy rainfall and decreasing trend of occurrence of moderate rainfall, as concluded from that study, are contradicted by the present results for some places in CI. The present analysis shows spatially varying mixed responses of global warming toward rainfall occurrence and amounts all over India. The perception of increase in daily rainfall amount and occurrence due to climate change is found to be not correct for some of the regions in India. The possible reason may be the spatial variability of local changes such as rapid urbanization, industrialization and deforestation. Copyright © 2009 Royal Meteorological Society [source] Structures of three diphtheria toxin repressor (DtxR) variants with decreased repressor activityACTA CRYSTALLOGRAPHICA SECTION D, Issue 5 2001Ehmke Pohl The diphtheria toxin repressor (DtxR) from Corynebacterium diphtheriae regulates the expression of the gene on corynebacteriophages that encodes diphtheria toxin (DT). Other genes regulated by DtxR include those that encode proteins involved in siderophore-mediated iron uptake. DtxR requires activation by divalent metals and holo-DtxR is a dimeric regulator with two distinct metal-binding sites per three-domain monomer. At site 1, three side chains and a sulfate or phosphate anion are involved in metal coordination. In the DtxR,DNA complex this anion is replaced by the side chain of Glu170 provided by the third domain of the repressor. At site 2 the metal ion is coordinated exclusively by constituents of the polypeptide chain. In this paper, five crystal structures of three DtxR variants focusing on residues Glu20, Arg80 and Cys102 are reported. The resolution of these structures ranges from 2.3 to 2.8,Å. The side chain of Glu20 provided by the DNA-binding domain forms a salt bridge to Arg80, which in turn interacts with the anion. Replacing either of the salt-bridge partners with an alanine reduces repressor activity substantially and it has been inferred that the salt bridge could possibly control the wedge angle between the DNA-binding domain and the dimerization domain, thereby modulating repressor activity. Cys102 is a key residue of metal site 2 and its substitution into a serine abolishes repressor activity. The crystal structures of Zn-Glu20Ala-DtxR, Zn-Arg80Ala-DtxR, Cd-Cys102Ser-DtxR and apo-Cys102Ser-DtxR in two related space groups reveal that none of these substitutions leads to dramatic rearrangements of the DtxR fold. However, the five crystal structures presented here show significant local changes and a considerable degree of flexibility of the DNA-binding domain with respect to the dimerization domain. Furthermore, all five structures deviate significantly from the structure in the DtxR,DNA complex with respect to overall domain orientation. These results confirm the importance of the hinge motion for repressor activity. Since the third domain has often been invisible in previous crystal structures of DtxR, it is also noteworthy that the SH3-like domain could be traced in four of the five crystal structures. [source] Emerging mechanisms in morphogen-mediated axon guidanceBIOESSAYS, Issue 10 2009Cristina Sánchez-Camacho Abstract Early in animal development, gradients of secreted morphogenic molecules, such as Sonic hedgehog (Shh), Wnt and TGF,/Bmp family members, regulate cell proliferation and determine the fate and phenotype of the target cells by activating well-characterized signalling pathways, which ultimately control gene transcription. Shh, Wnt and TGF,/Bmp signalling also play an important and evolutionary conserved role in neural circuit assembly. They regulate neuronal polarization, axon and dendrite development and synaptogenesis, processes that require rapid and local changes in cytoskeletal organization and plasma membrane components. A key question then is whether morphogen signalling at the growth cone uses similar mechanisms and intracellular pathway components to those described for morphogen-mediated cell specification. This review discusses recent advances towards the understanding of this problem, showing how Shh, Wnt and TGF,/Bmp have adapted their ,classical' signalling pathways or adopted alternative and novel molecular mechanisms to influence different aspects of neuronal circuit formation. [source] Apoptotic and Anti-Apoptotic Synaptic Signaling MechanismsBRAIN PATHOLOGY, Issue 2 2000Mark P. Mattson Although several prominent morphological features of apoptosis are evident in the cell body (e.g., cell shrinkage, membrane blebbing, and nuclear DNA condensation and fragmentation) the biochemical and molecular cascades that constitute the cell death machinery can be engaged in synaptic terminals and neurites. Initiating events such as oxyradical production and calcium influx, and effector processes such as Par-4 production, mitochondrial alterations and caspase activation, can be induced in synapses and neurites. Several prominent signal transduction pathways in synaptic terminals play important roles in either promoting or preventing neuronal death in physiological and pathological conditions. For example, activation of glutamate receptors in postsynaptic spines can induce neuronal apoptosis, whereas local activation of neurotrophic factor receptors in presynaptic terminals can prevent neuronal death. Factors capable of inducing nuclear chromatin condensation and fragmentation can be produced locally in synaptic terminals and neurites, and may propogate to the cell body. Recent findings suggest that, beyond their roles in inducing or preventing cell death, apoptotic and anti-apoptotic cascades play roles in synaptic plasticity (structural remodelling and long-term functional changes). For example, caspase activation results in proteolysis of glutamate receptor (AMPA) subunits, which results in altered neuronal responsivity to glutamate. Activation of neurotrophic factor receptors in synaptic terminals can result in local changes in energy metabolism and calcium homeostasis, and can induce long-term changes in synaptic transmission. The emerging data therefore suggest that synapses can be considered as autonomous compartments in which both pro- and anti-apoptotic signaling pathways are activated resulting in structural and functional changes in neuronal circuits. A better understanding of such synaptic signaling mechanisms may reveal novel approaches for preventing and treating an array of neurodegenerative conditions that are initiated by perturbed synaptic homeostasis. [source] Escherichia coli,-haemolysin induces focal leaks in colonic epithelium: a novel mechanism of bacterial translocationCELLULAR MICROBIOLOGY, Issue 10 2007Hanno Troeger Summary Extraintestinal pathogenic Escherichia coli (ExPEC) are usually harmless colonizer of the intestinal microflora. However, they are capable to translocate and cause life-threatening disease. Translocation of ExPEC isolates was quantified in colonic monolayers. Transepithelial resistance (Rt) was monitored and local changes in conductivity analysed with conductance scanning. Confocal microscopy visualized the translocation route. Corroboratory experiments were performed on native rat colon. One translocating strain E. coli O4 was identified. This translocation process was associated with an Rt decrease (36 ± 1% of initial resistance) beginning only 2 h after inoculation. The sites of translocation were small defects in epithelial integrity (focal leaks) exhibiting highly increased local ion permeability. Translocation was enhanced by preincubation of monolayers with tumour necrosis factor-, or interleukin-13. Mutant strains lacking alpha-haemolysin lost the ability to induce focal leaks, while this effect could be restored by re-introducing the haemolysin determinant. Filtrate of a laboratory strain carrying the alpha-haemolysin operon was sufficient for focal leak induction. In native rat colon, E. coli O4 decreased Rt and immunohistology demonstrated focal leaks resembling those in cell monolayers. E. coli,-haemolysin is able to induce focal leaks in colonic cell cultures as well as in native colon. This process represents a novel route of bacterial translocation facilitated by pro-inflammatory cytokines. [source] Local dynamic changes in confined extracellular environments within organsCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 10 2009Natasha Behrendorff Summary 1Herein we review past work that has studied the composition of luminal fluid in organs, with a focus on measures of calcium and pH in the exocrine glands. This luminal environment is ,external' to the mammalian body and is not subject to the usual mechanisms of homeostatic control. Instead, it is controlled by the behaviour of the cells that line the lumen. 2We discuss the likely possibility that rapid and local changes in calcium and pH occur within microdomains in the lumen. Further, we present preliminary evidence, using live cell imaging of intact pancreatic fragments, that supports the idea that pH changes do occur. Our evidence indicates that exocytosis of secretory granules in pancreatic acinar cells leads to a loss of protons from the granule and a subsequent local acidification of the lumen. 3These changes in luminal composition are placed in the context of diseases of the pancreas, such as cystic fibrosis and pancreatitis, both of which are known to result in perturbations of luminal fluid composition. [source] | ||||||||||||||||||||||||||||