324 research outputs found

    Processing asymmetry of transitions between order and disorder in human auditory cortex

    Get PDF
    Purpose: To develop an algorithm to resolve intrinsic problems with dose calculations using pencil beams when particles involved in each beam are overreaching a lateral density interface or when they are detouring in a laterally heterogeneous medium. Method and Materials: A finding on a Gaussian distribution, such that it can be approximately decomposed into multiple narrower, shifted, and scaled ones, was applied to dynamic splitting of pencil beams implemented in a dose calculation algorithm for proton and ion beams. The method was tested in an experiment with a range-compensated carbon-ion beam. Its effectiveness and efficiency were evaluated for carbon-ion and proton beams in a heterogeneous phantom model. Results: The splitting dose calculation reproduced the detour effect observed in the experiment, which amounted to about 10% at a maximum or as large as the lateral particle-disequilibrium effect. The proton-beam dose generally showed large scattering effects including the overreach and detour effects. The overall computational times were 9 s and 45 s for non-splitting and splitting carbon-ion beams and 15 s and 66 s for non-splitting and splitting proton beams. Conclusions: The beam-splitting method was developed and verified to resolve the intrinsic size limitation of the Gaussian pencil-beam model in dose calculation algorithms. The computational speed slowed down by factor of 5, which would be tolerable for dose accuracy improvement at a maximum of 10%, in our test case.AAPM Annual Meeting 200

    Human Auditory cortical processing of changes in interaural correlation

    Get PDF
    Sensitivity to the similarity of the acoustic waveforms at the two ears, and specifically to changes in similarity, is crucial to auditory scene analysis and extraction of objects from background. Here, we use the high temporal resolution of magnetoencephalography to investigate the dynamics of cortical processing of changes in interaural correlation, a measure of interaural similarity, and compare them with behavior. Stimuli are interaurally correlated or uncorrelated wideband noise, immediately followed by the same noise with intermediate degrees of interaural correlation. Behaviorally, listeners' sensitivity to changes in interaural correlation is asymmetrical. Listeners are faster and better at detecting transitions from correlated noise than transitions from uncorrelated noise. The cortical response to the change in correlation is characterized by an activation sequence starting from ∼50 ms after change. The strength of this response parallels behavioral performance: auditory cortical mechanisms are much less sensitive to transitions from uncorrelated noise than from correlated noise. In each case, sensitivity increases with interaural correlation difference. Brain responses to transitions from uncorrelated noise lag those from correlated noise by ∼80 ms, which may be the neural correlate of the observed behavioral response time differences. Importantly, we demonstrate differences in location and time course of neural processing: transitions from correlated noise are processed by a distinct neural population, and with greater speed, than transitions from uncorrelated noise

    Dynamics of Dynamin during Clathrin Mediated Endocytosis in PC12 Cells

    Get PDF
    Members of the dynamin super-family of GTPases are involved in disparate cellular pathways. Dynamin1 and dynamin2 have been implicated in clathrin-mediated endocytosis. While some models suggest that dynamin functions specifically at the point of vesicle fission, evidence also exists for a role prior to fission during vesicle formation and it is unknown if there is a role for dynamin after vesicle fission. Although dynamin2 is ubiquitously expressed, dynamin1 is restricted to the nervous system. These two structurally similar endocytic accessory proteins have not been studied in cells that endogenously express both.The present study quantitatively assesses the dynamics of dynamin1 and dynamin2 during clathrin-mediated endocytosis in PC12 cells, which endogenously express both proteins. Both dynamin isoforms co-localized with clathrin and showed sharp increases in fluorescence intensity immediately prior to internalization of the nascent clathrin-coated vesicle. The fluorescence intensity of both proteins then decreased with two time constants. The slower time constant closely matched the time constant for the decrease of clathrin intensity and likely represents vesicle movement away from the membrane. The faster rate may reflect release of dynamin at the neck of nascent vesicle following GTP hydrolysis.This study analyses the role of dynamin in clathrin-mediated endocytosis in a model for cellular neuroscience and these results may provide direct evidence for the existence of two populations of dynamin associated with nascent clathrin-coated vesicles

    New furocarbazole alkaloids from Lonicera quinquelocularis

    Get PDF
    Two new furocarbazole alkaloids, 3-formyl-6,7-dimethoxy-furo[1,2]carbazole (1) and methyl-6,7-dimethoxy-furo[1,2]carbazole-3-carboxylate (2), along with two known carbazole alkaloids, 3-formyl-2-hydroxy-7-methoxycarbazole (3) and methyl 2,7-dimethoxycarbazole-3-carboxylate (4) were isolated from the ethyl acetate soluble fraction of Lonicera quinquelocularis. Their structures were established on the basis of spectroscopic analysis

    Non‐Destructive X‐Ray Imaging of Patterned Delta‐Layer Devices in Silicon

    Get PDF
    The progress of miniaturization in integrated electronics has led to atomic and nanometer-sized dopant devices in silicon. Such structures can be fabricated routinely by hydrogen resist lithography, using various dopants such as P and As. However, the ability to non-destructively obtain atomic-species-specific images of the final structure, which would be an indispensable tool for building more complex nano-scale devices, such as quantum co-processors, remains an unresolved challenge. Here, X-ray fluorescence is exploited to create an element-specific image of As dopants in Si, with dopant densities in absolute units and a resolution limited by the beam focal size (here ≈1 µm), without affecting the device's low temperature electronic properties. The As densities provided by the X-ray data are compared to those derived from Hall effect measurements as well as the standard non-repeatable, scanning tunneling microscopy and secondary ion mass spectroscopy, techniques. Before and after the X-ray experiments, we also measured the magneto-conductance, which is dominated by weak localization, a quantum interference effect extremely sensitive to sample dimensions and disorder. Notwithstanding the 1.5 × 10^{10} Sv (1.5 × 10^{16} Rad cm^{−2}) exposure of the device to X-rays, all transport data are unchanged to within experimental errors, corresponding to upper bounds of 0.2 Angstroms for the radiation-induced motion of the typical As atom and 3% for the loss of activated, carrier-contributing dopants. With next generation synchrotron radiation sources and more advanced optics, the authors foresee that it will be possible to obtain X-ray images of single dopant atoms within resolved radii of 5 nm

    Higher Derivative Corrections to R-charged Black Holes: Boundary Counterterms and the Mass-Charge Relation

    Get PDF
    We carry out the holographic renormalization of Einstein-Maxwell theory with curvature-squared corrections. In particular, we demonstrate how to construct the generalized Gibbons-Hawking surface term needed to ensure a perturbatively well-defined variational principle. This treatment ensures the absence of ghost degrees of freedom at the linearized perturbative order in the higher-derivative corrections. We use the holographically renormalized action to study the thermodynamics of R-charged black holes with higher derivatives and to investigate their mass to charge ratio in the extremal limit. In five dimensions, there seems to be a connection between the sign of the higher derivative couplings required to satisfy the weak gravity conjecture and that violating the shear viscosity to entropy bound. This is in turn related to possible constraints on the central charges of the dual CFT, in particular to the sign of c-a.Comment: 30 pages. v2: references added, some equations simplifie

    Association between footwear use and neglected tropical diseases: a systematic review and meta-analysis

    Get PDF
    BACKGROUND The control of neglected tropical diseases (NTDs) has primarily focused on preventive chemotherapy and case management. Less attention has been placed on the role of ensuring access to adequate water, sanitation, and hygiene and personal preventive measures in reducing exposure to infection. Our aim was to assess whether footwear use was associated with a lower risk of selected NTDs. METHODOLOGY We conducted a systematic review and meta-analysis to assess the association between footwear use and infection or disease for those NTDs for which the route of transmission or occurrence may be through the feet. We included Buruli ulcer, cutaneous larva migrans (CLM), leptospirosis, mycetoma, myiasis, podoconiosis, snakebite, tungiasis, and soil-transmitted helminth (STH) infections, particularly hookworm infection and strongyloidiasis. We searched Medline, Embase, Cochrane, Web of Science, CINAHL Plus, and Popline databases, contacted experts, and hand-searched reference lists for eligible studies. The search was conducted in English without language, publication status, or date restrictions up to January 2014. Studies were eligible for inclusion if they reported a measure of the association between footwear use and the risk of each NTD. Publication bias was assessed using funnel plots. Descriptive study characteristics and methodological quality of the included studies were summarized. For each study outcome, both outcome and exposure data were abstracted and crude and adjusted effect estimates presented. Individual and summary odds ratio (OR) estimates and corresponding 95% confidence intervals (CIs) were calculated as a measure of intervention effect, using random effects meta-analyses. PRINCIPAL FINDINGS Among the 427 studies screened, 53 met our inclusion criteria. Footwear use was significantly associated with a lower odds of infection of Buruli ulcer (OR=0.15; 95% CI: 0.08-0.29), CLM (OR=0.24; 95% CI: 0.06-0.96), tungiasis (OR=0.42; 95% CI: 0.26-0.70), hookworm infection (OR=0.48; 95% CI: 0.37-0.61), any STH infection (OR=0.57; 95% CI: 0.39-0.84), strongyloidiasis (OR=0.56; 95% CI: 0.38-0.83), and leptospirosis (OR=0.59; 95% CI: 0.37-0.94). No significant association between footwear use and podoconiosis (OR=0.63; 95% CI: 0.38-1.05) was found and no data were available for mycetoma, myiasis, and snakebite. The main limitations were evidence of heterogeneity and poor study quality inherent to the observational studies included. CONCLUSIONS/SIGNIFICANCE Our results show that footwear use was associated with a lower odds of several different NTDs. Access to footwear should be prioritized alongside existing NTD interventions to ensure a lasting reduction of multiple NTDs and to accelerate their control and elimination. PROTOCOL REGISTRATION PROSPERO International prospective register of systematic reviews CRD42012003338

    Mis-Spliced Transcripts of Nicotinic Acetylcholine Receptor α6 Are Associated with Field Evolved Spinosad Resistance in Plutella xylostella (L.)

    Get PDF
    The evolution of insecticide resistance is a global constraint to agricultural production. Spinosad is a new, low-environmental-risk insecticide that primarily targets nicotinic acetylcholine receptors (nAChR) and is effective against a wide range of pest species. However, after only a few years of application, field evolved resistance emerged in the diamondback moth, Plutella xylostella, an important pest of brassica crops worldwide. Spinosad resistance in a Hawaiian population results from a single incompletely recessive and autosomal gene, and here we use AFLP linkage mapping to identify the chromosome controlling resistance in a backcross family. Recombinational mapping with more than 700 backcross progeny positioned a putative spinosad target, nAChR alpha 6 (Pxα6), at the resistance locus, PxSpinR. A mutation within the ninth intron splice junction of Pxα6 results in mis-splicing of transcripts, which produce a predicted protein truncated between the third and fourth transmembrane domains. Additional resistance-associated Pxα6 transcripts that excluded the mutation containing exon were detected, and these were also predicted to produce truncated proteins. Identification of the locus of resistance in this important crop pest will facilitate field monitoring of the spread of resistance and offer insights into the genetic basis of spinosad resistance in other species

    Stochastic Gravity: Theory and Applications

    Get PDF
    Whereas semiclassical gravity is based on the semiclassical Einstein equation with sources given by the expectation value of the stress-energy tensor of quantum fields, stochastic semiclassical gravity is based on the Einstein-Langevin equation, which has in addition sources due to the noise kernel. In the first part, we describe the fundamentals of this new theory via two approaches: the axiomatic and the functional. In the second part, we describe three applications of stochastic gravity theory. First, we consider metric perturbations in a Minkowski spacetime, compute the two-point correlation functions of these perturbations and prove that Minkowski spacetime is a stable solution of semiclassical gravity. Second, we discuss structure formation from the stochastic gravity viewpoint. Third, we discuss the backreaction of Hawking radiation in the gravitational background of a black hole and describe the metric fluctuations near the event horizon of an evaporating black holeComment: 100 pages, no figures; an update of the 2003 review in Living Reviews in Relativity gr-qc/0307032 ; it includes new sections on the Validity of Semiclassical Gravity, the Stability of Minkowski Spacetime, and the Metric Fluctuations of an Evaporating Black Hol
    corecore