767 research outputs found
Computational reconstitution of spine calcium transients from individual proteins
We have built a stochastic model in the program MCell that simulates Ca^(2+) transients in spines from the principal molecular components believed to control Ca^(2+) entry and exit. Proteins, with their kinetic models, are located within two segments of dendrites containing 88 intact spines, centered in a fully reconstructed 6 Ă 6 Ă 5 ÎŒm^3 cube of hippocampal neuropil. Protein components include AMPA- and NMDA-type glutamate receptors, L- and R-type voltage-dependent Ca^(2+) channels, Na^+/Ca^(2+) exchangers, plasma membrane Ca^(2+) ATPases, smooth endoplasmic reticulum Ca^(2+) ATPases, immobile Ca2+ buffers, and calbindin. Kinetic models for each protein were taken from published studies of the isolated proteins in vitro. For simulation of electrical stimuli, the time course of voltage changes in the dendritic spine was generated with the desired stimulus in the program NEURON. Voltage-dependent parameters were then continuously re-adjusted during simulations in MCell to reproduce the effects of the stimulus. Nine parameters of the model were optimized within realistic experimental limits by a process that compared results of simulations to published data. We find that simulations in the optimized model reproduce the timing and amplitude of Ca^(2+) transients measured experimentally in intact neurons. Thus, we demonstrate that the characteristics of individual isolated proteins determined in vitro can accurately reproduce the dynamics of experimentally measured Ca^(2+) transients in spines. The model will provide a test bed for exploring the roles of additional proteins that regulate Ca^(2+) influx into spines and for studying the behavior of protein targets in the spine that are regulated by Ca^(2+) influx
Prostate cancer detection rate in men undergoing transperineal template-guided saturation and targeted prostate biopsy
OBJECTIVES
To compare prostate cancer (PCa) detection rate of transperineal template-guided saturation prostate biopsy (SBx) and multiparametric magnetic resonance imaging (mpMRI)/transrectal ultrasound fusion guided targeted biopsy (TBx). MATERIALS ANDÂ METHODS: We prospectively enrolled 392 men who underwent SBx and TBx in case of suspicious lesions from November 2016 to October 2019. Triggers for a biopsy were an elevated prostate-specific antigen (PSA) and/or positive digital rectal examination and only treatment naĂŻve patients without a previous diagnosis of PCa were included. Study inclusion occurred before biopsy and a prebiopsy mpMRI was available in all men. SBx were taken from 20 different locations according to the modified Barzell zones. The primary endpoint was the detection rate of clinically significant PCa (csPCa) and insignificant PCa (ciPCa) by SBx and/or TBx by comparing the two methods alone and in combination. Additional TBx were taken for any prostate imaging-reporting and data system (PI-RADS) lesion â„3 seen on the mpMRI. csPCa was defined as any Gleason score â„7 and ciPCa as Gleason score 6.
RESULTS
A total of 392 men with a median age of 64 years (interquartile range [IQR]: 58-69), a median PSA of 7.0âng/ml (IQR: 4.8-10.1) were enrolled. Overall, PCa was found in 200 (51%) of all biopsied men, with 158 (79%) being csPCa and 42 (21%) ciPCa. A total of 268 (68%) men with a suspicious mpMRI and underwent a combined TBx and SBx, of whom csPCa was found in 139 (52%). In this subgroup, 116/139 (83%) csPCa would have been detected by TBx alone, and an additional 23 (17%) were found by SBx. Men with a negative mpMRI (PI-RADSâ<â3, nâ=â124, 32%) were found to have csPCa in 19 (15%) cases. In patients with a negative mpMRI in combination with a PSA density <0.1âng/ml , only 8% (3/36) had csPCa. If only TBx would have been performed and all men with a negative mpMRI would not have been biopsed, 42/158 (27%) of csPCa would have been missed, and 38/42 (90%) ciPCa would have not been detected. On multivariable analysis, significant predictors of csPCa were increasing PSA (odds ratio, OR: 1.07 [95% confidence interval, CI:Â 1.03-1.11]), increasing age (OR: 1.07 [95% CI: 1.03-1.11]), PI-RADS scoreââ„â3 (OR: 6.49 [95% CI: 3.55-11.89]), and smaller prostate volume (OR: 0.96 [95% CI: 0.95 -0.97] (pâ<â0.05 for all parameters).
CONCLUSION
In comparison to SBx, TBx alone detects csPCa in only Ÿ of all men with a positive mpMRI lesion. Thus, systematic biopsies in addition to TBx have to be considered at least in some who undergo a prostate biopsy. In men with a negative mpMRI, SBx still detects 15% csPCa, but similarly overdetecting ciPCa. According to our results, low PSA density and negative mpMRI findings could be used to decide which men can safely avoid biopsy
Deep exclusive electroproduction off the proton at CLAS
The exclusive electroproduction of above the resonance region was
studied using the Large Acceptance Spectrometer () at
Jefferson Laboratory by scattering a 6 GeV continuous electron beam off a
hydrogen target. The large acceptance and good resolution of ,
together with the high luminosity, allowed us to measure the cross section for
the process in 140 (, , ) bins:
, 1.6 GeV GeV and 0.1 GeV
GeV. For most bins, the statistical accuracy is on the order of a few
percent. Differential cross sections are compared to two theoretical models,
based either on hadronic (Regge phenomenology) or on partonic (handbag diagram)
degrees of freedom. Both can describe the gross features of the data reasonably
well, but differ strongly in their ingredients. If the handbag approach can be
validated in this kinematical region, our data contain the interesting
potential to experimentally access transversity Generalized Parton
Distributions.Comment: 18pages, 21figures,2table
Near-threshold Photoproduction of Phi Mesons from Deuterium
We report the first measurement of the differential cross section on
-meson photoproduction from deuterium near the production threshold for a
proton using the CLAS detector and a tagged-photon beam in Hall B at Jefferson
Lab. The measurement was carried out by a triple coincidence detection of a
proton, and near the theoretical production threshold of 1.57 GeV.
The extracted differential cross sections for the initial
photon energy from 1.65-1.75 GeV are consistent with predictions based on a
quasifree mechanism. This experiment establishes a baseline for a future
experimental search for an exotic -N bound state from heavier nuclear
targets utilizing subthreshold/near-threshold production of mesons
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International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci.
The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5-20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson's disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations
Differential cross sections and recoil polarizations for the reaction gamma p -> K+ Sigma0
High-statistics measurements of differential cross sections and recoil
polarizations for the reaction have been
obtained using the CLAS detector at Jefferson Lab. We cover center-of-mass
energies () from 1.69 to 2.84 GeV, with an extensive coverage in the
production angle. Independent measurements were made using the
() and () final-state topologies,
and were found to exhibit good agreement. Our differential cross sections show
good agreement with earlier CLAS, SAPHIR and LEPS results, while offering
better statistical precision and a 300-MeV increase in coverage.
Above GeV, - and -channel Regge scaling behavior
can be seen at forward- and backward-angles, respectively. Our recoil
polarization () measurements represent a substantial increase in
kinematic coverage and enhanced precision over previous world data. At forward
angles we find that is of the same magnitude but opposite sign as
, in agreement with the static SU(6) quark model prediction of
. This expectation is violated in some mid- and
backward-angle kinematic regimes, where and are of
similar magnitudes but also have the same signs. In conjunction with several
other meson photoproduction results recently published by CLAS, the present
data will help constrain the partial wave analyses being performed to search
for missing baryon resonances.Comment: 23 pages, 17 figure
Absorption of the and Mesons in Nuclei
Due to their long lifetimes, the and mesons are the ideal
candidates for the study of possible modifications of the in-medium
meson-nucleon interaction through their absorption inside the nucleus. During
the E01-112 experiment at the Thomas Jefferson National Accelerator Facility,
the mesons were photoproduced from H, C, Ti, Fe, and Pb targets. This
paper reports the first measurement of the ratio of nuclear transparencies for
the channel. The ratios indicate larger in-medium widths compared
with what have been reported in other reaction channels.Comment: 6 pages, 4 figure
Molecular excitation in the Interstellar Medium: recent advances in collisional, radiative and chemical processes
We review the different excitation processes in the interstellar mediumComment: Accepted in Chem. Re
Measurement of Exclusive Electroproduction Structure Functions and their Relationship to Transversity GPDs
Exclusive electroproduction at a beam energy of 5.75 GeV has been
measured with the Jefferson Lab CLAS spectrometer. Differential cross sections
were measured at more than 1800 kinematic values in , , , and
, in the range from 1.0 to 4.6 GeV,\ up to 2 GeV,
and from 0.1 to 0.58. Structure functions and were extracted as functions of for each of
17 combinations of and . The data were compared directly with two
handbag-based calculations including both longitudinal and transversity GPDs.
Inclusion of only longitudinal GPDs very strongly underestimates and fails to account for and ,
while inclusion of transversity GPDs brings the calculations into substantially
better agreement with the data. There is very strong sensitivity to the
relative contributions of nucleon helicity flip and helicity non-flip
processes. The results confirm that exclusive electroproduction offers
direct experimental access to the transversity GPDs.Comment: 6 pages, 2 figure
A Precise Measurement of the Neutron Magnetic Form Factor GMn in the Few-GeV2 Region
The neutron elastic magnetic form factor GMn has been extracted from
quasielastic electron scattering data on deuterium with the CEBAF Large
Acceptance Spectrometer (CLAS) at Jefferson Lab. The kinematic coverage of the
measurement is continuous from Q2=1 GeV2 to 4.8 GeV2. High precision was
achieved by employing a ratio technique in which many uncertainties cancel, and
by a simultaneous in-situ calibration of the neutron detection efficiency, the
largest correction to the data. Neutrons were detected using the CLAS
electromagnetic calorimeters and the time-of-flight scintillators. Data were
taken at two different electron beam energies, allowing up to four
semi-independent measurements of GMn to be made at each value of Q2. The dipole
parameterization is found to provide a good description of the data over the
measured Q2 range.Comment: 14 pages, 5 figures, revtex4, submitted to Physical Review Letters,
Revised version has changes recommended by journal referee
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