422 research outputs found
Gamma oscillations in V1 are correlated with GABA(A) receptor density: A multi-modal MEG and Flumazenil-PET study.
High-frequency oscillations in the gamma-band reflect rhythmic synchronization of spike timing in active neural networks. The modulation of gamma oscillations is a widely established mechanism in a variety of neurobiological processes, yet its neurochemical basis is not fully understood. Modeling, in-vitro and in-vivo animal studies suggest that gamma oscillation properties depend on GABAergic inhibition. In humans, search for evidence linking total GABA concentration to gamma oscillations has led to promising -but also to partly diverging- observations. Here, we provide the first evidence of a direct relationship between the density of GABA(A) receptors and gamma oscillatory gamma responses in human primary visual cortex (V1). By combining Flumazenil-PET (to measure resting-levels of GABA(A) receptor density) and MEG (to measure visually-induced gamma oscillations), we found that GABA(A) receptor densities correlated positively with the frequency and negatively with amplitude of visually-induced gamma oscillations in V1. Our findings demonstrate that gamma-band response profiles of primary visual cortex across healthy individuals are shaped by GABA(A)-receptor-mediated inhibitory neurotransmission. These results bridge the gap with in-vitro and animal studies and may have future clinical implications given that altered GABAergic function, including dysregulation of GABA(A) receptors, has been related to psychiatric disorders including schizophrenia and depression
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Relative contribution of clinicopathological variables, genomic markers, transcriptomic subtyping and microenvironment features for outcome prediction in stage II/III colorectal cancer
Background: It remains unknown to what extent consensus molecular subtype (CMS) groups and immune-stromal infiltration patterns improve our ability to predict outcomes over tumor-node-metastasis (TNM) staging and microsatellite instability (MSI) status in early-stage colorectal cancer (CRC). Patients and methods: We carried out a comprehensive retrospective biomarker analysis of prognostic markers in adjuvant chemotherapy-untreated (N = 1656) and treated (N = 980), stage II (N = 1799) and III (N = 837) CRCs. We defined CMS scores and estimated CD8+ cytotoxic lymphocytes (CytoLym) and cancer-associated fibroblasts (CAF) infiltration scores from bulk tumor tissue transcriptomes (CMSclassifier and MCPcounter R packages); constructed a stratified multivariable Cox model for disease-free survival (DFS); and calculated the relative proportion of explained variation by each marker (clinicopathological [ClinPath], genomics [Gen: MSI, BRAF and KRAS mutations], CMS scores [CMS] and microenvironment cells [MicroCells: CytoLym+CAF]). Results: In multivariable models, only ClinPath and MicroCells remained significant prognostic factors, with both CytoLym and CAF infiltration scores improving survival prediction beyond other markers. The explained variation for DFS models of ClinPath, MicroCells, Gen markers and CMS4 scores was 77%, 14%, 5.3% and 3.7%, respectively, in stage II; and 55.9%, 35.1%, 4.1% and 0.9%, respectively, in stage III. Patients whose tumors were CytoLym high/CAF low had better DFS than other strata [HR=0.71 (0.6-0.9); P = 0.004]. Microsatellite stable tumors had the strongest signal for improved outcomes with CytoLym high scores (interaction P = 0.04) and the poor prognosis linked to high CAF scores was limited to stage III disease (interaction P = 0.04). Conclusions: Our results confirm that tumor microenvironment infiltration patterns represent potent determinants of the risk for distant dissemination in early-stage CRC. Multivariable models suggest that the prognostic value of MSI and CMS groups is largely explained by CytoLym and CAF infiltration patterns
Glide and Superclimb of Dislocations in Solid He
Glide and climb of quantum dislocations under finite external stress,
variation of chemical potential and bias (geometrical slanting) in Peierls
potential are studied by Monte Carlo simulations of the effective string model.
We treat on unified ground quantum effects at finite temperatures . Climb at
low is assisted by superflow along dislocation core -- {\it superclimb}.
Above some critical stress avalanche-type creation of kinks is found. It is
characterized by hysteretic behavior at low . At finite biases gliding
dislocation remains rough even at lowest -- the behavior opposite to
non-slanted dislocations. In contrast to glide, superclimb is characterized by
quantum smooth state at low temperatures even for finite bias. In some
intermediate -range giant values of the compressibility as well as
non-Luttinger type behavior of the core superfluid are observed.Comment: Updated version submitted to JLTP as QFS2010 proceedings; 11 pages, 6
figure
Modulation of the nucleation rate pre-exponential in a low-temperature Ising system
A metastable lattice gas with nearest-neighbor interactions and
continuous-time dynamics is studied using a generalized Becker-Doring approach
in the multidimensional space of cluster configurations. The pre-exponential of
the metastable state lifetime (inverse of nucleation rate) is found to exhibit
distinct peaks at integer values of the inverse supersaturation. Peaks are
unobservable (infinitely narrow) in the strict limit T->0, but become
detectable and eventually dominate at higher temperatures.Comment: 4 pages, 2 Postscript figures, LaTeX, submitted to Phys. Rev. Lett.
Changes: updated references, re-written section around eqs.(5),(6), typos,
minor wording changes in conclusion and other parts of text (mostly in
response to referees' comments). Paper resubmitted to PR
Diffusion controlled initial recombination
This work addresses nucleation rates in systems with strong initial
recombination. Initial (or `geminate') recombination is a process where a
dissociated structure (anion, vortex, kink etc.) recombines with its twin
brother (cation, anti-vortex, anti-kink) generated in the same nucleation
event. Initial recombination is important if there is an asymptotically
vanishing interaction force instead of a generic saddle-type activation
barrier. At low temperatures, initial recombination strongly dominates
homogeneous recombination. In a first part, we discuss the effect in one-,
two-, and three-dimensional diffusion controlled systems with spherical
symmetry. Since there is no well-defined saddle, we introduce a threshold which
is to some extent arbitrary but which is restricted by physically reasonable
conditions. We show that the dependence of the nucleation rate on the specific
choice of this threshold is strongest for one-dimensional systems and decreases
in higher dimensions. We discuss also the influence of a weak driving force and
show that the transport current is directly determined by the imbalance of the
activation rate in the direction of the field and the rate against this
direction. In a second part, we apply the results to the overdamped sine-Gordon
system at equilibrium. It turns out that diffusive initial recombination is the
essential mechanism which governs the equilibrium kink nucleation rate. We
emphasize analogies between the single particle problem with initial
recombination and the multi-dimensional kink-antikink nucleation problem.Comment: LaTeX, 11 pages, 1 ps-figures Extended versio
Dislocation Kinks in Copper: Widths, Barriers, Effective Masses, and Quantum Tunneling
We calculate the widths, migration barriers, effective masses, and quantum
tunneling rates of kinks and jogs in extended screw dislocations in copper,
using an effective medium theory interatomic potential. The energy barriers and
effective masses for moving a unit jog one lattice constant are close to
typical atomic energies and masses: tunneling will be rare. The energy barriers
and effective masses for the motion of kinks are unexpectedly small due to the
spreading of the kinks over a large number of atoms. The effective masses of
the kinks are so small that quantum fluctuations will be important. We discuss
implications for quantum creep, kink--based tunneling centers, and Kondo
resonances
Heterogeneous condensation in dense media
The theoretical description of the heterogeneous nucleation kinetics is
presented. This description takes into account the perturbation of the vapor
phase initiated by the growing droplets. The form of the density profile around
the growing droplet is analyzed which leads to some special approximations.
Then the process of nucleation in the whole system is described. As the result
all main characteristics of the process are determined analytically.Comment: 50 pages, LATE
Loss of Y Chromosome in the Malignant Peripheral Nerve Sheet Tumor of a Patient with Neurofibromatosis Type 1
Neurofibromatosis type 1 (NF1) is one of the most commonly inherited autosomal dominant disorders. In order to determine whether genomic alterations and/or chromosomal aberrations involved in the malignant progression of NF1 were present in a Korean patient with NF1, molecular and cytogenetic analyses were performed on the pathologically normal, benign, and malignant tissues and primary cells cultured from those tissues of the patient. The comparative genomic hybridization (CGH) array revealed a Y chromosome loss in the malignant peripheral nerve sheet tumor (MPNST) tissue. G-banding analysis of 50 metaphase cells showed normal chromosomal patterns in the histopathologically normal and benign cultured cells, but a mosaic Y chromosome loss in the malignant cells. The final karyotype for the malignant cells from MPNST tissue was 45,X,-Y[28]/46,XY[22]. The data suggest that the somatic Y chromosome loss may be involved in the transformation of benign tumors to MPNSTs
“Conjugate Channeling” Effect in Dislocation Core Diffusion: Carbon Transport in Dislocated BCC Iron
Dislocation pipe diffusion seems to be a well-established phenomenon. Here we demonstrate an unexpected effect, that the migration of interstitials such as carbon in iron may be accelerated not in the dislocation line direction [symbol], but in a conjugate diffusion direction. This accelerated random walk arises from a simple crystallographic channeling effect. [c] is a function of the Burgers vector b, but not [symbol], thus a dislocation loop possesses the same everywhere. Using molecular dynamics and accelerated dynamics simulations, we further show that such dislocation-core-coupled carbon diffusion in iron has temperature-dependent activation enthalpy like a fragile glass. The 71° mixed dislocation is the only case in which we see straightforward pipe diffusion that does not depend on dislocation mobility.National Science Foundation (U.S.) (Grant No. CMMI-0728069)National Science Foundation (U.S.) (Grant No. DMR-1008104)National Science Foundation (U.S.) (Grant No. DMR-1120901
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