244 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
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
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
Intestinal PTGS2 mRNA Levels, PTGS2 Gene Polymorphisms, and Colorectal Carcinogenesis
<div><p>Background & Aims</p><p>Inflammation is a major risk factor for development of colorectal cancer (CRC). Prostaglandin synthase cyclooxygenase-2 (COX-2) encoded by the <i>PTGS2</i> gene is the rate limiting enzyme in prostaglandin synthesis and therefore plays a distinct role as regulator of inflammation.</p><p>Methods</p><p><i>PTGS2</i> mRNA levels were determined in intestinal tissues from 85 intestinal adenoma cases, 115 CRC cases, and 17 healthy controls. The functional <i>PTGS2</i> polymorphisms A-1195G (rs689466), G-765C (rs20417), T8473C (rs5275) were assessed in 200 CRC cases, 991 adenoma cases and 399 controls from the Norwegian KAM cohort.</p><p>Results</p><p><i>PTGS2</i> mRNA levels were higher in mild/moderate adenoma tissue compared to morphologically normal tissue from the same individual (P<0.0001) and (P<0.035) and compared to mucosa from healthy individuals (P<0.0039) and (P<0.0027), respectively. In CRC patients, <i>PTGS2</i> mRNA levels were 8–9 times higher both in morphologically normal tissue and in cancer tissue, compared to healthy individuals (P<0.0001). <i>PTGS2</i> A-1195G variant allele carriers were at reduced risk of CRC (odds ratio (OR) = 0.52, 95% confidence interval (95% CI): 0.28–0.99, P = 0.047). Homozygous carriers of the haplotype encompassing the A-1195G and G-765C wild type alleles and the T8473C variant allele <i>(PTGS2</i> AGC) were at increased risk of CRC as compared to homozygous carriers of the <i>PTGS2</i> AGT (<u>A</u>-1195G, <u>G</u>-765C, <u>T</u>8473C) haplotype (OR = 5.37, 95% CI: 1.40–20.5, P = 0.014). No association between the investigated polymorphisms and <i>PTGS2</i> mRNA levels could be detected.</p><p>Conclusion</p><p>High intestinal <i>PTGS2</i> mRNA level is an early event in colorectal cancer development as it occurs already in mild/moderate dysplasia. <i>PTGS2</i> polymorphisms that have been associated with altered <i>PTGS2</i> mRNA levels/COX-2 activity in some studies, although not the present study, were associated with colorectal cancer risk. Thus, both <i>PTGS2</i> polymorphisms and <i>PTGS2</i> mRNA levels may provide information regarding CRC risk.</p></div
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
Collagen mRNA levels changes during colorectal cancer carcinogenesis
<p>Abstract</p> <p>Background</p> <p>Invasive growth of epithelial cancers is a complex multi-step process which involves dissolution of the basement membrane. Type IV collagen is a major component in most basement membranes. Type VII collagen is related to anchoring fibrils and is found primarily in the basement membrane zone of stratified epithelia. Immunohistochemical studies have previously reported changes in steady-state levels of different α(IV) chains in several epithelial cancer types. In the present study we aimed to quantitatively determine the mRNA levels of <it>type IV collagen (α1/α4/α6) </it>and <it>type VII collagen (α1) </it>during colorectal cancer carcinogenesis.</p> <p>Methods</p> <p>Using quantitative RT-PCR, we have determined the mRNA levels for <it>α1(IV), α4(IV), α6(IV), and α1(VII) </it>in colorectal cancer tissue (n = 33), adenomas (n = 29) and in normal tissue from the same individuals. In addition, corresponding tissue was examined from healthy volunteers (n = 20). mRNA levels were normalized to <it>β-actin</it>. Immunohistochemical analysis of the distributions of type IV and type VII collagens were performed on normal and affected tissues from colorectal cancer patients.</p> <p>Results</p> <p>The <it>α1(IV) </it>and <it>α1(VII) </it>mRNA levels were statistically significantly higher in colorectal cancer tissue (p < 0.001) as compared to corresponding tissue from healthy controls. This is an early event as tissue from adenomas also displayed a higher level. There were small changes in the levels of <it>α4(IV)</it>. The level of <it>α6(IV) </it>was 5-fold lower in colorectal cancer tissue as compared to healthy individuals (p < 0.01). The localisation of type IV and type VII collagen was visualized by immunohistochemical staining.</p> <p>Conclusion</p> <p>Our results suggest that the down-regulation of <it>α6(IV</it>) mRNA coincides with the acquisition of invasive growth properties, whereas <it>α1(IV) </it>and <it>α1(VII) </it>mRNAs were up-regulated already in dysplastic tissue. There are no differences in collagen expression between tissues from healthy individuals and normal tissues from affected individuals.</p
“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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