Frequency-specific network topologies in the resting human brain

A community is a set of nodes with dense inter-connections, while there are sparse connections between different communities. A hub is a highly connected node with high centrality. It has been shown that both communities and hubs exist simultaneously in the brain’s functional connectivity network, as estimated by correlations among low-frequency spontaneous fluctuations in functional magnetic resonance imaging (fMRI) signal changes (0.01–0.10 Hz). This indicates that the brain has a spatial organization that promotes both segregation and integration of information. Here, we demonstrate that frequency-specific network topologies that characterize segregation and integration also exist within this frequency range. In investigating the coherence spectrum among 87 brain regions, we found that two frequency bands, 0.01–0.03 Hz (very low frequency [VLF] band) and 0.07–0.09 Hz (low frequency [LF] band), mainly contributed to functional connectivity. Comparing graph theoretical indices for the VLF and LF bands revealed that the network in the former had a higher capacity for information segregation between identified communities than the latter. Hubs in the VLF band were mainly located within the anterior cingulate cortices, whereas those in the LF band were located in the posterior cingulate cortices and thalamus. Thus, depending on the timescale of brain activity, at least two distinct network topologies contributed to information segregation and integration. This suggests that the brain intrinsically has timescale-dependent functional organizations

Neural networks for action representation: a functional magnetic-resonance imaging and dynamic causal modeling study

Automatic mimicry is based on the tight linkage between motor and perception action representations in which internal models play a key role. Based on the anatomical connection, we hypothesized that the direct effective connectivity from the posterior superior temporal sulcus (pSTS) to the ventral premotor area (PMv) formed an inverse internal model, converting visual representation into a motor plan, and that reverse connectivity formed a forward internal model, converting the motor plan into a sensory outcome of action. To test this hypothesis, we employed dynamic causal-modeling analysis with functional magnetic-resonance imaging (fMRI). Twenty-four normal participants underwent a change-detection task involving two visually-presented balls that were either manually rotated by the investigator's right hand (“Hand”) or automatically rotated. The effective connectivity from the pSTS to the PMv was enhanced by hand observation and suppressed by execution, corresponding to the inverse model. Opposite effects were observed from the PMv to the pSTS, suggesting the forward model. Additionally, both execution and hand observation commonly enhanced the effective connectivity from the pSTS to the inferior parietal lobule (IPL), the IPL to the primary sensorimotor cortex (S/M1), the PMv to the IPL, and the PMv to the S/M1. Representation of the hand action therefore was implemented in the motor system including the S/M1. During hand observation, effective connectivity toward the pSTS was suppressed whereas that toward the PMv and S/M1 was enhanced. Thus, the action-representation network acted as a dynamic feedback-control system during action observation

Bubble wall perturbations coupled with gravitational waves

We study a coupled system of gravitational waves and a domain wall which is the boundary of a vacuum bubble in de Sitter spacetime. To treat the system, we use the metric junction formalism of Israel. We show that the dynamical degree of the bubble wall is lost and the bubble wall can oscillate only while the gravitational waves go across it. It means that the gravitational backreaction on the motion of the bubble wall can not be ignored.Comment: 23 pages with 3 eps figure

Compact hyperbolic universe and singularities

Recently many people have discussed the possibility that the universe is hyperbolic and was in an inflationary phase in the early stage. Under these assumptions, it is shown that the universe cannot have compact hyperbolic time-slices. Though the universal covering space of the universe has a past Cauchy horizon and can be extended analytically beyond it, the extended region has densely many points which correspond to singularities of the compact universe. The result is essentially attributed to the ergodicity of the geodesic flow on a compact negatively curved manifold. Validity of the result is also discussed in the case of inhomogeneous universe. Relationship with the strong cosmic censorship conjecture is also discussed.Comment: 8 pages with 7 figure

Can the Acceleration of Our Universe Be Explained by the Effects of Inhomogeneities?

No. It is simply not plausible that cosmic acceleration could arise within the context of general relativity from a back-reaction effect of inhomogeneities in our universe, without the presence of a cosmological constant or ``dark energy.'' We point out that our universe appears to be described very accurately on all scales by a Newtonianly perturbed FLRW metric. (This assertion is entirely consistent with the fact that we commonly encounter $\delta \rho/\rho > 10^{30}$.) If the universe is accurately described by a Newtonianly perturbed FLRW metric, then the back-reaction of inhomogeneities on the dynamics of the universe is negligible. If not, then it is the burden of an alternative model to account for the observed properties of our universe. We emphasize with concrete examples that it is {\it not} adequate to attempt to justify a model by merely showing that some spatially averaged quantities behave the same way as in FLRW models with acceleration. A quantity representing the ``scale factor'' may ``accelerate'' without there being any physically observable consequences of this acceleration. It also is {\it not} adequate to calculate the second-order stress energy tensor and show that it has a form similar to that of a cosmological constant of the appropriate magnitude. The second-order stress energy tensor is gauge dependent, and if it were large, contributions of higher perturbative order could not be neglected. We attempt to clear up the apparent confusion between the second-order stress energy tensor arising in perturbation theory and the ``effective stress energy tensor'' arising in the ``shortwave approximation.''Comment: 20 pages, 1 figure, several footnotes and references added, version accepted for publication in CQG;some clarifying comments adde

Brane Big-Bang Brought by Bulk Bubble

We propose an alternative inflationary universe scenario in the context of Randall-Sundrum braneworld cosmology. In this new scenario the existence of extra-dimension(s) plays an essential role. First, the brane universe is initially in the inflationary phase driven by the effective cosmological constant induced by small mismatch between the vacuum energy in the 5-dimensional bulk and the brane tension. This mismatch arises since the bulk is initially in a false vacuum. Then, the false vacuum decay occurs, nucleating a true vacuum bubble with negative energy inside the bulk. The nucleated bubble expands in the bulk and consequently hits the brane, bringing a hot big-bang brane universe of the Randall-Sundrum type. Here, the termination of the inflationary phase is due to the change of the bulk vacuum energy. The bubble kinetic energy heats up the universe. As a simple realization, we propose a model, in which we assume an interaction between the brane and the bubble. We derive the constraints on the model parameters taking into account the following requirements: solving the flatness problem, no force which prohibits the bubble from colliding with the brane, sufficiently high reheating temperature for the standard nucleosynthesis to work, and the recovery of Newton's law up to 1mm. We find that a fine tuning is needed in order to satisfy the first and the second requirements simultaneously, although, the other constraints are satisfied in a wide range of the model parameters.Comment: 20pages, 5figures, some references added, the previous manuscript has been largely improve

Establishment of Functioning Human Corneal Endothelial Cell Line with High Growth Potential

Hexagonal-shaped human corneal endothelial cells (HCEC) form a monolayer by adhering tightly through their intercellular adhesion molecules. Located at the posterior corneal surface, they maintain corneal translucency by dehydrating the corneal stroma, mainly through the Na+- and K+-dependent ATPase (Na+/K+-ATPase). Because HCEC proliferative activity is low in vivo, once HCEC are damaged and their numbers decrease, the cornea begins to show opacity due to overhydration, resulting in loss of vision. HCEC cell cycle arrest occurs at the G1 phase and is partly regulated by cyclin-dependent kinase inhibitors (CKIs) in the Rb pathway (p16-CDK4/CyclinD1-pRb). In this study, we tried to activate proliferation of HCEC by inhibiting CKIs. Retroviral transduction was used to generate two new HCEC lines: transduced human corneal endothelial cell by human papillomavirus type E6/E7 (THCEC (E6/E7)) and transduced human corneal endothelial cell by Cdk4R24C/CyclinD1 (THCEH (Cyclin)). Reverse transcriptase polymerase chain reaction analysis of gene expression revealed little difference between THCEC (E6/E7), THCEH (Cyclin) and non-transduced HCEC, but cell cycle-related genes were up-regulated in THCEC (E6/E7) and THCEH (Cyclin). THCEH (Cyclin) expressed intercellular molecules including ZO-1 and N-cadherin and showed similar Na+/K+-ATPase pump function to HCEC, which was not demonstrated in THCEC (E6/E7). This study shows that HCEC cell cycle activation can be achieved by inhibiting CKIs even while maintaining critical pump function and morphology

Genomic characterization of biliary tract cancers identifies driver genes and predisposing mutations

Background & Aims Biliary tract cancers (BTCs) are clinically and pathologically heterogeneous and respond poorly to treatment. Genomic profiling can offer a clearer understanding of their carcinogenesis, classification and treatment strategy. We performed large-scale genome sequencing analyses on BTCs to investigate their somatic and germline driver events and characterize their genomic landscape. Methods We analyzed 412 BTC samples from Japanese and Italian populations, 107 by whole-exome sequencing (WES), 39 by whole-genome sequencing (WGS), and a further 266 samples by targeted sequencing. The subtypes were 136 intrahepatic cholangiocarcinomas (ICCs), 101 distal cholangiocarcinomas (DCCs), 109 peri-hilar type cholangiocarcinomas (PHCs), and 66 gallbladder or cystic duct cancers (GBCs/CDCs). We identified somatic alterations and searched for driver genes in BTCs, finding pathogenic germline variants of cancer-predisposing genes. We predicted cell-of-origin for BTCs by combining somatic mutation patterns and epigenetic features. Results We identified 32 significantly and commonly mutated genes including TP53 , KRAS , SMAD4 , NF1 , ARID1A , PBRM1 , and ATR , some of which negatively affected patient prognosis. A novel deletion of MUC17 at 7q22.1 affected patient prognosis. Cell-of-origin predictions using WGS and epigenetic features suggest hepatocyte-origin of hepatitis-related ICCs. Deleterious germline mutations of cancer-predisposing genes such as BRCA1 , BRCA2 , RAD51D , MLH1 , or MSH2 were detected in 11% (16/146) of BTC patients. Conclusions BTCs have distinct genetic features including somatic events and germline predisposition. These findings could be useful to establish treatment and diagnostic strategies for BTCs based on genetic information. Lay summary We here analyzed genomic features of 412 BTC samples from Japanese and Italian populations. A total of 32 significantly and commonly mutated genes were identified, some of which negatively affected patient prognosis, including a novel deletion of MUC17 at 7q22.1 . Cell-of-origin predictions using WGS and epigenetic features suggest hepatocyte-origin of hepatitis-related ICCs. Deleterious germline mutations of cancer-predisposing genes were detected in 11% of patients with BTC. BTCs have distinct genetic features including somatic events and germline predisposition

Brane World Cosmology - Gauge-Invariant Formalism for Perturbation

In the present paper the gauge-invariant formalism is developed for perturbations of the brane-world model in which our universe is realized as a boundary of a higher-dimensional spacetime. For the background model in which the bulk spacetime is $(n+m)$-dimensional and has the spatial symmetry corresponding to the isometry group of a $n$-dimensional maximally symmetric space, gauge-invariant equations are derived for perturbations of the bulk spacetime. Further for the case corresponding to the brane-world model in which $m=2$ and the brane is a boundary invariant under the spatial symmetry in the unperturbed background, relations between the gauge-invariant variables describing the bulk perturbations and those for brane perturbations are derived from Israel's junction condition under the assumption of \ZR_2 symmetry. In particular, for the case in which the bulk spacetime is a constant-curvature spacetime, it is shown that the bulk perturbation equations reduce to a single hyperbolic master equation for a master variable, and that the physical condition on the gauge-invariant variable describing the intrinsic stress perturbation of the brane yield a boundary condition for the master equation through the junction condition. On the basis of this formalism it is pointed out that it seems to be difficult to suppress brane perturbations corresponding to massive excitations for a brane motion giving a realistic expanding universe model.Comment: 25 pages, no figures, typos corrected, to appear in Phys.Rev.

Comparison of percutaneous radiofrequency thermal ablation and surgical resection for small hepatocellular carcinoma

<p>Abstract</p> <p>Background</p> <p>The purpose of this investigation was to compare the outcome of percutaneous radiofrequency thermal ablation therapy (PRFA) with surgical resection (SR) in the treatment of single and small hepatocellular carcinoma (HCC).</p> <p>Methods</p> <p>We conducted a retrospective cohort study on 231 treatment naive patients with a single HCC ≤ 3 cm who had received either curative PRFA (162 patients) or curative SR (69 patients). All patients were regularly followed up after treatment at our department with blood and radiologic tests.</p> <p>Results</p> <p>The 1-, 3- and 5-year overall survival rates after PRFA and SR were 95.4%, 79.6% and 63.1%, respectively in the PRFA group and 100%, 81.4% and 74.6%, respectively in the SR group. The corresponding recurrence free survival rates at 1, 3 and 5 years after PRFA and SR were 82.0%, 38.3% and 18.0%, respectively in the PRFA group and 86.0%, 47.2% and 26.0%, respectively in the SR group. In terms of overall survival and recurrence free survival, there were no significant differences between these two groups. In comparison of PRFA group patients with liver cirrhosis (LC) (n = 127) and SR group patients with LC (n = 50) and in comparison of PRFA group patients without LC (n = 35) and SR group patients without LC (n = 19), there were also no significant differences between two groups in terms of overall survival and recurrence free survival. In the multivariate analysis of the risk factors contributing to overall survival, serum albumin level was the sole significant factor. In the multivariate analysis of the risk factors contributing to recurrence free survival, presence of LC was the sole significant factor. The rate of serious adverse events in the SR group was significantly higher than that in the PRFA group (P = 0.023). Hospitalization length in the SR group was significantly longer than in the PRFA group (P = 0.013).</p> <p>Conclusions</p> <p>PRFA is as effective as SR in the treatment of single and small HCC, and is less invasive than SR. Therefore, PRFA could be a first choice for the treatment of single and small HCC.</p