Modeling the functional genomics of autism using human neurons.

Human neural progenitors from a variety of sources present new opportunities to model aspects of human neuropsychiatric disease in vitro. Such in vitro models provide the advantages of a human genetic background combined with rapid and easy manipulation, making them highly useful adjuncts to animal models. Here, we examined whether a human neuronal culture system could be utilized to assess the transcriptional program involved in human neural differentiation and to model some of the molecular features of a neurodevelopmental disorder, such as autism. Primary normal human neuronal progenitors (NHNPs) were differentiated into a post-mitotic neuronal state through addition of specific growth factors and whole-genome gene expression was examined throughout a time course of neuronal differentiation. After 4 weeks of differentiation, a significant number of genes associated with autism spectrum disorders (ASDs) are either induced or repressed. This includes the ASD susceptibility gene neurexin 1, which showed a distinct pattern from neurexin 3 in vitro, and which we validated in vivo in fetal human brain. Using weighted gene co-expression network analysis, we visualized the network structure of transcriptional regulation, demonstrating via this unbiased analysis that a significant number of ASD candidate genes are coordinately regulated during the differentiation process. As NHNPs are genetically tractable and manipulable, they can be used to study both the effects of mutations in multiple ASD candidate genes on neuronal differentiation and gene expression in combination with the effects of potential therapeutic molecules. These data also provide a step towards better understanding of the signaling pathways disrupted in ASD

Close Pairs as Proxies for Galaxy Cluster Mergers

Galaxy cluster merger statistics are an important component in understanding the formation of large-scale structure. Unfortunately, it is difficult to study merger properties and evolution directly because the identification of cluster mergers in observations is problematic. We use large N-body simulations to study the statistical properties of massive halo mergers, specifically investigating the utility of close halo pairs as proxies for mergers. We examine the relationship between pairs and mergers for a wide range of merger timescales, halo masses, and redshifts (0<z<1). We also quantify the utility of pairs in measuring merger bias. While pairs at very small separations will reliably merge, these constitute a small fraction of the total merger population. Thus, pairs do not provide a reliable direct proxy to the total merger population. We do find an intriguing universality in the relation between close pairs and mergers, which in principle could allow for an estimate of the statistical merger rate from the pair fraction within a scaled separation, but including the effects of redshift space distortions strongly degrades this relation. We find similar behavior for galaxy-mass halos, making our results applicable to field galaxy mergers at high redshift. We investigate how the halo merger rate can be statistically described by the halo mass function via the merger kernel (coagulation), finding an interesting environmental dependence of merging: halos within the mass resolution of our simulations merge less efficiently in overdense environments. Specifically, halo pairs with separations less than a few Mpc/h are more likely to merge in underdense environments; at larger separations, pairs are more likely to merge in overdense environments.Comment: 12 pages, 9 figures; Accepted for publication in ApJ. Significant additions to text and two figures changed. Added new findings on the universality of pair mergers and added analysis of the effect of FoF linking length on halo merger

Local conditions for the generalized covariant entropy bound

A set of sufficient conditions for the generalized covariant entropy bound given by Strominger and Thompson is as follows: Suppose that the entropy of matter can be described by an entropy current $s^a$. Let $k^a$ be any null vector along $L$ and $s\equiv -k^a s_a$. Then the generalized bound can be derived from the following conditions: (i) $s'\leq 2\pi T_{ab}k^ak^b$, where s'=k^a\grad_a s and $T_{ab}$ is the stress energy tensor; (ii) on the initial 2-surface $B$, $s(0)\leq -{1/4}\theta(0)$, where $\theta$ is the expansion of $k^a$. We prove that condition (ii) alone can be used to divide a spacetime into two regions: The generalized entropy bound holds for all light sheets residing in the region where $s<-{1/4}\theta$ and fails for those in the region where $s>-{1/4}\theta$. We check the validity of these conditions in FRW flat universe and a scalar field spacetime. Some apparent violations of the entropy bounds in the two spacetimes are discussed. These holographic bounds are important in the formulation of the holographic principle.Comment: 10 pages, 7 figure

Dual-mode mechanical resonance of individual ZnO nanobelts

©2003 American Institute of Physics. The electronic version of this article is the complete one and can be found online at: http://link.aip.org/link/?APPLAB/82/4806/1DOI:10.1063/1.1587878The mechanical resonance of a single ZnO nanobelt, induced by an alternative electric field, was studied by in situ transmission electron microscopy. Due to the rectangular cross section of the nanobelt, two fundamental resonance modes have been observed corresponding to two orthogonal transverse vibration directions, showing the versatile applications of nanobelts as nanocantilevers and nanoresonators. The bending modulus of the ZnO nanobelts was measured to be ~52 GPa and the damping time constant of the resonance in a vacuum of 5×10–8 Torr was ~1.2 ms and quality factor Q = 500

Hypotheses for near-surface exchange of methane on Mars

The Curiosity rover recently detected a background of 0.7 ppb and spikes of 7 ppb of methane on Mars. This in situ measurement reorients our understanding of the Martian environment and its potential for life, as the current theories do not entail any geological source or sink of methane that varies sub-annually. In particular, the 10-fold elevation during the southern winter indicates episodic sources of methane that are yet to be discovered. Here we suggest a near-surface reservoir could explain this variability. Using the temperature and humidity measurements from the rover, we find that perchlorate salts in the regolith deliquesce to form liquid solutions, and deliquescence progresses to deeper subsurface in the season of the methane spikes. We therefore formulate the following three testable hypotheses. The first scenario is that the regolith in Gale Crater adsorbs methane when dry and releases this methane to the atmosphere upon deliquescence. The adsorption energy needs to be 36 kJ/mol to explain the magnitude of the methane spikes, higher than existing laboratory measurements. The second scenario is that microorganisms convert organic matter in the soil to methane when they are in liquid solutions. This scenario does not require regolith adsorption, but entails extant life on Mars. The third scenario is that deep subsurface aquifers produce the bursts of methane. Continued in situ measurements of methane and water, as well as laboratory studies of adsorption and deliquescence, will test these hypotheses and inform the existence of the near-surface reservoir and its exchange with the atmosphere.Comment: Accepted for publication on Astrobiolog

Maximum relative excitation of a specific vibrational mode via optimum laser pulse duration

For molecules and materials responding to femtosecond-scale optical laser pulses, we predict maximum relative excitation of a Raman-active vibrational mode with period T when the pulse has an FWHM duration of 0.42 T. This result follows from a general analytical model, and is precisely confirmed by detailed density-functional-based dynamical simulations for C60 and a carbon nanotube, which include anharmonicity, nonlinearity, no assumptions about the polarizability tensor, and no averaging over rapid oscillations within the pulse. The mode specificity is, of course, best at low temperature and for pulses that are electronically off-resonance, and the energy deposited in any mode is proportional to the fourth power of the electric field.Comment: 5 pages, 4 figure

Reply to "Can gravitational dynamics be obtained by diffeomorphism invariance of action?"

In a previous work we showed that, in a suitable setting, one can use diffeomorphism invariance in order to derive gravitational field equations from boundary terms of the gravitational action. Standing by our results we reply here to a recent comment questioning their validity.Comment: Accepted for publication in PR

Transformation of Morphology and Luminosity Classes of the SDSS Galaxies

We present a unified picture on the evolution of galaxy luminosity and morphology. Galaxy morphology is found to depend critically on the local environment set up by the nearest neighbor galaxy in addition to luminosity and the large scale density. When a galaxy is located farther than the virial radius from its closest neighbor, the probability for the galaxy to have an early morphological type is an increasing function only of luminosity and the local density due to the nearest neighbor ($\rho_n$). The tide produced by the nearest neighbor is thought to be responsible for the morphology transformation toward the early type at these separations. When the separation is less than the virial radius, i.e. when $\rho_n > \rho_{\rm virial}$, its morphology depends also on the neighbor's morphology and the large-scale background density over a few Mpc scales ($\rho_{20}$) in addition to luminosity and $\rho_n$. The early type probability keeps increasing as $\rho_n$ increases if its neighbor is an early type. But the probability decreases as $\rho_n$ increases when the neighbor is a late type. The cold gas streaming from the late type neighbor can be the reason for the morphology transformation toward late type. The overall early-type fraction increases as $\rho_{20}$ increases when $\rho_n > \rho_{\rm virial}$. This can be attributed to the hot halo gas of the neighbor which is confined by the pressure of the ambient medium held by the background mass. We have also found that galaxy luminosity depends on $\rho_n$, and that the isolated bright galaxies are more likely to be recent merger products. We propose a scenario that a series of morphology and luminosity transformation occur through distant interactions and mergers, which results in the morphology--luminosity--local density relation.Comment: 14 pages, 7 figures, for higher resolution figures download PDF file at http://astro.kias.re.kr/docs/trans.pdf ; references added and typos in section 3.2 corrected; Final version accepted for publication in Ap

A general moment NRIXS approach to the determination of equilibrium Fe isotopic fractionation factors: application to goethite and jarosite

We measured the reduced partition function ratios for iron isotopes in goethite FeO(OH), potassium-jarosite KFe3(SO4)2(OH)6, and hydronium-jarosite (H3O)Fe3(SO4)2(OH)6, by Nuclear Resonant Inelastic X-Ray Scattering (NRIXS, also known as Nuclear Resonance Vibrational Spectroscopy -NRVS- or Nuclear Inelastic Scattering -NIS) at the Advanced Photon Source. These measurements were made on synthetic minerals enriched in 57Fe. A new method (i.e., the general moment approach) is presented to calculate {\beta}-factors from the moments of the NRIXS spectrum S(E). The first term in the moment expansion controls iron isotopic fractionation at high temperature and corresponds to the mean force constant of the iron bonds, a quantity that is readily measured and often reported in NRIXS studies.Comment: 38 pages, 2 tables, 8 figures. In press at Geochimica et Cosmochimica Acta. Appendix C contains new derivations relating the moments of the iron PDOS to the moments of the excitation probability function measured in Nuclear Resonant Inelastic X-ray Scatterin