Absorption of sunlight in the atmosphere of Venus

The profiles of upward, downward and net solar flux on Venus were measured at altitudes from about 62 km to the surface in three spectral bands at a vertical resolution of a few hundred meters. These data measured the penetration and absorption of solar energy in Venus' lower atmosphere quantities that are essential in evaluating the role of the greenhouse mechanism in supporting Venus' remarkably high surface temperature. In addition, the data constrained the vertical structure and optical properties of the Venus clouds

The single scattering phase functions of Jupiter's clouds

The determination of the single scattering phase functions of Jupiter's clouds and a thin upper haze by Tomasko et al. was refined and extended to seven latitudes in blue and red light. The phase function is well-constrained by the Pioneer 10 and 11 photometric data sets. Multiple scattering models were computed to match the limb darkening at each latitude at up to 15 phase angles from 12 deg to 151 deg. Ground-based observations were used for absolute calibration and to extend the data to lower phase angles. The phase functions were parameterized using the double Henyey-Greenstein function. The three Henyey-Greenstein parameters and the single scattering albedo were determined using a non-linear least squares method for the haze and the clouds below. The phase functions derived for the northen zone and belt are remarkably similar to the phase functions of the corresponding regions in the south, with most of the differences in brightness of the northern and southern features resulting from minor differences in single scattering albedo. Analysis of the Equatorial Region is complicated by the presence of numerous small features, but the phase function required is generally similar to that seen in the more homogeneous regions. Details of the phase functions of the haze and clouds are presented, and the differences between the cloud phase functions at low and high latitudes in red and blue light are discussed

Lunar maria and related deposits: Preliminary Galileo imaging results

During the Earth-Moon flyby the Galileo Solid State Imaging system obtained new information on lunar media. Imaging data in spectral bands from 0.4 to 1.0 micron wavelength provide color data for deposits on the western limb. General objectives were to determine the composition and stratigraphy of mare and related deposits for areas not previously seen well in color, and to compare the results with well-studied nearside maria. Initial results from images reduced with preliminary calibrations show that Galileo spectral reflectance data are consistent with previous earthbased observations

Intermittent existence of a southern Californian upwelling cell during submillennial climate change of the last 60 kyr

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95021/1/palo1108.pd

Genome-Wide Copy Number Variation in Epilepsy: Novel Susceptibility Loci in Idiopathic Generalized and Focal Epilepsies

Epilepsy is one of the most common neurological disorders in humans with a prevalence of 1% and a lifetime incidence of 3%. Several genes have been identified in rare autosomal dominant and severe sporadic forms of epilepsy, but the genetic cause is unknown in the vast majority of cases. Copy number variants (CNVs) are known to play an important role in the genetic etiology of many neurodevelopmental disorders, including intellectual disability (ID), autism, and schizophrenia. Genome-wide studies of copy number variation in epilepsy have not been performed. We have applied whole-genome oligonucleotide array comparative genomic hybridization to a cohort of 517 individuals with various idiopathic, non-lesional epilepsies. We detected one or more rare genic CNVs in 8.9% of affected individuals that are not present in 2,493 controls; five individuals had two rare CNVs. We identified CNVs in genes previously implicated in other neurodevelopmental disorders, including two deletions in AUTS2 and one deletion in CNTNAP2. Therefore, our findings indicate that rare CNVs are likely to contribute to a broad range of generalized and focal epilepsies. In addition, we find that 2.9% of patients carry deletions at 15q11.2, 15q13.3, or 16p13.11, genomic hotspots previously associated with ID, autism, or schizophrenia. In summary, our findings suggest common etiological factors for seemingly diverse diseases such as ID, autism, schizophrenia, and epilepsy

Cooperation of local motions in the Hsp90 molecular chaperone ATPase mechanism

The Hsp90 chaperone is a central node of protein homeostasis activating a large number of diverse client proteins. Hsp90 functions as a molecular clamp that closes and opens in response to the binding and hydrolysis of ATP. Crystallographic studies define distinct conformational states of the mechanistic core implying structural changes that have not yet been observed in solution. Here, we engineered one-nanometer fluorescence probes based on photo-induced electron transfer into yeast Hsp90 to observe these motions. We found that the ATPase activity of the chaperone was reflected in the kinetics of specific structural rearrangements at remote positions that acted cooperatively. Nanosecond single-molecule fluorescence fluctuation analysis uncovered that critical structural elements that undergo rearrangement are mobile on a sub-millisecond time scale. We identified a two-step mechanism for lid closure over the nucleotide-binding pocket. The activating co-chaperone Aha1 mobilizes the lid of apo Hsp90, suggesting an early role in the catalytic cycle

Bayesian inference of accurate population sizes and FRET efficiencies from single diffusing biomolecules.

It is of significant biophysical interest to obtain accurate intramolecular distance information and population sizes from single-molecule Förster resonance energy transfer (smFRET) data obtained from biomolecules in solution. Experimental methods of increasing cost and complexity are being developed to improve the accuracy and precision of data collection. However, the analysis of smFRET data sets currently relies on simplistic, and often arbitrary methods, for the selection and denoising of fluorescent bursts. Although these methods are satisfactory for the analysis of simple, low-noise systems with intermediate FRET efficiencies, they display systematic inaccuracies when applied to more complex systems. We have developed an inference method for the analysis of smFRET data from solution studies based on rigorous model-based Bayesian techniques. We implement a Monte Carlo Markov chain (MCMC) based algorithm that simultaneously estimates population sizes and intramolecular distance information directly from a raw smFRET data set, with no intermediate event selection and denoising steps. Here, we present both our parametric model of the smFRET process and the algorithm developed for data analysis. We test the algorithm using a combination of simulated data sets and data from dual-labeled DNA molecules. We demonstrate that our model-based method systematically outperforms threshold-based techniques in accurately inferring both population sizes and intramolecular distances.This is the final published version. It's also available from ACS in Analytical Chemistry: http://pubs.acs.org/doi/pdf/10.1021/ac501188r

Mutational mechanisms shaping the coding and noncoding genome of germinal center derived B-cell lymphomas

B cells have the unique property to somatically alter their immunoglobulin (IG) genes by V(D)J recombination, somatic hypermutation (SHM) and class-switch recombination (CSR). Aberrant targeting of these mechanisms is implicated in lymphomagenesis, but the mutational processes are poorly understood. By performing whole genome and transcriptome sequencing of 181 germinal center derived B-cell lymphomas (gcBCL) we identified distinct mutational signatures linked to SHM and CSR. We show that not only SHM, but presumably also CSR causes off-target mutations in non-IG genes. Kataegis clusters with high mutational density mainly affected early replicating regions and were enriched for SHM- and CSR-mediated off-target mutations. Moreover, they often co-occurred in loci physically interacting in the nucleus, suggesting that mutation hotspots promote increased mutation targeting of spatially co-localized loci (termed hypermutation by proxy). Only around 1% of somatic small variants were in protein coding sequences, but in about half of the driver genes, a contribution of B-cell specific mutational processes to their mutations was found. The B-cell-specific mutational processes contribute to both lymphoma initiation and intratumoral heterogeneity. Overall, we demonstrate that mutational processes involved in the development of gcBCL are more complex than previously appreciated, and that B cell-specific mutational processes contribute via diverse mechanisms to lymphomagenesis

Structural Heterogeneity and Quantitative FRET Efficiency Distributions of Polyprolines through a Hybrid Atomistic Simulation and Monte Carlo Approach

Förster Resonance Energy Transfer (FRET) experiments probe molecular distances via distance dependent energy transfer from an excited donor dye to an acceptor dye. Single molecule experiments not only probe average distances, but also distance distributions or even fluctuations, and thus provide a powerful tool to study biomolecular structure and dynamics. However, the measured energy transfer efficiency depends not only on the distance between the dyes, but also on their mutual orientation, which is typically inaccessible to experiments. Thus, assumptions on the orientation distributions and averages are usually made, limiting the accuracy of the distance distributions extracted from FRET experiments. Here, we demonstrate that by combining single molecule FRET experiments with the mutual dye orientation statistics obtained from Molecular Dynamics (MD) simulations, improved estimates of distances and distributions are obtained. From the simulated time-dependent mutual orientations, FRET efficiencies are calculated and the full statistics of individual photon absorption, energy transfer, and photon emission events is obtained from subsequent Monte Carlo (MC) simulations of the FRET kinetics. All recorded emission events are collected to bursts from which efficiency distributions are calculated in close resemblance to the actual FRET experiment, taking shot noise fully into account. Using polyproline chains with attached Alexa 488 and Alexa 594 dyes as a test system, we demonstrate the feasibility of this approach by direct comparison to experimental data. We identified cis-isomers and different static local environments as sources of the experimentally observed heterogeneity. Reconstructions of distance distributions from experimental data at different levels of theory demonstrate how the respective underlying assumptions and approximations affect the obtained accuracy. Our results show that dye fluctuations obtained from MD simulations, combined with MC single photon kinetics, provide a versatile tool to improve the accuracy of distance distributions that can be extracted from measured single molecule FRET efficiencies