Lycium barbarum Extracts Protect the Brain from Blood-Brain Barrier Disruption and Cerebral Edema in Experimental Stroke

BACKGROUND AND PURPOSE: Ischemic stroke is a destructive cerebrovascular disease and a leading cause of death. Yet, no ideal neuroprotective agents are available, leaving prevention an attractive alternative. The extracts from the fruits of Lycium barbarum (LBP), a Chinese anti-aging medicine and food supplement, showed neuroprotective function in the retina when given prophylactically. We aim to evaluate the protective effects of LBP pre-treatment in an experimental stroke model. METHODS: C57BL/6N male mice were first fed with either vehicle (PBS) or LBP (1 or 10 mg/kg) daily for 7 days. Mice were then subjected to 2-hour transient middle cerebral artery occlusion (MCAO) by the intraluminal method followed by 22-hour reperfusion upon filament removal. Mice were evaluated for neurological deficits just before sacrifice. Brains were harvested for infarct size estimation, water content measurement, immunohistochemical analysis, and Western blot experiments. Evans blue (EB) extravasation was determined to assess blood-brain barrier (BBB) disruption after MCAO. RESULTS: LBP pre-treatment significantly improved neurological deficits as well as decreased infarct size, hemispheric swelling, and water content. Fewer apoptotic cells were identified in LBP-treated brains by TUNEL assay. Reduced EB extravasation, fewer IgG-leaky vessels, and up-regulation of occludin expression were also observed in LBP-treated brains. Moreover, immunoreactivity for aquaporin-4 and glial fibrillary acidic protein were significantly decreased in LBP-treated brains. CONCLUSIONS: Seven-day oral LBP pre-treatment effectively improved neurological deficits, decreased infarct size and cerebral edema as well as protected the brain from BBB disruption, aquaporin-4 up-regulation, and glial activation. The present study suggests that LBP may be used as a prophylactic neuroprotectant in patients at high risk for ischemic stroke.published_or_final_versio

BMDO materials testing in the EOIM-3 experiment

The NASA Evaluation of Oxygen Interactions with Materials-3 (EOIM-3) experiment served as a testbed for a variety of materials that are candidates for Ballistic Missile Defense Organization (BMDO) space assets. The materials evaluated on this flight experiment were provided by BMDO contractors and technology laboratories. A parallel ground-based exposure evaluation was conducted using the Fast Atom Sample Tester (FAST) atomic-oxygen simulation facility at Physical Sciences, Inc. The EOIM-3 flight materials were exposed to an atomic oxygen fluence of approximately 2.3 x 10(exp 20) atoms/sq cm. The ground-based exposure fluence of 2.0 - 2.5 x 10(exp 20) atoms/sq cm permits direct comparison with that of the flight-exposed specimens. The results from the flight test conducted aboard STS-46 and the correlative ground-based exposure are summarized here. A more detailed correlation study is presented in the JPL Publication 93-31 entitled 'Flight-and Ground-Test Correlation Study of BMDO SDS Materials: Phase 1 Report'. In general, the majority of the materials survived the AO environment with their performance tolerances maintained for the duration of the exposure. Optical materials, baffles, and coatings performed extremely well as did most of the thermal coatings and tribological materials. A few of the candidate radiator, threat shielding, and structural materials showed significant degradation. Many of the coatings designed to protect against AO erosion of sensitive materials performed this function well

The use of duplex-specific nuclease in ribosome profiling and a user-friendly software package for Ribo-seq data analysis.

Ribosome profiling is a technique that permits genome-wide, quantitative analysis of translation and has found broad application in recent years. Here we describe a modified profiling protocol and software package designed to benefit more broadly the translation community in terms of simplicity and utility. The protocol, applicable to diverse organisms, including organelles, is based largely on previously published profiling methodologies, but uses duplex-specific nuclease (DSN) as a convenient, species-independent way to reduce rRNA contamination. We show that DSN-based depletion compares favorably with other commonly used rRNA depletion strategies and introduces little bias. The profiling protocol typically produces high levels of triplet periodicity, facilitating the detection of coding sequences, including upstream, downstream, and overlapping open reading frames (ORFs) and an alternative ribosome conformation evident during termination of protein synthesis. In addition, we provide a software package that presents a set of methods for parsing ribosomal profiling data from multiple samples, aligning reads to coding sequences, inferring alternative ORFs, and plotting average and transcript-specific aspects of the data. Methods are also provided for extracting the data in a form suitable for differential analysis of translation and translational efficiency.This work was supported by an EMBL long-term postdoctoral fellowship to B.Y.C., Sir Henry Wellcome Fellowships to B.Y.C. and N.I., a Wellcome Trust PhD scholarship to J.D.J., a Wellcome Trust Fellowship to A.E.F. (088789), and UK Biotechnology and Biological Sciences Research Council grants to I.B. (BB/L000334/ 1) and A.E.F. (BB/J007072/1). Work in the Baulcombe laboratory is supported by The Gatsby Charitable Foundation and the European Research Council Advanced Investigator grant TRIBE. D.C.B. is the Royal Society Edward Penley Abraham Research Professor. We wish to thank Professor Stuart G. Siddell, University of Bristol, for providing the murine 17 clone 1 cellsThis is the final version of the article. It was first available from Cold Springs Harbor Press via http://dx.doi.org/10.1261/rna.052548.11

The DEEP2 Galaxy Redshift Survey: Clustering of Groups and Group Galaxies at z~1

We study the clustering properties of groups and of galaxies in groups in the DEEP2 Galaxy Redshift Survey dataset at z~1. Four clustering measures are presented: 1) the group correlation function for 460 groups with estimated velocity dispersions of sigma>200 km/s, 2) the galaxy correlation for the full galaxy sample, using a flux-limited sample of 9800 objects between 0.7<z<1.0, 3) the galaxy correlation for galaxies in groups, and 4) the group-galaxy cross-correlation function. Using the observed number density and clustering amplitude of the groups, the estimated minimum group dark matter halo mass is M_min~6 10^12 h^-1 M_Sun for a flat LCDM cosmology. Groups are more clustered than galaxies, with a relative bias of b=1.7 +/-0.04 on scales r_p=0.5-15 Mpc/h. Galaxies in groups are also more clustered than the full galaxy sample, with a scale-dependent relative bias which falls from b~2.5 +/-0.3 at r_p=0.1 Mpc/h to b~1 +/-0.5 at r_p=10 Mpc/h. The correlation functions for all galaxies and galaxies in groups can be fit by a power-law on scales r_p=0.05-20 Mpc/h. We empirically measure the contribution to the projected correlation function for galaxies in groups from a `one-halo' term and a `two-halo' term by counting pairs of galaxies in the same or in different groups. The projected cross-correlation between shows that red galaxies are more centrally concentrated in groups than blue galaxies at z~1. DEEP2 galaxies in groups appear to have a shallower radial distribution than that of mock galaxy catalogs made from N-body simulations, which assume a central galaxy surrounded by satellite galaxies with an NFW profile. We show that the clustering of galaxies in groups can be used to place tighter constraints on the halo model than can be gained from using the usual galaxy correlation function alone.Comment: 22 pages, 12 figures, in emulateapj format, accepted to ApJ, minor changes made to match published versio

Electron affinity of Li: A state-selective measurement

We have investigated the threshold of photodetachment of Li^- leading to the formation of the residual Li atom in the $2p ^2P$ state. The excited residual atom was selectively photoionized via an intermediate Rydberg state and the resulting Li^+ ion was detected. A collinear laser-ion beam geometry enabled both high resolution and sensitivity to be attained. We have demonstrated the potential of this state selective photodetachment spectroscopic method by improving the accuracy of Li electron affinity measurements an order of magnitude. From a fit to the Wigner law in the threshold region, we obtained a Li electron affinity of 0.618 049(20) eV.Comment: 5 pages,6 figures,22 reference

Statistical Mechanics Analysis of LDPC Coding in MIMO Gaussian Channels

Using analytical methods of statistical mechanics, we analyse the typical behaviour of a multiple-input multiple-output (MIMO) Gaussian channel with binary inputs under LDPC network coding and joint decoding. The saddle point equations for the replica symmetric solution are found in particular realizations of this channel, including a small and large number of transmitters and receivers. In particular, we examine the cases of a single transmitter, a single receiver and the symmetric and asymmetric interference channels. Both dynamical and thermodynamical transitions from the ferromagnetic solution of perfect decoding to a non-ferromagnetic solution are identified for the cases considered, marking the practical and theoretical limits of the system under the current coding scheme. Numerical results are provided, showing the typical level of improvement/deterioration achieved with respect to the single transmitter/receiver result, for the various cases.Comment: 25 pages, 7 figure

Parallel symbolic state-space exploration is difficult, but what is the alternative?

State-space exploration is an essential step in many modeling and analysis problems. Its goal is to find the states reachable from the initial state of a discrete-state model described. The state space can used to answer important questions, e.g., "Is there a dead state?" and "Can N become negative?", or as a starting point for sophisticated investigations expressed in temporal logic. Unfortunately, the state space is often so large that ordinary explicit data structures and sequential algorithms cannot cope, prompting the exploration of (1) parallel approaches using multiple processors, from simple workstation networks to shared-memory supercomputers, to satisfy large memory and runtime requirements and (2) symbolic approaches using decision diagrams to encode the large structured sets and relations manipulated during state-space generation. Both approaches have merits and limitations. Parallel explicit state-space generation is challenging, but almost linear speedup can be achieved; however, the analysis is ultimately limited by the memory and processors available. Symbolic methods are a heuristic that can efficiently encode many, but not all, functions over a structured and exponentially large domain; here the pitfalls are subtler: their performance varies widely depending on the class of decision diagram chosen, the state variable order, and obscure algorithmic parameters. As symbolic approaches are often much more efficient than explicit ones for many practical models, we argue for the need to parallelize symbolic state-space generation algorithms, so that we can realize the advantage of both approaches. This is a challenging endeavor, as the most efficient symbolic algorithm, Saturation, is inherently sequential. We conclude by discussing challenges, efforts, and promising directions toward this goal

Quantum Effects in Small-Capacitance Single Josephson Junctions

We have measured the current-voltage (I-V) characteristics of small-capacitance single Josephson junctions at low temperatures (T=0.02-0.6 K), where the strength of the coupling between the single junction and the electromagnetic environment was controlled with one-dimensional arrays of dc SQUIDs. The single-junction I-V curve is sensitive to the impedance of the environment, which can be tuned IN SITU. We have observed Coulomb blockade of Cooper-pair tunneling and even a region of negative differential resistance, when the zero-bias resistance R_0' of the SQUID arrays is much higher than the quantum resistance R_K = h/e^2 = 26 kohm. The negative differential resistance is evidence of coherent single-Cooper-pair tunneling within the theory of current-biased single Josephson junctions. Based on the theory, we have calculated the I-V curves numerically in order to compare with the experimental ones at R_0' >> R_K. The numerical calculation agrees with the experiments qualitatively. We also discuss the R_0' dependence of the single-Josephson-junction I-V curve in terms of the superconductor-insulator transition driven by changing the coupling to the environment.Comment: 11 pages with 14 embedded figures, RevTeX4, final versio

Distinct roles of Argonaute in the green alga Chlamydomonas reveal evolutionary conserved mode of miRNA-mediated gene expression

Abstract: The unicellular green alga Chlamydomonas reinhardtii is evolutionarily divergent from higher plants, but has a fully functional silencing machinery including microRNA (miRNA)-mediated translation repression and mRNA turnover. However, distinct from the metazoan machinery, repression of gene expression is primarily associated with target sites within coding sequences instead of 3′UTRs. This feature indicates that the miRNA-Argonaute (AGO) machinery is ancient and the primary function is for post transcriptional gene repression and intermediate between the mechanisms in the rest of the plant and animal kingdoms. Here, we characterize AGO2 and 3 in Chlamydomonas, and show that cytoplasmically enriched Cr-AGO3 is responsible for endogenous miRNA-mediated gene repression. Under steady state, mid-log phase conditions, Cr-AGO3 binds predominantly miR-C89, which we previously identified as the predominant miRNA with effects on both translation repression and mRNA turnover. In contrast, the paralogue Cr-AGO2 is nuclear enriched and exclusively binds to 21-nt siRNAs. Further analysis of the highly similar Cr-AGO2 and Cr-AGO 3 sequences (90% amino acid identity) revealed a glycine-arginine rich N-terminal extension of ~100 amino acids that, given previous work on unicellular protists, may associate AGO with the translation machinery. Phylogenetic analysis revealed that this glycine-arginine rich N-terminal extension is present outside the animal kingdom and is highly conserved, consistent with our previous proposal that miRNA-mediated CDS-targeting operates in this green alga