bluuebunny/crossref_metadata_2025 huggingface dataset:
Well–definedness and efficient inference for probabilistic logic programming under the distribution semantics
Authors: RIGUZZI FABRIZIO , SWIFT TERRANCE
Published: January 2012

Distribution semantics is one of the most prominent approaches for the combination of logic programming and probability theory. Many languages follow this semantics, such as Independent Choice Logic, PRISM, pD, Logic Programs with Annotated Disjunctions (LPADs), and ProbLog. When a program contains functions symbols, the distribution semantics is well–defined only if the set of explanations for a query is finite and so is each explanation. Well–definedness is usually either explicitly imposed or is achieved by severely limiting the class of allowed programs. In this paper, we identify a larger class of programs for which the semantics is well–defined together with an efficient procedure for computing the probability of queries. Since Logic Programs with Annotated Disjunctions offer the most general syntax, we present our results for them, but our results are applicable to all languages under the distribution semantics. We present the algorithm “Probabilistic Inference with Tabling and Answer subsumption” (PITA) that computes the probability of queries by transforming a probabilistic program into a normal program and then applying SLG resolution with answer subsumption. PITA has been implemented in XSB and tested on six domains: two with function symbols and four without. The execution times are compared with those of ProbLog,cplint, and CVE. PITA was almost always able to solve larger problems in a shorter time, on domains with and without function symbols.
Type II solar radio bursts: Modeling and extraction of shock parameters
Authors: Hillan D. S. , Cairns I. H. , Robinson P. A.
Published: January 2012

This first paper in a two part series summarizes the current theory and the data‐driven solar wind model for simulating dynamic spectra of type II radio bursts. It also introduces performance metrics and techniques for extraction of model shock parameters from these dynamic spectra. We use an iterative downhill simplex method which compares two dynamic spectra and quantitatively assesses and improves the agreement using two figures of merit: the first is based on the correlation function and the second is based on a normalized differences over the data set. By maximizing the agreement we are able to extract the input model shock parameters to within 30% or better when using model solar winds of increasing complexity. The effects on the spectra predicted and on the figures of merit from changing the model shock parameters and solar wind model are also investigated. The iterative downhill extraction method is then applied to the type II dynamic spectrum predicted using a realistic model solar wind and a shock model estimated for an observed type II event. The shock parameters are recovered to within 10% of the correct solution.
MESSENGER orbital observations of large‐amplitude Kelvin‐Helmholtz waves at Mercury's magnetopause
Authors: Sundberg Torbjörn , Boardsen Scott A. , Slavin James A. , Anderson Brian J. , Korth Haje , Zurbuchen Thomas H. , Raines Jim M. , Solomon Sean C.
Published: January 2012

We present a survey of Kelvin‐Helmholtz (KH) waves at Mercury's magnetopause during MESSENGER's first Mercury year in orbit. The waves were identified on the basis of the well‐established sawtooth wave signatures that are associated with nonlinear KH vortices at the magnetopause. MESSENGER frequently observed such KH waves in the dayside region of the magnetosphere where the magnetosheath flow velocity is still subsonic, which implies that instability growth rates at Mercury's magnetopause are much larger than at Earth. We attribute these greater rates to the limited wave energy dissipation in Mercury's highly resistive regolith. The wave amplitude was often on the order of 100 nT or more, and the wave periods were ∼10–20 s. A clear dawn‐dusk asymmetry is present in the data, in that all of the observed wave events occurred in the postnoon and duskside sectors of the magnetopause. This asymmetry is likely related to finite Larmor‐radius effects and is in agreement with results from particle‐in‐cell simulations of the instability. The waves were observed almost exclusively during periods when the north‐south component of the magnetosheath magnetic field was northward, a pattern similar to that for most terrestrial KH wave events. Accompanying plasma measurements show that the waves were associated with the transport of magnetosheath plasma into the magnetosphere.
Numerical simulation of the equatorial wind jet in the thermosphere
Authors: Miyoshi Yasunobu , Fujiwara Hitoshi , Jin Hidekatsu , Shinagawa Hiroyuki , Liu Huixin
Published: January 2012

We have examined excitation mechanism of the fast jet of the neutral atmosphere along the dip equator in the upper thermosphere. The zonal momentum balance of the neutral atmosphere is estimated using an atmosphere‐ionosphere coupled model. The coupled model used in this study is a self‐consistent global model of the atmosphere and ionosphere covering the height range from the ground surface to the exobase. It can reproduce the observed equatorial fast jet above 250 km heights. The analysis of the zonal momentum balance reveals that the pressure gradient and ion drag play an important role on the formation of the fast jet near the dip equator. In particular, the fast jet near the equator is closely related with the latitudinal difference of the ion drag force. We also investigate the zonal momentum balance of the longitudinal wave‐4 structure of the zonal wind in the fixed local time frame. Furthermore, significant day‐to‐day variations in the neutral zonal wind and the ion drift near the dip equator are obtained although the solar UV/EUV fluxes and the energy input from the magnetosphere are assumed to be constant during the numerical simulation. This result indicates the importance of the lower atmospheric variability on day‐to‐day variations in the thermosphere/ionosphere.
Complex fluid flow revealed by monitoring CO2 injection in a fluvial formation
Authors: Lu Jiemin , Cook Paul J. , Hosseini Seyyed A. , Yang Changbing , Romanak Katherine D. , Zhang Tongwei , Freifeld Barry M. , Smyth Rebecca C. , Zeng Hongliu , Hovorka Susan D.
Published: January 2012

At Cranfield, Mississippi, United States, a large‐scale carbon dioxide (CO2) injection through an injection well (∼3,080 m deep) was continuously monitored using U‐tube samplers in two observation wells located 68 and 112 m east of the injector. The Lower Tuscaloosa Formation injection zone, which consists of amalgamated fluvial point‐bar and channel‐fill deposits, presents an interesting environment for studying fluid flow in heterogeneous formations. Continual fluid sampling was carried out during the first month of CO2 injection. Two subsequent tracer tests using sulfur hexafluoride (SF6) and krypton were conducted at different injection rates to measure flow velocity change. The field observations showed significant heterogeneity of fluid flow and for the first time clearly demonstrated that fluid flow evolved with time and injection rate. It was found the wells were connected through numerous, separate flow pathways. CO2 flowed through an increasing fraction of the reservoir and sweep efficiency improved with time. The field study also first documented in situ component exchange between brine and gas phases during CO2 injection. It was found that CH4 degassed from brine and is enriched along the gas–water contact. Multiple injectate flow fronts with high CH4 concentration arrived at different times and led to gas composition fluctuations in the observation wells. The findings provide valuable insights into heterogeneous multiphase flow in rock formations and show that conventional geological models and static fluid flow simulations are unable to fully describe the heterogeneous and dynamic flow during fluid injection.
Poleward coastal jets induced by westerlies in the Bay of Biscay
Authors: Batifoulier Francois , Lazure Pascal , Bonneton Philippe
Published: January 2012

Two hydrodynamic surveys based on acoustic Doppler current profiler (ADCP) and drift buoys measurements taken in summer 2008 and 2009 revealed poleward coastal jets of up to 32 cm s−1 that lasted up to 22 d along the Aquitaine shelf in the southeastern area of the Bay of Biscay. A strong increase in bottom temperature was associated with these currents, up to 4°C in 5 d at 54 m depth. These observations occurred after a few days of westerlies, cross‐shore winds which were thought to have only a limited impact on longshore circulation. Here, the MARS3D hydrodynamic model was used with a schematic bathymetry of the southeastern area of the Bay of Biscay to reproduce and analyze these coastal jets. Simulations revealed that the triggering mechanism of the poleward currents is unequivocally due to downwelling circulation induced along the Spanish coast. This downwelling induces an external longshore pressure gradient which generates a high‐speed coastal‐trapped wave that propagates along the French coast with a phase velocity of about 3 to 4 m s−1 and an internal baroclinic Kelvin wave with a phase velocity of about 1 m s−1. A sensitivity study of the role of stratification conditions, wind strength and duration was then carried out to determine the periods that are the most sensitive to this wind‐induced circulation.
Influences of shifts in climate, landscape, and permafrost on terrestrial hydrology
Authors: Bosson Emma , Sabel Ulrika , Gustafsson Lars‐Göran , Sassner Mona , Destouni Georgia
Published: January 2012

This study has simulated the terrestrial hydrology associated with different climate, landscape, and permafrost regime scenarios for the field case example of the relatively well characterized coastal catchment of Forsmark, Sweden. The regime scenarios were selected from long‐term simulation results of climate, topographical, shoreline, and associated Quaternary deposit and vegetation development in this catchment with a time perspective of 100,000 years or more and were used as drivers for hydrological simulations with the three‐dimensional model MIKE SHE. The hydrological simulations quantify the responses of different water flow and water storage components of terrestrial hydrology to shifts from the present cool temperate climate landscape regime in Forsmark to a possible future Arctic periglacial landscape regime with or without permafrost. The results show complexity and nonlinearity in the runoff responses to precipitation changes due to parallel changes in evapotranspiration, along with changes in surface and subsurface water storage dynamics and flow pathways through the landscape. The results further illuminate different possible perspectives of what constitutes wetter/drier landscape conditions, in contrast to the clearer concept of what constitutes a warmer/colder climate.
Sensitivity analysis of dispersion modeling of volcanic ash from Eyjafjallajökull in May 2010
Authors: Devenish B. J. , Francis P. N. , Johnson B. T. , Sparks R. S. J. , Thomson D. J.
Published: January 2012

We analyze the sensitivity of a mathematical model of volcanic ash dispersion in the atmosphere to the representation of key physical processes. These include the parameterization of subgrid‐scale atmospheric processes and source parameters such as the height of the eruption column, the mass emission rate, the size of the particulates, and the amount of ash that falls out close to the source. By comparing the results of the mathematical model with satellite and airborne observations of the ash cloud that erupted from Eyjafjallajökull volcano in May 2010, we are able to gain some insight into the processes and parameters that govern the long‐range dispersion of ash in the atmosphere. The structure of the ash cloud, particularly its width and depth, appears to be sensitive to the source profile (i.e., whether ash is released over a deep vertical column or not) and to the level of subgrid diffusion. Of central importance to the quantitative estimates of ash concentration in the distal ash cloud is the fallout of ash close to the source. By comparing the mass of the ash and the column loadings in the modeled and observed distal ash cloud, we estimate the fraction of fine ash that survives into the distal ash cloud albeit with considerable uncertainty. The processes that contribute to this uncertainty are discussed.
Estimation of errors in the inverse modeling of accidental release of atmospheric pollutant: Application to the reconstruction of the cesium‐137 and iodine‐131 source terms from the Fukushima Daiichi power plant
Authors: Winiarek Victor , Bocquet Marc , Saunier Olivier , Mathieu Anne
Published: January 2012

A major difficulty when inverting the source term of an atmospheric tracer dispersion problem is the estimation of the prior errors: those of the atmospheric transport model, those ascribed to the representativity of the measurements, those that are instrumental, and those attached to the prior knowledge on the variables one seeks to retrieve. In the case of an accidental release of pollutant, the reconstructed source is sensitive to these assumptions. This sensitivity makes the quality of the retrieval dependent on the methods used to model and estimate the prior errors of the inverse modeling scheme. We propose to use an estimation method for the errors' amplitude based on the maximum likelihood principle. Under semi‐Gaussian assumptions, it takes into account, without approximation, the positivity assumption on the source. We apply the method to the estimation of the Fukushima Daiichi source term using activity concentrations in the air. The results are compared to an L‐curve estimation technique and to Desroziers's scheme. The total reconstructed activities significantly depend on the chosen method. Because of the poor observability of the Fukushima Daiichi emissions, these methods provide lower bounds for cesium‐137 and iodine‐131 reconstructed activities. These lower bound estimates, 1.2 × 1016 Bq for cesium‐137, with an estimated standard deviation range of 15%–20%, and 1.9 − 3.8 × 1017 Bq for iodine‐131, with an estimated standard deviation range of 5%–10%, are of the same order of magnitude as those provided by the Japanese Nuclear and Industrial Safety Agency and about 5 to 10 times less than the Chernobyl atmospheric releases.
Limits to reconstructing paleotopography from thermochronometer data
Authors: Olen Stephanie M. , Ehlers Todd A. , Densmore Mathew S.
Published: January 2012

Recent studies suggest that orogens can achieve a topographic steady state whereby equilibrium is reached between tectonics and erosion. However, steady state topography may not be the norm in many orogens experiencing large changes in climate or tectonics, which can produce topographic transients. The quantification of transient topography over geologic timescales requires reconstructing paleotopography, but this has proven difficult in many cases. This study investigates the utility of bedrock thermochronometer data to reconstruct orogen paleotopography over million year timescales. Apatite (U‐Th)/He and fission track ages are integrated with a thermokinematic model for a single‐parameter inversion of paleotopography. An iterative scheme is used that minimizes the misfit between predicted and observed cooling ages to identify the range of paleotopographies that could produce observed ages within sample uncertainty. Two approaches are considered. First, synthetic 2‐D topographies are used to test the robustness of the approach. The following topographic evolution scenarios are considered: (1) lateral ridge migration, (2) topographic relief change, and (3) valley widening and deepening from glaciation. Second, the method is applied in three dimensions to existing data from the Coast Mountains of British Columbia, Canada. Results from both applications of the model suggest that (1) paleotopographic reconstruction will typically underpredict the magnitude of topographic change, especially relief change; (2) paleotopography is most successfully reconstructed after lateral ridge migration in long‐wavelength topographies; and (3) reconstructed paleotopography from the Coast Mountains, British Columbia, suggests that glacial erosion may have the potential to remove drainage divides and laterally shift topographic ridges and peaks.
Protective Effect of Delayed Remote Limb Ischemic Postconditioning: Role of Mitochondrial KATP Channels in a Rat Model of Focal Cerebral Ischemic Reperfusion Injury
Authors: Sun Jing , Li Tong , Luan Qi , Deng Jiao , Li Yan , Li Zhaoju , Dong Hailong , Xiong Lize
Published: January 2012

Delayed remote ischemic postconditioning (DRIPost) has been shown to protect the rat brain from ischemic injury. However, extremely short therapeutic time windows hinder its translational use and the mechanism of action remains elusive. Because opening of the mitochondria KATP channel is crucial for cell apoptosis, we hypothesized that the neuroprotective effect of DRIPost may be associated with KATP channels. In the present study, the neuroprotective effects of DRIPost were investigated using adult male Sprague-Dawley rats. Rats were exposed to 90 minutes of middle cerebral artery occlusion followed by 72 hours of reperfusion. Delayed remote ischemic postconditioning was performed with three cycles of bilateral femoral artery occlusion/reperfusion for 5 minutes at 3 or 6 hours after reperfusion. Neurologic deficit scores and infarct volumes were assessed, and cellular apoptosis was monitored by terminal deoxynucleotidyl transferase nick-end labeling. Our results showed that DRIPost applied at 6 hours after reperfusion exerted neuroprotective effects. The KATP opener, diazoxide, protected rat brains from ischemic injury, while the KATP blocker, 5-hydroxydecanote, reversed the neuroprotective effects of DRIPost. These findings indicate that DRIPost reduces focal cerebral ischemic injury and that the neuroprotective effects of DRIPost may be achieved through opening of KATP channels.
A novel lectin fromAgrocybe aegeritashows high binding selectivity for terminalN-acetylglucosamine
Authors: Jiang Shuai , Chen Yijie , Wang Man , Yin Yalin , Pan Yongfu , Gu Bianli , Yu Guojun , Li Yamu , Wong Barry Hon Cheung , Liang Yi , Sun Hui
Published: January 2012

A novel lectin was isolated from the mushroom Agrocybe aegerita (designated AAL-2) by affinity chromatography with GlcNAc (N-acetylglucosamine)-coupled Sepharose 6B after ammonium sulfate precipitation. The AAL-2 coding sequence (1224 bp) was identified by performing a homologous search of the five tryptic peptides identified by MS against the translated transcriptome of A. aegerita. The molecular mass of AAL-2 was calculated to be 43.175 kDa from MS, which was consistent with the data calculated from the amino acid sequence. To analyse the carbohydrate-binding properties of AAL-2, a glycan array composed of 465 glycan candidates was employed, and the result showed that AAL-2 bound with high selectivity to terminal non-reducing GlcNAc residues, and further analysis revealed that AAL-2 bound to terminal non-reducing GlcNAc residues with higher affinity than previously well-known GlcNAc-binding lectins such as WGA (wheatgerm agglutinin) and GSL-II (Griffonia simplicifolia lectin-II). ITC (isothermal titration calorimetry) showed further that GlcNAc bound to AAL-2 in a sequential manner with moderate affinity. In the present study, we also evaluated the anti-tumour activity of AAL-2. The results showed that AAL-2 could bind to the surface of hepatoma cells, leading to induced cell apoptosis in vitro. Furthermore, AAL-2 exerted an anti-hepatoma effect via inhibition of tumour growth and prolongation of survival time of tumour-bearing mice in vivo.
Interaction of oxidized chaperonin GroEL with an unfolded protein at low temperatures
Authors: Melkani Girish C. , Sielaff Robin , Zardeneta Gustavo , Mendoza Jose A.
Published: January 2012

The chaperonin GroEL binds to non-native substrate proteins via hydrophobic interactions, preventing their aggregation, which is minimized at low temperatures. In the present study, we investigated the refolding of urea-denatured rhodanese at low temperatures, in the presence of ox-GroEL (oxidized GroEL), which contains increased exposed hydrophobic surfaces and retains its ability to hydrolyse ATP. We found that ox-GroEL could efficiently bind the urea-unfolded rhodanese at 4°C, without requiring excess amount of chaperonin relative to normal GroEL (i.e. non-oxidized). The release/reactivation of rhodanese from GroEL was minimal at 4°C, but was found to be optimal between 22 and 37°C. It was found that the loss of the ATPase activity of ox-GroEL at 4°C prevented the release of rhodanese from the GroEL–rhodanese complex. Thus ox-GroEL has the potential to efficiently trap recombinant or non-native proteins at 4°C and release them at higher temperatures under appropriate conditions.
A Mixed (Long- and Medium-chain) Triglyceride Lipid Emulsion Extracts Local Anesthetic from Human Serum In Vitro More Effectively than a Long-chain Emulsion
Authors: Ruan Weiming , French Deborah , Wong Alicia , Drasner Kenneth , Wu Alan H. B.
Published: January 2012

Background

Lipid emulsion infusion reverses cardiac toxicity of local anesthetics. The predominant effect is likely creation of a "lipid sink." This in vitro study determined the extent to which Intralipid® (Fresenius Kabi, Uppsala, Sweden) and Lipofundin® (B. Braun Melsungen AG, Melsungen, Germany) sequester anesthetics from serum, and whether it varies with pH.

Methods

Bupivacaine, ropivacaine, and mepivacaine were added to human drug-free serum (pH 7.4) at 10 μg/ml. The lipid emulsions were added, and the mixture shaken and incubated at 37°C. Lipid was removed by ultracentrifugation and drug remaining in the serum measured. Additional experiments were performed using 100 μg/ml bupivacaine and at pH 6.9.

Results

Lipofundin® extracted all three anesthetics to a greater extent than Intralipid® (34.7% vs..22.3% for bupivacaine, 25.8% vs..16.5% for ropivacaine, and 7.3% vs..4.7% for mepivacaine). By increasing either concentration of bupivacaine or lipid, there was an increase in drug extraction from serum. Adjusting the pH to 6.9 had no statistically significant effect on the percentage of bupivacaine sequestered.

Conclusions

Bupivacaine, ropivacaine, and mepivacaine were sequestered to an extent consistent with their octanol:water partition constants (logP). In contrast with previous studies of extraction of lipids from buffer solutions, an emulsion containing 50% each of medium- and long-chain triglycerides extracted local anesthetics to a greater extent from human serum than one containing exclusively long-chain triglycerides, calling into question recent advanced cardiac life support guidelines for resuscitation from anesthetic toxicity that specify use of a long-chain triglyceride. The current data also do not support recent recommendations to delay administration until pH is normalized.
Tikiguania
and the antiquity of squamate reptiles (lizards and snakes)
Authors: Hutchinson Mark N. , Skinner Adam , Lee Michael S. Y.
Published: January 2012

Tikiguania estesi
is widely accepted to be the earliest member of Squamata, the reptile group that includes lizards and snakes. It is based on a lower jaw from the Late Triassic of India, described as a primitive lizard related to agamids and chamaeleons. However,
Tikiguania
is almost indistinguishable from living agamids; a combined phylogenetic analysis of morphological and molecular data places it with draconines, a prominent component of the modern Asian herpetofauna. It is unlikely that living agamids have retained the
Tikiguania
morphotype unchanged for over 216 Myr; it is much more conceivable that
Tikiguania
is a Quaternary or Late Tertiary agamid that was preserved in sediments derived from the Triassic beds that have a broad superficial exposure. This removes the only fossil evidence for lizards in the Triassic. Studies that have employed
Tikiguana
for evolutionary, biogeographical and molecular dating inferences need to be reassessed.
Multi-scale modelling of elastic moduli of trabecular bone
Authors: Hamed Elham , Jasiuk Iwona , Yoo Andrew , Lee YikHan , Liszka Tadeusz
Published: January 2012

We model trabecular bone as a nanocomposite material with hierarchical structure and predict its elastic properties at different structural scales. The analysis involves a bottom-up multi-scale approach, starting with nanoscale (mineralized collagen fibril) and moving up the scales to sub-microscale (single lamella), microscale (single trabecula) and mesoscale (trabecular bone) levels. Continuum micromechanics methods, composite materials laminate theory and finite-element methods are used in the analysis. Good agreement is found between theoretical and experimental results.
Diverse societies are more productive: a lesson from ants
Authors: Modlmeier Andreas P. , Liebmann Julia E. , Foitzik Susanne
Published: January 2012

The fitness consequences of animal personalities (also known as behavioural syndromes) have recently been studied in several solitary species. However, the adaptive significance of collective personalities in social insects and especially of behavioural variation among group members remains largely unexplored. Although intracolonial behavioural variation is an important component of division of labour, and as such a key feature for the success of societies, empirical links between behavioural variation and fitness are scarce. We investigated aggression, exploration and brood care behaviour in
Temnothorax longispinosus
ant colonies. We focused on two distinct aspects: intercolonial variability and its consistency across time and contexts, and intracolonial variability and its influence on productivity. Aggressiveness was consistent over four to five months with a new generation of workers emerging in between trial series. Other behaviours were not consistent over time. Exploration of novel environments responded to the sequence of assays: colonies were faster in discovering when workers previously encountered opponents in aggression experiments. Suites of correlated behaviours (e.g. aggression–exploration syndrome) present in the first series did not persist over time. Finally, colonies with more intracolonial behavioural variation in brood care and exploration of novel objects were more productive under standardized conditions than colonies with less variation.
Larger female fish contribute disproportionately more to self-replenishment
Authors: Beldade R. , Holbrook S. J. , Schmitt R. J. , Planes S. , Malone D. , Bernardi G.
Published: January 2012

While chance events, oceanography and selective pressures inject stochasticity into the replenishment of marine populations with dispersing life stages, some determinism may arise as a result of characteristics of breeding individuals. It is well known that larger females have higher fecundity, and recent laboratory studies have shown that maternal traits such as age and size can be positively associated with offspring growth, size and survival. Whether such fecundity and maternal effects translate into higher recruitment in marine populations remains largely unanswered. We studied a population ofAmphiprion chrysopterus(orange-fin anemonefish) in Moorea, French Polynesia, to test whether maternal size influenced the degree of self-recruitment on the island through body size–fecundity and/or additional size-related maternal effects of offspring. We non-lethally sampled 378 adult and young juveniles at Moorea, and, through parentage analysis, identified the mothers of 27 self-recruits (SRs) out of 101 recruits sampled. We also identified the sites occupied by each mother of an SR and, taking into account variation in maternal size among sites, we found that females that produced SRs were significantly larger than those that did not (approx. 7% greater total length, approx. 20% greater biomass). Our analyses further reveal that the contribution of larger females to self-recruitment was significantly greater than expected on the basis of the relationship between body size and fecundity, indicating that there were important maternal effects of female size on traits of their offspring. These results show, for the first time in a natural population, that larger female fish contribute more to local replenishment (self-recruitment) and, more importantly, that size-specific fecundity alone could not explain the disparity.
SMARCAL1 catalyzes fork regression and Holliday junction migration to maintain genome stability during DNA replication
Authors: Bétous Rémy , Mason Aaron C. , Rambo Robert P. , Bansbach Carol E. , Badu-Nkansah Akosua , Sirbu Bianca M. , Eichman Brandt F. , Cortez David
Published: January 2012

SMARCAL1 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A-like1) maintains genome integrity during DNA replication. Here we investigated its mechanism of action. We found that SMARCAL1 travels with elongating replication forks, and its absence leads to MUS81-dependent double-strand break formation. Binding to specific nucleic acid substrates activates SMARCAL1 activity in a reaction that requires its HARP2 (Hep-A-related protein 2) domain. Homology modeling indicates that the HARP domain is similar in structure to the DNA-binding domain of the PUR proteins. Limited proteolysis, small-angle X-ray scattering, and functional assays indicate that the core enzymatic unit consists of the HARP2 and ATPase domains that fold into a stable structure. Surprisingly, SMARCAL1 is capable of binding three-way and four-way Holliday junctions and model replication forks that lack a designed ssDNA region. Furthermore, SMARCAL1 remodels these DNA substrates by promoting branch migration and fork regression. SMARCAL1 mutations that cause Schimke immunoosseous dysplasia or that inactivate the HARP2 domain abrogate these activities. These results suggest that SMARCAL1 continuously surveys replication forks for damage. If damage is present, it remodels the fork to promote repair and restart. Failures in the process lead to activation of an alternative repair mechanism that depends on MUS81-catalyzed cleavage of the damaged fork.
R-loop-mediated genome instability in mRNA cleavage and polyadenylation mutants
Authors: Stirling Peter C. , Chan Yujia A. , Minaker Sean W. , Aristizabal Maria J. , Barrett Irene , Sipahimalani Payal , Kobor Michael S. , Hieter Philip
Published: January 2012

Genome instability via RNA:DNA hybrid-mediated R loops has been observed in mutants involved in various aspects of transcription and RNA processing. The prevalence of this mechanism among essential chromosome instability (CIN) genes remains unclear. In a secondary screen for increased Rad52 foci in CIN mutants, representing ∼25% of essential genes, we identified seven essential subunits of the mRNA cleavage and polyadenylation (mCP) machinery. Genome-wide analysis of fragile sites by chromatin immunoprecipitation (ChIP) and microarray (ChIP–chip) of phosphorylated H2A in these mutants supported a transcription-dependent mechanism of DNA damage characteristic of R loops. In parallel, we directly detected increased RNA:DNA hybrid formation in mCP mutants and demonstrated that CIN is suppressed by expression of the R-loop-degrading enzyme RNaseH. To investigate the conservation of CIN in mCP mutants, we focused on FIP1L1, the human ortholog of yeast FIP1, a conserved mCP component that is part of an oncogenic fusion in eosinophilic leukemia. We found that truncation fusions of yeast FIP1 analogous to those in cancer cause loss of function and that siRNA knockdown of FIP1L1 in human cells increases DNA damage and chromosome breakage. Our findings illuminate how mCP maintains genome integrity by suppressing R-loop formation and suggest that this function may be relevant to certain human cancers.
Multistep Assembly of Chloroplast NADH Dehydrogenase-Like Subcomplex A Requires Several Nucleus-Encoded Proteins, Including CRR41 and CRR42, in Arabidopsis
Authors: Peng Lianwei , Fukao Yoichiro , Fujiwara Masayuki , Shikanai Toshiharu
Published: January 2012

Chloroplast NADH dehydrogenase-like complex (NDH) mediates photosystem I cyclic electron transport and chlororespiration in thylakoids. Recently, substantial progress has been made in understanding the structure of NDH, but our knowledge of its assembly has been limited. In this study, a series of interactive proteomic analyses identified several stroma-localized factors required for the assembly of a stroma-protruding arm of NDH (subcomplex A). In addition to further characterization of the previously identified CHLORORESPIRATORY REDUCTION1 (CRR1), CRR6, and CRR7, two novel stromal proteins, CRR41 and CRR42, were discovered. Arabidopsis thaliana mutants lacking these proteins are specifically defective in the accumulation of subcomplex A. A total of 10 mutants lacking subcomplex A, including crr27/cpn60β4, which is specifically defective in the folding of NdhH, and four mutants lacking NdhL–NdhO subunits, were extensively characterized. We propose a model for subcomplex A assembly: CRR41, NdhO, and native NdhH, as well as unknown factors, are first assembled to form an NDH subcomplex A assembly intermediate (NAI500). Subsequently, NdhJ, NdhM, NdhK, and NdhI are incorporated into NAI500 to form NAI400. CRR1, CRR6, and CRR42 are involved in this process. CRR7 is likely to be involved in the final step, in which the fully assembled NAI, including NdhN, is inserted into thylakoids.
ThePh1Locus Suppresses Cdk2-Type Activity during Premeiosis and Meiosis in Wheat
Authors: Greer Emma , Martín Azahara C. , Pendle Ali , Colas Isabelle , Jones Alexandra M.E. , Moore Graham , Shaw Peter
Published: January 2012

Despite possessing multiple sets of related (homoeologous) chromosomes, hexaploid wheat (Triticum aestivum) restricts pairing to just true homologs at meiosis. Deletion of a single major locus, Pairing homoeologous1 (Ph1), allows pairing of homoeologs. How can the same chromosomes be processed as homologs instead of being treated as nonhomologs? Ph1 was recently defined to a cluster of defective cyclin-dependent kinase (Cdk)-like genes showing some similarity to mammalian Cdk2. We reasoned that the cluster might suppress Cdk2-type activity and therefore affect replication and histone H1 phosphorylation. Our study does indeed reveal such effects, suggesting that Cdk2-type phosphorylation has a major role in determining chromosome specificity during meiosis.
Meta‐analysis: antiviral treatment for hepatitis D
Authors: Triantos C. , Kalafateli M. , Nikolopoulou V. , Burroughs A.
Published: January 2012

Background

There is no satisfactory treatment for patients with hepatitis D (HDV).

Aim

To evaluate treatment for HDV using meta‐analysis.

Methods

Medline, Scopus, Cochrane Library and ISI Web of Knowledge searches using the textwords ‘Hepatitis D’, ‘therapy’, “interferon”, “peginterferon”, “pegylated interferon”, “lamivudine”, “pegifn”, “ifn” and “Hepatitis D”, and abstracts from major Gastroenterology/Liver meetings. Endpoints: end of treatment biochemical (biochemical EOT) and virological response (virological EOT), end of follow‐up virological response (EOFUP VR), histological improvement and intrahepatic HDAg clearance.

Results

We included randomised clinical trials (RCTs) comparing Group A: interferon‐A (IFNa) vs. no treatment (three RCTs, n ;= ;137 patients), Group B: low dose vs. high dose IFNa (two RCTs, n ;= ;60), Group C: IFNa ;+ ;lamivudine vs. IFNa (two RCTs, n ;= ;48) and Group D: pegylated IFNa (PEG‐IFNa) vs. other medications (two RCTs, n ;= ;157). Group A. IFNa was better for biochemical EOT [OR, 0.11 (95% CI, 0.04–0.2)] and virological EOT [OR, 0.08 (95% CI, 0.03–0.2)], but not for EOFUP VR. Group B. High dose IFNa was better for biochemical EOT [OR, 0.24 (95% CI,0.08–0.73)] and virological EOT [OR, 0.27 (95% CI, 0.1–0.74)]. Group C. There was a trend favouring histological improvement [OR, 2.9 (95% CI, 0.6–13.4)]. Group D. PEG‐IFNa was better for virological EOT [OR, 0.419 (95% CI, 0.18–0.974)], EOFUP VR [OR, 0.404 (95% CI, 0.189–0.866)] and improvement in necroinflammatory activity [OR, 0.308 (95% CI, 0.129–0.732)].

Conclusions

Long‐term suppression of HDV RNA by IFNa is not maintained despite an end of treatment response; adding lamivudine is not beneficial. PEG‐IFNa is superior to other medications with respect to EOT and EOFUP. New RCTs should test combinations of PEG‐IFNa and newest antivirals.
Template‐based synoptic reports improve the quality of pathology reports of prostatectomy specimens
Authors: Aumann Konrad , Amann Dominic , Gumpp Vera , Hauschke Dieter , Kayser Gian , May Annette M , Wetterauer Ulrich , Werner Martin
Published: January 2012

Aumann K, Amann D, Gumpp V, Hauschke D, Kayser G, May A M, Wetterauer U & Werner M  (2012) Histopathology 60, 634–644 Template‐based synoptic reports improve the quality of pathology reports of prostatectomy specimens

Aims:  Traditionally, pathology reports have been textual, with a high degree of variability. In part, they miss some of the information needed, e.g. for therapy decisions. To meet all requirements, it would be helpful to have a tool providing reminders of the necessary data and facilitating the transfer of these data into a pathology information system (PIS). Here, we describe a TNM‐adapted toolset including a PIS‐integrated structured template that contributes to improving pathology reports of prostatectomy specimens.

Methods and results:  All prostatectomy reports between January 2002 and August 2010 (n = 1049) were classified into descriptive reports (DRs) (n = 411), structured reports (SRs) arranged according to tumour spread, lymph node status, and surgical margin status (n = 333), and template‐based synoptic reports (TBSRs) (n = 305). The report types were compared with regard to the content of 11 organ‐specific essential data (ED) items crucial for exact TNM classification, therapy decisions, or prognostication. All 11 ED items were included in 2.7% of DRs, 43.5% of SRs and 97.2% of TBSRs, with a statistically highly significant difference (P < 0.001).

Conclusions:  SRs, and particularly TBSRs, are advantageous as compared with DRs regarding the content of ED and the clarity of the data layout. The use of TBSRs leads to a reduction in failed data transfer and therefore to an increase in the quality of pathology reports.
Tracing patients on antiretroviral treatment lost‐to‐follow‐up in an urban slum in India
Authors: Errol Lisa , Isaakidis Petros , Zachariah Rony , Ali Mohammed , Pilankar Gurudas , Maurya Sanjana , Geraets Claudia , Ladomirska Joanna , Patel Sunil , Reid Tony
Published: January 2012

errol l., isaakidis p., zachariah r., ali m., pilankar g., maurya s., geraets c., ladomirska j., patel s. & reid t. (2012) Tracing patients on antiretroviral treatment lost‐to‐follow‐up in an urban slum in India. Journal of Advanced Nursing68(11), 2399–2409.

Aim.  This article describes a cooperative initiative between an HIV‐clinic and non‐government organization network providing lost‐to‐follow‐up tracing and delayed appointment follow‐up of patients on antiretroviral treatment.

Background.  Loss‐to‐follow‐up among patients on antiretroviral treatment is a major challenge in resource‐constrained settings. A model of cooperation between a Médecins Sans Frontières HIV‐clinic and a non‐governmental‐organization network was piloted in a Mumbai slum. A steady decline in delayed appointments and loss‐to‐follow‐up was observed over 4 years.

Design.  Mixed method study.

Methods.  A study conducted in January 2011 explored potential reasons for declining loss‐to‐follow‐up‐rates. A retrospective, quantitative analysis of patient data was undertaken complemented by 22 semi‐structured interviews, four focus‐group discussions to explore patients’ and providers’ perceptions of tracing activities.

Results/findings.  The clinic loss‐to‐follow‐up‐rate has steadily declined from mid‐2008–2011. Thirty‐eight (4·6%) of 819 patients registered during the period were lost‐to‐follow‐up with most lost during the first year. Rates of loss‐to‐follow‐up between 0·3–2·4% were observed over the last 2 years. Phoning the day before an appointment was perceived as the most useful intervention to avoid missing appointments. The analysis revealed a widespread fear of forced disclosure by patients during home visits.

Conclusions.  The low loss‐to‐follow‐up‐rate cannot be attributed to the network tracing activities alone. Phoning before appointments may result in fewer delayed appointments and prevent loss‐to‐follow‐up. Home visits should be a last resort method of patient tracing because of the risk of HIV‐status disclosure and the opportunity of discrimination from family and neighbours.
Evaluation of mental health recovery and Wellness Recovery Action Planning education in Ireland: a mixed methods pre–postevaluation
Authors: Higgins Agnes , Callaghan Patrick , deVries Jan , Keogh Brian , Morrissey Jean , Nash Michael , Ryan Denis , Gijbels Harry , Carter Tim
Published: January 2012

higgins a., callaghan p., devries j., keogh b., morrissey j., nash m., ryan d., gijbels h. & carter t. (2012) Evaluation of mental health recovery and Wellness Recovery Action Planning education in Ireland: a mixed methods pre–postevaluation. Journal of Advanced Nursing68(11), 2418–2428.

Aim.  To report a study evaluating the effectiveness of a Wellness Recovery Action Planning education programme.

Background.  Internationally, mental health policy is advocating using recovery approaches to care. Underpinning these approaches is investment in education in recovery principles and methods and a need to provide evidence of the impact of this education.

Design.  The study design employed a mixed methods approach.

Methods.  Using questionnaires and focus groups, we evaluated 2‐ and 5‐day Wellness Recovery Action Planning Education Programmes and assessed participants’ attitudes towards recovery, knowledge of recovery and Wellness Recovery Action Planning beliefs. Data were collected between 2009 and 2010. Participants were people with personal experience of mental health problems, practitioners in mental health services and family members/carers of those with mental health problems.

Results.  Comparing the pre and postmeasures showed that the programme increased participants’ knowledge of and attitudes towards recovery and Wellness Recovery Action Planning. Although this increase was statistically significant for the 2‐day programme, it was not so for the 5‐day programme. Participants reported being very positive and enthusiastic about the programme and the benefits they had achieved personally and professionally as a result of participating.

Conclusions.  This exploratory study shows that providing mental health practitioners and people with personal experience of mental health problems with a systematic education and training in recovery principles using the Wellness Recovery Action Planning approach leads to positive changes in people’s knowledge, skills and attitudes towards recovery. This education appeared to inspire, invigorate and empower people, and for many, it was a life changing experience.
Improved equity in measles vaccination from integrating insecticide‐treated bednets in a vaccination campaign, Madagascar
Authors: Goodson James L. , Kulkarni Manisha A. , Vanden Eng Jodi L. , Wannemuehler Kathleen A. , Cotte Annett H. , Desrochers Rachelle E. , Randriamanalina Bakolalao , Luman Elizabeth T.
Published: January 2012

Objective  To evaluate the effect of integrating ITN distribution on measles vaccination campaign coverage in Madagascar.

Methods  Nationwide cross‐sectional survey to estimate measles vaccination coverage, nationally, and in districts with and without ITN integration. To evaluate the effect of ITN integration, propensity score matching was used to create comparable samples in ITN and non‐ITN districts. Relative risks (RR) and 95% confidence intervals (CI) were estimated via log‐binomial models. Equity ratios, defined as the coverage ratio between the lowest and highest household wealth quintile (Q), were used to assess equity in measles vaccination coverage.

Results  National measles vaccination coverage during the campaign was 66.9% (95% CI 63.0–70.7). Among the propensity score subset, vaccination campaign coverage was higher in ITN districts (70.8%) than non‐ITN districts (59.1%) (RR = 1.3, 95% CI 1.1–1.6). Among children in the poorest wealth quintile, vaccination coverage was higher in ITN than in non‐ITN districts (Q1; RR = 2.4, 95% CI 1.2–4.8) and equity for measles vaccination was greater in ITN districts (equity ratio = 1.0, 95% CI 0.8–1.3) than in non‐ITN districts (equity ratio = 0.4, 95% CI 0.2–0.8).

Conclusion  Integration of ITN distribution with a vaccination campaign might improve measles vaccination coverage among the poor, thus providing protection for the most vulnerable and difficult to reach children.
Everybody Needs Good Neighbours: Coalition Formation Influences Floater Fight Choice
Authors: Milner Richard N. C.
Published: January 2012

In territorial species, it is sometimes less costly to help a neighbour fight off an intruder than to re‐establish territory boundaries with a new, potentially stronger neighbour. In fiddler crabs, a male resident will only help his neighbour if he is larger than the intruder who, in turn, is larger than the challenged neighbour. Does this influence with whom a territory‐seeking male decides to fight? I show that territory‐seeking males appear to choose opponents based partly on the size of the resident’s nearest neighbour. By avoiding challenging resident males with larger neighbours, territory‐seeking males can reduce the likelihood of initiating a fight with a resident who might gain help from his neighbour that decreases the likelihood that the intruder will win the fight.
Transplantation of human central nervous system stem cells – neuroprotection in retinal degeneration
Authors: McGill Trevor J. , Cottam Benjamin , Lu Bin , Wang Shaomei , Girman Sergej , Tian Chunyu , Huhn Stephen L. , Lund Ray D. , Capela Alexandra
Published: January 2012

Stem cells derived from the human brain and grown as neurospheres (HuCNS‐SC) have been shown to be effective in treating central neurodegenerative conditions in a variety of animal models. Human safety data in neurodegenerative disorders are currently being accrued. In the present study, we explored the efficacy of HuCNS‐SC in a rodent model of retinal degeneration, the Royal College of Surgeons (RCS) rat, and extended our previous cell transplantation studies to include an in‐depth examination of donor cell behavior and phenotype post‐transplantation. As a first step, we have shown that HuCNS‐SC protect host photoreceptors and preserve visual function after transplantation into the subretinal space of postnatal day 21 RCS rats. Moreover, cone photoreceptor density remained relatively constant over several months, consistent with the sustained visual acuity and luminance sensitivity functional outcomes. The novel findings of this study include the characterization and quantification of donor cell radial migration from the injection site and within the subretinal space as well as the demonstration that donor cells maintain an immature phenotype throughout the 7 months of the experiment and undergo very limited proliferation with no evidence of uncontrolled growth or tumor‐like formation. Given the efficacy findings and lack of adverse events in the RCS rat in combination with the results from ongoing clinical investigations, HuCNS‐SC appear to be a well‐suited candidate for cell therapy in retinal degenerative conditions.