Knowing Values and Public Inspection

We present a basic dynamic epistemic logic of "knowing the value". Analogous to public announcement in standard DEL, we study "public inspection", a new dynamic operator which updates the agents' knowledge about the values of constants. We provide a sound and strongly complete axiomatization for the single and multi-agent case, making use of the well-known Armstrong axioms for dependencies in databases

Receiver function study of the Hellenic subduction zone: imaging crustal thickness variations and the oceanic Moho of the descending African lithosphere

We use data from recently installed broad-band seismographs on the islands of Crete, Gavdos, Santorini, Naxos and Samos in the Hellenic subduction zone to construct receiver function images of the crust and upper mantle from south of Crete into the Aegean Sea. The stations are equipped with STS-2 seismometers and they are operated by GFZ Potsdam, University of Chania and ETH Zürich. Teleseismic earthquakes recorded by these stations at epicentral distances between 35° and 95° have been used to calculate receiver functions. The receiver function method is a routinely used tool to detect crustal and upper-mantle discontinuities beneath a seismic station by isolating the P-S converted waves from the coda of the P wave. Converted P-S energy from the oceanic Moho of the subducted African Plate is clearly observed beneath Gavdos and Crete at a depth ranging from 44 to 69 km. This boundary continues to the north to nearly 100 km depth beneath Santorini island. Because of a lack of data the correlation of this phase is uncertain north of Santorini beneath the Aegean Sea. Moho depths were calculated from primary converted waves and multiply reflected waves between the Moho and the Earth's surface. Beneath southern and eastern Crete the Moho lies between 31 and 34 km depth. Beneath western and northern Crete the Moho is located at 32 and 39 km depth, respectively, and behaves as a reversed crust-mantle velocity contrast, possibly caused by hydration and serpentinization of the forearc mantle peridotite. The Moho beneath Gavdos island located south of Crete in the Libyan Sea is at 26 km depth, indicating that the crust south of the Crete microcontinent is also thinning towards the Mediterranean ridge. This makes it unlikely that part of the crust in Crete consists of accreted sediments transported there during the present-day subduction process which began approximately 15 Ma because the backstop, i.e. the boundary between the current accretionary wedge of the Mediterranean ridge and the Crete microcontinent, is located approximately 100 km south of Gavdos. A seismic boundary at 32 km depth beneath Santorini island probably marks the crustal base of the Crete microcontinent. A shallower seismic interface beneath Santorini at 20-25 km depth may mark the depth of the detachment between the Crete microcontinent and the overlying Aegean subplate. The Moho in the central and northern Aegean, at Naxos and Samos, is observed at 25 and 28 km depth, respectively. Assuming a stretching factor of 1.2-1.3, crustal thickness in the Aegean was 30-35 km at the inception of the extensional regime in the Middle Miocen

Characterization of the seismic environment at the Sanford Underground Laboratory, South Dakota

An array of seismometers is being developed at the Sanford Underground Laboratory, the former Homestake mine, in South Dakota to study the properties of underground seismic fields and Newtonian noise, and to investigate the possible advantages of constructing a third-generation gravitational-wave detector underground. Seismic data were analyzed to characterize seismic noise and disturbances. External databases were used to identify sources of seismic waves: ocean-wave data to identify sources of oceanic microseisms, and surface wind-speed data to investigate correlations with seismic motion as a function of depth. In addition, sources of events contributing to the spectrum at higher frequencies are characterized by studying the variation of event rates over the course of a day. Long-term observations of spectral variations provide further insight into the nature of seismic sources. Seismic spectra at three different depths are compared, establishing the 4100-ft level as a world-class low seismic-noise environment.Comment: 29 pages, 16 figure

Optimum allocation of resources for QTL detection using a nested association mapping strategy in maize

In quantitative trait locus (QTL) mapping studies, it is mandatory that the available financial resources are spent in such a way that the power for detection of QTL is maximized. The objective of this study was to optimize for three different fixed budgets the power of QTL detection 1 − β* in recombinant inbred line (RIL) populations derived from a nested design by varying (1) the genetic complexity of the trait, (2) the costs for developing, genotyping, and phenotyping RILs, (3) the total number of RILs, and (4) the number of environments and replications per environment used for phenotyping. Our computer simulations were based on empirical data of 653 single nucleotide polymorphism markers of 26 diverse maize inbred lines which were selected on the basis of 100 simple sequence repeat markers out of a worldwide sample of 260 maize inbreds to capture the maximum genetic diversity. For the standard scenario of costs, the optimum number of test environments (Eopt) ranged across the examined total budgets from 7 to 19 in the scenarios with 25 QTL. In comparison, the Eopt values observed for the scenarios with 50 and 100 QTL were slightly higher. Our finding of differences in 1 − β* estimates between experiments with optimally and sub-optimally allocated resources illustrated the potential to improve the power for QTL detection without increasing the total resources necessary for a QTL mapping experiment. Furthermore, the results of our study indicated that also in studies using the latest genomics tools to dissect quantitative traits, it is required to evaluate the individuals of the mapping population in a high number of environments with a high number of replications per environment

Huntingtin mediates dendritic transport of β-actin mRNA in rat neurons

Transport of mRNAs to diverse neuronal locations via RNA granules serves an important function in regulating protein synthesis within restricted sub-cellular domains. We recently detected the Huntington's disease protein huntingtin (Htt) in dendritic RNA granules; however, the functional significance of this localization is not known. Here we report that Htt and the huntingtin-associated protein 1 (HAP1) are co-localized with the microtubule motor proteins, the KIF5A kinesin and dynein, during dendritic transport of β-actin mRNA. Live cell imaging demonstrated that β-actin mRNA is associated with Htt, HAP1, and dynein intermediate chain in cultured neurons. Reduction in the levels of Htt, HAP1, KIF5A, and dynein heavy chain by lentiviral-based shRNAs resulted in a reduction in the transport of β-actin mRNA. These findings support a role for Htt in participating in the mRNA transport machinery that also contains HAP1, KIF5A, and dynein

Human PAPS Synthase Isoforms Are Dynamically Regulated Enzymes with Access to Nucleus and Cytoplasm

In higher eukaryotes, PAPS synthases are the only enzymes producing the essential sulphate-donor 3′-phospho-adenosine-5′-phosphosulphate (PAPS). Recently, PAPS synthases have been associated with several genetic diseases and retroviral infection. To improve our understanding of their pathobiological functions, we analysed the intracellular localisation of the two human PAPS synthases, PAPSS1 and PAPSS2. For both enzymes, we observed pronounced heterogeneity in their subcellular localisation. PAPSS1 was predominantly nuclear, whereas PAPSS2 localised mainly within the cytoplasm. Treatment with the nuclear export inhibitor leptomycin B had little effect on their localisation. However, a mutagenesis screen revealed an Arg-Arg motif at the kinase interface exhibiting export activity. Notably, both isoforms contain a conserved N-terminal basic Lys-Lys-Xaa-Lys motif indispensable for their nuclear localisation. This nuclear localisation signal was more efficient in PAPSS1 than in PAPSS2. The activities of the identified localisation signals were confirmed by microinjection studies. Collectively, we describe unusual localisation signals of both PAPS synthase isoforms, mobile enzymes capable of executing their function in the cytoplasm as well as in the nucleus

Physics Design Requirements for the National Spherical Torus Experiment Liquid Lithium Divertor

Recent NSTX high power divertor experiments have shown significant and recurring benefits of solid lithium coatings on PFC's to the performance of divertor plasmas in both L- and H- mode confinement regimes heated by high-power neutral beams. The next step in this work is installation of a liquid lithium divertor (LLD) to achieve density control for inductionless current drive capability (e.g., about a 15-25% ne decrease from present highest non-inductionless fraction discharges which often evolve toward the density limit, ne/nGW~1), to enable ne scan capability (x2) in the H-mode, to test the ability to operate at significantly lower density for future ST-CTF reactor designs (e.g., ne/nGW = 0.25), and eventually to investigate high heat-flux power handling (10 MW/m2) with longpulse discharges (>1.5s). The first step (LLD-1) physics design encompasses the desired plasma requirements, the experimental capabilities and conditions, power handling, radial location, pumping capability, operating temperature, lithium filling, MHD forces, and diagnostics for control and characterization

Impaired Heat Shock Response in Cells Expressing Full-Length Polyglutamine-Expanded Huntingtin

The molecular mechanisms by which polyglutamine (polyQ)-expanded huntingtin (Htt) causes neurodegeneration in Huntington's disease (HD) remain unclear. The malfunction of cellular proteostasis has been suggested as central in HD pathogenesis and also as a target of therapeutic interventions for the treatment of HD. We present results that offer a previously unexplored perspective regarding impaired proteostasis in HD. We find that, under non-stress conditions, the proteostatic capacity of cells expressing full length polyQ-expanded Htt is adequate. Yet, under stress conditions, the presence of polyQ-expanded Htt impairs the heat shock response, a key component of cellular proteostasis. This impaired heat shock response results in a reduced capacity to withstand the damage caused by cellular stress. We demonstrate that in cells expressing polyQ-expanded Htt the levels of heat shock transcription factor 1 (HSF1) are reduced, and, as a consequence, these cells have an impaired a heat shock response. Also, we found reduced HSF1 and HSP70 levels in the striata of HD knock-in mice when compared to wild-type mice. Our results suggests that full length, non-aggregated polyQ-expanded Htt blocks the effective induction of the heat shock response under stress conditions and may thus trigger the accumulation of cellular damage during the course of HD pathogenesis

Identification of Rice Transcription Factors Associated with Drought Tolerance Using the Ecotilling Method

The drought tolerance (DT) of plants is a complex quantitative trait. Under natural and artificial selection, drought tolerance represents the crop survival ability and production capacity under drought conditions (Luo, 2010). To understand the regulation mechanism of varied drought tolerance among rice genotypes, 95 diverse rice landraces or varieties were evaluated within a field screen facility based on the ‘line–source soil moisture gradient’, and their resistance varied from extremely resistant to sensitive. The method of Ecotype Targeting Induced Local Lesions in Genomes (Ecotilling) was used to analyze the diversity in the promoters of 24 transcription factor families. The bands separated by electrophoresis using Ecotilling were converted into molecular markers. STRUCTURE analysis revealed a value of K = 2, namely, the population with two subgroups (i.e., indica and japonica), which coincided very well with the UPGMA clusters (NTSYS-pc software) using distance-based analysis and InDel markers. Then the association analysis between the promoter diversity of these transcription factors and the DT index/level of each variety was performed. The results showed that three genes were associated with the DT index and that five genes were associated with the DT level. The sequences of these associated genes are complex and variable, especially at approximately 1000 bp upstream of the transcription initiation sites. The study illuminated that association analysis aimed at Ecotilling diversity of natural groups could facilitate the isolation of rice genes related to complex quantitative traits

HDNetDB: A Molecular Interaction Database for Network-Oriented Investigations into Huntington’s Disease

Huntington's disease (HD) is a progressive and fatal neurodegenerative disorder caused by an expanded CAG repeat in the huntingtin gene. Although HD is monogenic, its molecular manifestation appears highly complex and involves multiple cellular processes. The recent application of high throughput platforms such as microarrays and mass-spectrometry has indicated multiple pathogenic routes. The massive data generated by these techniques together with the complexity of the pathogenesis, however, pose considerable challenges to researchers. Network-based methods can provide valuable tools to consolidate newly generated data with existing knowledge, and to decipher the interwoven molecular mechanisms underlying HD. To facilitate research on HD in a network-oriented manner, we have developed HDNetDB, a database that integrates molecular interactions with many HD-relevant datasets. It allows users to obtain, visualize and prioritize molecular interaction networks using HD-relevant gene expression, phenotypic and other types of data obtained from human samples or model organisms. We illustrated several HDNetDB functionalities through a case study and identified proteins that constitute potential cross-talk between HD and the unfolded protein response (UPR). HDNetDB is publicly accessible at http://hdnetdb.sysbiolab.eu.CHDI Foundation [A-2666]; Portuguese Fundacao para a Ciencia e a Tecnologia [SFRH/BPD/70718/2010, SFRH/BPD/96890/2013, IF/00881/2013, UID/BIM/04773/2013 - CBMR, UID/Multi/04326/2013 - CCMAR]info:eu-repo/semantics/publishedVersio