Wikis in Tuple Spaces

We consider storing the pages of a wiki in a tuple space and the effects this might have on the wiki experience. In particular, wiki pages are stored in tuples with a few identifying values such as title, author, revision date, content, etc. and pages are retrieved by sending the tuple space templates, such as one that gives the title but nothing else, leaving the tuple space to resolve to a single tuple. We use a tuple space wiki to avoid deadlocks, infinite loops, and wasted efforts when page edit contention arises and examine how a tuple space wiki changes the wiki experience.Comment: To appear at WMSCI 200

Applications of quantum message sealing

In 2003, Bechmann-Pasquinucci introduced the concept of quantum seals, a quantum analogue to wax seals used to close letters and envelopes. Since then, some improvements on the method have been found. We first review the current quantum sealing techniques, then introduce and discuss potential applications of quantum message sealing, and conclude with some discussion of the limitations of quantum seals.Comment: Presented as SPIE paper 5815-25 at Quantum Information and Computation III, part of the SPIE Defense & Security Symposium 200

Robustness to fundamental uncertainty in AGI alignment

The AGI alignment problem has a bimodal distribution of outcomes with most outcomes clustering around the poles of total success and existential, catastrophic failure. Consequently, attempts to solve AGI alignment should, all else equal, prefer false negatives (ignoring research programs that would have been successful) to false positives (pursuing research programs that will unexpectedly fail). Thus, we propose adopting a policy of responding to points of metaphysical and practical uncertainty associated with the alignment problem by limiting and choosing necessary assumptions to reduce the risk false positives. Herein we explore in detail some of the relevant points of uncertainty that AGI alignment research hinges on and consider how to reduce false positives in response to them

Orai and TRPC channel characterization in FcεRI-mediated calcium signaling and mediator secretion in human mast cells.

Inappropriate activation of mast cells via the FcεRI receptor leads to the release of inflammatory mediators and symptoms of allergic disease. Calcium influx is a critical regulator of mast cell signaling and is required for exocytosis of preformed mediators and for synthesis of eicosanoids, cytokines and chemokines. Studies in rodent and human mast cells have identified Orai calcium channels as key contributors to FcεRI-initiated mediator release. However, until now the role of TRPC calcium channels in FcεRI-mediated human mast cell signaling has not been published. Here, we show evidence for the expression of Orai 1,2, and 3 and TRPC1 and 6 in primary human lung mast cells and the LAD2 human mast cell line but, we only find evidence of functional contribution of Orai and not TRPC channels to FcεRI-mediated calcium entry. Calcium imaging experiments, utilizing an Orai selective antagonist (Synta66) showed the contribution of Orai to FcεRI-mediated signaling in human mast cells. Although, the use of a TRPC3/6 selective antagonist and agonist (GSK-3503A and GSK-2934A, respectively) did not reveal evidence for TRPC6 contribution to FcεRI-mediated calcium signaling in human mast cells. Similarly, inactivation of STIM1-regulated TRPC1 in human mast cells (as tested by transfecting cells with STIM1-KK(684-685)EE - TRPC1 gating mutant) failed to alter FcεRI-mediated calcium signaling in LAD2 human mast cells. Mediator release assays confirm that FcεRI-mediated calcium influx through Orai is necessary for histamine and TNFα release but is differentially involved in the generation of cytokines and eicosanoids

The potential of urinary metabolites for diagnosing multiple sclerosis

A definitive diagnostic test for multiple sclerosis (MS) does not exist; instead physicians use a combination of medical history, magnetic resonance imaging, and cerebrospinal fluid analysis (CSF). Significant effort has been employed to identify biomarkers from CSF to facilitate MS diagnosis; however none of the proposed biomarkers have been successful to date. Urine is a proven source of metabolite biomarkers and has the potential to be a rapid, non-invasive, inexpensive, and efficient diagnostic tool for various human diseases. Nevertheless, urinary metabolites have not been extensively explored as a source of biomarkers for MS. Instead, we demonstrate that urinary metabolites have significant promise for monitoring disease-progression, and response to treatment in MS patients. NMR analysis of urine permitted the identification of metabolites that differentiate experimental autoimmune encephalomyelitis (EAE)-mice (prototypic disease model for MS) from healthy and MS drug-treated EAE mice

Genomic innovations, transcriptional plasticity and gene loss underlying the evolution and divergence of two highly polyphagous and invasive <i>Helicoverpa</i> pest species

BACKGROUND: Helicoverpa armigera and Helicoverpa zea are major caterpillar pests of Old and New World agriculture, respectively. Both, particularly H. armigera, are extremely polyphagous, and H. armigera has developed resistance to many insecticides. Here we use comparative genomics, transcriptomics and resequencing to elucidate the genetic basis for their properties as pests. RESULTS: We find that, prior to their divergence about 1.5 Mya, the H. armigera/H. zea lineage had accumulated up to more than 100 more members of specific detoxification and digestion gene families and more than 100 extra gustatory receptor genes, compared to other lepidopterans with narrower host ranges. The two genomes remain very similar in gene content and order, but H. armigera is more polymorphic overall, and H. zea has lost several detoxification genes, as well as about 50 gustatory receptor genes. It also lacks certain genes and alleles conferring insecticide resistance found in H. armigera. Non-synonymous sites in the expanded gene families above are rapidly diverging, both between paralogues and between orthologues in the two species. Whole genome transcriptomic analyses of H. armigera larvae show widely divergent responses to different host plants, including responses among many of the duplicated detoxification and digestion genes. CONCLUSIONS: The extreme polyphagy of the two heliothines is associated with extensive amplification and neofunctionalisation of genes involved in host finding and use, coupled with versatile transcriptional responses on different hosts. H. armigera's invasion of the Americas in recent years means that hybridisation could generate populations that are both locally adapted and insecticide resistant

Sooty Mangabey Genome Sequence Provides Insight into AIDS Resistance in a Natural SIV Host

In contrast to infections with human immunodeficiency virus (HIV) in humans and simian immunodeficiency virus (SIV) in macaques, SIV infection of a natural host, sooty mangabeys (Cercocebus atys), is non-pathogenic despite high viraemia. Here we sequenced and assembled the genome of a captive sooty mangabey. We conducted genome-wide comparative analyses of transcript assemblies from C. atys and AIDS-susceptible species, such as humans and macaques, to identify candidates for host genetic factors that influence susceptibility. We identified several immune-related genes in the genome of C. atys that show substantial sequence divergence from macaques or humans. One of these sequence divergences, a C-terminal frameshift in the toll-like receptor-4 (TLR4) gene of C. atys, is associated with a blunted in vitro response to TLR-4 ligands. In addition, we found a major structural change in exons 3-4 of the immune-regulatory protein intercellular adhesion molecule 2 (ICAM-2); expression of this variant leads to reduced cell surface expression of ICAM-2. These data provide a resource for comparative genomic studies of HIV and/or SIV pathogenesis and may help to elucidate the mechanisms by which SIV-infected sooty mangabeys avoid AIDS

Genomic and epigenetic evidence for oxytocin receptor deficiency in autism

<p>Abstract</p> <p>Background</p> <p>Autism comprises a spectrum of behavioral and cognitive disturbances of childhood development and is known to be highly heritable. Although numerous approaches have been used to identify genes implicated in the development of autism, less than 10% of autism cases have been attributed to single gene disorders.</p> <p>Methods</p> <p>We describe the use of high-resolution genome-wide tilepath microarrays and comparative genomic hybridization to identify copy number variants within 119 probands from multiplex autism families. We next carried out DNA methylation analysis by bisulfite sequencing in a proband and his family, expanding this analysis to methylation analysis of peripheral blood and temporal cortex DNA of autism cases and matched controls from independent datasets. We also assessed oxytocin receptor (OXTR) gene expression within the temporal cortex tissue by quantitative real-time polymerase chain reaction (PCR).</p> <p>Results</p> <p>Our analysis revealed a genomic deletion containing the oxytocin receptor gene, <it>OXTR </it>(MIM accession no.: 167055), previously implicated in autism, was present in an autism proband and his mother who exhibits symptoms of obsessive-compulsive disorder. The proband's affected sibling did not harbor this deletion but instead may exhibit epigenetic misregulation of this gene through aberrant gene silencing by DNA methylation. Further DNA methylation analysis of the CpG island known to regulate <it>OXTR </it>expression identified several CpG dinucleotides that show independent statistically significant increases in the DNA methylation status in the peripheral blood cells and temporal cortex in independent datasets of individuals with autism as compared to control samples. Associated with the increase in methylation of these CpG dinucleotides is our finding that <it>OXTR </it>mRNA showed decreased expression in the temporal cortex tissue of autism cases matched for age and sex compared to controls.</p> <p>Conclusion</p> <p>Together, these data provide further evidence for the role of OXTR and the oxytocin signaling pathway in the etiology of autism and, for the first time, implicate the epigenetic regulation of <it>OXTR </it>in the development of the disorder.</p> <p>See the related commentary by Gurrieri and Neri: <url>http://www.biomedcentral.com/1741-7015/7/63</url></p

High Density SNP Screen in A Large Multiplex Neural Tube Defect Family Refines Linkage to Loci at 7p21-Pter And 2q33.1-35

Neural tube defects (NTDs) are considered complex with both genetic and environmental factors implicated. To date, no major causative genes have been identified in humans despite several investigations. The first genomewide screen in NTDs (Rampersaud et al. 2005) demonstrated evidence of linkage to chromosomes 7 and 10. This screen included forty-four multiplex families and consisted of 402 microsatellite markers spaced approximately 10 cM apart. Further investigation of the genomic screen data identified a single large multiplex family, pedigree 8776, as primarily driving the linkage results on chromosome 7