Grammar-Based Geodesics in Semantic Networks

A geodesic is the shortest path between two vertices in a connected network. The geodesic is the kernel of various network metrics including radius, diameter, eccentricity, closeness, and betweenness. These metrics are the foundation of much network research and thus, have been studied extensively in the domain of single-relational networks (both in their directed and undirected forms). However, geodesics for single-relational networks do not translate directly to multi-relational, or semantic networks, where vertices are connected to one another by any number of edge labels. Here, a more sophisticated method for calculating a geodesic is necessary. This article presents a technique for calculating geodesics in semantic networks with a focus on semantic networks represented according to the Resource Description Framework (RDF). In this framework, a discrete "walker" utilizes an abstract path description called a grammar to determine which paths to include in its geodesic calculation. The grammar-based model forms a general framework for studying geodesic metrics in semantic networks.Comment: First draft written in 200

A novel link between the proteasome pathway and the signal transduction pathway of the Bone Morphogenetic Proteins (BMPs)

BACKGROUND: The intracellular signaling events of the Bone Morphogenetic Proteins (BMPs) involve the R-Smad family members Smad1, Smad5, Smad8 and the Co-Smad, Smad4. Smads are currently considered to be DNA-binding transcriptional modulators and shown to recruit the master transcriptional co-activator CBP/p300 for transcriptional activation. SNIP1 is a recently discovered novel repressor of CBP/p300. Currently, the detailed molecular mechanisms that allow R-Smads and Co-Smad to co-operatively modulate transcription events are not fully understood. RESULTS: Here we report a novel physical and functional link between Smad1 and the 26S proteasome that contributes to Smad1- and Smad4-mediated transcriptional regulation. Smad1 forms a complex with a proteasome β subunit HsN3 and the ornithine decarboxylase antizyme (Az). The interaction is enhanced upon BMP type I receptor activation and occur prior to the incorporation of HsN3 into the mature 20S proteasome. Furthermore, BMPs trigger the translocation of Smad1, HsN3 and Az into the nucleus, where the novel CBP/p300 repressor protein SNIP1 is further recruited to Smad1/HsN3/Az complex and degraded in a Smad1-, Smad4- and Az-dependent fashion. The degradation of the CBP/p300 repressor SNIP1 is likely an essential step for Smad1-, Smad4-mediated transcriptional activation, since increased SNIP1 expression inhibits BMP-induced gene responses. CONCLUSIONS: Our studies thus add two additional important functional partners of Smad1 into the signaling web of BMPs and also suggest a novel mechanism for Smad1 and Smad4 to co-modulate transcription via regulating proteasomal degradation of CBP/p300 repressor SNIP1

Genome-wide features of neuroendocrine regulation in Drosophila by the basic helix-loop-helix transcription factor DIMMED.

Neuroendocrine (NE) cells use large dense core vesi-cles (LDCVs) to traffic, process, store and secrete neuropeptide hormones through the regulated secre-tory pathway. The dimmed (DIMM) basic helix-loop-helix transcription factor of Drosophila controls the level of regulated secretory activity in NE cells. To pursue its mechanisms, we have performed two in-dependent genome-wide analyses of DIMM’s activi-ties: (i) in vivo chromatin immunoprecipitation (ChIP) to define genomic sites of DIMM occupancy and (ii) deep sequencing of purified DIMM neurons to char-acterize their transcriptional profile. By this com-bined approach, we showed that DIMM binds to con-served E-boxes in enhancers of 212 genes whose expression is enriched in DIMM-expressing NE cells. DIMM binds preferentially to certain E-boxes within first introns of specific gene isoforms. Statistical ma-chine learning revealed that flanking regions of puta-tive DIMM binding sites contribute to its DNA binding specificity. DIMM’s transcriptional repertoire features at least 20 LDCV constituents. In addition, DIMM no-tably targets the pro-secretory transcription factor, creb-A, but significantly, DIMM does not target any neuropeptide genes. DIMM therefore prescribes the scale of secretory activity in NE neurons, by a sys-tematic control of both proximal and distal points in the regulated secretory pathway

AEGIS: Enhancement of Dust-enshrouded Star Formation in Close Galaxy Pairs and Merging Galaxies up to z ~ 1

Using data from the DEEP2 Galaxy Redshift Survey and HST/ACS imaging in the Extended Groth Strip, we select nearly 100 interacting galaxy systems including kinematic close pairs and morphologically identified merging galaxies. Spitzer MIPS 24 micron fluxes of these systems reflect the current dusty star formation activity, and at a fixed stellar mass (M_{*}) the median infrared luminosity (L_{IR}) among merging galaxies and close pairs of blue galaxies is twice (1.9 +/- 0.4) that of control pairs drawn from isolated blue galaxies. Enhancement declines with galaxy separation, being strongest in close pairs and mergers and weaker in wide pairs compared to the control sample. At z ~ 0.9, 7.1% +/- 4.3% of massive interacting galaxies (M_{*} > 2*10^{10} M_{solar}) are found to be ULIRGs, compared to 2.6% +/- 0.7% in the control sample. The large spread of IR luminosity to stellar mass ratio among interacting galaxies suggests that this enhancement may depend on the merger stage as well as other as yet unidentified factors (e.g., galaxy structure, mass ratio, orbital characteristics, presence of AGN or bar). The contribution of interacting systems to the total IR luminosity density is moderate (<= 36 %).Comment: 12 pages, 2 figures, 1 table, minor changes to match the proof version, accepted for publication in the ApJL AEGIS Special Issu

Estrogen and progesterone-related gene variants and colorectal cancer risk in women

<p>Abstract</p> <p>Background</p> <p>Observational studies and randomized trials have suggested that estrogens and/or progesterone may lower the risk for colorectal cancer. Inherited variation in the sex-hormone genes may be one mechanism by which sex hormones affect colorectal cancer, although data are limited.</p> <p>Method</p> <p>We conducted a comprehensive evaluation of single nucleotide polymorphisms (SNPs) in genes encoding 3 hormone receptors (<it>ESR1, ESR2, PGR</it>) and 5 hormone synthesizers (<it>CYP19A1 and CYP17A1, HSD17B1, HSD17B2, HSD17B4</it>) among 427 women with incident colorectal cancer and 871 matched controls who were Caucasians of European ancestry from 93676 postmenopausal women enrolled in the Women's Health Initiative Observational cohort. A total of 242 haplotype-tagging and functional SNPs in the 8 genes were included for analysis. Unconditional logistic regression with adjustment for age and hysterectomy status was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).</p> <p>Results</p> <p>We observed a weak association between the <it>CYP17A1 </it>rs17724534 SNP and colorectal cancer risk (OR per risk allele (A) = 1.39, 95% CI = 1.09-1.78, corrected p-value = 0.07). In addition, a suggestive interaction between rs17724534 and rs10883782 in 2 discrete LD blocks of <it>CYP17A1 </it>was observed in relation to colorectal cancer (empirical p value = 0.04). Moreover, one haplotype block of <it>CYP19A1 </it>was associated with colorectal cancer (corrected global p value = 0.02), which likely reflected the association with the tagging SNP, rs1902584, in the block.</p> <p>Conclusion</p> <p>Our findings offer some support for a suggestive association of <it>CYP17A1 </it>and <it>CYP19A1 </it>variants with colorectal cancer risk.</p

Habitual intake of flavonoid subclasses and risk of colorectal cancer in two large prospective cohorts

Background: Flavonoids inhibit the growth of colon cancer cells in vitro. In a secondary analysis of a randomized controlled trial, the Polyp Prevention Trial, a higher intake of one sub-class, flavonols, was significantly associated with reduced risk of recurrent advanced adenoma. Most previous prospective studies on colorectal cancer evaluated only a limited number of flavonoid sub-classes and intake ranges, yielding inconsistent results.  Objective: To examine whether higher habitual dietary intakes of flavonoid subclasses (flavonols, flavones, flavanones, flavan-3-ols and anthocyanins) are associated with lower risk of colorectal cancer.  Design: Using data from validated food frequency questionnaires administered every four years and an updated flavonoid food composition database flavonoid intakes were calculated for 42,478 male participants from the Health Professionals Follow-up Study and for 76,364 female participants from the Nurses’ Health Study.  Results: During up to 26 years of follow-up, 2,519 colorectal cancer cases (1,061 in men, 1,458 in women) were documented. Intakes of flavonoid subclasses were not associated with risk of colorectal cancer in either cohort. Pooled multivariable adjusted relative risks (95% confidence interval) comparing the highest with the lowest quintile were 1.04 (0.91, 1.18) for flavonols; 1.01 (0.89, 1.15) for flavones; 0.96 (0.84, 1.10) for flavanones; 1.07 (0.95, 1.21) for flavan-3-ols; and 0.98 (0.81, 1.19) for anthocyanins (all p-values for heterogeneity by sex >0.19). In subsite analyses, flavonoid intake was also not associated with colon or rectal cancer risk.  Conclusion: Our findings do not support the hypothesis that a higher habitual intake of any flavonoid sub-class decreases the risk of colorectal cancer

Green's Functions and Non-Singlet Glueballs on Deformed Conifolds

We study the Laplacian on Stenzel spaces (generalized deformed conifolds), which are tangent bundles of spheres endowed with Ricci flat metrics. The (2d-2)-dimensional Stenzel space has SO(d) symmetry and can be embedded in C^d through the equation \sum_{i = 1}^d {z_i^2} = \epsilon^2. We discuss the Green's function with a source at a point on the S^{d-1} zero section of TS^{d-1}. Its calculation is complicated by mixing between different harmonics with the same SO(d) quantum numbers due to the explicit breaking by the \epsilon-deformation of the U(1) symmetry that rotates z_i by a phase. A similar mixing affects the spectrum of normal modes of warped deformed conifolds that appear in gauge/gravity duality. We solve the mixing problem numerically to determine certain bound state spectra in various representations of SO(d) for the d=4 and d=5 examples.Comment: 52 pages, 3 figure

The Aromatase Gene (CYP19A1) Variants and Circulating Hepatocyte Growth Factor in Postmenopausal Women

Background: Estrogen and androgen have been linked to the regulation of circulating hepatocyte growth factor (HGF), an adipose tissue-derived cytokine. It is possible that the CYP19A1 gene which alters sex hormones production may influence HGF levels. We examined the association between the CYP19A1 gene variants and plasma HGF concentrations. Design We evaluated 45 common and putative functional variants of CYP19A1 and circulating levels of HGF among 260 postmenopausal women who later developed colorectal cancer from the Women's Health Initiative Observational Cohort. As the distribution of HGF levels was highly skewed, we transformed HGF concentrations for all women into a log-, ranked-, or normal score-scale value. Multiple linear regression with adjustment for age was used to evaluate the associations. Results: We observed an association between the rs7172156, rs1008805, rs6493494, rs749292, and rs11636639 variants and HGF levels in ranked and normal score scales (corrected p values ≤0.02), although the association of these 5 SNPs with log-scale HGF was not significant (corrected p values ≥0.16). The associations remained unchanged after additional adjustment for hormone therapy use and estradiol levels. These 5 SNPs, which were in linkage disequilibrium (pairwise D′≥97%, r2≥56%), constituted a block with 2 common haplotypes accounting for 82% frequency. The most common haplotype, TCCCA, was associated with lower ranked- or normal score-transformed HGF levels (corrected p values ≤0.001), whereas the second most common haplotype, CTTCA, was associated with higher ranked- or normal score-transformed HGF levels (corrected p values ≤0.02). Conclusion: Our findings of a potential association between the CYP19A1 variants and circulating HGF levels warrant confirmation in studies with larger sample size