Predicted Number, Multiplicity, and Orbital Dynamics of TESS M Dwarf Exoplanets

We present a study of the M dwarf exoplanetary systems forthcoming from NASA's TESS mission. While the mission's footprint is too complex to be characterized by a single detection completeness, we extract an ensemble completeness function that recovers the M dwarf planet detections from previous work. We employ this completeness function, together with a dual-population planet occurrence model that includes compact multiple planetary systems, to infer anew the planet yield. We predict both the number of M dwarf planets likely from TESS and their system architectures. We report four main findings: first, that TESS will likely detect more planets orbiting M dwarfs that previously predicted. Around stars with spectral types between M1V--M4V, we predict TESS will find 990$\pm$350 planets orbiting 715$\pm$255 stars, a 1.5-fold increase over previous predictions. Secondly, TESS will find two or more transiting planets around 20% of these host stars, a number similar to the multiplicity yield of NASA's Kepler mission. Thirdly, TESS light curves in which one or more planets are detected will often contain transits of additional planets below the detection threshold of TESS. Among a typical set of 200 TESS hosts to one or more detected planets, 116$\pm$28 transiting planets will be missed. Transit follow-up efforts with the photometric sensitivity to detect an Earth or larger around a mid-M dwarf, even with very modest period completeness, will readily result in additional planet discoveries. And fourth, the strong preference of TESS for systems of compact multiples indicates that TESS planets will be dynamically cooler on average than Kepler planets, with 90% of TESS-detected planets residing in orbits with $e<0.15$.Comment: 14 pages, 11 figures, submitted to Ap

Primary Mucinous Adenocarcinoma of the Testis

Ovarian-type surface epithelial neoplasms of the testis and paratestis are uncommon, and the mucinous subtype is particularly rare. These tumors represent a counterpart to ovarian cancer. Malignant tumors have the potential for metastatic spread and are often fatal. The case of a 59-year-old man with testicular mucinous adenocarcinoma is presented. Computed tomography indicated involvement of the paraaortic and pelvic lymph nodes, so chemotherapy was initiated. To the best of our knowledge, this is the second paper regarding responsiveness to chemotherapies used in ovarian cancer

Phases of a two dimensional large N gauge theory on a torus

We consider two-dimensional large N gauge theory with D adjoint scalars on a torus, which is obtained from a D+2 dimensional pure Yang-Mills theory on T^{D+2} with D small radii. The two dimensional model has various phases characterized by the holonomy of the gauge field around non-contractible cycles of the 2-torus. We determine the phase boundaries and derive the order of the phase transitions using a method, developed in an earlier work (arxiv:0910.4526), which is nonperturbative in the 'tHooft coupling and uses a 1/D expansion. We embed our phase diagram in the more extensive phase structure of the D+2 dimensional Yang-Mills theory and match with the picture of a cascade of phase transitions found earlier in lattice calculations (arxiv:0710.0098). We also propose a dual gravity system based on a Scherk-Schwarz compactification of a D2 brane wrapped on a 3-torus and find a phase structure which is similar to the phase diagram found in the gauge theory calculation.Comment: 28 pages (+ 17 pages of appendix + 6 pages of ref.); 8 figures; (v2) LaTeX Showkeys command deleted; (v3) refs and minor clarifications added; emphasized the new proposal for applying holography to nonsupersymmetric gauge theory; (v4) modified the arguments about holography; (v5) minor corrections, version appeared in PR

Drug interaction prediction using ontology-driven hypothetical assertion framework for pathway generation followed by numerical simulation

<p>Abstract</p> <p>Background</p> <p>In accordance with the increasing amount of information concerning individual differences in drug response and molecular interaction, the role of <it>in silico </it>prediction of drug interaction on the pathway level is becoming more and more important. However, in view of the interferences for the identification of new drug interactions, most conventional information models of a biological pathway would have limitations. As a reflection of real world biological events triggered by a stimulus, it is important to facilitate the incorporation of known molecular events for inferring (unknown) possible pathways and hypothetic drug interactions. Here, we propose a new Ontology-Driven Hypothetic Assertion (OHA) framework including pathway generation, drug interaction detection, simulation model generation, numerical simulation, and hypothetic assertion. Potential drug interactions are detected from drug metabolic pathways dynamically generated by molecular events triggered after the administration of certain drugs. Numerical simulation enables to estimate the degree of side effects caused by the predicted drug interactions. New hypothetic assertions of the potential drug interactions and simulation are deduced from the Drug Interaction Ontology (DIO) written in Web Ontology Language (OWL).</p> <p>Results</p> <p>The concept of the Ontology-Driven Hypothetic Assertion (OHA) framework was demonstrated with known interactions between irinotecan (CPT-11) and ketoconazole. Four drug interactions that involved cytochrome p450 (CYP3A4) and albumin as potential drug interaction proteins were automatically detected from Drug Interaction Ontology (DIO). The effect of the two interactions involving CYP3A4 were quantitatively evaluated with numerical simulation. The co-administration of ketoconazole may increase AUC and Cmax of SN-38(active metabolite of irinotecan) to 108% and 105%, respectively. We also estimates the potential effects of genetic variations: the AUC and Cmax of SN-38 may increase to 208% and 165% respectively with the genetic variation UGT1A1*28/*28 which reduces the expression of UGT1A1 down to 30%.</p> <p>Conclusion</p> <p>These results demonstrate that the Ontology-Driven Hypothetic Assertion framework is a promising approach for <it>in silico </it>prediction of drug interactions. The following future researches for the <it>in silico </it>prediction of individual differences in the response to the drug and drug interactions after the administration of multiple drugs: expansion of the Drug Interaction Ontology for other drugs, and incorporation of virtual population model for genetic variation analysis, as well as refinement of the pathway generation rules, the drug interaction detection rules, and the numerical simulation models.</p

Rikkunshito Ameliorates Cancer Cachexia Partly through Elevation of Glucarate in Plasma

Cancer cachexia, which is characterized by decreased food intake, weight loss and systemic inflammation, increases patient’s morbidity and mortality. We previously showed that rikkunshito (RKT), a Japanese traditional herbal medicine (Kampo), ameliorated the symptoms of cancer cachexia through ghrelin signaling-dependent and independent pathways. To investigate other mechanisms of RKT action in cancer cachexia, we performed metabolome analysis of plasma in a rat model bearing the Yoshida AH-130 hepatoma. A total of 110 metabolites were detected in plasma and RKT treatment significantly altered levels of 23 of those metabolites in cachexia model rats. Among them, glucarate, which is known to have anticarcinogenic activity through detoxification of carcinogens via inhibition of β-glucuronidase, was increased in plasma following administration of RKT. In our AH-130 ascites-induced cachexia rat model, administration of glucarate delayed onset of weight loss, improved muscle atrophy, and reduced ascites content. Additionally, glucarate reduced levels of plasma interferon-γ (IFN-γ) in tumor-bearing rats and was also found to suppress LPS-induced IFN-γ expression in splenocytes in vitro. These results suggest that glucarate has anti-inflammatory activity via a direct effect on immune host cells and suggest that RKT may also ameliorate inflammation partly through the elevation of glucarate in plasma

Oral Treatment with Extract of Agaricus blazei Murill Enhanced Th1 Response through Intestinal Epithelial Cells and Suppressed OVA-Sensitized Allergy in Mice

To clarify the mechanism of the antiallergic activity of Agaricus blazei Murill extract (ABME), the present paper used an in vivo allergy model and an in vitro intestinal gut model. During OVA sensitization, the serum IgE levels decreased significantly in ABME group. Interleukin (IL)-4 and -5 produced from OVA-restimulated splenocytes was significantly decreased, and anti-CD3ε/CD28 antibody treatment also reduced IL-10, -4, and -5 production and increased IFN-γ production in ABME group. These results suggest that oral administration of ABME improves Th1/Th2 balance. Moreover, a coculture system constructed of Caco-2 cells and splenocytes from OT-II mice or RAW 264.7 cells indicated that the significant increases in IFN-γ production by ABME treatment. Therefore, it was concluded that the antiallergic activity of ABME was due to the activation of macrophages by epithelial cells and the promotion of the differentiation of naïve T cells into Th1 cells in the immune

Evolution in an oncogenic bacterial species with extreme genome plasticity: Helicobacter pylori East Asian genomes

<p>Abstract</p> <p>Background</p> <p>The genome of <it>Helicobacter pylori</it>, an oncogenic bacterium in the human stomach, rapidly evolves and shows wide geographical divergence. The high incidence of stomach cancer in East Asia might be related to bacterial genotype. We used newly developed comparative methods to follow the evolution of East Asian <it>H. pylori </it>genomes using 20 complete genome sequences from Japanese, Korean, Amerind, European, and West African strains.</p> <p>Results</p> <p>A phylogenetic tree of concatenated well-defined core genes supported divergence of the East Asian lineage (hspEAsia; Japanese and Korean) from the European lineage ancestor, and then from the Amerind lineage ancestor. Phylogenetic profiling revealed a large difference in the repertoire of outer membrane proteins (including <it>oipA</it>, <it>hopMN</it>, <it>babABC</it>, <it>sabAB </it>and <it>vacA-2</it>) through gene loss, gain, and mutation. All known functions associated with molybdenum, a rare element essential to nearly all organisms that catalyzes two-electron-transfer oxidation-reduction reactions, appeared to be inactivated. Two pathways linking acetyl~CoA and acetate appeared intact in some Japanese strains. Phylogenetic analysis revealed greater divergence between the East Asian (hspEAsia) and the European (hpEurope) genomes in proteins in host interaction, specifically virulence factors (<it>tipα</it>), outer membrane proteins, and lipopolysaccharide synthesis (human Lewis antigen mimicry) enzymes. Divergence was also seen in proteins in electron transfer and translation fidelity (<it>miaA, tilS</it>), a DNA recombinase/exonuclease that recognizes genome identity (<it>addA</it>), and DNA/RNA hybrid nucleases (<it>rnhAB</it>). Positively selected amino acid changes between hspEAsia and hpEurope were mapped to products of <it>cagA</it>, <it>vacA</it>, <it>homC </it>(outer membrane protein), <it>sotB </it>(sugar transport), and a translation fidelity factor (<it>miaA</it>). Large divergence was seen in genes related to antibiotics: <it>frxA </it>(metronidazole resistance), <it>def </it>(peptide deformylase, drug target), and <it>ftsA </it>(actin-like, drug target).</p> <p>Conclusions</p> <p>These results demonstrate dramatic genome evolution within a species, especially in likely host interaction genes. The East Asian strains appear to differ greatly from the European strains in electron transfer and redox reactions. These findings also suggest a model of adaptive evolution through proteome diversification and selection through modulation of translational fidelity. The results define <it>H. pylori </it>East Asian lineages and provide essential information for understanding their pathogenesis and designing drugs and therapies that target them.</p