D-branes on Three-dimensional Nonabelian Orbifolds

We study D-branes on a three complex dimensional nonabelian orbifold ${\bf C}^3/\Gamma$ with $\Gamma$ a finite subgroup of SU(3). We present general formulae necessary to obtain quiver diagrams which represent the gauge group and the spectrum of the D-brane worldvolume theory for dihedral-like subgroups $\Delta(3n^2)$ and $\Delta(6n^2)$. It is found that the quiver diagrams have a similar structure to webs of branes.Comment: 13 pages, LaTex, 2 figures, minor corrections, to appear in JHE

Stability of Quiver Representations and Topology Change

We study phase structure of the moduli space of a D0-brane on the orbifold C^3/Z_2 \times Z_2 based on stability of quiver representations. It is known from an analysis using toric geometry that this model has multiple phases connected by flop transitions. By comparing the results of the two methods, we obtain a correspondence between quiver representations and geometry of toric resolutions of the orbifold. It is shown that a redundancy of coordinates arising in the toric description of the D-brane moduli space, which is a key ingredient of disappearance of non-geometric phases, is understood from the monodromy around the orbifold point. We also discuss why only geometric phases appear from the viewpoint of stability of D0-branes.Comment: 16 pages, 7 figures, minor corrections, references adde

Brane Cube Realization of Three-dimensional Nonabelian Orbifolds

We study D-branes on three-dimensional orbifolds ${\bf C}^3/\Gamma$ where $\Gamma$ are finite subgroups of SU(3). The quiver diagram of \ZnZn \in SU(3) can be expressed in three-dimensional form. According to the correspondence between quiver diagrams and brane configurations, we construct a brane configuration for {\bf C}^3/\ZnZn which has essentially three-dimensional structrue. Brane configurations for nonabelian orbifolds \C^3/\Delta(3n^2) and \C^3/\Delta(6n^2) are obtained from that for \C^3/\ZnZn by certain quotienting procedure.Comment: 19 pages, 14 figure

A relation between moduli space of D-branes on orbifolds and Ising model

We study D-branes transverse to an abelian orbifold C^3/Z_n Z_n. The moduli space of the gauge theory on the D-branes is analyzed by combinatorial calculation based on toric geometry. It is shown that the calculation is related to a problemto count the number of ground states of an antiferromagnetic Ising model. The lattice on which the Ising model is defined is a triangular one defined on the McKay quiver of the orbifold.Comment: 20 pages, 13 figure

D-branes on Orbifolds and Topology Change

We consider D-branes on an orbifold $C^3/Z_n$ and investigate the moduli space of the D-brane world-volume gauge theory by using toric geometry and gauged linear sigma models. For $n=11$, we find that there are five phases, which are topologically distinct and connected by flops to each other. We also verify that non-geometric phases are projected out for $n=7,9,11$ cases as expected. Resolutions of non-isolated singularities are also investigated.Comment: 21 pages + 12 eps figures, LaTeX, minor correction

On thermodynamics of black p-branes

Thermodynamic properties of a class of black $p$-branes in $D$-dimensions considered by Duff and Lu are investigated semi-classically. For black $(d-1)$-brane, thermodynamic quantities depend on $D$ and $d$ only through the combination $\tilde d \equiv D-d-2$. The behavior of the Hawking temperature and the lifetime vary with $\tilde d$, with a critical value $\tilde d=2$. For $\tilde d>2$, there remains a remnant, in which non-zero entropy is stored. Implications of the fact that the Bekenstein-Hawking entropy of the black $(d-1)$-brane depend only on $\tilde d=D-d-2$ is discussed from the point of view of duality.Comment: 8 pages, LaTe

Axial-Vector Duality as a Mirror Symmetry

We study $N=2$ supersymmetric $SU(2)/U(1)$ and $SL(2,R)/U(1)$ gauged Wess-Zumino-Witten models. It is shown that the vector gauged model is transformed to the axial gauged model by a mirror transformation. Therefore the vector gauged model and the axial gauged model are equivalent as $N=(2,2)$ superconformal field theories. In the $SL(2,R)/U(1)$ model, it is known that axial-vector duality relates a background with a singularity to that without a singularity. Implications of the equivalence of these two models to space-time singularities are discussed.Comment: 12 pages, LaTeX, KUNS 129

HER2 G776S mutation promotes oncogenic potential in colorectal cancer cells when accompanied by loss of APC function

Clinical cancer genome sequencing detects oncogenic variants that are potential targets for cancer treatment, but it also detects variants of unknown significance. These variants may interact with each other to influence tumor pathophysiology, however, such interactions have not been fully elucidated. Additionally, the effect of target therapy for those variants also unclarified. In this study, we investigated the biological functions of a HER2 mutation (G776S mutation) of unknown pathological significance, which was detected together with APC mutation by cancer genome sequencing of samples from a colorectal cancer (CRC) patient. Transfection of the HER2 G776S mutation alone slightly increased the kinase activity and phosphorylation of HER2 protein, but did not activate HER2 downstream signaling or alter the cell phenotype. On the other hand, the HER2 G776S mutation was shown to have strong oncogenic potential when loss of APC function was accompanied. We revealed that loss of APC function increased Wnt pathway activity but also increased RAS-GTP, which increased ERK phosphorylation triggered by HER2 G776S transfection. In addition, afatinib, a pan-HER tyrosine kinase inhibitor, suppressed tumor growth in xenografts derived from HER2 G776S-transfected CRC cells. These findings suggest that this HER2 mutation in CRC may be a potential therapeutic target

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target