Deformations of calibrated subbundles of Euclidean spaces via twisting by special sections

We extend the "bundle constructions" of calibrated submanifolds, due to Harvey--Lawson in the special Lagrangian case, and to Ionel--Karigiannis--Min-Oo in the cases of exceptional calibrations, by "twisting" the bundles by a special (harmonic, holomorphic, parallel) section of a complementary bundle. The existence of such deformations shows that the moduli space of calibrated deformations of these "calibrated subbundles" includes deformations which destroy the linear structure of the fibre.Comment: 16 pages, no figures. Version 2: Only minor cosmetic and typographical revisions. To appear in "Annals of Global Analysis and Geometry.

Asymptotically cylindrical 7-manifolds of holonomy G_2 with applications to compact irreducible G_2-manifolds

We construct examples of exponentially asymptotically cylindrical Riemannian 7-manifolds with holonomy group equal to G_2. To our knowledge, these are the first such examples. We also obtain exponentially asymptotically cylindrical coassociative calibrated submanifolds. Finally, we apply our results to show that one of the compact G_2-manifolds constructed by Joyce by desingularisation of a flat orbifold T^7/\Gamma can be deformed to one of the compact G_2-manifolds obtainable as a generalized connected sum of two exponentially asymptotically cylindrical SU(3)-manifolds via the method given by the first author (math.DG/0012189).Comment: 36 pages; v2: corrected trivial typos; v3: some arguments corrected and improved; v4: a number of improvements on presentation, paritularly in sections 4 and 6, including an added picture

Super Calabi-Yau's and Special Lagrangians

We apply mirror symmetry to the super Calabi-Yau manifold CP^{(n|n+1)} and show that the mirror can be recast in a form which depends only on the superdimension and which is reminiscent of a generalized conifold. We discuss its geometrical properties in comparison to the familiar conifold geometry. In the second part of the paper examples of special-Lagrangian submanifolds are constructed for a class of super Calabi-Yau's. We finally comment on their infinitesimal deformations.Comment: 20 pages, no figures, latex; v2: references added; v3: minor clarifications added, version published in JHE

Type IIA Orientifold Limit of M-Theory on Compact Joyce 8-Manifold of Spin(7)-Holonomy

We show that M-theory compactified on a compact Joyce 8-manifold of $Spin(7)$-holonomy, which yields an effective theory in $D = 3$ with $\N$ = 1 supersymmetry, admits at some special points in it moduli space a description in terms of type IIA theory on an orientifold of compact Joyce 7-manifold of $G_2$-holonomy. We find the evidence in favour of this duality by computing the massless spectra on both M-thory side and type IIA side. For the latter, we compute the massless spectra by going to the orbifold limit of the Joyce 7-manifold.Comment: 26 pages, 2 eps figures, Latex file, two references and one footnote added, corrected some typo

Chirality Change in String Theory

It is known that string theory compactifications leading to low energy effective theories with different chiral matter content ({\it e.g.} different numbers of standard model generations) are connected through phase transitions, described by non-trivial quantum fixed point theories. We point out that such compactifications are also connected on a purely classical level, through transitions that can be described using standard effective field theory. We illustrate this with examples, including some in which the transition proceeds entirely through supersymmetric configurations.Comment: 50 pages, 2 figure

D6-branes and torsion

The D6-brane spectrum of type IIA vacua based on twisted tori and RR background fluxes is analyzed. In particular, we compute the torsion factors of the (co)homology groups H_n and describe the effect that they have on D6-brane physics. For instance, the fact that H_3 contains Z_N subgroups explains why RR tadpole conditions are affected by geometric fluxes. In addition, the presence of torsional (co)homology shows why some D6-brane moduli are lifted, and it suggests how the D-brane discretum appears in type IIA flux compactifications. Finally, we give a clear, geometrical understanding of the Freed-Witten anomaly in the present type IIA setup, and discuss its consequences for the construction of semi-realistic flux vacua.Comment: 35 pages, 1 figure. One reference adde

On moduli and effective theory of N=1 warped flux compactifications

The moduli space of N=1 type II warped compactions to flat space with generic internal fluxes is studied. Using the underlying integrable generalized complex structure that characterizes these vacua, the different deformations are classified by H-twisted generalized cohomologies and identified with chiral and linear multiplets of the effective four-dimensional theory. The Kaehler potential for chiral fields corresponding to classically flat moduli is discussed. As an application of the general results, type IIB warped Calabi-Yau compactifications and other SU(3)-structure subcases are considered in more detail.Comment: 54 pages; v3: comments and references added, version published in JHE

Deformations of calibrated D-branes in flux generalized complex manifolds

We study massless deformations of generalized calibrated cycles, which describe, in the language of generalized complex geometry, supersymmetric D-branes in N=1 supersymmetric compactifications with fluxes. We find that the deformations are classified by the first cohomology group of a Lie algebroid canonically associated to the generalized calibrated cycle, seen as a generalized complex submanifold with respect to the integrable generalized complex structure of the bulk. We provide examples in the SU(3) structure case and in a `genuine' generalized complex structure case. We discuss cases of lifting of massless modes due to world-volume fluxes, background fluxes and a generalized complex structure that changes type.Comment: 52 pages, added references, added comment on ellipticity in appendix B, made minor changes according to instructions referee JHE

An investigation of the clinical impact and therapeutic relevance of a DNA damage immune response (DDIR) signature in patients with advanced gastroesophageal adenocarcinoma

Background: An improved understanding of which gastroesophageal adenocarcinoma (GOA) patients respond to both chemotherapy and immune checkpoint inhibitors (ICI) is needed. We investigated the predictive role and underlying biology of a 44-gene DNA damage immune response (DDIR) signature in patients with advanced GOA. Materials and methods: Transcriptional profiling was carried out on pretreatment tissue from 252 GOA patients treated with platinum-based chemotherapy (three dose levels) within the randomized phase III GO2 trial. Cross-validation was carried out in two independent GOA cohorts with transcriptional profiling, immune cell immunohistochemistry and epidermal growth factor receptor (EGFR) fluorescent in situ hybridization (FISH) (n = 430). Results: In the GO2 trial, DDIR-positive tumours had a greater radiological response (51.7% versus 28.5%, P = 0.022) and improved overall survival in a dose-dependent manner (P = 0.028). DDIR positivity was associated with a pretreatment inflamed tumour microenvironment (TME) and increased expression of biomarkers associated with ICI response such as CD274 (programmed death-ligand 1, PD-L1) and a microsatellite instability RNA signature. Consensus pathway analysis identified EGFR as a potential key determinant of the DDIR signature. EGFR amplification was associated with DDIR negativity and an immune cold TME. Conclusions: Our results indicate the importance of the GOA TME in chemotherapy response, its relationship to DNA damage repair and EGFR as a targetable driver of an immune cold TME. Chemotherapy-sensitive inflamed GOAs could benefit from ICI delivered in combination with standard chemotherapy. Combining EGFR inhibitors and ICIs warrants further investigation in patients with EGFR-amplified tumours

An investigation of the clinical impact and therapeutic relevance of a DNA damage immune response (DDIR) signature in patients with advanced gastroesophageal adenocarcinoma

BackgroundAn improved understanding of which gastroesophageal adenocarcinoma (GOA) patients respond to both chemotherapy and immune checkpoint inhibitors (ICI) is needed. We investigated the predictive role and underlying biology of a 44-gene DNA damage immune response (DDIR) signature in patients with advanced GOA.Materials and methodsTranscriptional profiling was carried out on pretreatment tissue from 252 GOA patients treated with platinum-based chemotherapy (three dose levels) within the randomized phase III GO2 trial. Cross-validation was carried out in two independent GOA cohorts with transcriptional profiling, immune cell immunohistochemistry and epidermal growth factor receptor (EGFR) fluorescent in situ hybridization (FISH) (n = 430).ResultsIn the GO2 trial, DDIR-positive tumours had a greater radiological response (51.7% versus 28.5%, P = 0.022) and improved overall survival in a dose-dependent manner (P = 0.028). DDIR positivity was associated with a pretreatment inflamed tumour microenvironment (TME) and increased expression of biomarkers associated with ICI response such as CD274 (programmed death-ligand 1, PD-L1) and a microsatellite instability RNA signature. Consensus pathway analysis identified EGFR as a potential key determinant of the DDIR signature. EGFR amplification was associated with DDIR negativity and an immune cold TME.ConclusionsOur results indicate the importance of the GOA TME in chemotherapy response, its relationship to DNA damage repair and EGFR as a targetable driver of an immune cold TME. Chemotherapy-sensitive inflamed GOAs could benefit from ICI delivered in combination with standard chemotherapy. Combining EGFR inhibitors and ICIs warrants further investigation in patients with EGFR-amplified tumours