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

Rms-flux relation in the optical fast variability data of BL Lacertae object S5 0716+714

The possibility that BL Lac S5 0716+714 exhibits a linear root mean square (rms)-flux relation in its IntraDay Variability (IDV) is analysed. The results may be used as an argument in the existing debate regarding the source of optical IDV in Active Galactic Nuclei. 63 time series in different optical bands were used. A linear rms-flux relation at a confidence level higher than 65% was recovered for less than 8% of the cases. We were able to check if the magnitude is log-normally distributed for eight timeseries and found, with a confidence > 95%, that this is not the case.Comment: Accepted by Astrophysics and Space Scienc

Towards mirror symmetry \`a la SYZ for generalized Calabi-Yau manifolds

Fibrations of flux backgrounds by supersymmetric cycles are investigated. For an internal six-manifold M with static SU(2) structure and mirror \hat{M}, it is argued that the product M x \hat{M} is doubly fibered by supersymmetric three-tori, with both sets of fibers transverse to M and \hat{M}. The mirror map is then realized by T-dualizing the fibers. Mirror-symmetric properties of the fluxes, both geometric and non-geometric, are shown to agree with previous conjectures based on the requirement of mirror symmetry for Killing prepotentials. The fibers are conjectured to be destabilized by fluxes on generic SU(3)xSU(3) backgrounds, though they may survive at type-jumping points. T-dualizing the surviving fibers ensures the exchange of pure spinors under mirror symmetry.Comment: 30 pages, 3 figures, LaTeX; v2: references adde

Holographic dual of the Standard Model on the throat

We apply recent techniques to construct geometries, based on local Calabi-Yau manifolds, leading to warped throats with 3-form fluxes in string theory, with interesting structure at their bottom. We provide their holographic dual description in terms of RG flows for gauge theories with almost conformal duality cascades and infrared confinement. We describe a model of a throat with D-branes at its bottom, realizing a 3-family Standard Model like chiral sector. We provide the explicit holographic dual gauge theory RG flow, and describe the appearance of the SM degrees of freedom after confinement. As a second application, we describe throats within throats, namely warped throats with discontinuous warp factor in different regions of the radial coordinate, and discuss possible model building applications.Comment: 46 pages, 21 figures, reference adde

Mutations of the BRAF gene in human cancer

Cancers arise owing to the accumulation of mutations in critical genes that alter normal programmes of cell proliferation, differentiation and death. As the first stage of a systematic genome-wide screen for these genes, we have prioritized for analysis signalling pathways in which at least one gene is mutated in human cancer. The RAS RAF MEK ERK MAP kinase pathway mediates cellular responses to growth signals. RAS is mutated to an oncogenic form in about 15% of human cancer. The three RAF genes code for cytoplasmic serine/threonine kinases that are regulated by binding RAS. Here we report BRAF somatic missense mutations in 66% of malignant melanomas and at lower frequency in a wide range of human cancers. All mutations are within the kinase domain, with a single substitution (V599E) accounting for 80%. Mutated BRAF proteins have elevated kinase activity and are transforming in NIH3T3 cells. Furthermore, RAS function is not required for the growth of cancer cell lines with the V599E mutation. As BRAF is a serine/threonine kinase that is commonly activated by somatic point mutation in human cancer, it may provide new therapeutic opportunities in malignant melanoma

Yersinia effectors target mammalian signalling pathways

Animals have an immune system to fight off challenges from both viruses and bacteria. The first line of defence is innate immunity, which is composed of cells that engulf pathogens as well as cells that release potent signalling molecules to activate an inflammatory response and the adaptive immune system. Pathogenic bacteria have evolved a set of weapons, or effectors, to ensure survival in the host. Yersinia spp. use a type III secretion system to translocate these effector proteins, called Yops, into the host. This report outlines how Yops thwart the signalling machinery of the host immune system.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73466/1/j.1462-5822.2002.00182.x.pd

A mission control architecture for robotic lunar sample return as field tested in an analogue deployment to the Sudbury impact structure

A Mission Control Architecture is presented for a Robotic Lunar Sample Return Mission which builds upon the experience of the landed missions of the NASA Mars Exploration Program. This architecture consists of four separate processes working in parallel at Mission Control and achieving buy-in for plans sequentially instead of simultaneously from all members of the team. These four processes were: Science Processing, Science Interpretation, Planning and Mission Evaluation. Science Processing was responsible for creating products from data downlinked from the field and is organized by instrument. Science Interpretation was responsible for determining whether or not science goals are being met and what measurements need to be taken to satisfy these goals. The Planning process, responsible for scheduling and sequencing observations, and the Evaluation process that fostered inter-process communications, reporting and documentation assisted these processes. This organization is advantageous for its flexibility as shown by the ability of the structure to produce plans for the rover every two hours, for the rapidity with which Mission Control team members may be trained and for the relatively small size of each individual team. This architecture was tested in an analogue mission to the Sudbury impact structure from June 6-17, 2011. A rover was used which was capable of developing a network of locations that could be revisited using a teach and repeat method. This allowed the science team to process several different outcrops in parallel, downselecting at each stage to ensure that the samples selected for caching were the most representative of the site. Over the course of 10 days, 18 rock samples were collected from 5 different outcrops, 182 individual field activities - such as roving or acquiring an image mosaic or other data product - were completed within 43 command cycles, and the rover travelled over 2,200 m. Data transfer from communications passes were filled to 74%. Sample triage was simulated to allow down-selection to 1kg of material for return to Earth

Mutational processes molding the genomes of 21 breast cancers

All cancers carry somatic mutations. The patterns of mutation in cancer genomes reflect the DNA damage and repair processes to which cancer cells and their precursors have been exposed. To explore these mechanisms further, we generated catalogs of somatic mutation from 21 breast cancers and applied mathematical methods to extract mutational signatures of the underlying processes. Multiple distinct single- and double-nucleotide substitution signatures were discernible. Cancers with BRCA1 or BRCA2 mutations exhibited a characteristic combination of substitution mutation signatures and a distinctive profile of deletions. Complex relationships between somatic mutation prevalence and transcription were detected. A remarkable phenomenon of localized hypermutation, termed "kataegis," was observed. Regions of kataegis differed between cancers but usually colocalized with somatic rearrangements. Base substitutions in these regions were almost exclusively of cytosine at TpC dinucleotides. The mechanisms underlying most of these mutational signatures are unknown. However, a role for the APOBEC family of cytidine deaminases is proposed