153 research outputs found
Central Exclusive Scalar Luminosities from the Linked Dipole Chain Model gluon densities
We investigate the implication of uncertainties in the unintegrated gluon
distribution for the predictions for central exclusive production of scalars at
hadron colliders. We use parameterizations of the kT-unintegrated gluon density
obtained from the Linked Dipole Chain model, applying different options for the
treatment of non-leading terms. We find that the luminosity function for
central exclusive production is very sensitive to details of the transverse
momentum distribution of the gluon which, contrary to the kT-integrated
distribution, is not very well constrained experimentally
On the renormalization of multiparton webs
We consider the recently developed diagrammatic approach to soft-gluon
exponentiation in multiparton scattering amplitudes, where the exponent is
written as a sum of webs - closed sets of diagrams whose colour and kinematic
parts are entangled via mixing matrices. A complementary approach to
exponentiation is based on the multiplicative renormalizability of intersecting
Wilson lines, and their subsequent finite anomalous dimension. Relating this
framework to that of webs, we derive renormalization constraints expressing all
multiple poles of any given web in terms of lower-order webs. We examine these
constraints explicitly up to four loops, and find that they are realised
through the action of the web mixing matrices in conjunction with the fact that
multiple pole terms in each diagram reduce to sums of products of lower-loop
integrals. Relevant singularities of multi-eikonal amplitudes up to three loops
are calculated in dimensional regularization using an exponential infrared
regulator. Finally, we formulate a new conjecture for web mixing matrices,
involving a weighted sum over column entries. Our results form an important
step in understanding non-Abelian exponentiation in multiparton amplitudes, and
pave the way for higher-loop computations of the soft anomalous dimension.Comment: 60 pages, 15 figure
Mini Black Holes in the first year of the LHC
The experimental signatures of TeV-mass black hole (BH) formation in heavy
ion collisions at the LHC is examined. We find that the black hole production
results in a complete disappearance of all very high ({} GeV)
back-to-back correlated di-jets of total mass {}TeV. We show
that the subsequent Hawking-decay produces multiple hard mono-jets and discuss
their detection. We study the possibility of cold black hole remnant (BHR)
formation of mass and the experimental distinguishability of
scenarios with BHRs and those with complete black hole decay. Due to the rather
moderate luminosity in the first year of LHC running the least chance for the
observation of BHs or BHRs at this early stage will be by ionizing tracks in
the ALICE TPC. Finally we point out that stable BHRs would be interesting
candidates for energy production by conversion of mass to Hawking radiation.Comment: 10 pages, 2 figure
Factorization constraints for soft anomalous dimensions in QCD scattering amplitudes
We study the factorization of soft and collinear singularities in
dimensionally-regularized fixed-angle scattering amplitudes in massless gauge
theories. Our factorization is based on replacing the hard massless partons by
light-like Wilson lines, and defining gauge-invariant jet and soft functions in
dimensional regularization. In this scheme the factorized amplitude admits a
powerful symmetry: it is invariant under rescaling of individual Wilson-line
velocities. This symmetry is broken by cusp singularities in both the soft and
the eikonal jet functions. We show that the cancellation of these cusp
anomalies in any multi-leg amplitude imposes all-order constraints on the
kinematic dependence of the corresponding soft anomalous dimension, relating it
to the cusp anomalous dimension. For amplitudes with two or three hard partons
the solution is unique: the constraints fully determine the kinematic
dependence of the soft function. For amplitudes with four or more hard partons
we present a minimal solution where the soft anomalous dimension is a sum over
colour dipoles, multiplied by the cusp anomalous dimension. In this case
additional contributions to the soft anomalous dimension at three loops or
beyond are not excluded, but they are constrained to be functions of conformal
cross ratios of kinematic variables.Comment: v1: 35 pages, v2: minor changes - some clarifying remarks and
references added. Journal version (to appear in JHEP
Integrated Genomic and Gene Expression Profiling Identifies Two Major Genomic Circuits in Urothelial Carcinoma
Similar to other malignancies, urothelial carcinoma (UC) is characterized by specific recurrent chromosomal aberrations and gene mutations. However, the interconnection between specific genomic alterations, and how patterns of chromosomal alterations adhere to different molecular subgroups of UC, is less clear. We applied tiling resolution array CGH to 146 cases of UC and identified a number of regions harboring recurrent focal genomic amplifications and deletions. Several potential oncogenes were included in the amplified regions, including known oncogenes like E2F3, CCND1, and CCNE1, as well as new candidate genes, such as SETDB1 (1q21), and BCL2L1 (20q11). We next combined genome profiling with global gene expression, gene mutation, and protein expression data and identified two major genomic circuits operating in urothelial carcinoma. The first circuit was characterized by FGFR3 alterations, overexpression of CCND1, and 9q and CDKN2A deletions. The second circuit was defined by E3F3 amplifications and RB1 deletions, as well as gains of 5p, deletions at PTEN and 2q36, 16q, 20q, and elevated CDKN2A levels. TP53/MDM2 alterations were common for advanced tumors within the two circuits. Our data also suggest a possible RAS/RAF circuit. The tumors with worst prognosis showed a gene expression profile that indicated a keratinized phenotype. Taken together, our integrative approach revealed at least two separate networks of genomic alterations linked to the molecular diversity seen in UC, and that these circuits may reflect distinct pathways of tumor development
Endoplasmic reticulum stress and cell death in mTORC1-overactive cells is induced by nelfinavir and enhanced by chloroquine
Inappropriate activation of mammalian/mechanistic target of rapamycin complex 1 (mTORC1) is common in cancer and has many cellular consequences including elevated endoplasmic reticulum (ER) stress. Cells employ autophagy as a critical compensatory survival mechanism during ER stress. This study utilised drug-induced ER stress through nelfinavir in order to examine ER stress tolerance in cell lines with hyper-active mTORC1 signalling. Our initial findings in wild type cells showed nelfinavir inhibited mTORC1 signalling and upregulated autophagy, as determined by decreased rpS6 and S6K1 phosphorylation, and SQTSM1 protein expression, respectively. Contrastingly, cells with hyper-active mTORC1 displayed basally elevated levels of ER stress which was greatly exaggerated following nelfinavir treatment, seen through increased CHOP mRNA and XBP1 splicing. To further enhance the effects of nelfinavir, we introduced chloroquine as an autophagy inhibitor. Combination of nelfinavir and chloroquine significantly increased ER stress and caused selective cell death in multiple cell line models with hyper-active mTORC1, whilst control cells with normalised mTORC1 signalling tolerated treatment. By comparing chloroquine to other autophagy inhibitors, we uncovered that selective toxicity invoked by chloroquine was independent of autophagy inhibition yet entrapment of chloroquine to acidified lysosomal/endosomal compartments was necessary for cytotoxicity. Our research demonstrates that combination of nelfinavir and chloroquine has therapeutic potential for treatment of mTORC1-driven tumours
Transfemoral amputee recovery strategies following trips to their sound and prosthesis sides throughout swing phase
PIK3CA dependence and sensitivity to therapeutic targeting in urothelial carcinoma
Background
Many urothelial carcinomas (UC) contain activating PIK3CA mutations. In telomerase-immortalized normal urothelial cells (TERT-NHUC), ectopic expression of mutant PIK3CA induces PI3K pathway activation, cell proliferation and cell migration. However, it is not clear whether advanced UC tumors are PIK3CA-dependent and whether PI3K pathway inhibition is a good therapeutic option in such cases.
Methods
We used retrovirus-mediated delivery of shRNA to knock down mutant PIK3CA in UC cell lines and assessed effects on pathway activation, cell proliferation, migration and tumorigenicity. The effect of the class I PI3K inhibitor GDC-0941 was assessed in a panel of UC cell lines with a range of known molecular alterations in the PI3K pathway.
Results
Specific knockdown of PIK3CA inhibited proliferation, migration, anchorage-independent growth and in vivo tumor growth of cells with PIK3CA mutations. Sensitivity to GDC-0941 was dependent on hotspot PIK3CA mutation status. Cells with rare PIK3CA mutations and co-occurring TSC1 or PTEN mutations were less sensitive. Furthermore, downstream PI3K pathway alterations in TSC1 or PTEN or co-occurring AKT1 and RAS gene mutations were associated with GDC-0941 resistance.
Conclusions
Mutant PIK3CA is a potent oncogenic driver in many UC cell lines and may represent a valuable therapeutic target in advanced bladder cancer
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