The impact of chromosomal translocation locus and fusion oncogene coding sequence in synovial sarcomagenesis.

Synovial sarcomas are aggressive soft-tissue malignancies that express chromosomal translocation-generated fusion genes, SS18-SSX1 or SS18-SSX2 in most cases. Here, we report a mouse sarcoma model expressing SS18-SSX1, complementing our prior model expressing SS18-SSX2. Exome sequencing identified no recurrent secondary mutations in tumors of either genotype. Most of the few mutations identified in single tumors were present in genes that were minimally or not expressed in any of the tumors. Chromosome 6, either entirely or around the fusion gene expression locus, demonstrated a copy number gain in a majority of tumors of both genotypes. Thus, by fusion oncogene coding sequence alone, SS18-SSX1 and SS18-SSX2 can each drive comparable synovial sarcomagenesis, independent from other genetic drivers. SS18-SSX1 and SS18-SSX2 tumor transcriptomes demonstrated very few consistent differences overall. In direct tumorigenesis comparisons, SS18-SSX2 was slightly more sarcomagenic than SS18-SSX1, but equivalent in its generation of biphasic histologic features. Meta-analysis of human synovial sarcoma patient series identified two tumor-gentoype-phenotype correlations that were not modeled by the mice, namely a scarcity of male hosts and biphasic histologic features among SS18-SSX2 tumors. Re-analysis of human SS18-SSX1 and SS18-SSX2 tumor transcriptomes demonstrated very few consistent differences, but highlighted increased native SSX2 expression in SS18-SSX1 tumors. This suggests that the translocated locus may drive genotype-phenotype differences more than the coding sequence of the fusion gene created. Two possible roles for native SSX2 in synovial sarcomagenesis are explored. Thus, even specific partial failures of mouse genetic modeling can be instructive to human tumor biology

Brane Localization and Stabilization via Regional Physics

Extra-dimensional scenarios have become widespread among particle and gravitational theories of physics to address several outstanding problems, including cosmic acceleration, the weak hierarchy problem, and the quantization of gravity. In general, the topology and geometry of the full spacetime manifold will be non-trivial, even if our ordinary dimensions have the topology of their covering space. Most compact manifolds are inhomogeneous, even if they admit a homogeneous geometry, and it will be physically relevant where in the extra-dimensions one is located. In this letter, we explore the use of both local and global effects in a braneworld scenario to naturally provide position-dependent forces that determine and stabilize the location of a single brane. For illustrative purposes, we consider the 2-dimensional hyperbolic horn and the Euclidean cone as toy models of the extra-dimensional manifold, and add a brane wrapped around one of the two spatial dimensions. We calculate the total energy due to brane tension and bending (extrinsic curvature) as well as that due to the Casimir energy of a bulk scalar satisfying a Dirchlet boundary condition on the brane. From the competition of at least two of these effects there can exist a stable minimum of the effective potential for the brane location. However, on more generic spaces (on which more symmetries are broken) any one of these effects may be sufficient to stabilize the brane. We discuss this as an example of physics that is neither local nor global, but regional.Comment: 4 pages, 2 figures. PRL submitte

Exotic Differentiable Structures and General Relativity

We review recent developments in differential topology with special concern for their possible significance to physical theories, especially general relativity. In particular we are concerned here with the discovery of the existence of non-standard (``fake'' or ``exotic'') differentiable structures on topologically simple manifolds such as $S^7$, \R and $S^3\times {\bf R^1}.$ Because of the technical difficulties involved in the smooth case, we begin with an easily understood toy example looking at the role which the choice of complex structures plays in the formulation of two-dimensional vacuum electrostatics. We then briefly review the mathematical formalisms involved with differentiable structures on topological manifolds, diffeomorphisms and their significance for physics. We summarize the important work of Milnor, Freedman, Donaldson, and others in developing exotic differentiable structures on well known topological manifolds. Finally, we discuss some of the geometric implications of these results and propose some conjectures on possible physical implications of these new manifolds which have never before been considered as physical models.Comment: 11 pages, LaTe

Constraints on Non-Newtonian Gravity from Recent Casimir Force Measurements

Corrections to Newton's gravitational law inspired by extra dimensional physics and by the exchange of light and massless elementary particles between the atoms of two macrobodies are considered. These corrections can be described by the potentials of Yukawa-type and by the power-type potentials with different powers. The strongest up to date constraints on the corrections to Newton's gravitational law are reviewed following from the E\"{o}tvos- and Cavendish-type experiments and from the measurements of the Casimir and van der Waals force. We show that the recent measurements of the Casimir force gave the possibility to strengthen the previously known constraints on the constants of hypothetical interactions up to several thousand times in a wide interaction range. Further strengthening is expected in near future that makes Casimir force measurements a prospective test for the predictions of fundamental physical theories.Comment: 20 pages, crckbked.cls is used, to be published in: Proceedings of the 18th Course of the School on Cosmology and Gravitation: The Gravitational Constant. Generalized Gravitational Theories and Experiments (30 April- 10 May 2003, Erice). Ed. by G. T. Gillies, V. N. Melnikov and V. de Sabbata, 20pp. (Kluwer, in print, 2003

Top Quarks as a Window to String Resonances

We study the discovery potential of string resonances decaying to $t\bar{t}$ final state at the LHC. We point out that top quark pair production is a promising and an advantageous channel for studying such resonances, due to their low Standard Model background and unique kinematics. We study the invariant mass distribution and angular dependence of the top pair production cross section via exchanges of string resonances. The mass ratios of these resonances and the unusual angular distribution may help identify their fundamental properties and distinguish them from other new physics. We find that string resonances for a string scale below 4 TeV can be detected via the $t\bar{t}$ channel, either from reconstructing the $t\bar{t}$ semi-leptonic decay or recent techniques in identifying highly boosted tops.Comment: 22 pages, 6 figure

Bulk Axions, Brane Back-reaction and Fluxes

Extra-dimensional models can involve bulk pseudo-Goldstone bosons (pGBs) whose shift symmetry is explicitly broken only by physics localized on branes. Reliable calculation of their low-energy potential is often difficult because it requires details of the stabilization of the extra dimensions. In rugby ball solutions, for which two compact extra dimensions are stabilized in the presence of only positive-tension brane sources, the effects of brane back-reaction can be computed explicitly. This allows the calculation of the shape of the low-energy pGB potential and response of the extra dimensional geometry as a function of the perturbing brane properties. If the pGB-dependence is a small part of the total brane tension a very general analysis is possible, permitting an exploration of how the system responds to frustration when the two branes disagree on what the proper scalar vacuum should be. We show how the low-energy potential is given by the sum of brane tensions (in agreement with common lore) when only the brane tensions couple to the pGB. We also show how a direct brane coupling to the flux stabilizing the extra dimensions corrects this result in a way that does not simply amount to the contribution of the flux to the brane tensions. We calculate the mass of the would-be zero mode, and briefly describe several potential applications, including a brane realization of `natural inflation,' and a dynamical mechanism for suppressing the couplings of the pGB to matter localized on the branes. Since the scalar can be light enough to be relevant to precision tests of gravity (in a technically natural way) this mechanism can be relevant to evading phenomenological bounds.Comment: 36 pages, JHEP styl

Soft branes in supersymmetry-breaking backgrounds

We revisit the analysis of effective field theories resulting from non-supersymmetric perturbations to supersymmetric flux compactifications of the type-IIB superstring with an eye towards those resulting from the backreaction of a small number of anti-D3-branes. Independently of the background, we show that the low-energy Lagrangian describing the fluctuations of a stack of probe D3-branes exhibits soft supersymmetry breaking, despite perturbations to marginal operators that were not fully considered in some previous treatments. We take this as an indication that the breaking of supersymmetry by anti-D3-branes or other sources may be spontaneous rather than explicit. In support of this, we consider the action of an anti-D3-brane probing an otherwise supersymmetric configuration and identify a candidate for the corresponding goldstino.Comment: 36+5 pages. References added, minor typos correcte

Happiness matters : exploring the linkages between personality, personal happiness, and work-related psychological health among priests and sisters in Italy

This study responds to the challenge posed by Rossetti’s work to explore the antecedents and consequences of individual differences in happiness among priests and religious sisters. The Oxford Happiness Questionnaire was completed together with measures of personality and work-related psychological health by 95 priests and 61 religious sisters. Overall the data demonstrated high levels of personal happiness among priests and religious sisters, but also significant signs of vulnerability. Personality provided significant prediction of individual differences in both personal happiness and work-related psychological health. However, personal happiness provided additional protection against work-related emotional exhaustion and additional enhancement of work-related satisfaction. These findings suggest that acknowledging and affirming personal happiness may enhance the work-related psychological health of Catholic priests and religious sisters

On Supersymmetric D7-branes in the Warped Deformed Conifold

We study the supersymmetric properties of D7-branes in the warped deformed conifold. We consider the $\kappa$-symmetry conditions on D7-branes in this specific warped background, taking into account the background NS-NS 2-form flux. While any holomorphic embedding defines a supersymmetric D7-brane in the absence of background H-flux, most of the D7-brane embeddings considered in the literature do not preserve supersymmetry for the warped deformed conifold without also including brane worldvolume flux. For the simplest such embedding, we construct numerically the worldvolume fluxnecessary to restore supersymmetry. We also comment on the dual field theory descriptions in terms of cascading N=1 supersymmetric gauge theories with flavors. Finally, we discuss some possible applications of our results to moduli stabilization and vacuum energy uplifting, gauge/gravity duality, and string inflationary model building.Comment: 37 pages, 2 figures, v3:many clarifications and improvements to susy restoring flu

The Role of Individual Variables, Organizational Variables and Moral Intensity Dimensions in Libyan Management Accountants’ Ethical Decision Making

This study investigates the association of a broad set of variables with the ethical decision making of management accountants in Libya. Adopting a cross-sectional methodology, a questionnaire including four different ethical scenarios was used to gather data from 229 participants. For each scenario, ethical decision making was examined in terms of the recognition, judgment and intention stages of Rest’s model. A significant relationship was found between ethical recognition and ethical judgment and also between ethical judgment and ethical intention, but ethical recognition did not significantly predict ethical intention—thus providing support for Rest’s model. Organizational variables, age and educational level yielded few significant results. The lack of significance for codes of ethics might reflect their relative lack of development in Libya, in which case Libyan companies should pay attention to their content and how they are supported, especially in the light of the under-development of the accounting profession in Libya. Few significant results were also found for gender, but where they were found, males showed more ethical characteristics than females. This unusual result reinforces the dangers of gender stereotyping in business. Personal moral philosophy and moral intensity dimensions were generally found to be significant predictors of the three stages of ethical decision making studied. One implication of this is to give more attention to ethics in accounting education, making the connections between accounting practice and (in Libya) Islam. Overall, this study not only adds to the available empirical evidence on factors affecting ethical decision making, notably examining three stages of Rest’s model, but also offers rare insights into the ethical views of practising management accountants and provides a benchmark for future studies of ethical decision making in Muslim majority countries and other parts of the developing world