The mRNA expression of SETD2 in human breast cancer: Correlation with clinico-athological parameters

BACKGROUND: SET domain containing protein 2 (SETD2) is a histone methyltransferase that is involved in transcriptional elongation. There is evidence that SETD2 interacts with p53 and selectively regulates its downstream genes. Therefore, it could be implicated in the process of carcinogenesis. Furthermore, this gene is located on the short arm of chromosome 3p and we previously demonstrated that the 3p21.31 region of chromosome 3 was associated with permanent growth arrest of breast cancer cells. This region includes closely related genes namely: MYL3, CCDC12, KIF9, KLHL18 and SETD2. Based on the biological function of these genes, SETD2 is the most likely gene to play a tumour suppressor role and explain our previous findings. Our objective was to determine, using quantitative PCR, whether the mRNA expression levels of SETD2 were consistent with a tumour suppressive function in breast cancer. This is the first study in the literature to examine the direct relationship between SETD2 and breast cancer. METHODS: A total of 153 samples were analysed. The levels of transcription of SETD2 were determined using quantitative PCR and normalized against (CK19). Transcript levels within breast cancer specimens were compared to normal background tissues and analyzed against conventional pathological parameters and clinical outcome over a 10 year follow-up period. RESULTS: The levels of SETD2 mRNA were significantly lower in malignant samples (p = 0.0345) and decreased with increasing tumour stage. SETD2 expression levels were significantly lower in samples from patients who developed metastasis, local recurrence, or died of breast cancer when compared to those who were disease free for > 10 years (p = 0.041). CONCLUSION: This study demonstrates a compelling trend for SETD2 transcription levels to be lower in cancerous tissues and in patients who developed progressive disease. These findings are consistent with a possible tumour suppressor function of this gene in breast cancer

Supersymmetry in the shadow of photini

Additional neutral gauge fermions -- "photini" -- arise in string compactifications as superpartners of U(1) gauge fields. Unlike their vector counterparts, the photini can acquire weak-scale masses from soft SUSY breaking and lead to observable signatures at the LHC through mass mixing with the bino. In this work we investigate the collider consequences of adding photini to the neutralino sector of the MSSM. Relatively large mixing of one or more photini with the bino can lead to prompt decays of the lightest ordinary supersymmetric particle; these extra cascades transfer most of the energy of SUSY decay chains into Standard Model particles, diminishing the power of missing energy as an experimental handle for signal discrimination. We demonstrate that the missing energy in SUSY events with photini is reduced dramatically for supersymmetric spectra with MSSM neutralinos near the weak scale, and study the effects on limits set by the leading hadronic SUSY searches at ATLAS and CMS. We find that in the presence of even one light photino the limits on squark masses from hadronic searches can be reduced by 400 GeV, with comparable (though more modest) reduction of gluino mass limits. We also consider potential discovery channels such as dilepton and multilepton searches, which remain sensitive to SUSY spectra with photini and can provide an unexpected route to the discovery of supersymmetry. Although presented in the context of photini, our results apply in general to theories in which additional light neutral fermions mix with MSSM gauginos.Comment: 23 pages, 8 figures, references adde

The ZZ' kinetic mixing in the light of the recent direct and indirect dark matter searches

Several constructions, of stringy origins or not, generate abelian gauge extensions of the Standard Model (SM). Even if the particles of the SM are not charged under this extra $U'(1)$, one cannot avoid the presence of a kinetic mixing between $U'(1)$ and the hypercharge $U_Y(1)$. In this work, we constraint drastically this kinetic mixing, taking into account the recent experimental data from accelerator physics, direct detection and indirect detection of dark matter. We show that the region respecting WMAP and experimental constraints is now very narrowed along the pole line where $M_{Z_D}\simeq 2 m_{DM}$, $Z_D$ being the gauge boson associated to the extra $U'(1)$.Comment: 9 pages, 3 figures, final version to appear in JCA

The kinetic dark-mixing in the light of CoGENT and XENON100

Several string or GUT constructions motivate the existence of a dark U(1)_D gauge boson which interacts with the Standard Model only through its kinetic mixing. We compute the dark matter abundance in such scenario and the constraints in the light of the recent data from CoGENT, CDMSII and XENON100. We show in particular that a region with relatively light WIMPS, M_{Z_D}< 40 GeV and a kinetic mixing 10^-4 < delta < 10^-3 is not yet excluded by the last experimental data and seems to give promising signals in a near future. We also compute the value of the kinetic mixing needed to explain the DAMA/CoGENT/CRESST excesses and find that for M_{Z_D}< 30 GeV, delta ~ 10^-3 is sufficient to fit with the data.Comment: 6 pages, 5figure

Complementarity of Galactic radio and collider data in constraining WIMP dark matter models

In this work we confront dark matter models to constraints that may be derived from radio synchrotron radiation from the Galaxy, taking into account the astrophysical uncertainties and we compare these to bounds set by accelerator and complementary indirect dark matter searches. Specifically we apply our analysis to three popular particle physics models. First, a generic effective operator approach, in which case we set bounds on the corresponding mass scale, and then, two specific UV completions, the Z' and Higgs portals. We show that for many candidates, the radio synchrotron limits are competitive with the other searches, and could even give the strongest constraints (as of today) with some reasonable assumptions regarding the astrophysical uncertainties.Comment: 22 pages, 12 figure

Low-Energy Signals from Kinetic Mixing with a Warped Abelian Hidden Sector

We investigate the detailed phenomenology of a light Abelian hidden sector in the Randall-Sundrum framework. Relative to other works with light hidden sectors, the main new feature is a tower of hidden Kaluza-Klein vectors that kinetically mix with the Standard Model photon and Z. We investigate the decay properties of the hidden sector fields in some detail, and develop an approach for calculating processes initiated on the ultraviolet brane of a warped space with large injection momentum relative to the infrared scale. Using these results, we determine the detailed bounds on the light warped hidden sector from precision electroweak measurements and low-energy experiments. We find viable regions of parameter space that lead to significant production rates for several of the hidden Kaluza-Klein vectors in meson factories and fixed-target experiments. This offers the possibility of exploring the structure of an extra spacetime dimension with lower-energy probes.Comment: (1+32) Pages, 13 Figures. v2: JHEP version (minor modifications, results unchanged

Massive Abelian Gauge Symmetries and Fluxes in F-theory

F-theory compactified on a Calabi-Yau fourfold naturally describes non-Abelian gauge symmetries through the singularity structure of the elliptic fibration. In contrast Abelian symmetries are more difficult to study because of their inherently global nature. We argue that in general F-theory compactifications there are massive Abelian symmetries, such as the uplift of the Abelian part of the U(N) gauge group on D7-branes, that arise from non-Kahler resolutions of the dual M-theory setup. The four-dimensional F-theory vacuum with vanishing expectation values for the gauge fields corresponds to the Calabi-Yau limit. We propose that fluxes that are turned on along these U(1)s are uplifted to non-harmonic four-form fluxes. We derive the effective four-dimensional gauged supergravity resulting from F-theory compactifications in the presence of the Abelian gauge factors including the effects of possible fluxes on the gauging, tadpoles and matter spectrum.Comment: 49 page

Validation of techniques to mitigate copper surface contamination in CUORE

In this article we describe the background challenges for the CUORE experiment posed by surface contamination of inert detector materials such as copper, and present three techniques explored to mitigate these backgrounds. Using data from a dedicated test apparatus constructed to validate and compare these techniques we demonstrate that copper surface contamination levels better than 10E-07 - 10E-08 Bq/cm2 are achieved for 238U and 232Th. If these levels are reproduced in the final CUORE apparatus the projected 90% C.L. upper limit on the number of background counts in the region of interest is 0.02-0.03 counts/keV/kg/y depending on the adopted mitigation technique.Comment: 10 pages, 6 figures, 6 table

The low energy spectrum of TeO2 bolometers: results and dark matter perspectives for the CUORE-0 and CUORE experiments

We collected 19.4 days of data from four 750 g TeO2 bolometers, and in three of them we were able to set the energy threshold around 3 keV using a new analysis technique. We found a background rate ranging from 25 cpd/keV/kg at 3 keV to 2 cpd/keV/kg at 25 keV, and a peak at 4.7 keV. The origin of this peak is presently unknown, but its presence is confirmed by a reanalysis of 62.7 kg.days of data from the finished CUORICINO experiment. Finally, we report the expected sensitivities of the CUORE0 (52 bolometers) and CUORE (988 bolometers) experiments to a WIMP annual modulation signal.Comment: 9 pages, 10 figure

Low-Energy Probes of a Warped Extra Dimension

We investigate a natural realization of a light Abelian hidden sector in an extended Randall-Sundrum (RS) model. In addition to the usual RS bulk we consider a second warped space containing a bulk U(1)_x gauge theory with a characteristic IR scale of order a GeV. This Abelian hidden sector can couple to the standard model via gauge kinetic mixing on a common UV brane. We show that if such a coupling induces significant mixing between the lightest U(1)_x gauge mode and the standard model photon and Z, it can also induce significant mixing with the heavier U(1)_x Kaluza-Klein (KK) modes. As a result it might be possible to probe several KK modes in upcoming fixed-target experiments and meson factories, thereby offering a new way to investigate the structure of an extra spacetime dimension.Comment: 26 pages, 1 figure, added references, corrected minor typos, same as journal versio