Spin-2 spectrum of defect theories

We study spin-2 excitations in the background of the recently-discovered type-IIB solutions of D'Hoker et al. These are holographically-dual to defect conformal field theories, and they are also of interest in the context of the Karch-Randall proposal for a string-theory embedding of localized gravity. We first generalize an argument by Csaki et al to show that for any solution with four-dimensional anti-de Sitter, Poincare or de Sitter invariance the spin-2 excitations obey the massless scalar wave equation in ten dimensions. For the interface solutions at hand this reduces to a Laplace-Beltrami equation on a Riemann surface with disk topology, and in the simplest case of the supersymmetric Janus solution it further reduces to an ordinary differential equation known as Heun's equation. We solve this equation numerically, and exhibit the spectrum as a function of the dilaton-jump parameter $\Delta\phi$. In the limit of large $\Delta\phi$ a nearly-flat linear-dilaton dimension grows large, and the Janus geometry becomes effectively five-dimensional. We also discuss the difficulties of localizing four-dimensional gravity in the more general backgrounds with NS5-brane or D5-brane charge, which will be analyzed in detail in a companion paper.Comment: 41 pages, 6 figure

Digital reconstruction of the inner ear of Leptictidium auderiense (Leptictida, Mammalia) and North American leptictids reveals new insight into leptictidan locomotor agility

Leptictida are basal Paleocene to Oligocene eutherians from Europe and North America comprising species with highly specialized postcranial features including elongated hind limbs. Among them, the European Leptictidium was probably a bipedal runner or jumper. Because the semicircular canals of the inner ear are involved in detecting angular acceleration of the head, their morphometry can be used as a proxy to elucidate the agility in fossil mammals. Here we provide the first insight into inner ear anatomy and morphometry of Leptictida based on high-resolution computed tomography of a new specimen of Leptictidium auderiense from the middle Eocene Messel Pit (Germany) and specimens of the North American Leptictis and Palaeictops. The general morphology of the bony labyrinth reveals several plesiomorphic mammalian features, such as a secondary crus commune. Leptictidium is derived from the leptictidan groundplan in lacking the secondary bony lamina and having proportionally larger semicircular canals than the leptictids under study. Our estimations reveal that Leptictidium was a very agile animal with agility score values (4.6 and 5.5, respectively) comparable to Macroscelidea and extant bipedal saltatory placentals. Leptictis and Palaeictops have lower agility scores (3.4 to 4.1), which correspond to the more generalized types of locomotion (e.g., terrestrial, cursorial) of most extant mammals. In contrast, the angular velocity magnitude predicted from semicircular canal angles supports a conflicting pattern of agility among leptictidans, but the significance of these differences might be challenged when more is known about intraspecific variation and the pattern of semicircular canal angles in non-primate mammals

Blockade of Fatty Acid Synthase Triggers Significant Apoptosis in Mantle Cell Lymphoma

Fatty acid synthase (FASN), a key player in the de novo synthetic pathway of long-chain fatty acids, has been shown to contribute to the tumorigenesis in various types of solid tumors. We here report that FASN is highly and consistently expressed in mantle cell lymphoma (MCL), an aggressive form of B-cell lymphoid malignancy. Specifically, the expression of FASN was detectable in all four MCL cell lines and 15 tumors examined. In contrast, benign lymphoid tissues and peripheral blood mononuclear cells from normal donors were negative. Treatment of MCL cell lines with orlistat, a FASN inhibitor, resulted in significant apoptosis. Knockdown of FASN expression using siRNA, which also significantly decreased the growth of MCL cells, led to a dramatic decrease in the cyclin D1 level. β-catenin, which has been previously reported to be upregulated in a subset of MCL tumors, contributed to the high level of FASN in MCL cells, Interesting, siRNA knock-down of FASN in turn down-regulated β-catenin. In conclusion, our data supports the concept that FASN contributes to the pathogenesis of MCL, by collaborating with β-catenin. In view of its high and consistent expression in MCL, FASN inhibitors may hold promises for treating MCL

Identification and Interpretation of Longitudinal Gene Expression Changes in Trauma

The relationship between leukocyte gene expression and recovery of respiratory function after injury may provide information on the etiology of multiple organ dysfunction.To find a list of genes for which expression after injury predicts respiratory recovery, and to identify which networks and pathways characterize these genes.Blood was sampled at 12 hours and at 1, 4, 7, 21 and 28 days from 147 patients who had been admitted to the hospital after blunt trauma. Leukocyte gene expression was measured using Affymetrix oligonucleotide arrays. A linear model, fit to each probe-set expression value, was used to impute the gene expression trajectory over the entire follow-up period. The proportional hazards model score test was used to calculate the statistical significance of each probe-set trajectory in predicting respiratory recovery. A list of genes was determined such that the expected proportion of false positive results was less than 10%. These genes were compared to the Gene Ontology for 'response to stimulus' and, using Ingenuity software, were mapped into networks and pathways.The median time to respiratory recovery was 6 days. There were 170 probe-sets representing 135 genes that were found to be related to respiratory recovery. These genes could be mapped to nine networks. Two known pathways that were activated were antigen processing and presentation and JAK-signaling.The examination of the relationship of gene expression over time with a patient's clinical course can provide information which may be useful in determining the mechanism of recovery or lack of recovery after severe injury

Transcriptional analysis of adipose tissue during development reveals depot-specific responsiveness to maternal dietary supplementation

Brown adipose tissue (BAT) undergoes pronounced changes after birth coincident with the loss of the BAT-specifc uncoupling protein (UCP)1 and rapid fat growth. The extent to which this adaptation may vary between anatomical locations remains unknown, or whether the process is sensitive to maternal dietary supplementation. We, therefore, conducted a data mining based study on the major fat depots (i.e. epicardial, perirenal, sternal (which possess UCP1 at 7 days), subcutaneous and omental) (that do not possess UCP1) of young sheep during the frst month of life. Initially we determined what effect adding 3% canola oil to the maternal diet has on mitochondrial protein abundance in those depots which possessed UCP1. This demonstrated that maternal dietary supplementation delayed the loss of mitochondrial proteins, with the amount of cytochrome C actually being increased. Using machine learning algorithms followed by weighted gene co-expression network analysis, we demonstrated that each depot could be segregated into a unique and concise set of modules containing co-expressed genes involved in adipose function. Finally using lipidomic analysis following the maternal dietary intervention, we confrmed the perirenal depot to be most responsive. These insights point at new research avenues for examining interventions to modulate fat development in early life

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Search for direct pair production of the top squark in all-hadronic final states in proton-proton collisions at s√=8 TeV with the ATLAS detector

The results of a search for direct pair production of the scalar partner to the top quark using an integrated luminosity of 20.1fb−1 of proton–proton collision data at √s = 8 TeV recorded with the ATLAS detector at the LHC are reported. The top squark is assumed to decay via t˜→tχ˜01 or t˜→ bχ˜±1 →bW(∗)χ˜01 , where χ˜01 (χ˜±1 ) denotes the lightest neutralino (chargino) in supersymmetric models. The search targets a fully-hadronic final state in events with four or more jets and large missing transverse momentum. No significant excess over the Standard Model background prediction is observed, and exclusion limits are reported in terms of the top squark and neutralino masses and as a function of the branching fraction of t˜ → tχ˜01 . For a branching fraction of 100%, top squark masses in the range 270–645 GeV are excluded for χ˜01 masses below 30 GeV. For a branching fraction of 50% to either t˜ → tχ˜01 or t˜ → bχ˜±1 , and assuming the χ˜±1 mass to be twice the χ˜01 mass, top squark masses in the range 250–550 GeV are excluded for χ˜01 masses below 60 GeV

Search for pair-produced long-lived neutral particles decaying to jets in the ATLAS hadronic calorimeter in ppcollisions at √s=8TeV

The ATLAS detector at the Large Hadron Collider at CERN is used to search for the decay of a scalar boson to a pair of long-lived particles, neutral under the Standard Model gauge group, in 20.3fb−1of data collected in proton–proton collisions at √s=8TeV. This search is sensitive to long-lived particles that decay to Standard Model particles producing jets at the outer edge of the ATLAS electromagnetic calorimeter or inside the hadronic calorimeter. No significant excess of events is observed. Limits are reported on the product of the scalar boson production cross section times branching ratio into long-lived neutral particles as a function of the proper lifetime of the particles. Limits are reported for boson masses from 100 GeVto 900 GeV, and a long-lived neutral particle mass from 10 GeVto 150 GeV

Oncogenic Stress Induced by Acute Hyper-Activation of Bcr-Abl Leads to Cell Death upon Induction of Excessive Aerobic Glycolysis

In response to deregulated oncogene activation, mammalian cells activate disposal programs such as programmed cell death. To investigate the mechanisms behind this oncogenic stress response we used Bcr-Abl over-expressing cells cultivated in presence of imatinib. Imatinib deprivation led to rapid induction of Bcr-Abl activity and over-stimulation of PI3K/Akt-, Ras/MAPK-, and JAK/STAT pathways. This resulted in a delayed necrosis-like cell death starting not before 48 hours after imatinib withdrawal. Cell death was preceded by enhanced glycolysis, glutaminolysis, and amino acid metabolism leading to elevated ATP and protein levels. This enhanced metabolism could be linked to induction of cell death as inhibition of glycolysis or glutaminolysis was sufficient to sustain cell viability. Therefore, these data provide first evidence that metabolic changes induced by Bcr-Abl hyper-activation are important mediators of oncogenic stress-induced cell death

Loss of NOTCH2 Positively Predicts Survival in Subgroups of Human Glial Brain Tumors

The structural complexity of chromosome 1p centromeric region has been an obstacle for fine mapping of tumor suppressor genes in this area. Loss of heterozygosity (LOH) on chromosome 1p is associated with the longer survival of oligodendroglioma (OD) patients. To test the clinical relevance of 1p loss in glioblastomas (GBM) patients and identifiy the underlying tumor suppressor locus, we constructed a somatic deletion map on chromosome 1p in 26 OG and 118 GBM. Deletion hotspots at 4 microsatellite markers located at 1p36.3, 1p36.1, 1p22 and 1p11 defined 10 distinct haplotypes that were related to patient survival. We found that loss of 1p centromeric marker D1S2696 within NOTCH2 intron 12 was associated with favorable prognosis in OD (P = 0.0007) as well as in GBM (P = 0.0175), while 19q loss, concomitant with 1p LOH in OD, had no influence on GBM survival (P = 0.918). Assessment of the intra-chromosomal ratio between NOTCH2 and its 1q21 pericentric duplication N2N (N2/N2N-test) allowed delineation of a consistent centromeric breakpoint in OD that also contained a minimally lost area in GBM. OD and GBM showed distinct deletion patterns that converged to the NOTCH2 gene in both glioma subtypes. Moreover, the N2/N2N-test disclosed homozygous deletions of NOTCH2 in primary OD. The N2/N2N test distinguished OD from GBM with a specificity of 100% and a sensitivity of 97%. Combined assessment of NOTCH2 genetic markers D1S2696 and N2/N2N predicted 24-month survival with an accuracy (0.925) that is equivalent to histological classification combined with the D1S2696 status (0.954) and higher than current genetic evaluation by 1p/19q LOH (0.762). Our data propose NOTCH2 as a powerful new molecular test to detect prognostically favorable gliomas