Crime and Deterrence: Correlation Analysis

A correlation analysis of the severity and certainty of punish ment and offense rates for the major index crimes produces results consistent with the predictions of deterrence theory. Certainty of punishment proves to be the chief deterrent for most crimes. Homicide, however, is influenced by severity, pos sibly reflecting the differences between homicide and other of fenses. Little evidence of interaction is found between certainty and severity in effects on crime rate. A powerfunction proves to better describe the relationship between the punishment varia bles and crime rates than a rectilinear equation-a conclusion which, even apart from the date, appears more reasonable than the reverse

Heterotic-type IIA duality with fluxes

In this paper we study a possible non-perturbative dual of the heterotic string compactified on K3 x T^2 in the presence of background fluxes. We show that type IIA string theory compactified on manifolds with SU(3) structure can account for a subset of the possible heterotic fluxes. This extends our previous analysis to a case of a non-perturbative duality with fluxes.Comment: 26 pages, minor corrections; version to appear in JHE

Relationship between interRAI HC and the ICF: opportunity for operationalizing the ICF

Background: The International Classification of Functioning, Disability and Health (ICF) is embraced as a framework to conceptualize human functioning and disability. Health professionals choose measures to represent the domains of the framework. The ICF coding classification is an administrative system but multiple studies have linked diverse clinical assessments to ICF codes. InterRAI-HC (home care) is an assessment designed to assist planning of care for patients receiving home care. Examining the relationship between the ICF and the interRAI HC is of particular interest because the interRAI assessments are widely used in clinical practice and research, are computerized, and uploaded to databases that serve multiple purposes including public reporting of quality in Canada and internationally. The objective of this study was to examine the relationship between the interRAI HC (home care) assessment and the ICF. Specifically, the goal was to determine the proportion of interRAI HC items that can be linked to each of the major domains of the ICF (Body Function, Body Structure, Activities and Participation, and the Environmental Factors), the chapters and the specific ICF codes

Topological mirror symmetry with fluxes

Motivated by SU(3) structure compactifications, we show explicitly how to construct half--flat topological mirrors to Calabi--Yau manifolds with NS fluxes. Units of flux are exchanged with torsion factors in the cohomology of the mirror; this is the topological complement of previous differential--geometric mirror rules. The construction modifies explicit SYZ fibrations for compact Calabi--Yaus. The results are of independent interest for SU(3) compactifications. For example one can exhibit explicitly which massive forms should be used for Kaluza--Klein reduction, proving previous conjectures. Formality shows that these forms carry no topological information; this is also confirmed by infrared limits and old classification theorems.Comment: 35 pages, 5 figure

Molecular rationale for the use of PI3K/AKT/mTOR pathway inhibitors in combination with crizotinib in ALK-mutated neuroblastoma

Mutations in the ALK tyrosine kinase receptor gene represent important therapeutic targets in neuroblastoma, yet their clinical translation has been challenging. The ALKF1174L mutation is sensitive to the ALK inhibitor crizotinib only at high doses and mediates acquired resistance to crizotinib in ALK-translocated cancers. We have shown that the combination of crizotinib and an inhibitor of downstream signaling induces a favorable response in transgenic mice bearing ALKF1174L/MYCN-positive neuroblastoma. Here, we investigated the molecular basis of this effect and assessed whether a similar strategy would be effective in ALK-mutated tumors lacking MYCN overexpression. We show that in ALK-mutated, MYCN-amplified neuroblastoma cells, crizotinib alone does not affect mTORC1 activity as indicated by persistent RPS6 phosphorylation. Combined treatment with crizotinib and an ATP-competitive mTOR inhibitor abrogated RPS6 phosphorylation, leading to reduced tumor growth and prolonged survival in ALKF1174L/MYCN-positive models compared to single agent treatment. By contrast, this combination, while inducing mTORC1 downregulation, caused reciprocal upregulation of PI3K activity in ALK-mutated cells expressing wild-type MYCN. Here, an inhibitor with potency against both mTOR and PI3K was more effective in promoting cytotoxicity when combined with crizotinib. Our findings should enable a more precise selection of molecularly targeted agents for patients with ALK-mutated tumors

Towards Minkowski Vacua in Type II String Compactifications

We study the vacuum structure of compactifications of type II string theories on orientifolds with SU(3)xSU(3) structure. We argue that generalised geometry enables us to treat these non-geometric compactifications using a supergravity analysis in a way very similar to geometric compactifications. We find supersymmetric Minkowski vacua with all the moduli stabilised at weak string coupling and all the tadpole conditions satisfied. Generically the value of the moduli fields in the vacuum is parametrically controlled and can be taken to arbitrarily large values.Comment: 33 pages; v2 minor corrections, references added, version to appear in JHE

Evidence that 5-HT2A Receptors in the Hypothalamic Paraventricular Nucleus Mediate Neuroendocrine Responses to (-)DOI

This is the publisher's version, also available electronically from "http://www.jneurosci.org".The present study determined whether the serotonin2A (5-HT2A) receptors in the hypothalamic paraventricular nucleus mediate the neuroendocrine responses to a peripheral injection of the 5-HT2A/2Creceptor agonist (−)DOI [(−)1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane]. The 5-HT2A receptor antagonist MDL100,907 ((±)-α-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenylethyl)]-4-piperidinemethanol), the 5-HT2C receptor antagonist SB-242084 (6-chloro-5-methyl-1-[[2-[(2-methyl-3-pyridyl)oxy]-5-pyridyl]carbamoyl]-indoline), or vehicle were microinjected bilaterally through a chronically implanted double-barreled cannula into the hypothalamic paraventricular nucleus 15 min before a peripheral injection of (−)DOI in conscious rats. (−)DOI significantly elevated plasma levels of oxytocin, prolactin, ACTH, corticosterone, and renin. Neither the 5-HT2A receptor antagonist nor the 5-HT2Creceptor antagonist, injected alone, altered the basal levels of these hormones. MDL100,907 (0.748, 7.48, and 18.7 nmol) dose dependently inhibited the (−)DOI-induced increase in all of the hormones except corticosterone. In contrast, SB-242084 (10 nmol) did not inhibit (−)DOI-increased hormone levels. To confirm the presence of 5-HT2A receptors in the hypothalamic paraventricular nucleus, 5-HT2A receptors were mapped using immunohistochemistry. Densely labeled magnocellular neurons were observed throughout the anterior and posterior magnocellular subdivisions of the hypothalamic paraventricular nucleus. Moderately to densely labeled cells were also observed in parvicellular regions. Thus, it is likely that 5-HT2A receptors are present on neuroendocrine cells in the hypothalamic paraventricular nucleus. These data provide the first direct evidence that neuroendocrine responses to a peripheral injection of (−)DOI are predominantly mediated by activation of 5-HT2A receptors in the hypothalamic paraventricular nucleus

Evidence for Neutrino Oscillations from Muon Decay at Rest

A search for nu_bar_mu to nu_bar_e oscillations has been conducted at the Los Alamos Meson Physics Facility using nu_bar_mu from mu+ decay at rest. The nu_bar_e are detected via the reaction (nu_bar_e,p) -> (e+,n), correlated with the 2.2 MeV gamma from (n,p) -> (d,gamma). The use of tight cuts to identify e+ events with correlated gamma rays yields 22 events with e+ energy between 36 and 60 MeV and only 4.6 (+/- 0.6) background events. The probability that this excess is due entirely to a statistical fluctuation is 4.1E-08. A chi^2 fit to the entire e+ sample results in a total excess of 51.8 (+18.7) (-16.9) (+/- 8.0) events with e+ energy between 20 and 60 MeV. If attributed to nu_bar_mu -> nu_bar_e oscillations, this corresponds to an oscillation probability (averaged over the experimental energy and spatial acceptance) of 0.0031 (+0.0011) (-0.0010) (+/- 0.0005).Comment: 57 pages, 34 figures, revtex, additional information available at http://nu1.lampf.lanl.gov/~lsnd

Analysis of circulating tumour cells in early-stage uveal melanoma: Evaluation of tumour marker expression to increase capture

Background: The stratification of uveal melanoma (UM) patients into prognostic groups is critical for patient management and for directing patients towards clinical trials. Current classification is based on clinicopathological and molecular features of the tumour. Analysis of circulating tumour cells (CTCs) has been proposed as a tool to avoid invasive biopsy of the primary tumour. However, the clinical utility of such liquid biopsy depends on the detection rate of CTCs. Methods: The expression of melanoma, melanocyte, and stem cell markers was tested in a primary tissue microarray (TMA) and UM cell lines. Markers found to be highly expressed in primary UM were used to either immunomagnetically isolate or immunostain UM CTCs prior to treatment of the primary lesion. (3) Results: TMA and cell lines had heterogeneous expression of common melanoma, melanocyte, and stem cell markers. A multi-marker panel of immunomagnetic beads enabled isolation of CTCs in 37/43 (86%) patients with UM. Detection of three or more CTCs using the multi-marker panel, but not MCSP alone, was a significant predictor of shorter progression free (p = 0.040) and overall (p = 0.022) survival. Conclusions: The multi-marker immunomagnetic isolation protocol enabled the detection of CTCs in most primary UM patients. Overall, our results suggest that a multi-marker approach could be a powerful tool for CTC separation for non-invasive prognostication of UM

Lectures on Nongeometric Flux Compactifications

These notes present a pedagogical review of nongeometric flux compactifications. We begin by reviewing well-known geometric flux compactifications in Type II string theory, and argue that one must include nongeometric "fluxes" in order to have a superpotential which is invariant under T-duality. Additionally, we discuss some elementary aspects of the worldsheet description of nongeometric backgrounds. This review is based on lectures given at the 2007 RTN Winter School at CERN.Comment: 31 pages, JHEP