Higher-Derivative Terms in N=2 Supersymmetric Effective Actions

We show how to systematically construct higher-derivative terms in effective actions in harmonic superspace despite the infinite redundancy in their description due to the infinite number of auxiliary fields. Making an assumption about the absence of certain superspace Chern-Simons-like terms involving vector multiplets, we write all 3- and 4-derivative terms on Higgs, Coulomb, and mixed branches. Among these terms are several with only holomorphic dependence on fields, and at least one satisfies a non-renormalization theorem. These holomorphic terms include a novel 3-derivative term on mixed branches given as an integral over 3/4 of superspace. As an illustration of our method, we search for Wess-Zumino terms in the low energy effective action of N=2 supersymmetric QCD. We show that such terms occur only on mixed branches. We also present an argument showing that the combination of space-time locality with supersymmetry implies locality in the anticommuting superspace coordinates of for unconstrained superfields.Comment: 30 pages. Added references and simplified final form of WZ ter

Production of inflammatory mediators by human macrophages obtained from ascites

Ascites is a readily available source of human macrophages (Mø), which can be used to study Mø functions in vitro. We characterized the mediators of inflammation produced by human peritoneal Mø (hp-Mø) obtained from patients with portal hypertension and ascites. The production of the cytokines interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) was found to be lipopolysaccharide (LPS) concentration dependent (0–10 μg/ml) with a maximal production at 10 μg/ml and also dependent on the time of exposure to the stimulus (0–36 h). IL-1β, IL-6 and TNF-α production after LPS administration reached a plateau at 24 h. In vitro stimulation for 24 h with LPS does not influence the eicosanoid production from endogenous arachidonate. 13 min of exposure of the cells to the calcium ionophore A23187 gives a significant increase in eicosanoid production from both exogenous and endogenous arachidonate. The main eicosanoids produced are the 5-lipoxgenase products LTB4 and 5-hydroxyeicosatetraenoic acid (HETE). The increase in production of the other eicosanoids is not significant. The eicosanoid production depends on the stimulus concentration. The optimal A23187 concentration is 1 μM. Oxygen radical production was measured in the Mø by a flowcytometric method. The fluorescence intensity of phorbol 12-myristate 13-acetate stimulated and dihydro-rhodamine 123 loaded. hp-Mø increases significantly after 15 min. We conclude that LPS stimulation of hp-Mø from liver disease results in similar production of IL-1β, IL-6 and TNF-α, but that the profile of the eicosanoid production of these Mø stimulated with LPS and A23187 differs from Mø of other origin and species

Levels of soluble intercellular adhesion molecule 1, eicosanoids and cytokines in ascites of patients with liver cirrhosis, peritoneal cancer and spontaneous bacterial peritonitis

The levels of the eicosanoids leukotriene B4, prostaglandin E2, prostacycline and thromboxane B2, the cytokines interleukin-1β, interleukin-6 and tumour necrosis factor-α and soluble intercellular adhesion molecule 1 were measured in ascites and plasma samples of patients with liver cirrhosis (53), peritoneal cancer (26) and spontaneous bacterial peritonitis (10) to assess their value as a possible diagnostic and prognostic parameter in the course of the disease. Soluble intercellular adhesion molecule 1, of the eicosanoids prostaglandin E2 and leukotriene B4, and the protein concentration in ascites were all significantly elevated in ascites of patients with peritoneal cancer in comparison to ascites of patients with liver cirrhosis. In ascites of patients with spontaneous bacterial infection interleukin-6 concentration was significantly elevated and the protein concentration was significantly lower in comparison to the other two groups. None of these parameters, however, seems to be of practical use as a diagnostic parameter, as there is an overlap between all the levels of these mediators in ascites of liver cirrhosis, peritoneal cancer and spontaneous bacterial peritonitis group. Soluble intercellular adhesion molecule 1 levels were much higher in plasma than in ascites, in contrast to interleukin-6 levels which were much higher in ascites than in plasma. Soluble intercellular adhesion molecule 1 in ascites correlated with soluble intercellular adhesion molecule 1 in plasma (r = 0.6926, P = 0.0001). Soluble intercellular adhesion molecule 1, interleukin-6 and the number of polymorphonuclear cells in peritoneal fluid correlated during episodes of infection in patients with a peritonitis. For this reason soluble intercellular adhesion molecule 1 and interleukin-6 could be of prognostic value for patients with peritonitis

Supergeometry in locally covariant quantum field theory

In this paper we analyze supergeometric locally covariant quantum field theories. We develop suitable categories SLoc of super-Cartan supermanifolds, which generalize Lorentz manifolds in ordinary quantum field theory, and show that, starting from a few representation theoretic and geometric data, one can construct a functor A : SLoc --> S*Alg to the category of super-*-algebras which can be interpreted as a non-interacting super-quantum field theory. This construction turns out to disregard supersymmetry transformations as the morphism sets in the above categories are too small. We then solve this problem by using techniques from enriched category theory, which allows us to replace the morphism sets by suitable morphism supersets that contain supersymmetry transformations as their higher superpoints. We construct super-quantum field theories in terms of enriched functors eA : eSLoc --> eS*Alg between the enriched categories and show that supersymmetry transformations are appropriately described within the enriched framework. As examples we analyze the superparticle in 1|1-dimensions and the free Wess-Zumino model in 3|2-dimensions

Geometric Second Order Field Equations for General Tensor Gauge Fields

Higher spin tensor gauge fields have natural gauge-invariant field equations written in terms of generalised curvatures, but these are typically of higher than second order in derivatives. We construct geometric second order field equations and actions for general higher spin boson fields, and first order ones for fermions, which are non-local but which become local on gauge-fixing, or on introducing auxiliary fields. This generalises the results of Francia and Sagnotti to all representations of the Lorentz group.Comment: 34 pages, LaTeX. Reference adde

Functional determinants for general self-adjoint extensions of Laplace-type operators resulting from the generalized cone

In this article we consider the zeta regularized determinant of Laplace-type operators on the generalized cone. For {\it arbitrary} self-adjoint extensions of a matrix of singular ordinary differential operators modelled on the generalized cone, a closed expression for the determinant is given. The result involves a determinant of an endomorphism of a finite-dimensional vector space, the endomorphism encoding the self-adjoint extension chosen. For particular examples, like the Friedrich's extension, the answer is easily extracted from the general result. In combination with \cite{BKD}, a closed expression for the determinant of an arbitrary self-adjoint extension of the full Laplace-type operator on the generalized cone can be obtained.Comment: 27 pages, 2 figures; to appear in Manuscripta Mathematic

Measurement of qubits

We describe in detail the theory underpinning the measurement of density matrices of a pair of quantum two-level systems (qubits). Our particular emphasis is on qubits realized by the two polarization degrees of freedom of a pair of entangled photons generated in a down-conversion experiment; however, the discussion applies in general, regardless of the actual physical realization. Two techniques are discussed, namely, a tomographic reconstruction (in which the density matrix is linearly related to a set of measured quantities) and a maximum likelihood technique which requires numerical optimization (but has the advantage of producing density matrices that are always non-negative definite). In addition, a detailed error analysis is presented, allowing errors in quantities derived from the density matrix, such as the entropy or entanglement of formation, to be estimated. Examples based on down-conversion experiments are used to illustrate our results

Genetic predisposition to ductal carcinoma in situ of the breast

Background: Ductal carcinoma in situ (DCIS) is a non-invasive form of breast cancer. It is often associated with invasive ductal carcinoma (IDC), and is considered to be a non-obligate precursor of IDC. It is not clear to what extent these two forms of cancer share low-risk susceptibility loci, or whether there are differences in the strength of association for shared loci. Methods: To identify genetic polymorphisms that predispose to DCIS, we pooled data from 38 studies comprising 5,067 cases of DCIS, 24,584 cases of IDC and 37,467 controls, all genotyped using the iCOGS chip. Results: Most (67 %) of the 76 known breast cancer predisposition loci showed an association with DCIS in the same direction as previously reported for invasive breast cancer. Case-only analysis showed no evidence for differences between associations for IDC and DCIS after considering multiple testing. Analysis by estrogen receptor (ER) status confirmed that loci associated with ER positive IDC were also associated with ER positive DCIS. Analysis of DCIS by grade suggested that two independent SNPs at 11q13.3 near CCND1 were specific to low/intermediate grade DCIS (rs75915166, rs554219). These associations with grade remained after adjusting for ER status and were also found in IDC. We found no novel DCIS-specific loci at a genome wide significance level of P < 5.0x10-8. Conclusion: In conclusion, this study provides the strongest evidence to date of a shared genetic susceptibility for IDC and DCIS. Studies with larger numbers of DCIS are needed to determine if IDC or DCIS specific loci exist

No evidence that protein truncating variants in BRIP1 are associated with breast cancer risk: implications for gene panel testing.

BACKGROUND: BRCA1 interacting protein C-terminal helicase 1 (BRIP1) is one of the Fanconi Anaemia Complementation (FANC) group family of DNA repair proteins. Biallelic mutations in BRIP1 are responsible for FANC group J, and previous studies have also suggested that rare protein truncating variants in BRIP1 are associated with an increased risk of breast cancer. These studies have led to inclusion of BRIP1 on targeted sequencing panels for breast cancer risk prediction. METHODS: We evaluated a truncating variant, p.Arg798Ter (rs137852986), and 10 missense variants of BRIP1, in 48 144 cases and 43 607 controls of European origin, drawn from 41 studies participating in the Breast Cancer Association Consortium (BCAC). Additionally, we sequenced the coding regions of BRIP1 in 13 213 cases and 5242 controls from the UK, 1313 cases and 1123 controls from three population-based studies as part of the Breast Cancer Family Registry, and 1853 familial cases and 2001 controls from Australia. RESULTS: The rare truncating allele of rs137852986 was observed in 23 cases and 18 controls in Europeans in BCAC (OR 1.09, 95% CI 0.58 to 2.03, p=0.79). Truncating variants were found in the sequencing studies in 34 cases (0.21%) and 19 controls (0.23%) (combined OR 0.90, 95% CI 0.48 to 1.70, p=0.75). CONCLUSIONS: These results suggest that truncating variants in BRIP1, and in particular p.Arg798Ter, are not associated with a substantial increase in breast cancer risk. Such observations have important implications for the reporting of results from breast cancer screening panels.The COGS project is funded through a European Commission's Seventh Framework Programme grant (agreement number 223175 - HEALTH-F2-2009-223175). BCAC is funded by Cancer Research UK [C1287/A10118, C1287/A12014] and by the European Community´s Seventh Framework Programme under grant agreement number 223175 (grant number HEALTH-F2-2009-223175) (COGS). Funding for the iCOGS infrastructure came from: the European Community's Seventh Framework Programme under grant agreement n° 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, C8197/A16565), the National Institutes of Health (CA128978) and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 16 CA148065 and 1U19 CA148112 - the GAME-ON initiative), the Department of Defense (W81XWH-10-1- 0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund. This study made use of data generated by the Wellcome Trust Case Control consortium. Funding for the project was provided by the Wellcome Trust under award 076113. The results published here are in part based upon data generated by The Cancer Genome Atlas Project established by the National Cancer Institute and National Human Genome Research Institute.This is the author accepted manuscript. The final version is available from BMJ Group at http://dx.doi.org/10.1136/jmedgenet-2015-103529

Assessment of variation in immunosuppressive pathway genes reveals TGFBR2 to be associated with prognosis of estrogen receptor-negative breast cancer after chemotherapy

Introduction: Tumor lymphocyte infiltration is associated with clinical response to chemotherapy in estrogen receptor (ER) negative breast cancer. To identify variants in immunosuppressive pathway genes associated with prognosis after adjuvant chemotherapy for ER-negative patients, we studied stage I-III invasive breast cancer patients of European ancestry, including 9,334 ER-positive (3,151 treated with chemotherapy) and 2,334 ER-negative patients (1,499 treated with chemotherapy). Methods: We pooled data from sixteen studies from the Breast Cancer Association Consortium (BCAC), and employed two independent studies for replications. Overall 3,610 single nucleotide polymorphisms (SNPs) in 133 genes were genotyped as part of the Collaborative Oncological Gene-environment Study, in which phenotype and clinical data were collected and harmonized. Multivariable Cox proportional hazard regression was used to assess genetic associations with overall survival (OS) and breast