Calabi-Yau Orbifolds and Torus Coverings

The theory of coverings of the two-dimensional torus is a standard part of algebraic topology and has applications in several topics in string theory, for example, in topological strings. This paper initiates applications of this theory to the counting of orbifolds of toric Calabi-Yau singularities, with particular attention to Abelian orbifolds of C^D. By doing so, the work introduces a novel analytical method for counting Abelian orbifolds, verifying previous algorithm results. One identifies a p-fold cover of the torus T^{D-1} with an Abelian orbifold of the form C^D/Z_p, for any dimension D and a prime number p. The counting problem leads to polynomial equations modulo p for a given Abelian subgroup of S_D, the group of discrete symmetries of the toric diagram for C^D. The roots of the polynomial equations correspond to orbifolds of the form C^D/Z_p, which are invariant under the corresponding subgroup of S_Ds. In turn, invariance under this subgroup implies a discrete symmetry for the corresponding quiver gauge theory, as is clearly seen by its brane tiling formulation.Comment: 33 pages, 5 figures, 7 tables; version published on JHE

From counting to construction of BPS states in N=4 SYM

We describe a universal element in the group algebra of symmetric groups, whose characters provides the counting of quarter and eighth BPS states at weak coupling in N=4 SYM, refined according to representations of the global symmetry group. A related projector acting on the Hilbert space of the free theory is used to construct the matrix of two-point functions of the states annihilated by the one-loop dilatation operator, at finite N or in the large N limit. The matrix is given simply in terms of Clebsch-Gordan coefficients of symmetric groups and dimensions of U(N) representations. It is expected, by non-renormalization theorems, to contain observables at strong coupling. Using the stringy exclusion principle, we interpret a class of its eigenvalues and eigenvectors in terms of giant gravitons. We also give a formula for the action of the one-loop dilatation operator on the orthogonal basis of the free theory, which is manifestly covariant under the global symmetry.Comment: 41 pages + Appendices, 4 figures; v2 - refs and acknowledgments adde

FAK/src-Family Dependent Activation of the Ste20-Like Kinase SLK Is Required for Microtubule-Dependent Focal Adhesion Turnover and Cell Migration

Cell migration involves a multitude of signals that converge on cytoskeletal reorganization, essential for development, immune responses and tissue repair. Using knockdown and dominant negative approaches, we show that the microtubule-associated Ste20-like kinase SLK is required for focal adhesion turnover and cell migration downstream of the FAK/c-src complex. Our results show that SLK co-localizes with paxillin, Rac1 and the microtubules at the leading edge of migrating cells and is activated by scratch wounding. SLK activation is dependent on FAK/c-src/MAPK signaling, whereas SLK recruitment to the leading edge is src-dependent but FAK independent. Our results show that SLK represents a novel focal adhesion disassembly signal

A large age for the pulsar B1757-24 from an upper limit on its proper motion

The "characteristic age" of a pulsar usually is considered to approximate its true age, but this assumption has led to some puzzling results, including the fact that many pulsars with small characteristic ages have no associated supernova remnants. The pulsar B1757-24 is located just beyond the edge of a supernova remnant; the properties of the system indicate that the pulsar was born at the centre of the remnant, but that it has subsequently overtaken the expanding blast-wave. With a characteristic age of 16,000 yr, this implies an expected proper motion by the pulsar of 63-80 milliarcsec per year. Here we report observations of the nebula surrounding the pulsar which limit its proper motion to less than 25 mas/yr, implying a minimum age of 39,000 yr. A more detailed analysis argues for a true age as great as 170,000 yr, significantly larger than the characteristic age. From this result and other discrepancies associated with pulsars, we conclude that characteristic ages seriously underestimate the true ages of pulsars

Multi-Determinants Analysis of Molecular Alterations for Predicting Clinical Benefit to EGFR-Targeted Monoclonal Antibodies in Colorectal Cancer

KRAS mutations occur in 35-45% of metastatic colorectal cancers (mCRC) and preclude responsiveness to EGFR-targeted therapy with cetuximab or panitumumab. However, less than 20% patients displaying wild-type KRAS tumors achieve objective response. Alterations in other effectors downstream of the EGFR, such as BRAF, and deregulation of the PIK3CA/PTEN pathway have independently been found to give rise to resistance. We present a comprehensive analysis of KRAS, BRAF, PIK3CA mutations, and PTEN expression in mCRC patients treated with cetuximab or panitumumab, with the aim of clarifying the relative contribution of these molecular alterations to resistance.We retrospectively analyzed objective tumor response, progression-free (PFS) and overall survival (OS) together with the mutational status of KRAS, BRAF, PIK3CA and expression of PTEN in 132 tumors from cetuximab or panitumumab treated mCRC patients. Among the 106 non-responsive patients, 74 (70%) had tumors with at least one molecular alteration in the four markers. The probability of response was 51% (22/43) among patients with no alterations, 4% (2/47) among patients with 1 alteration, and 0% (0/24) for patients with > or =2 alterations (p<0.0001). Accordingly, PFS and OS were increasingly worse for patients with tumors harboring none, 1, or > or =2 molecular alteration(s) (p<0.001).When expression of PTEN and mutations of KRAS, BRAF and PIK3CA are concomitantly ascertained, up to 70% of mCRC patients unlikely to respond to anti-EGFR therapies can be identified. We propose to define as 'quadruple negative', the CRCs lacking alterations in KRAS, BRAF, PTEN and PIK3CA. Comprehensive molecular dissection of the EGFR signaling pathways should be considered to select mCRC patients for cetuximab- or panitumumab-based therapies

Occupational stress, work-home interference and burnout among Belgian veterinary practitioners

There have been few formal studies on stress in veterinary surgeons and, in the rare studies available, stress is not examined jointly through the levels of job strain and job engagement, the sources of stress in the issue of work environment and the work-home interference. The authors' goal in this study was to analyse job engagement, job strain, burnout, work-home interference and job stress factors among 216 Belgian veterinary surgeons. Rural practice was compared to small animal and mixed activity. The mean job strain and job engagement level in veterinary surgeons was not higher than what we found in other working populations. However, 15.6% of the group were found to be suffering from high burnout. Rural practitioners had a lower level of job engagement than small animal veterinary surgeons. These small animal practitioners had a lower level of job strain than the mixed practitioners. The level of burnout did not differ significantly across the three types of activity. In comparison to other Belgian and Dutch workers, veterinary surgeons perceived more negative work-home interference. Bovine and mixed practitioners were the most concerned with this problem. The two most important sources of stress reported by bovine practitioners were relations to farmers and working time management (including emergencies and availability)

Pontiac fever: an operational definition for epidemiological studies

BACKGROUND: Pontiac fever is usually described in epidemic settings. Detection of Pontiac fever is a marker of an environmental contamination by Legionella and should thereby call for prevention measures in order to prevent outbreak of Legionnaire's disease. The objective of this study is to propose an operational definition of Pontiac fever that is amenable to epidemiological surveillance and investigation in a non epidemic setting. METHODS: A population of 560 elderly subjects residing in 25 nursing homes was followed during 4 months in order to assess the daily incidence of symptoms associated, in the literature, with Pontiac fever. The water and aerosol of one to 8 showers by nursing home were characterized combining conventional bacterial culture of Legionella and the Fluorescence In Situ Hybridization (FISH) technique that used oligonucleotides probes specific for Legionellaceae. A definition of Pontiac fever was devised based on clinical symptoms described in epidemic investigations and on their timing after the exposure event. The association between incidence of Pontiac fever and shower contamination levels was evaluated to test the relevance of this definition. RESULTS: The proposed definition of Pontiac fever associated the following criteria: occurrence of at least one symptom among headache, myalgia, fever and shivers, possibly associated with other 'minor' symptoms, within three days after a shower contaminated by Legionella, during a maximum of 8 days (minimum 2 days). 23 such cases occurred during the study (incidence rate: 0.125 cases per person-year [95% CI: 0.122–0.127]). A concentration of Legionella in water equal to or greater than 10(4).L(-1 )(FISH method) was associated with a significant increase of incidence of Pontiac fever (p = 0.04). CONCLUSION: Once validated in other settings, the proposed definition of Pontiac fever might be used to develop epidemiological surveillance and help draw attention on sources of Legionella