Genome stability pathways in head and neck cancers

Genomic instability underlies the transformation of host cells toward malignancy, promotes development of invasion and metastasis and shapes the response of established cancer to treatment. In this review, we discuss recent advances in our understanding of genomic stability in squamous cell carcinoma of the head and neck (HNSCC), with an emphasis on DNA repair pathways. HNSCC is characterized by distinct profiles in genome stability between similarly staged cancers that are reflected in risk, treatment response and outcomes. Defective DNA repair generates chromosomal derangement that can cause subsequent alterations in gene expression, and is a hallmark of progression toward carcinoma. Variable functionality of an increasing spectrum of repair gene polymorphisms is associated with increased cancer risk, while aetiological factors such as human papillomavirus, tobacco and alcohol induce significantly different behaviour in induced malignancy, underpinned by differences in genomic stability. Targeted inhibition of signalling receptors has proven to be a clinically-validated therapy, and protein expression of other DNA repair and signalling molecules associated with cancer behaviour could potentially provide a more refined clinical model for prognosis and treatment prediction. Development and expansion of current genomic stability models is furthering our understanding of HNSCC pathophysiology and uncovering new, promising treatment strategies

Complete Analysis of Baryon Magnetic Moments in 1/N_c

We generate a complete basis of magnetic moment operators for the N_c = 3 ground-state baryons in the 1/N_c expansion, and compute and tabulate all associated matrix elements. We then compare to previous results derived in the literature and predict additional relations among baryon magnetic moments holding to subleading order in 1/N_c and flavor SU(3) breaking. Finally, we predict all unknown diagonal and transition magnetic moments to <= 0.15 mu_N accuracy, and suggest possible experimental measurements to improve the analysis even further.Comment: 28 pages (including 11 tables), ReVTeX. One reference and grant acknowledgment adde

Magnetic anisotropy of the noncollinear antiferromagnet IrMn3

The magnetic anisotropy of antiferromagnets plays a crucial role in stabilizing the magnetization of many spintronic devices. In noncollinear antiferromagnets such as IrMn, the symmetry and temperature dependence of the effective anisotropy are poorly understood. Theoretical calculations and experimental measurements of the effective anisotropy constant for IrMn differ by two orders of magnitude, while the symmetry has been inferred as uniaxial in contradiction to the assumed relationship between crystallographic symmetry and temperature dependence of the anisotropy from the Callen-Callen law. In this Rapid Communication, we determine the effective anisotropy energy surface of L12-IrMn3 using an atomistic spin model and constrained Monte Carlo simulations. We find a unique cubiclike symmetry of the anisotropy not seen in ferromagnets and that metastable spin structures lower the overall energy barrier to a tenth of that estimated from simple geometrical considerations, removing the discrepancy between experiment and theory. The temperature scaling of the anisotropy energy barrier shows an exponent of 3.92, close to a uniaxial exponent of 3. Our results demonstrate the importance of noncollinear spin states on the thermal stability of antiferromagnets with consequences for the practical application of antiferromagnets in devices operating at elevated temperatures

Whole-genome sequencing for national surveillance of Shiga toxin–producing Escherichia coli O157

Background. National surveillance of gastrointestinal pathogens, such as Shiga toxin–producing Escherichia coli O157 (STEC O157), is key to rapidly identifying linked cases in the distributed food network to facilitate public health interventions. In this study, we used whole-genome sequencing (WGS) as a tool to inform national surveillance of STEC O157 in terms of identifying linked cases and clusters and guiding epidemiological investigation. Methods. We retrospectively analyzed 334 isolates randomly sampled from 1002 strains of STEC O157 received by the Gastrointestinal Bacteria Reference Unit at Public Health England, Colindale, in 2012. The genetic distance between each isolate, as estimated by WGS, was calculated and phylogenetic methods were used to place strains in an evolutionary context. Results. Estimates of linked clusters representing STEC O157 outbreaks in England and Wales increased by 2-fold when WGS was used instead of traditional typing techniques. The previously unidentified clusters were often widely geographically distributed and small in size. Phylogenetic analysis facilitated identification of temporally distinct cases sharing common exposures and delineating those that shared epidemiological and temporal links. Comparison with multi locus variable number tandem repeat analysis (MLVA) showed that although MLVA is as sensitive as WGS, WGS provides a more timely resolution to outbreak clustering. Conclusions. WGS has come of age as a molecular typing tool to inform national surveillance of STEC O157; it can be used in real time to provide the highest strain-level resolution for outbreak investigation. WGS allows linked cases to be identified with unprecedented specificity and sensitivity that will facilitate targeted and appropriate public health investigations

Large N_c, Constituent Quarks, and N, Delta Charge Radii

We show how one may define baryon constituent quarks in a rigorous manner, given physical assumptions that hold in the large-N_c limit of QCD. This constituent picture gives rise to an operator expansion that has been used to study large-N_c baryon observables; here we apply it to the case of charge radii of the N and Delta states, using minimal dynamical assumptions. For example, one finds the relation r_p^2 - r_{Delta^+}^2 = r_n^2 - r_{Delta^0}^2 to be broken only by three-body, O(1/N_c^2) effects for any N_c.Comment: 15 pages, 1 eps figure. Version to appear in Phys. Rev.

Long-term modifications of coastal defences enhance marine biodiversity

Realization that hard coastal infrastructures support lower biodiversity than natural habitats has prompted a wealth of research seeking to identify design enhancements offering ecological benefits. Some studies showed that artificial structures could be modified to increase levels of diversity. Most studies, however, only considered the short-term ecological effects of such modifications, even though reliance on results from short-term studies may lead to serious misjudgements in conservation. In this study, a seven-year experiment examined how the addition of small pits to otherwise featureless seawalls may enhance the stocks of a highly-exploited limpet. Modified areas of the seawall supported enhanced stocks of limpets seven years after the addition of pits. Modified areas of the seawall also supported a community that differed in the abundance of littorinids, barnacles and macroalgae compared to the controls. Responses to different treatments (numbers and size of pits) were species-specific and, while some species responded directly to differences among treatments, others might have responded indirectly via changes in the distribution of competing species. This type of habitat enhancement can have positive long-lasting effects on the ecology of urban seascapes. Understanding of species interactions could be used to develop a rule-based approach to enhance biodiversity

The Subduction experiment : cruise report RRS Charles Darwin cruise number 73 subduction 3 mooring deployment and recovery cruise, 30 September-26 October 1992

Subduction is the mechanism by which water masses formed in the mixed layer and near the surface of the ocean find their way into the upper thermocline. The subduction process and its underlying mechanisms were studied through a combination of Eulerian and Langrangian measurements of velocity, measurements of tracer distrbutions and hydrographic properties and modeling. An array of five surface moorings carrying meteorological and oceanographic instrumentation were deployed for a period of two years beginning in June 1991 as part of an Office of Naval Research (ONR) funded Subduction experiment. Three eight month deployments were planned. The moorings were deployed at 18°N 34°W, 18°N 22°W, 25.5°N 29°W, 33°N 22°W and 33°N 34°W. A Vector Averaging Wind Recorder (VAWR) and an Improved Meteorological Recorder (IMET) collected wind speed and wind direction, sea surface temperature, air temperature, short wave radiation, barometric pressure and relative humidity. The IMET also measured precipitation. The moorings were heavily instrumented below the surface with Vector Measuring Current Meters (VMCM), and single point temperature recorders. Expendable bathythermograph (XBT) data were collected and meteorological observations were made while transitting between mooring locations. In addition a series of 59 cm stations were made and water samples taken to be analyzed for tritium levels, salinity and dissolved oxygen content. This report describes the work that took place during RRS Charles Darwin cruise number 73 which was the third scheduled Subduction mooring cruise. During this cruise the second setting of the moorings were recovered and redeployed for a third eight month period. This report includes a description of the instrumentation that was deployed and recovered, has information about the underway measurements (XBT and meteorological observations) that were made including plots of the data, includes a description of the work conducted in conjunction with the tracer/hydrography program and presents a chronology of the cruise events.Funding was provided by the Office of Naval Research under contract N00014-90-J-1490

Compassion, Dominance/Submission, and Curled Lips: A Thematic Analysis of Dacryphilic Experience

Paraphilias are often discussed in the psychological literature as pathological problems, yet relatively little research exists that looks into non-pathological paraphilias (i.e., non-normative sexual interests). Empirical evidence suggests that many individuals incorporate a range of non-normative sexual interests into their sexual lifestyles. Dacryphilia is a non-normative sexual interest that involves enjoyment or arousal from tears and crying, and to date has never been researched empirically. The present study set out to discover the different interests within dacryphilia and explore the range of dacryphilic experience. A set of online interviews was carried out with individuals with dacryphilic preferences and interests (six females and two males) from four countries. The data were analysed for semantic and latent themes using thematic analysis. The respondents' statements focused attention on three distinct areas that may be relevant to the experience of dacryphilia: (i) compassion; (ii) dominance/submission; and (iii) curled-lips. The data provided detailed descriptions of features within all three interests, which are discussed in relation to previous quantitative and qualitative research within emotional crying and tears, and the general area of non-normative sexual interests. The study suggests new directions for potential research both within dacryphilia and with regard to other non-normative sexual interests