ERCC1 expression and RAD51B activity correlate with cell cycle response to platinum drug treatment not DNA repair

Background: The H69CIS200 and H69OX400 cell lines are novel models of low-level platinum-drug resistance. Resistance was not associated with increased cellular glutathione or decreased accumulation of platinum, rather the resistant cell lines have a cell cycle alteration allowing them to rapidly proliferate post drug treatment. Results: A decrease in ERCC1 protein expression and an increase in RAD51B foci activity was observed in association with the platinum induced cell cycle arrest but these changes did not correlate with resistance or altered DNA repair capacity. The H69 cells and resistant cell lines have a p53 mutation and consequently decrease expression of p21 in response to platinum drug treatment, promoting progression of the cell cycle instead of increasing p21 to maintain the arrest. Conclusion: Decreased ERCC1 protein and increased RAD51B foci may in part be mediating the maintenance of the cell cycle arrest in the sensitive cells. Resistance in the H69CIS200 and H69OX400 cells may therefore involve the regulation of ERCC1 and RAD51B independent of their roles in DNA repair. The novel mechanism of platinum resistance in the H69CIS200 and H69OX400 cells demonstrates the multifactorial nature of platinum resistance which can occur independently of alterations in DNA repair capacity and changes in ERCC1

Heavy fermions and two loop electroweak corrections to b→s+γb\rightarrow s+\gamma

Applying effective Lagrangian method and on-shell scheme, we analyze the electroweak corrections to the rare decay $b\rightarrow s+\gamma$ from some special two loop diagrams in which a closed heavy fermion loop is attached to the virtual charged gauge bosons or Higgs. At the decoupling limit where the virtual fermions in inner loop are much heavier than the electroweak scale, we verify the final results satisfying the decoupling theorem explicitly when the interactions among Higgs and heavy fermions do not contain the nondecoupling couplings. Adopting the universal assumptions on the relevant couplings and mass spectrum of new physics, we find that the relative corrections from those two loop diagrams to the SM theoretical prediction on the branching ratio of $B\rightarrow X_{_s}\gamma$ can reach 5% as the energy scale of new physics $\Lambda_{_{\rm NP}}=200$ GeV.Comment: 30 pages,4 figure

A framework for integrating sustainability estimation with concepts of rules of building measurement

BIM promises improvement in project delivery efficiencies such as reduction in costs and errors and timely completion. Benefits are also expected in sustainable construction aspect with research efforts being extended to sustainable design and assessment. These efforts are still been explored for the purposes of unifying quantification methodologies, the standardisation of system boundaries, terms of references and sustainability measures. Embodied energy and CO2 are two common measures that have been widely used in the construction sector. Although a number calculation system exists, they are not useful to the iterations that occur at the early stages of the project life cycle. At the procurement stage, professionals often rely on schedules and bill of quantities with no reference to sustainability credentials. It is therefore important to integrate sustainability measure with concepts in standard measurement methods. As such, we propose a framework to integrate sustainability credential with the concepts in rule of building measurement. We conclude that this framework can be applicable to any rule of building measurement and it is implementable in a computer programmable environment

Classical Conformal Blocks and Accessory Parameters from Isomonodromic Deformations

Classical conformal blocks naturally appear in the large central charge limit of 2D Virasoro conformal blocks. In the $AdS_{3}/CFT_{2}$ correspondence, they are related to classical bulk actions and are used to calculate entanglement entropy and geodesic lengths. In this work, we discuss the identification of classical conformal blocks and the Painlev\'e VI action showing how isomonodromic deformations naturally appear in this context. We recover the accessory parameter expansion of Heun's equation from the isomonodromic $\tau$-function. We also discuss how the $c = 1$ expansion of the $\tau$-function leads to a novel approach to calculate the 4-point classical conformal block.Comment: 32+10 pages, 2 figures; v3: upgraded notation, discussion on moduli space and monodromies, numerical and analytic checks; v2: added refs, fixed emai

Fermionic T-duality in the pp-wave limit

AdS5 X S5 and its pp-wave limit are self-dual under transformations involving eight fermionic T-dualities, a property which accounts for symmetries seen in scattering amplitudes in N=4 super-Yang-Mills. Despite strong evidence for similar symmetries in the amplitudes of three-dimensional N=6 ABJM theory, a corresponding self-duality in the dual geometry AdS4 X CP3 currently eludes us. Here, working with the type IIA pp-wave limit of AdS4 X CP3 preserving twenty four supercharges, we show that the pp-wave is self-dual with respect to eight commuting fermionic T-dualities and not the six expected. In addition, we show the same symmetry can be found in a superposition pp-wave and a generic pp-wave with twenty and sixteen unbroken supersymmetries respectively, strongly suggesting that self-duality under fermionic T-duality may be a symmetry of all pp-waves.Comment: 21 pages, typos fixe

Self-duality of the D1-D5 near-horizon

We explore fermionic T-duality and self-duality in the geometry AdS3 x S3 x T4 in type IIB supergravity. We explicitly construct the Killing spinors and the fermionic T-duality isometries and show that the geometry is self-dual under a combination of two bosonic AdS3 T-dualities, four fermionic T-dualities and either two additional T-dualities along T4 or two T-dualities along S3. In addition, we show that the presence of a B-field acts as an obstacle to self-duality, a property attributable to S- duality and fermionic T-duality not commuting. Finally, we argue that fermionic T-duality may be extended to CY2 = K3, a setting where we cannot explicitly construct the Killing spinors.Comment: 24 pages, references added, changes made to reinforce the point that S-duality and fermionic T-duality generically do not commute, version accepted to JHE

Hierarchies of Susy Splittings and Invisible Photinos as Dark Matter

We explore how to generate hierarchies in the splittings between superpartners. Some of the consequences are the existence of invisible components of dark matter, new inflaton candidates, invisible monopoles and a number of invisible particles that might dominate during various eras, in particular between BBN and recombination and decay subsequently.Comment: 16 pages. v3: Ref. 27 has been modified. v4: Published versio

"Obesity" and "Clinical Obesity" Men's understandings of obesity and its relation to the risk of diabetes: A qualitative study

<p>Abstract</p> <p>Background</p> <p>The 2007 Wanless report highlights the ever increasing problem of obesity and the consequent health problems. Obesity is a significant cause of diabetes. An increasing evidence base suggests that in terms of reducing diabetes and CVD risk, it is better to be "fit and fat" than unfit and of normal weight. There has been very little previous research into the understandings that men in the general population hold about the issues of weight, exercise and health; we therefore undertook this study in order to inform the process of health promotion and diabetes prevention in this group.</p> <p>Methods</p> <p>A qualitative study in North East England General Practice using a purposive sample of men aged 25 and 45 years (selection process designed to include 'normal', 'overweight' and 'obese' men). One to one audio-recorded semi structured interviews focused on: overweight and obesity, diet, physical activity and diabetes. Transcripts were initially analysed using framework analysis. Emerging themes interlinked.</p> <p>Results</p> <p>The men in this study (n = 17) understand the word obesity differently from the clinical definition; "obesity" was used as a description of those with fat in a central distribution, and understandings of the term commonly take into account fitness as well as weight. Men in their late 30s and early 40s described becoming more aware of health issues. Knowledge of what constitutes a 'healthy lifestyle' was generally good, but men described difficulty acting upon this knowledge for various reasons e.g. increasing responsibilities at home and at work. Knowledge of diabetes and the link between obesity and diabetes was poor.</p> <p>Conclusion</p> <p>Men in this study had a complex understanding of the interlinked importance of weight and fitness in relation to health. Obesity is understood as a description of people with centrally distributed fat, in association with low fitness levels. There is a need to increase understanding of the causes and consequences of diabetes. Discussion of increased health awareness by men round the age of 40 may indicate a window of opportunity to intervene at this time.</p

Statistical modeling of ground motion relations for seismic hazard analysis

We introduce a new approach for ground motion relations (GMR) in the probabilistic seismic hazard analysis (PSHA), being influenced by the extreme value theory of mathematical statistics. Therein, we understand a GMR as a random function. We derive mathematically the principle of area-equivalence; wherein two alternative GMRs have an equivalent influence on the hazard if these GMRs have equivalent area functions. This includes local biases. An interpretation of the difference between these GMRs (an actual and a modeled one) as a random component leads to a general overestimation of residual variance and hazard. Beside this, we discuss important aspects of classical approaches and discover discrepancies with the state of the art of stochastics and statistics (model selection and significance, test of distribution assumptions, extreme value statistics). We criticize especially the assumption of logarithmic normally distributed residuals of maxima like the peak ground acceleration (PGA). The natural distribution of its individual random component (equivalent to exp(epsilon_0) of Joyner and Boore 1993) is the generalized extreme value. We show by numerical researches that the actual distribution can be hidden and a wrong distribution assumption can influence the PSHA negatively as the negligence of area equivalence does. Finally, we suggest an estimation concept for GMRs of PSHA with a regression-free variance estimation of the individual random component. We demonstrate the advantages of event-specific GMRs by analyzing data sets from the PEER strong motion database and estimate event-specific GMRs. Therein, the majority of the best models base on an anisotropic point source approach. The residual variance of logarithmized PGA is significantly smaller than in previous models. We validate the estimations for the event with the largest sample by empirical area functions. etc