Early growth response 2 (EGR2) is a novel regulator of the senescence programme.

Senescence, a state of stable growth arrest, plays an important role in ageing and age-related diseases in vivo. Although the INK4/ARF locus is known to be essential for senescence programmes, the key regulators driving p16 and ARF transcription remain largely underexplored. Using siRNA screening for modulators of the p16/pRB and ARF/p53/p21 pathways in deeply senescent human mammary epithelial cells (DS HMECs) and fibroblasts (DS HMFs), we identified EGR2 as a novel regulator of senescence. EGR2 expression is up-regulated during senescence, and its ablation by siRNA in DS HMECs and HMFs transiently reverses the senescent phenotype. We demonstrate that EGR2 activates the ARF and p16 promoters and directly binds to both the ARF and p16 promoters. Loss of EGR2 down-regulates p16 levels and increases the pool of p16- p21- 'reversed' cells in the population. Moreover, EGR2 overexpression is sufficient to induce senescence. Our data suggest that EGR2 is a direct transcriptional activator of the p16/pRB and ARF/p53/p21 pathways in senescence and a novel marker of senescence

Bi-local Construction of Sp(2N)/dS Higher Spin Correspondence

We derive a collective field theory of the singlet sector of the Sp(2N) sigma model. Interestingly the hamiltonian for the bilocal collective field is the same as that of the O(N) model. However, the large-N saddle points of the two models differ by a sign. This leads to a fluctuation hamiltonian with a negative quadratic term and alternating signs in the nonlinear terms which correctly reproduces the correlation functions of the singlet sector. Assuming the validity of the connection between O(N) collective fields and higher spin fields in AdS, we argue that a natural interpretation of this theory is by a double analytic continuation, leading to the dS/CFT correspondence proposed by Anninos, Hartman and Strominger. The bi-local construction gives a map into the bulk of de Sitter space-time. Its geometric pseudospin-representation provides a framework for quantization and definition of the Hilbert space. We argue that this is consistent with finite N grassmanian constraints, establishing the bi-local representation as a nonperturbative framework for quantization of Higher Spin Gravity in de Sitter space.Comment: 1 figur

Regional movements of the tiger shark, Galeocerdo cuvier, off northeastern Brazil: inferences regarding shark attack hazard

An abnormally high shark attack rate verified off Recife could be related to migratory behavior of tiger sharks. This situation started after the construction of the Suape port to the south of Recife. A previous study suggested that attacking sharks could be following northward currents and that they were being attracted shoreward by approaching vessels. In this scenario, such northward movement pattern could imply a higher probability of sharks accessing the littoral area of Recife after leaving Suape. Pop-up satellite archival taus were deployed on five tiger sharks caught off Recife to assess their movement patterns off northeastern Brazil. All tags transmitted from northward latitudes after 7-74 days of freedom. The shorter, soak distance between deployment and pop-up locations ranged between 33-209 km and implied minimum average speeds of 0.02-0.98 km.h(-1). Both pop-up locations and depth data suggest that tiger shark movements were conducted mostly over the continental shelf. The smaller sharks moved to deeper waters within 24 hours after releasing, but they assumed a shallower (< 50 m) vertical distribution for most of the monitoring period. While presenting the first data on tiger shark movements in the South Atlantic, this study also adds new information for the reasoning of the high shark attack rate verified in this region,State Government of Pernambuco and Petrobras (Brazil); Fundacao para a Ciencia e Tecnologia (Portugal) [MCTES/FCT/SFRH/BD/37065/2007

Congestive Heart Failure Leads to Prolongation of the PR Interval and Atrioventricular Junction Enlargement and Ion Channel Remodelling in the Rabbit.

Heart failure is a major killer worldwide. Atrioventricular conduction block is common in heart failure; it is associated with worse outcomes and can lead to syncope and bradycardic death. We examine the effect of heart failure on anatomical and ion channel remodelling in the rabbit atrioventricular junction (AVJ). Heart failure was induced in New Zealand rabbits by disruption of the aortic valve and banding of the abdominal aorta resulting in volume and pressure overload. Laser micro-dissection and real-time polymerase chain reaction (RT-PCR) were employed to investigate the effects of heart failure on ion channel remodelling in four regions of the rabbit AVJ and in septal tissues. Investigation of the AVJ anatomy was performed using micro-computed tomography (micro-CT). Heart failure animals developed first degree heart block. Heart failure caused ventricular myocardial volume increase with a 35% elongation of the AVJ. There was downregulation of HCN1 and Cx43 mRNA transcripts across all regions and downregulation of Cav1.3 in the transitional tissue. Cx40 mRNA was significantly downregulated in the atrial septum and AVJ tissues but not in the ventricular septum. mRNA abundance for ANP, CLCN2 and Navβ1 was increased with heart failure; Nav1.1 was increased in the inferior nodal extension/compact node area. Heart failure in the rabbit leads to prolongation of the PR interval and this is accompanied by downregulation of HCN1, Cav1.3, Cx40 and Cx43 mRNAs and anatomical enlargement of the entire heart and AVJ

A comparison of the seasonal movements of tiger sharks and green turtles provides insight into their predator-prey relationship

During the reproductive season, sea turtles use a restricted area in the vicinity of their nesting beaches, making them vulnerable to predation. At Raine Island (Australia), the highest density green turtle Chelonia mydas rookery in the world, tiger sharks Galeocerdo cuvier have been observed to feed on green turtles, and it has been suggested that they may specialise on such air-breathing prey. However there is little information with which to examine this hypothesis. We compared the spatial and temporal components of movement behaviour of these two potentially interacting species in order to provide insight into the predator-prey relationship. Specifically, we tested the hypothesis that tiger shark movements are more concentrated at Raine Island during the green turtle nesting season than outside the turtle nesting season when turtles are not concentrated at Raine Island. Turtles showed area-restricted search behaviour around Raine Island for ~3&ndash;4 months during the nesting period (November&ndash;February). This was followed by direct movement (transit) to putative foraging grounds mostly in the Torres Straight where they switched to area-restricted search mode again, and remained resident for the remainder of the deployment (53&ndash;304 days). In contrast, tiger sharks displayed high spatial and temporal variation in movement behaviour which was not closely linked to the movement behaviour of green turtles or recognised turtle foraging grounds. On average, tiger sharks were concentrated around Raine Island throughout the year. While information on diet is required to determine whether tiger sharks are turtle specialists our results support the hypothesis that they target this predictable and plentiful prey during turtle nesting season, but they might not focus on this less predictable food source outside the nesting season

Quantification of atopy, lung function and airway hypersensitivity in adults

<p>Abstract</p> <p>Background</p> <p>Studies in children have shown that concentration of specific serum IgE (sIgE) and size of skin tests to inhalant allergens better predict wheezing and reduced lung function than the information on presence or absence of atopy. However, very few studies in adults have investigated the relationship of quantitative atopy with lung function and airway hyperresponsiveness (AHR).</p> <p>Objective</p> <p>To determine the association between lung function and AHR and quantitative atopy in a large sample of adults from the UK.</p> <p>Methods</p> <p>FEV₁ and FVC (% predicted) were measured using spirometry and airway responsiveness by methacholine challenge (5-breath dosimeter protocol) in 983 subjects (random sample of 800 parents of children enrolled in a population-based birth cohort enriched with 183 patients with physician-diagnosed asthma). Atopic status was assessed by skin prick tests (SPT) and measurement of sIgE (common inhalant allergens). We also measured indoor allergen exposure in subjects' homes.</p> <p>Results</p> <p>Spirometry was completed by 792 subjects and 626 underwent methacholine challenge, with 100 (16.0%) having AHR (dose-response slope>25). Using sIgE as a continuous variable in a multiple linear regression analysis, we found that increasing levels of sIgE to mite, cat and dog were significantly associated with lower FEV₁ (mite p = 0.001, cat p = 0.0001, dog p = 2.95 × 10^-8). Similar findings were observed when using the size of wheal on skin testing as a continuous variable, with significantly poorer lung function with increasing skin test size (mite p = 8.23 × 10^-8, cat p = 3.93 × 10^-10, dog p = 3.03 × 10^-15, grass p = 2.95 × 10^-9). The association between quantitative atopy with lung function and AHR remained unchanged when we repeated the analyses amongst subjects defined as sensitised using standard definitions (sIgE>0.35 kUa/l, SPT-3 mm>negative control).</p> <p>Conclusions</p> <p>In the studied population, lung function decreased and AHR increased with increasing sIgE levels or SPT wheal diameter to inhalant allergens, suggesting that atopy may not be a dichotomous outcome influencing lung function and AHR.</p

The geography of recent genetic ancestry across Europe

The recent genealogical history of human populations is a complex mosaic formed by individual migration, large-scale population movements, and other demographic events. Population genomics datasets can provide a window into this recent history, as rare traces of recent shared genetic ancestry are detectable due to long segments of shared genomic material. We make use of genomic data for 2,257 Europeans (the POPRES dataset) to conduct one of the first surveys of recent genealogical ancestry over the past three thousand years at a continental scale. We detected 1.9 million shared genomic segments, and used the lengths of these to infer the distribution of shared ancestors across time and geography. We find that a pair of modern Europeans living in neighboring populations share around 10-50 genetic common ancestors from the last 1500 years, and upwards of 500 genetic ancestors from the previous 1000 years. These numbers drop off exponentially with geographic distance, but since genetic ancestry is rare, individuals from opposite ends of Europe are still expected to share millions of common genealogical ancestors over the last 1000 years. There is substantial regional variation in the number of shared genetic ancestors: especially high numbers of common ancestors between many eastern populations likely date to the Slavic and/or Hunnic expansions, while much lower levels of common ancestry in the Italian and Iberian peninsulas may indicate weaker demographic effects of Germanic expansions into these areas and/or more stably structured populations. Recent shared ancestry in modern Europeans is ubiquitous, and clearly shows the impact of both small-scale migration and large historical events. Population genomic datasets have considerable power to uncover recent demographic history, and will allow a much fuller picture of the close genealogical kinship of individuals across the world.Comment: Full size figures available from http://www.eve.ucdavis.edu/~plralph/research.html; or html version at http://ralphlab.usc.edu/ibd/ibd-paper/ibd-writeup.xhtm

Constraining noncommutative field theories with holography

An important window to quantum gravity phenomena in low energy noncommutative (NC) quantum field theories (QFTs) gets represented by a specific form of UV/IR mixing. Yet another important window to quantum gravity, a holography, manifests itself in effective QFTs as a distinct UV/IR connection. In matching these two principles, a useful relationship connecting the UV cutoff $\Lambda_{\rm UV}$, the IR cutoff $\Lambda_{\rm IR}$ and the scale of noncommutativity $\Lambda_{\rm NC}$, can be obtained. We show that an effective QFT endowed with both principles may not be capable to fit disparate experimental bounds simultaneously, like the muon $g-2$ and the masslessness of the photon. Also, the constraints from the muon $g-2$ preclude any possibility to observe the birefringence of the vacuum coming from objects at cosmological distances. On the other hand, in NC theories without the UV completion, where the perturbative aspect of the theory (obtained by truncating a power series in $\Lambda_{\rm NC}^{-2}$) becomes important, a heuristic estimate of the region where the perturbative expansion is well-defined $E/ \Lambda_{\rm NC} \lesssim 1$, gets affected when holography is applied by providing the energy of the system $E$ a $\Lambda_{\rm NC}$-dependent lower limit. This may affect models which try to infer the scale $\Lambda_{\rm NC}$ by using data from low-energy experiments.Comment: 4 pages, version to be published in JHE

Visual change detection on tunnel linings

We describe an automated system for detecting, localising, clustering and ranking visual changes on tunnel surfaces. The system is designed to provide assistance to expert human inspectors carrying out structural health monitoring and maintenance on ageing tunnel networks. A three-dimensional tunnel surface model is first recovered from a set of reference images using Structure from Motion techniques. New images are localised accurately within the model and changes are detected versus the reference images and model geometry. We formulate the problem of detecting changes probabilistically and evaluate the use of different feature maps and a novel geometric prior to achieve invariance to noise and nuisance sources such as parallax and lighting changes. A clustering and ranking method is proposed which efficiently presents detected changes and further improves the inspection efficiency. System performance is assessed on a real data set collected using a low-cost prototype capture device and labelled with ground truth. Results demonstrate that our system is a step towards higher frequency visual inspection at a reduced cost.The authors gratefully acknowledge the support by Toshiba Research Europe.This is the accepted manuscript. The final publication is available at Springer via http://dx.doi.org/10.1007/s00138-014-0648-8