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    Constructive Relationships Between Algebraic Thickness and Normality

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    We study the relationship between two measures of Boolean functions; \emph{algebraic thickness} and \emph{normality}. For a function ff, the algebraic thickness is a variant of the \emph{sparsity}, the number of nonzero coefficients in the unique GF(2) polynomial representing ff, and the normality is the largest dimension of an affine subspace on which ff is constant. We show that for 0<ϵ<20 < \epsilon<2, any function with algebraic thickness n3ϵn^{3-\epsilon} is constant on some affine subspace of dimension Ω(nϵ2)\Omega\left(n^{\frac{\epsilon}{2}}\right). Furthermore, we give an algorithm for finding such a subspace. We show that this is at most a factor of Θ(n)\Theta(\sqrt{n}) from the best guaranteed, and when restricted to the technique used, is at most a factor of Θ(logn)\Theta(\sqrt{\log n}) from the best guaranteed. We also show that a concrete function, majority, has algebraic thickness Ω(2n1/6)\Omega\left(2^{n^{1/6}}\right).Comment: Final version published in FCT'201

    MRE11 complex links RECQ5 helicase to sites of DNA damage

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    RECQ5 DNA helicase suppresses homologous recombination (HR) possibly through disruption of RAD51 filaments. Here, we show that RECQ5 is constitutively associated with the MRE11-RAD50-NBS1 (MRN) complex, a primary sensor of DNA double-strand breaks (DSBs) that promotes DSB repair and regulates DNA damage signaling via activation of the ATM kinase. Experiments with purified proteins indicated that RECQ5 interacts with the MRN complex through both MRE11 and NBS1. Functional assays revealed that RECQ5 specifically inhibited the 3′→5′ exonuclease activity of MRE11, while MRN had no effect on the helicase activity of RECQ5. At the cellular level, we observed that the MRN complex was required for the recruitment of RECQ5 to sites of DNA damage. Accumulation of RECQ5 at DSBs was neither dependent on MDC1 that mediates binding of MRN to DSB-flanking chromatin nor on CtIP that acts in conjunction with MRN to promote resection of DSBs for repair by HR. Collectively, these data suggest that the MRN complex recruits RECQ5 to sites of DNA damage to regulate DNA repai

    Involvement of Werner syndrome protein in MUTYH-mediated repair of oxidative DNA damage

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    Reactive oxygen species constantly generated as by-products of cellular metabolism readily attack genomic DNA creating mutagenic lesions such as 7,8-dihydro-8-oxo-guanine (8-oxo-G) that promote aging. 8-oxo-G:A mispairs arising during DNA replication are eliminated by base excision repair initiated by the MutY DNA glycosylase homologue (MUTYH). Here, by using formaldehyde crosslinking in mammalian cell extracts, we demonstrate that the WRN helicase/exonuclease defective in the premature aging disorder Werner syndrome (WS) is recruited to DNA duplex containing an 8-oxo-G:A mispair in a manner dependent on DNA polymerase λ (Polλ) that catalyzes accurate DNA synthesis over 8-oxo-G. Similarly, by immunofluorescence, we show that Polλ is required for accumulation of WRN at sites of 8-oxo-G lesions in human cells. Moreover, we show that nuclear focus formation of WRN and Polλ induced by oxidative stress is dependent on ongoing DNA replication and on the presence of MUTYH. Cell viability assays reveal that depletion of MUTYH suppresses the hypersensitivity of cells lacking WRN and/or Polλ to oxidative stress. Biochemical studies demonstrate that WRN binds to the catalytic domain of Polλ and specifically stimulates DNA gap filling by Polλ over 8-oxo-G followed by strand displacement synthesis. Our results suggest that WRN promotes long-patch DNA repair synthesis by Polλ during MUTYH-initiated repair of 8-oxo-G:A mispair

    Security challenges of small cell as a service in virtualized mobile edge computing environments

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    Research on next-generation 5G wireless networks is currently attracting a lot of attention in both academia and industry. While 5G development and standardization activities are still at their early stage, it is widely acknowledged that 5G systems are going to extensively rely on dense small cell deployments, which would exploit infrastructure and network functions virtualization (NFV), and push the network intelligence towards network edges by embracing the concept of mobile edge computing (MEC). As security will be a fundamental enabling factor of small cell as a service (SCaaS) in 5G networks, we present the most prominent threats and vulnerabilities against a broad range of targets. As far as the related work is concerned, to the best of our knowledge, this paper is the first to investigate security challenges at the intersection of SCaaS, NFV, and MEC. It is also the first paper that proposes a set of criteria to facilitate a clear and effective taxonomy of security challenges of main elements of 5G networks. Our analysis can serve as a staring point towards the development of appropriate 5G security solutions. These will have crucial effect on legal and regulatory frameworks as well as on decisions of businesses, governments, and end-users

    Outcomes of less invasive J-incision approach to aortic valve surgery

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    ObjectiveLess invasive approaches to aortic valve surgery are increasingly used; however, few studies have investigated their impact on outcome. We sought to compare clinical outcomes after these approaches with full sternotomy using propensity-matching methods.MethodsFrom January 1995 to January 2004, a total of 2689 patients underwent isolated aortic valve surgery, 1193 via upper J-hemisternotomy and 1496 via full sternotomy. Because of important differences in patient characteristics between these groups, a propensity score based on 42 variables was used to obtain 832 well-matched patient pairs (70% of possible cases).ResultsIn-hospital mortality was identical for propensity-matched patients, 0.96% (8 in each). Occurrences of stroke (P > .9), renal failure (P = .8), and myocardial infarction (P = .7) were similar. However, 24-hour mediastinal drainage was a third less after less invasive surgery (median, 250 vs 350 mL; P < .0001), and fewer patients received transfusions (24% vs 34%; P < .0001). More patients undergoing less invasive surgery were extubated in the operating room (12% vs 1.6%; P < .0001), postoperative forced 1-second expiratory volume was higher (P = .009), and fewer had respiratory failure (P = .01). Early after operation, pain scores were lower (P < .0001) after less-invasive surgery and postoperative length of stay shorter (P < .0001).ConclusionsWithin that portion of the spectrum of isolated aortic valve surgery where propensity matching was possible, minimally invasive aortic valve surgery had not only cosmetic advantages, but blood product use, respiratory, pain, and resource utilization advantages over full sternotomy, and no apparent detriments. Less invasive aortic valve surgery should be considered for most aortic valve operations

    Molecular characterization of old local grapevine varieties from South East European countries

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    South East European (SEE) viticulture partially relies on native grapevine varieties, previously scarcely described. In order to characterize old local grapevine varieties and assess the level of synonymy and genetic diversity from SEE countries, we described and genotyped 122 accessions from Albania, Federation of Bosnia and Herzegovina (B&amp;H), Croatia, Macedonia, Moldova, Montenegro, Republika Srpska (Bosnia and Herzegovina) and Romania on nine most commonly used microsatellite loci. As a result of the study a total of 86 different genotypes were identified. All loci were very polymorphic and a total of 96 alleles were detected, ranging from 8 to 14 alleles per locus, with an average allele number of 10.67. Overall observed heterozygosity was 0.759 and slightly lower than expected (0.789) while gene diversity per locus varied between 0.600 (VVMD27) and 0.906 (VVMD28). Eleven cases of synonymy and three of homonymy have been recorded for samples harvested from different countries. Cultivars with identical genotypes were mostly detected between neighboring countries. No clear differentiation between countries was detected although several specific alleles were detected. The integration of the obtained genetic data with ampelographic ones is very important for accurate identification of the SEE cultivars and provides a significant tool in cultivar preservation and utilization.

    Extent of Thoracic Aortic Atheroma Burden and Long-Term Mortality After Cardiothoracic Surgery A Computed Tomography Study

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    ObjectivesWe hypothesized that the extent of aortic atheroma of the entire thoracic aorta, determined by pre-operative multidetector-row computed tomographic angiography (MDCTA), is associated with long-term mortality following nonaortic cardiothoracic surgery.BackgroundIn patients evaluated for cardiothoracic surgery, presence of severe aortic atheroma is associated with adverse short- and long-term post-operative outcome. However, the relationship between aortic plaque burden and mortality remains unknown.MethodsWe reviewed clinical and imaging data from all patients who underwent electrocardiographic-gated contrast-enhanced MDCTA prior to coronary bypass or valvular heart surgery at our institution between 2002 and 2008. MDCTA studies were analyzed for thickness and circumferential extent of aortic atheroma in 5 segments of the thoracic aorta. A semiquantitative total plaque-burden score (TPBS) was calculated by assigning a score of 1 to 3 to plaque thickness and to circumferential plaque extent. When combined, this resulted in a score of 0 to 6 for each of the 5 segments and, hence, an overall score from 0 to 30. The primary end point was all-cause mortality during long-term follow-up.ResultsA total of 862 patients (71% men, 67.8 years) were included and followed over a mean period of 25 ± 16 months. The mean TPBS was 8.6 (SD: ±6.0). The TPBS was a statistically significant predictor of mortality (p < 0.0001) while controlling for baseline demographics, cardiovascular risk factors, and type of surgery including reoperative status. The estimated hazard ratio for TPBS was 1.08 (95% confidence interval: 1.045 to 1.12). Other independent predictors of mortality were glomerular filtration rate (p = 0.015), type of surgery (p = 0.007), and peripheral artery disease (p = 0.03).ConclusionsExtent of thoracic aortic atheroma burden is independently associated with increased long-term mortality in patients following cardiothoracic surgery. Although our data do not provide definitive evidence, they suggest a relationship to the systemic atherosclerotic disease process and, therefore, have important implications for secondary prevention in post-operative rehabilitation programs
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