Siglec receptors impact mammalian lifespan by modulating oxidative stress.

Aging is a multifactorial process that includes the lifelong accumulation of molecular damage, leading to age-related frailty, disability and disease, and eventually death. In this study, we report evidence of a significant correlation between the number of genes encoding the immunomodulatory CD33-related sialic acid-binding immunoglobulin-like receptors (CD33rSiglecs) and maximum lifespan in mammals. In keeping with this, we show that mice lacking Siglec-E, the main member of the CD33rSiglec family, exhibit reduced survival. Removal of Siglec-E causes the development of exaggerated signs of aging at the molecular, structural, and cognitive level. We found that accelerated aging was related both to an unbalanced ROS metabolism, and to a secondary impairment in detoxification of reactive molecules, ultimately leading to increased damage to cellular DNA, proteins, and lipids. Taken together, our data suggest that CD33rSiglecs co-evolved in mammals to achieve a better management of oxidative stress during inflammation, which in turn reduces molecular damage and extends lifespan

Airborne observations of regional variation in fluorescent aerosol across the United States

Airborne observations of fluorescent aerosol were made aboard an airship during CloudLab, a series of flights that took place in September and October of 2013 and covered a wideband of longitude across the continental U.S. between Florida and California and between 28 and 37-N latitudes. Sampling occurred from near the surface to 1000-m above the ground. A Wideband Integrated Bioaerosol Sensor (WIBS-4) measured average concentrations of supermicron fluorescent particles aloft (1-μm to 10-μm), revealing number concentrations ranging from 2.1-±-0.8 to 8.7-±-2.2-×-104 particles m-3 and representing up to 24% of total supermicron particle number. We observed distinct variations in size distributions and fluorescent characteristics in different regions, and attribute these to geographically diverse bioaerosol. Fluorescent aerosol detected in the east is largely consistent with mold spores observed in a laboratory setting, while a shift to larger sizes associated with different fluorescent patterns is observed in the west. Fluorescent bioaerosol loadings in the desert west were as high as those near the Gulf of Mexico, suggesting that bioaerosol is a substantial component of supermicron aerosol both in humid and arid environments. The observations are compared to model fungal and bacterial loading predictions, and good agreement in both particle size and concentrations is observed in the east. In the west, the model underestimated observed concentrations by a factor between 2 and 4 and the prescribed particle sizes are smaller than the observed fluorescent aerosol. A classification scheme for use with WIBS data is also presented. Key Points Fluorescent supermicron aerosol loads are reported across the southern U.S. Regional variations in fluorescent behavior and particle size are observed Comparison to modeled emissions shows an underestimate in the wes

On duality symmetry in perturbative quantum theory

Non-compact symmetries of extended 4d supergravities involve duality rotations of vectors and thus are not manifest off-shell invariances in standard "second-order" formulation. To study how such symmetries are realised in the quantum theory we consider examples in 2 dimensions where vector-vector duality is replaced by scalar-scalar one. Using a "doubled" formulation, where fields and their momenta are treated on an equal footing and the duality becomes a manifest symmetry of the action (at the expense of Lorentz symmetry), we argue that the corresponding on-shell quantum effective action or S-matrix are duality symmetric as well as Lorentz invariant. The simplest case of discrete Z_2 duality corresponds to a symmetry of the S-matrix under flipping the sign of the negative-chirality scalars in 2 dimensions or phase rotations of chiral (definite-helicity) parts of vectors in 4 dimensions. We also briefly discuss some 4d models and comment on implications of our analysis for extended supergravities.Comment: 21 pages, Latex v2: comments and references added v3: references and minor comments adde

R^4 counterterm and E7(7) symmetry in maximal supergravity

The coefficient of a potential R^4 counterterm in N=8 supergravity has been shown previously to vanish in an explicit three-loop calculation. The R^4 term respects N=8 supersymmetry; hence this result poses the question of whether another symmetry could be responsible for the cancellation of the three-loop divergence. In this article we investigate possible restrictions from the coset symmetry E7(7)/SU(8), exploring the limits as a single scalar becomes soft, as well as a double-soft scalar limit relation derived recently by Arkani-Hamed et al. We implement these relations for the matrix elements of the R^4 term that occurs in the low-energy expansion of closed-string tree-level amplitudes. We find that the matrix elements of R^4 that we investigated all obey the double-soft scalar limit relation, including certain non-maximally-helicity-violating six-point amplitudes. However, the single-soft limit does not vanish for this latter set of amplitudes, which suggests that the E7(7) symmetry is broken by the R^4 term.Comment: 33 pages, typos corrected, published versio

Oscillatory surface rheotaxis of swimming E. coli bacteria

Bacterial contamination of biological conducts, catheters or water resources is a major threat to public health and can be amplified by the ability of bacteria to swim upstream. The mechanisms of this rheotaxis, the reorientation with respect to flow gradients, often in complex and confined environments, are still poorly understood. Here, we follow individual E. coli bacteria swimming at surfaces under shear flow with two complementary experimental assays, based on 3D Lagrangian tracking and fluorescent flagellar labelling and we develop a theoretical model for their rheotactic motion. Three transitions are identified with increasing shear rate: Above a first critical shear rate, bacteria shift to swimming upstream. After a second threshold, we report the discovery of an oscillatory rheotaxis. Beyond a third transition, we further observe coexistence of rheotaxis along the positive and negative vorticity directions. A full theoretical analysis explains these regimes and predicts the corresponding critical shear rates. The predicted transitions as well as the oscillation dynamics are in good agreement with experimental observations. Our results shed new light on bacterial transport and reveal new strategies for contamination prevention.Comment: 12 pages, 5 figure

SVCEval-RA: an evaluation framework for adaptive scalable video streaming

[EN] Multimedia content adaption strategies are becoming increasingly important for effective video streaming over the actual heterogeneous networks. Thus, evaluation frameworks for adaptive video play an important role in the designing and deploying process of adaptive multimedia streaming systems. This paper describes a novel simulation framework for rate-adaptive video transmission using the Scalable Video Coding standard (H.264/SVC). Our approach uses feedback information about the available bandwidth to allow the video source to select the most suitable combination of SVC layers for the transmission of a video sequence. The proposed solution has been integrated into the network simulator NS-2 in order to support realistic network simulations. To demonstrate the usefulness of the proposed solution we perform a simulation study where a video sequence was transmitted over a three network scenarios. The experimental results show that the Adaptive SVC scheme implemented in our framework provides an efficient alternative that helps to avoid an increase in the network congestion in resource-constrained networks. Improvements in video quality, in terms of PSNR (Peak Signal to Noise Ratio) and SSIM (Structural Similarity Index) are also obtained.Castellanos Hernández, WE.; Guerri Cebollada, JC.; Arce Vila, P. (2017). SVCEval-RA: an evaluation framework for adaptive scalable video streaming. Multimedia Tools and Applications. 76(1):437-461. doi:10.1007/s11042-015-3046-yS437461761Akhshabi S, Begen AC, Dovrolis C (2011) An experimental evaluation of rate-adaptation algorithms in adaptive streaming over HTTP. In: Proceedings of the second annual ACM conference on Multimedia systems. ACM, pp 157–168Alabdulkarim MN, Rikli N-E (2012) QoS Provisioning for H.264/SVC Streams over Ad-Hoc ZigBee Networks Using Cross-Layer Design. In: 8th International Conference on Wireless Communications, Networking and Mobile Computing (WiCOM). pp 1–8Birkos K, Tselios C, Dagiuklas T, Kotsopoulos S (2013) Peer selection and scheduling of H. 264 SVC video over wireless networks. In: Wireless Communications and Networking Conference (WCNC), 2013 IEEE. pp 1633–1638Castellanos W (2014) SVCEval-RA - An Evaluation Framework for Adaptive Scalable Video Streaming. In: SourceForge Project. http://sourceforge.net/projects/svceval-ra/ . Accessed 1 May 2015Castellanos W, Guerri JC, Arce P (2015) A QoS-aware routing protocol with adaptive feedback scheme for video streaming for mobile networks. Comput Commun. http://dx.doi.org/10.1016/j.comcom.2015.08.012Castellanos W, Arce P, Acelas P, Guerri JC (2012) Route Recovery Algorithm for QoS-Aware Routing in MANETs. Springer Berlin Heidelberg, Bilbao, pp. 81–93Chikkerur S, Sundaram V, Reisslein M, Karam LJ (2011) Objective video quality assessment methods: A classification, review, and performance comparison. Broadcast, IEEE Trans on 57:165–182Choupani R, Wong S, Tolun M (2014) Multiple description coding for SNR scalable video transmission over unreliable networks. Multimed Tools Appl 69:843–858. doi: 10.1007/s11042-012-1150-9CISCO Corp. (2014) Cisco Visual Networking Index Forecast and Methodology. In: White Paper. http://www.cisco.com/c/en/us/solutions/collateral/service-provider/ip-ngn-ip-next-generation-network/white_paper_c11-481360.pdf.Dai M, Zhang Y, Loguinov D (2009) A unified traffic model for MPEG-4 and H. 264 video traces. IEEE Trans Multimedia 11:1010–1023Detti A, Bianchi G, Pisa C, et al. (2009) SVEF: an open-source experimental evaluation framework for H.264 scalable video streaming. In: IEEE Symposium on Computers and Communications. pp 36–41Espina F, Morato D, Izal M, Magaña E (2014) Analytical model for MPEG video frame loss rates and playback interruptions on packet networks. Multimed Tools Appl 72:361–383. doi: 10.1007/s11042-012-1344-1Fiems D, Steyaert B, Bruneel H (2012) A genetic approach to Markovian characterisation of H.264 scalable video. Multimedia Tools Appl 58:125–146Floyd S, Handley M, Kohler E Datagram Congestion Control Protocol (DCCP). http://tools.ietf.org/html/rfc4340 . Accessed 17 Feb 2014Floyd S, Padhye J, Widmer J TCP Friendly Rate Control (TFRC): Protocol Specification. http://tools.ietf.org/html/rfc5348 . Accessed 17 Feb 2014Fraz M, Malkani YA, Elahi MA (2009) Design and implementation of real time video streaming and ROI transmission system using RTP on an embedded digital signal processing (DSP) platform. In: 2nd International Conference on Computer, Control and Communication, 2009. IC4 2009. pp 1–6ISO/IEC (2014) Information technology - Dynamic adaptive streaming over HTTP (DASH) - Part 1: Media presentation description and segment formats.ITU-T (2013) Rec. H.264 & ISO/IEC 14496-10 AVC. Advanced Video Coding for Generic Audiovisual Services.Ivrlač MT, Choi LU, Steinbach E, Nossek JA (2009) Models and analysis of streaming video transmission over wireless fading channels. Signal Process Image Commun 24:651–665. doi: 10.1016/j.image.2009.04.005Karki R, Seenivasan T, Claypool M, Kinicki R (2010) Performance Analysis of Home Streaming Video Using Orb. In: Proceedings of the 20th International Workshop on Network and Operating Systems Support for Digital Audio and Video. ACM, New York, NY, USA, pp 111–116Ke C-H (2012) myEvalSVC-an Integrated Simulation Framework for Evaluation of H. 264/SVC Transmission. KSII Trans Internet Inf Syst (TIIS) 6:377–392. doi: 10.3837/tiis.2012.01.021Ke C-H, Shieh C-K, Hwang W-S, Ziviani A (2008) An Evaluation Framework for More Realistic Simulations of MPEG Video Transmission. J Inf Sci Eng 24:425–440Klaue J, Rathke B, Wolisz A (2003) Evalvid–A framework for video transmission and quality evaluation. In: Computer Performance Evaluation. Modelling Techniques and Tools. Springer, pp 255–272Le TA, Nguyen H (2014) End-to-end transmission of scalable video contents: performance evaluation over EvalSVC—a new open-source evaluation platform. Multimed Tools Appl 72:1239–1256. doi: 10.1007/s11042-013-1444-6Lie A, Klaue J (2008) Evalvid-RA: trace driven simulation of rate adaptive MPEG-4 VBR video. Multimedia Systems 14:33–50. doi: 10.1007/s00530-007-0110-0Moving Pictures Experts Group and ITU-T Video Coding Experts Group (2011) H. 264/SVC reference software (JSVM 9.19.14) and Manual.Nightingale J, Wang Q, Grecos C (2014) Empirical evaluation of H.264/SVC streaming in resource-constrained multihomed mobile networks. Multimed Tools Appl 70:2011–2035. doi: 10.1007/s11042-012-1219-5Parmar H, Thornburgh M (2012) Real-Time Messaging Protocol (RTMP) Specification. AdobePolitis I, Dounis L, Dagiuklas T (2012) H. 264/SVC vs. H. 264/AVC video quality comparison under QoE-driven seamless handoff. Signal Process Image Commun 27:814–826Pozueco L, Pañeda XG, García R, et al. (2013) Adaptable system based on Scalable Video Coding for high-quality video service. Comput Electr Eng 39:775–789. doi: 10.1016/j.compeleceng.2013.01.015Pozueco L, Pañeda XG, García R, et al. (2014) Adaptation engine for a streaming service based on MPEG-DASH. Multimed Tools Appl 1–20. doi: 10.1007/s11042-014-2034-ySchwarz H, Marpe D, Wiegand T (2007) Overview of the Scalable Video Coding Extension of the H.264/AVC Standard. IEEE Trans Circ Syst Video Technol 17:1103–1120. doi: 10.1109/TCSVT.2007.905532Seo H-Y (2013) An Efficient Transmission Scheme of MPEG2-TS over RTP for a Hybrid DMB System. ETRI J 35:655–665. doi: 10.4218/etrij.13.0112.0124Sohn H, Yoo H, De Neve W, et al. (2010) Full-Reference Video Quality Metric for Fully Scalable and Mobile SVC Content. IEEE Trans Broadcast 56:269–280. doi: 10.1109/TBC.2010.2050628Sousa-Vieira M-E (2011) Suitability of the M/G/∞ process for modeling scalable H.264 video traffic. In: Analytical and Stochastic Modeling Techniques and Applications. Springer, pp 149–158Tanwir S, Perros H (2013) A Survey of VBR Video Traffic Models. IEEE Commun Surv Tutor 15:1778–1802. doi: 10.1109/SURV.2013.010413.00071Tanwir S, Perros HG (2014) VBR Video Traffic Models. Wiley, HobokenThe Network Simulator (NS-2). http://www.isi.edu/nsnam/ns . Accessed 6 Feb 2015Unanue I, Urteaga I, Husemann R, et al. (2011) A Tutorial on H. 264/SVC Scalable Video Coding and its Tradeoff between Quality, Coding Efficiency and Performance. Recent Advances on Video Coding 1–24.Van der Auwera G, David PT, Reisslein M, Karam LJ (2008) Traffic and quality characterization of the H. 264/AVC scalable video coding extension. Adv Multimedia 2008:1Wang Y, Claypool M (2005) RealTracer—Tools for Measuring the Performance of RealVideo on the Internet. Multimed Tools Appl 27:411–430. doi: 10.1007/s11042-005-3757-6Wang Z, Lu L, Bovik AC (2004) Video quality assessment based on structural distortion measurement. Signal Process Image Commun 19:121–132. doi: 10.1016/S0923-5965(03)00076–6Wien M, Schwarz H, Oelbaum T (2007) Performance Analysis of SVC. IEEE Trans Circ Syst for Video Technol 17:1194–1203. doi: 10.1109/TCSVT.2007.905530YUV video repository. ftp://ftp.tnt.uni-hannover.de/pub/svc/testsequences/ . Accessed 10 Jan 201

Zinc and silica are active components to efficiently treat in vitro simulated eroded dentin.

Objectives: Biomaterials for treating dentin hypersensitivity and dentin wear were evaluated, to efficiently occlude the dentinal tubules and to increase dentin resistance to abrasion. Materials and Methods: 24 dentin surfaces were treated with EDTA to expose dentinal tubules, and were: 1) non-brushed, 2) brushed with distilled water, or with pastes containing 3) Monetite, 4) Brushite, 5) Zn-Monetite, 6) Zn-Brushite, 7) Silica-Brushite and 8) NovaMin®. Topography, nanomechanical and chemical analysis were assessed on dentin surfaces (n=3) after artificial saliva immersion for 24 h, and after citric acid challenge. 21 further dentin specimens were created to evaluate dentin permeability after brushing, saliva storage and acid application (n=3). ANOVA, Student-Newman-Keuls (p<0.05) and Student t-test (p<0.001) were used. Results: Particles containing major proportion of silica attained intratubular occlusion by carbonate crystals (Raman carbonate peak heights: 15.17 and 19.24 au; complex modulus: 110 and 140 GPa, at intratubular dentin). When brushing with pastes containing higher proportion of silica or zinc, phosphate calcium compounds were encountered into tubules and over dentin surfaces (Raman intratubular phosphate peak heights: 49 to 70 au, and at the intertubular dentin: 78 to 92). The formed carbonated apatite and calcium phosphate layer were resistant to citric acid application. Zinc compounds drastically increased tubule occlusion, decreased dentin permeability (up to 30%) and augmented mechanical properties at the intertubular dentin (90-130 GPa), it was maintained after acid challenging. Conclusions: Zinc-containing pastes occluded dentinal tubules and improved dentin mechanical properties. Clinical Relevance: Using zinc as an active component to treat eroded dentin is encouraged.Projects RTC-2014-1731-1 and MAT2014-52036-P supported by the Ministry of Economy and Competitiveness and European Regional Development Fund

Common Variants at 10 Genomic Loci Influence Hemoglobin A(1C) Levels via Glycemic and Nonglycemic Pathways

OBJECTIVE Glycated hemoglobin (HbA1c), used to monitor and diagnose diabetes, is influenced by average glycemia over a 2- to 3-month period. Genetic factors affecting expression, turnover, and abnormal glycation of hemoglobin could also be associated with increased levels of HbA1c. We aimed to identify such genetic factors and investigate the extent to which they influence diabetes classification based on HbA1c levels. RESEARCH DESIGN AND METHODS We studied associations with HbA1c in up to 46,368 nondiabetic adults of European descent from 23 genome-wide association studies (GWAS) and 8 cohorts with de novo genotyped single nucleotide polymorphisms (SNPs). We combined studies using inverse-variance meta-analysis and tested mediation by glycemia using conditional analyses. We estimated the global effect of HbA1c loci using a multilocus risk score, and used net reclassification to estimate genetic effects on diabetes screening. RESULTS Ten loci reached genome-wide significant association with HbA1c, including six new loci near FN3K (lead SNP/P value, rs1046896/P = 1.6 × 10−26), HFE (rs1800562/P = 2.6 × 10−20), TMPRSS6 (rs855791/P = 2.7 × 10−14), ANK1 (rs4737009/P = 6.1 × 10−12), SPTA1 (rs2779116/P = 2.8 × 10−9) and ATP11A/TUBGCP3 (rs7998202/P = 5.2 × 10−9), and four known HbA1c loci: HK1 (rs16926246/P = 3.1 × 10−54), MTNR1B (rs1387153/P = 4.0 × 10−11), GCK (rs1799884/P = 1.5 × 10−20) and G6PC2/ABCB11 (rs552976/P = 8.2 × 10−18). We show that associations with HbA1c are partly a function of hyperglycemia associated with 3 of the 10 loci (GCK, G6PC2 and MTNR1B). The seven nonglycemic loci accounted for a 0.19 (% HbA1c) difference between the extreme 10% tails of the risk score, and would reclassify ∼2% of a general white population screened for diabetes with HbA1c. CONCLUSIONS GWAS identified 10 genetic loci reproducibly associated with HbA1c. Six are novel and seven map to loci where rarer variants cause hereditary anemias and iron storage disorders. Common variants at these loci likely influence HbA1c levels via erythrocyte biology, and confer a small but detectable reclassification of diabetes diagnosis by HbA1c

A systematic, large-scale comparison of transcription factor binding site models

Background The modelling of gene regulation is a major challenge in biomedical research. This process is dominated by transcription factors (TFs) and mutations in their binding sites (TFBSs) may cause the misregulation of genes, eventually leading to disease. The consequences of DNA variants on TF binding are modelled in silico using binding matrices, but it remains unclear whether these are capable of accurately representing in vivo binding. In this study, we present a systematic comparison of binding models for 82 human TFs from three freely available sources: JASPAR matrices, HT-SELEX-generated models and matrices derived from protein binding microarrays (PBMs). We determined their ability to detect experimentally verified “real” in vivo TFBSs derived from ENCODE ChIP-seq data. As negative controls we chose random downstream exonic sequences, which are unlikely to harbour TFBS. All models were assessed by receiver operating characteristics (ROC) analysis. Results While the area- under-curve was low for most of the tested models with only 47 % reaching a score of 0.7 or higher, we noticed strong differences between the various position-specific scoring matrices with JASPAR and HT-SELEX models showing higher success rates than PBM-derived models. In addition, we found that while TFBS sequences showed a higher degree of conservation than randomly chosen sequences, there was a high variability between individual TFBSs. Conclusions Our results show that only few of the matrix-based models used to predict potential TFBS are able to reliably detect experimentally confirmed TFBS. We compiled our findings in a freely accessible web application called ePOSSUM (http:/mutationtaster.charite.de/ePOSSUM/) which uses a Bayes classifier to assess the impact of genetic alterations on TF binding in user-defined sequences. Additionally, ePOSSUM provides information on the reliability of the prediction using our test set of experimentally confirmed binding sites

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes