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Showing papers by "University of Rennes published in 2016"


Journal ArticleDOI
Daniel J. Klionsky1, Kotb Abdelmohsen2, Akihisa Abe3, Joynal Abedin4  +2519 moreInstitutions (695)
TL;DR: In this paper, the authors present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macro-autophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes.
Abstract: In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagy-related protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.

5,187 citations


Journal ArticleDOI
B. P. Abbott1, Richard J. Abbott1, T. D. Abbott2, M. R. Abernathy3  +970 moreInstitutions (114)
TL;DR: This second gravitational-wave observation provides improved constraints on stellar populations and on deviations from general relativity.
Abstract: We report the observation of a gravitational-wave signal produced by the coalescence of two stellar-mass black holes. The signal, GW151226, was observed by the twin detectors of the Laser Interferometer Gravitational-Wave Observatory (LIGO) on December 26, 2015 at 03:38:53 UTC. The signal was initially identified within 70 s by an online matched-filter search targeting binary coalescences. Subsequent off-line analyses recovered GW151226 with a network signal-to-noise ratio of 13 and a significance greater than 5 σ. The signal persisted in the LIGO frequency band for approximately 1 s, increasing in frequency and amplitude over about 55 cycles from 35 to 450 Hz, and reached a peak gravitational strain of 3.4+0.7−0.9×10−22. The inferred source-frame initial black hole masses are 14.2+8.3−3.7M⊙ and 7.5+2.3−2.3M⊙ and the final black hole mass is 20.8+6.1−1.7M⊙. We find that at least one of the component black holes has spin greater than 0.2. This source is located at a luminosity distance of 440+180−190 Mpc corresponding to a redshift 0.09+0.03−0.04. All uncertainties define a 90 % credible interval. This second gravitational-wave observation provides improved constraints on stellar populations and on deviations from general relativity.

3,448 citations


Journal ArticleDOI
Mingxun Wang1, Jeremy Carver1, Vanessa V. Phelan2, Laura M. Sanchez2, Neha Garg2, Yao Peng1, Don D. Nguyen1, Jeramie D. Watrous2, Clifford A. Kapono1, Tal Luzzatto-Knaan2, Carla Porto2, Amina Bouslimani2, Alexey V. Melnik2, Michael J. Meehan2, Wei-Ting Liu3, Max Crüsemann4, Paul D. Boudreau4, Eduardo Esquenazi, Mario Sandoval-Calderón5, Roland D. Kersten6, Laura A. Pace2, Robert A. Quinn7, Katherine R. Duncan8, Cheng-Chih Hsu1, Dimitrios J. Floros1, Ronnie G. Gavilan, Karin Kleigrewe4, Trent R. Northen9, Rachel J. Dutton10, Delphine Parrot11, Erin E. Carlson12, Bertrand Aigle13, Charlotte Frydenlund Michelsen14, Lars Jelsbak14, Christian Sohlenkamp5, Pavel A. Pevzner1, Anna Edlund15, Anna Edlund16, Jeffrey S. McLean15, Jeffrey S. McLean17, Jörn Piel18, Brian T. Murphy19, Lena Gerwick4, Chih-Chuang Liaw20, Yu-Liang Yang21, Hans-Ulrich Humpf22, Maria Maansson14, Robert A. Keyzers23, Amy C. Sims24, Andrew R. Johnson25, Ashley M. Sidebottom25, Brian E. Sedio26, Andreas Klitgaard14, Charles B. Larson2, Charles B. Larson4, Cristopher A. Boya P., Daniel Torres-Mendoza, David Gonzalez2, Denise Brentan Silva27, Denise Brentan Silva28, Lucas Miranda Marques27, Daniel P. Demarque27, Egle Pociute, Ellis C. O’Neill4, Enora Briand4, Enora Briand11, Eric J. N. Helfrich18, Eve A. Granatosky29, Evgenia Glukhov4, Florian Ryffel18, Hailey Houson, Hosein Mohimani1, Jenan J. Kharbush4, Yi Zeng1, Julia A. Vorholt18, Kenji L. Kurita30, Pep Charusanti1, Kerry L. McPhail31, Kristian Fog Nielsen14, Lisa Vuong, Maryam Elfeki19, Matthew F. Traxler32, Niclas Engene33, Nobuhiro Koyama2, Oliver B. Vining31, Ralph S. Baric24, Ricardo Pianta Rodrigues da Silva27, Samantha J. Mascuch4, Sophie Tomasi11, Stefan Jenkins9, Venkat R. Macherla, Thomas Hoffman, Vinayak Agarwal4, Philip G. Williams34, Jingqui Dai34, Ram P. Neupane34, Joshua R. Gurr34, Andrés M. C. Rodríguez27, Anne Lamsa1, Chen Zhang1, Kathleen Dorrestein2, Brendan M. Duggan2, Jehad Almaliti2, Pierre-Marie Allard35, Prasad Phapale, Louis-Félix Nothias36, Theodore Alexandrov, Marc Litaudon36, Jean-Luc Wolfender35, Jennifer E. Kyle37, Thomas O. Metz37, Tyler Peryea38, Dac-Trung Nguyen38, Danielle VanLeer38, Paul Shinn38, Ajit Jadhav38, Rolf Müller, Katrina M. Waters37, Wenyuan Shi15, Xueting Liu39, Lixin Zhang39, Rob Knight1, Paul R. Jensen4, Bernhard O. Palsson1, Kit Pogliano1, Roger G. Linington30, Marcelino Gutiérrez, Norberto Peporine Lopes27, William H. Gerwick4, William H. Gerwick2, Bradley S. Moore4, Bradley S. Moore2, Pieter C. Dorrestein2, Pieter C. Dorrestein4, Nuno Bandeira1, Nuno Bandeira2 
TL;DR: In GNPS, crowdsourced curation of freely available community-wide reference MS libraries will underpin improved annotations and data-driven social-networking should facilitate identification of spectra and foster collaborations.
Abstract: The potential of the diverse chemistries present in natural products (NP) for biotechnology and medicine remains untapped because NP databases are not searchable with raw data and the NP community has no way to share data other than in published papers. Although mass spectrometry (MS) techniques are well-suited to high-throughput characterization of NP, there is a pressing need for an infrastructure to enable sharing and curation of data. We present Global Natural Products Social Molecular Networking (GNPS; http://gnps.ucsd.edu), an open-access knowledge base for community-wide organization and sharing of raw, processed or identified tandem mass (MS/MS) spectrometry data. In GNPS, crowdsourced curation of freely available community-wide reference MS libraries will underpin improved annotations. Data-driven social-networking should facilitate identification of spectra and foster collaborations. We also introduce the concept of 'living data' through continuous reanalysis of deposited data.

2,365 citations


Journal ArticleDOI
B. P. Abbott1, Richard J. Abbott1, T. D. Abbott2, M. R. Abernathy1  +976 moreInstitutions (107)
TL;DR: It is found that the final remnant's mass and spin, as determined from the low-frequency and high-frequency phases of the signal, are mutually consistent with the binary black-hole solution in general relativity.
Abstract: The LIGO detection of GW150914 provides an unprecedented opportunity to study the two-body motion of a compact-object binary in the large-velocity, highly nonlinear regime, and to witness the final merger of the binary and the excitation of uniquely relativistic modes of the gravitational field. We carry out several investigations to determine whether GW150914 is consistent with a binary black-hole merger in general relativity. We find that the final remnant’s mass and spin, as determined from the low-frequency (inspiral) and high-frequency (postinspiral) phases of the signal, are mutually consistent with the binary black-hole solution in general relativity. Furthermore, the data following the peak of GW150914 are consistent with the least-damped quasinormal mode inferred from the mass and spin of the remnant black hole. By using waveform models that allow for parametrized general-relativity violations during the inspiral and merger phases, we perform quantitative tests on the gravitational-wave phase in the dynamical regime and we determine the first empirical bounds on several high-order post-Newtonian coefficients. We constrain the graviton Compton wavelength, assuming that gravitons are dispersed in vacuum in the same way as particles with mass, obtaining a 90%-confidence lower bound of 1013 km. In conclusion, within our statistical uncertainties, we find no evidence for violations of general relativity in the genuinely strong-field regime of gravity.

1,421 citations


Journal ArticleDOI
B. P. Abbott1, Richard J. Abbott1, T. D. Abbott2, Matthew Abernathy1  +984 moreInstitutions (116)
TL;DR: The data around the time of the event were analyzed coherently across the LIGO network using a suite of accurate waveform models that describe gravitational waves from a compact binary system in general relativity.
Abstract: On September 14, 2015, the Laser Interferometer Gravitational-wave Observatory (LIGO) detected a gravitational-wave transient (GW150914); we characterise the properties of the source and its parameters. The data around the time of the event were analysed coherently across the LIGO network using a suite of accurate waveform models that describe gravitational waves from a compact binary system in general relativity. GW150914 was produced by a nearly equal mass binary black hole of $36^{+5}_{-4} M_\odot$ and $29^{+4}_{-4} M_\odot$ (for each parameter we report the median value and the range of the 90% credible interval). The dimensionless spin magnitude of the more massive black hole is bound to be $0.7$ (at 90% probability). The luminosity distance to the source is $410^{+160}_{-180}$ Mpc, corresponding to a redshift $0.09^{+0.03}_{-0.04}$ assuming standard cosmology. The source location is constrained to an annulus section of $590$ deg$^2$, primarily in the southern hemisphere. The binary merges into a black hole of $62^{+4}_{-4} M_\odot$ and spin $0.67^{+0.05}_{-0.07}$. This black hole is significantly more massive than any other known in the stellar-mass regime.

874 citations


Journal ArticleDOI
TL;DR: An update on the current knowledge of the oral microbiome in health and disease is given and implications for modern-day oral healthcare are discussed.
Abstract: For millions of years, our resident microbes have coevolved and coexisted with us in a mostly harmonious symbiotic relationship. We are not distinct entities from our microbiome, but together we form a 'superorganism' or holobiont, with the microbiome playing a significant role in our physiology and health. The mouth houses the second most diverse microbial community in the body, harbouring over 700 species of bacteria that colonise the hard surfaces of teeth and the soft tissues of the oral mucosa. Through recent advances in technology, we have started to unravel the complexities of the oral microbiome and gained new insights into its role during both health and disease. Perturbations of the oral microbiome through modern-day lifestyles can have detrimental consequences for our general and oral health. In dysbiosis, the finely-tuned equilibrium of the oral ecosystem is disrupted, allowing disease-promoting bacteria to manifest and cause conditions such as caries, gingivitis and periodontitis. For practitioners and patients alike, promoting a balanced microbiome is therefore important to effectively maintain or restore oral health. This article aims to give an update on our current knowledge of the oral microbiome in health and disease and to discuss implications for modern-day oral healthcare.

706 citations


Journal ArticleDOI
TL;DR: Alectinib is highly active and well tolerated in patients with advanced, crizotinib-refractory ALK-positive NSCLC, including those with CNS metastases, and the cumulative CNS progression rate was lower than the cumulative non-CNS progression rate at 12 months for all patients.
Abstract: PurposeCrizotinib confers improved progression-free survival compared with chemotherapy in anaplastic lymphoma kinase (ALK)-rearranged non–small-cell lung cancer (NSCLC), but progression invariably occurs. We investigated the efficacy and safety of alectinib, a potent and selective ALK inhibitor with excellent CNS penetration, in patients with crizotinib-refractory ALK-positive NSCLC.Patients and MethodsAlectinib 600 mg was administered orally twice daily. The primary end point was objective response rate (ORR) by central independent review committee (IRC).ResultsOf the 138 patients treated, 84 patients (61%) had CNS metastases at baseline, and 122 were response evaluable (RE) by IRC. ORR by IRC was 50% (95% CI, 41% to 59%), and the median duration of response (DOR) was 11.2 months (95% CI, 9.6 months to not reached). In 96 patients (79%) previously treated with chemotherapy, the ORR was 45% (95% CI, 35% to 55%). Median IRC-assessed progression-free survival for all 138 patients was 8.9 months (95% CI, 5....

537 citations


Journal ArticleDOI
TL;DR: It is shown that the slow photocurrent degradation in thin-film photovoltaic devices is due to the formation of light-activated meta-stable deep-level trap states, and the creation of small polaronic states involving localized cooperative lattice strain and molecular orientations emerges as a credible microscopic mechanism requiring further detailed studies.
Abstract: Solution-processed organometallic perovskite solar cells have emerged as one of the most promising thin-film photovoltaic technology. However, a key challenge is their lack of stability over prolonged solar irradiation. Few studies have investigated the effect of light soaking on hybrid perovskites and have attributed the degradation in the optoelectronic properties to photochemical or field-assisted ion migration. Here we show that the slow photocurrent degradation in thin-film photovoltaic devices is due to the formation of light-activated meta-stable deep-level trap states. However, the devices can self-heal completely by resting them in the dark for <1 min or the degradation can be completely prevented by operating the devices at 0 °C. We investigate several physical mechanisms to explain the microscopic origin for the formation of these trap states, among which the creation of small polaronic states involving localized cooperative lattice strain and molecular orientations emerges as a credible microscopic mechanism requiring further detailed studies.

531 citations


Journal ArticleDOI
TL;DR: This paper aims at presenting a brief but almost self-contented introduction to the most important approaches dedicated to vision-based camera localization along with a survey of several extension proposed in the recent years.
Abstract: Augmented reality (AR) allows to seamlessly insert virtual objects in an image sequence. In order to accomplish this goal, it is important that synthetic elements are rendered and aligned in the scene in an accurate and visually acceptable way. The solution of this problem can be related to a pose estimation or, equivalently, a camera localization process. This paper aims at presenting a brief but almost self-contented introduction to the most important approaches dedicated to vision-based camera localization along with a survey of several extension proposed in the recent years. For most of the presented approaches, we also provide links to code of short examples. This should allow readers to easily bridge the gap between theoretical aspects and practical implementations.

506 citations


Journal ArticleDOI
TL;DR: It is shown that the selective N-alkylation of amines with alcohols can be catalysed by defined PNP manganese pincer complexes and the chemoselective monomethylations of primary amines using methanol under mild conditions are reported.
Abstract: Borrowing hydrogen (or hydrogen autotransfer) reactions represent straightforward and sustainable C-N bond-forming processes. In general, precious metal-based catalysts are employed for this effective transformation. In recent years, the use of earth abundant and cheap non-noble metal catalysts for this process attracted considerable attention in the scientific community. Here we show that the selective N-alkylation of amines with alcohols can be catalysed by defined PNP manganese pincer complexes. A variety of substituted anilines are monoalkylated with different (hetero)aromatic and aliphatic alcohols even in the presence of other sensitive reducible functional groups. As a special highlight, we report the chemoselective monomethylation of primary amines using methanol under mild conditions.

436 citations



Journal ArticleDOI
B. P. Abbott1, Richard J. Abbott1, T. D. Abbott2, Matthew Abernathy1  +977 moreInstitutions (106)
TL;DR: In this paper, the results of a matched-filter search using relativistic models of compact-object binaries that recovered GW150914 as the most significant event during the coincident observations between the two LIGO detectors were reported.
Abstract: On September 14, 2015, at 09∶50:45 UTC the two detectors of the Laser Interferometer Gravitational-Wave Observatory (LIGO) simultaneously observed the binary black hole merger GW150914. We report the results of a matched-filter search using relativistic models of compact-object binaries that recovered GW150914 as the most significant event during the coincident observations between the two LIGO detectors from September 12 to October 20, 2015 GW150914 was observed with a matched-filter signal-to-noise ratio of 24 and a false alarm rate estimated to be less than 1 event per 203000 years, equivalent to a significance greater than 5.1 σ.

Journal ArticleDOI
26 Apr 2016
TL;DR: Holobionts and hologenomes are incontrovertible, multipartite entities that result from ecological, evolutionary, and genetic processes at various levels that constitute a wider vocabulary and framework for host biology in light of the microbiome.
Abstract: Given the complexity of host-microbiota symbioses, scientists and phi- losophers are asking questions at new biological levels of hierarchical organization— what is a holobiont and hologenome? When should this vocabulary be applied? Are these concepts a null hypothesis for host-microbe systems or limited to a certain spectrum of symbiotic interactions such as host-microbial coevolution? Critical dis- course is necessary in this nascent area, but productive discourse requires that skep- tics and proponents use the same lexicon. For instance, critiquing the hologenome concept is not synonymous with critiquing coevolution, and arguing that an entity is not a primary unit of selection dismisses the fact that the hologenome concept has always embraced multilevel selection. Holobionts and hologenomes are incontro- vertible, multipartite entities that result from ecological, evolutionary, and genetic processes at various levels. They are not restricted to one special process but consti- tute a wider vocabulary and framework for host biology in light of the microbiome.

Journal ArticleDOI
03 Jun 2016-Science
TL;DR: Results suggest that dogs may have been domesticated independently in Eastern and Western Eurasia from distinct wolf populations, and East Eurasian dogs were then possibly transported to Europe with people, where they partially replaced European Paleolithic dogs.
Abstract: The geographic and temporal origins of dogs remain controversial. We generated genetic sequences from 59 ancient dogs and a complete (28x) genome of a late Neolithic dog (dated to ~4800 calendar years before the present) from Ireland. Our analyses revealed a deep split separating modern East Asian and Western Eurasian dogs. Surprisingly, the date of this divergence (~14,000 to 6400 years ago) occurs commensurate with, or several millennia after, the first appearance of dogs in Europe and East Asia. Additional analyses of ancient and modern mitochondrial DNA revealed a sharp discontinuity in haplotype frequencies in Europe. Combined, these results suggest that dogs may have been domesticated independently in Eastern and Western Eurasia from distinct wolf populations. East Eurasian dogs were then possibly transported to Europe with people, where they partially replaced European Paleolithic dogs.

Journal ArticleDOI
01 Mar 2016-Geology
TL;DR: In this article, a compilation of whole-rock geochemical data available in the literature is used to show that fractional crystallization alone is not sufficient to explain the distribution of Niobium/Tantalum (Nb/Ta) in most peraluminous granites.
Abstract: In their late stages of evolution, peraluminous granitic melts exsolve large amounts of fluidswhich can modify the chemical composition of granitic whole-rock samples. The niobium/tantalum (Nb/Ta) ratio is expected to decrease during the magmatic differentiation of graniticmelts, but the behavior of both elements at the magmatic-hydrothermal transition remainsunclear. Using a compilation of whole-rock geochemical data available in the literature, wedemonstrate that fractional crystallization alone is not sufficient to explain the distribution ofNb-Ta in most peraluminous granites. However, we notice that most of the granitic samplesdisplaying evidence of interactions with fluids have Nb/Ta < 5. We propose that the decreaseof the Nb/Ta ratio in evolved melts is the consequence of both fractional crystallization andsub-solidus hydrothermal alteration. We suggest that the Nb/Ta value of ~5 fingerprints themagmatic-hydrothermal transition in peraluminous granites. Furthermore, a Nb/Ta ratio of ~5appears to be a good marker to discriminate mineralized from barren peraluminous granites.

Journal ArticleDOI
B. P. Abbott1, Richard J. Abbott1, T. D. Abbott2, Matthew Abernathy1  +953 moreInstitutions (106)
TL;DR: It is concluded that the stochastic gravitational-wave background from binary black holes, created from the incoherent superposition of all the merging binaries in the Universe, is potentially measurable by the Advanced LIGO and Advanced Virgo detectors operating at their projected final sensitivity.
Abstract: The LIGO detection of the gravitational wave transient GW150914, from the inspiral and merger of two black holes with masses $\gtrsim 30\, \text{M}_\odot$, suggests a population of binary black holes with relatively high mass. This observation implies that the stochastic gravitational-wave background from binary black holes, created from the incoherent superposition of all the merging binaries in the Universe, could be higher than previously expected. Using the properties of GW150914, we estimate the energy density of such a background from binary black holes. In the most sensitive part of the Advanced LIGO/Virgo band for stochastic backgrounds (near 25 Hz), we predict $\Omega_\text{GW}(f=25 Hz) = 1.1_{-0.9}^{+2.7} \times 10^{-9}$ with 90\% confidence. This prediction is robustly demonstrated for a variety of formation scenarios with different parameters. The differences between models are small compared to the statistical uncertainty arising from the currently poorly constrained local coalescence rate. We conclude that this background is potentially measurable by the Advanced LIGO/Virgo detectors operating at their projected final sensitivity.

Journal ArticleDOI
TL;DR: Recommendations for further investigation into the application and performance of stress echocardiography in the evaluation of non-ischaemic heart disease are summarized.
Abstract: A unique and highly versatile technique, stress echocardiography (SE) is increasingly recognized for its utility in the evaluation of non-ischaemic heart disease. SE allows for simultaneous assessment of myocardial function and haemodynamics under physiological or pharmacological conditions. Due to its diagnostic and prognostic value, SE has become widely implemented to assess various conditions other than ischaemic heart disease. It has thus become essential to establish guidance for its applications and performance in the area of non-ischaemic heart disease. This paper summarizes these recommendations.

Journal ArticleDOI
TL;DR: It is demonstrated that a significant subset of GnRH neurons both in mice and humans express the AMH receptor, and that AMH potently activates the GnRH neuron firing in mice, supporting a central action of AMH on Gn RH neurons.
Abstract: Anti-Mullerian hormone (AMH) plays crucial roles in sexual differentiation and gonadal functions. However, the possible extragonadal effects of AMH on the hypothalamic-pituitary-gonadal axis remain unexplored. Here we demonstrate that a significant subset of GnRH neurons both in mice and humans express the AMH receptor, and that AMH potently activates the GnRH neuron firing in mice. Combining in vivo and in vitro experiments, we show that AMH increases GnRH-dependent LH pulsatility and secretion, supporting a central action of AMH on GnRH neurons. Increased LH pulsatility is an important pathophysiological feature in many cases of polycystic ovary syndrome (PCOS), the most common cause of female infertility, in which circulating AMH levels are also often elevated. However, the origin of this dysregulation remains unknown. Our findings raise the intriguing hypothesis that AMH-dependent regulation of GnRH release could be involved in the pathophysiology of fertility and could hold therapeutic potential for treating PCOS.

Journal ArticleDOI
B. P. Abbott1, Richard J. Abbott1, T. D. Abbott2, M. R. Abernathy1  +985 moreInstitutions (106)
Abstract: A transient gravitational-wave signal, GW150914, was identified in the twin Advanced LIGO detectors on September 14, 2015 at 09:50:45 UTC. To assess the implications of this discovery, the detectors remained in operation with unchanged configurations over a period of 39 d around the time of the signal. At the detection statistic threshold corresponding to that observed for GW150914, our search of the 16 days of simultaneous two-detector observational data is estimated to have a false alarm rate (FAR) of < 4.9 × 10^(−6) yr^(−1), yielding a p-value for GW150914 of < 2 × 10^(−7). Parameter estimation followup on this trigger identifies its source as a binary black hole (BBH) merger with component masses (m_1, m_2) = (36^(+5)_(−4), 29^(+4)_(−4)) M_⊙ at redshift z = 0.09^(+0.03)_(−0.04) (median and 90\% credible range). Here we report on the constraints these observations place on the rate of BBH coalescences. Considering only GW150914, assuming that all BBHs in the Universe have the same masses and spins as this event, imposing a search FAR threshold of 1 per 100 years, and assuming that the BBH merger rate is constant in the comoving frame, we infer a 90% credible range of merger rates between 2--53 Gpc^(−3) yr^(−1) (comoving frame). Incorporating all search triggers that pass a much lower threshold while accounting for the uncertainty in the astrophysical origin of each trigger, we estimate a higher rate, ranging from 13--600 Gpc^(−3) yr^(−1) depending on assumptions about the BBH mass distribution. All together, our various rate estimates fall in the conservative range 2--600 Gpc^(−3) yr^(−1).

Journal ArticleDOI
TL;DR: This article proposes a participatory cultural mapping approach based on collective behavior in LBSNs, and shows that the approach can subtly capture cultural features and generate representative cultural maps that correspond well with traditional cultural maps based on survey data.
Abstract: Culture has been recognized as a driving impetus for human development. It co-evolves with both human belief and behavior. When studying culture, Cultural Mapping is a crucial tool to visualize different aspects of culture (e.g., religions and languages) from the perspectives of indigenous and local people. Existing cultural mapping approaches usually rely on large-scale survey data with respect to human beliefs, such as moral values. However, such a data collection method not only incurs a significant cost of both human resources and time, but also fails to capture human behavior, which massively reflects cultural information. In addition, it is practically difficult to collect large-scale human behavior data. Fortunately, with the recent boom in Location-Based Social Networks (LBSNs), a considerable number of users report their activities in LBSNs in a participatory manner, which provides us with an unprecedented opportunity to study large-scale user behavioral data. In this article, we propose a participatory cultural mapping approach based on collective behavior in LBSNs. First, we collect the participatory sensed user behavioral data from LBSNs. Second, since only local users are eligible for cultural mapping, we propose a progressive “home” location identification method to filter out ineligible users. Third, by extracting three key cultural features from daily activity, mobility, and linguistic perspectives, respectively, we propose a cultural clustering method to discover cultural clusters. Finally, we visualize the cultural clusters on the world map. Based on a real-world LBSN dataset, we experimentally validate our approach by conducting both qualitative and quantitative analysis on the generated cultural maps. The results show that our approach can subtly capture cultural features and generate representative cultural maps that correspond well with traditional cultural maps based on survey data.

Journal ArticleDOI
13 Sep 2016-JAMA
TL;DR: Among patients undergoing TAVR, younger age, male sex, history of diabetes mellitus, and moderate to severe residual aortic regurgitation were significantly associated with an increased risk of infective endocarditis.
Abstract: Importance Limited data exist on clinical characteristics and outcomes of patients who had infective endocarditis after undergoing transcatheter aortic valve replacement (TAVR). Objective To determine the associated factors, clinical characteristics, and outcomes of patients who had infective endocarditis after TAVR. Design, Setting, and Participants The Infectious Endocarditis after TAVR International Registry included patients with definite infective endocarditis after TAVR from 47 centers from Europe, North America, and South America between June 2005 and October 2015. Exposure Transcatheter aortic valve replacement for incidence of infective endocarditis and infective endocarditis for in-hospital mortality. Main Outcomes and Measures Infective endocarditis and in-hospital mortality after infective endocarditis. Results A total of 250 cases of infective endocarditis occurred in 20 006 patients after TAVR (incidence, 1.1% per person-year; 95% CI, 1.1%-1.4%; median age, 80 years; 64% men). Median time from TAVR to infective endocarditis was 5.3 months (interquartile range [IQR], 1.5-13.4 months). The characteristics associated with higher risk of progressing to infective endocarditis after TAVR was younger age (78.9 years vs 81.8 years; hazard ratio [HR], 0.97 per year; 95% CI, 0.94-0.99), male sex (62.0% vs 49.7%; HR, 1.69; 95% CI, 1.13-2.52), diabetes mellitus (41.7% vs 30.0%; HR, 1.52; 95% CI, 1.02-2.29), and moderate to severe aortic regurgitation (22.4% vs 14.7%; HR, 2.05; 95% CI, 1.28-3.28). Health care–associated infective endocarditis was present in 52.8% (95% CI, 46.6%-59.0%) of patients. Enterococci species and Staphylococcus aureus were the most frequently isolated microorganisms (24.6%; 95% CI, 19.1%-30.1% and 23.3%; 95% CI, 17.9%-28.7%, respectively). The in-hospital mortality rate was 36% (95% CI, 30.0%-41.9%; 90 deaths; 160 survivors), and surgery was performed in 14.8% (95% CI, 10.4%-19.2%) of patients during the infective endocarditis episode. In-hospital mortality was associated with a higher logistic EuroSCORE (23.1% vs 18.6%; odds ratio [OR], 1.03 per 1% increase; 95% CI, 1.00-1.05), heart failure (59.3% vs 23.7%; OR, 3.36; 95% CI, 1.74-6.45), and acute kidney injury (67.4% vs 31.6%; OR, 2.70; 95% CI, 1.42-5.11). The 2-year mortality rate was 66.7% (95% CI, 59.0%-74.2%; 132 deaths; 115 survivors). Conclusions and Relevance Among patients undergoing TAVR, younger age, male sex, history of diabetes mellitus, and moderate to severe residual aortic regurgitation were significantly associated with an increased risk of infective endocarditis. Patients who developed endocarditis had high rates of in-hospital mortality and 2-year mortality.

Journal ArticleDOI
TL;DR: The prevention of NR to CRT is essential to improve the overall performance of this treatment and lower its risk-benefit ratio, and precise recommendations are offered regarding the optimal device programming, use of telemonitoring and optimization of management of HF.
Abstract: Over two decades after the introduction of cardiac resynchronization therapy (CRT) into clinical practice, ∼30% of candidates continue to fail to respond to this highly effective treatment of drug-refractory heart failure (HF). Since the causes of this non-response (NR) are multifactorial, it will require multidisciplinary efforts to overcome. Progress has, thus far, been slowed by several factors, ranging from a lack of consensus regarding the definition of NR and technological limitations to the delivery of therapy. We critically review the various endpoints that have been used in landmark clinical trials of CRT, and the variability in response rates that has been observed as a result of these different investigational designs, different sample populations enrolled and different means of therapy delivered, including new means of multisite and left ventricular endocardial simulation. Precise recommendations are offered regarding the optimal device programming, use of telemonitoring and optimization of management of HF. Potentially reversible causes of NR to CRT are reviewed, with emphasis on loss of biventricular stimulation due to competing arrhythmias. The prevention of NR to CRT is essential to improve the overall performance of this treatment and lower its risk-benefit ratio. These objectives require collaborative efforts by the HF team, the electrophysiologists and the cardiac imaging experts.

Journal ArticleDOI
TL;DR: The present document is an expert consensus from the European Association of Cardiovascular Imaging (EACVI) and the European Heart Rhythm Association and may serve as a guide for both imagers and electrophysiologists for best selecting the imaging technique and for best interpreting its results in AF patients.
Abstract: Atrial fibrillation (AF) is the commonest cardiac rhythm disorder. Evaluation of patients with AF requires an electrocardiogram, but imaging techniques should be considered for defining management and driving treatment. The present document is an expert consensus from the European Association of Cardiovascular Imaging (EACVI) and the European Heart Rhythm Association. The clinical value of echocardiography, cardiac magnetic resonance (CMR), computed tomography (CT), and nuclear imaging in AF patients are challenged. Left atrial (LA) volume and strain in echocardiography as well as assessment of LA fibrosis in CMR are discussed. The value of CT, especially in planning interventions, is highlighted. Fourteen consensus statements have been reached. These may serve as a guide for both imagers and electrophysiologists for best selecting the imaging technique and for best interpreting its results in AF patients.


Journal ArticleDOI
TL;DR: The addition of 25 mM trehalose to pancreatic beta-cell exosome-like vesicle isolation and storage buffer narrows the particle size distribution and increases the number of individual particles per microgram of protein.
Abstract: Exosomes are important mediators in intercellular communication. Released by many cell types, they transport proteins, lipids, and nucleic acids to distant recipient cells and contribute to important physiopathological processes. Standard current exosome isolation methods based on differential centrifugation protocols tend to induce aggregation of particles in highly concentrated suspensions and freezing of exosomes can induce damage and inconsistent biological activity. Trehalose is a natural, non-toxic sugar widely used as a protein stabilizer and cryoprotectant by the food and drug industry. Here we report that addition of 25 mM trehalose to pancreatic beta-cell exosome-like vesicle isolation and storage buffer narrows the particle size distribution and increases the number of individual particles per microgram of protein. Repeated freeze-thaw cycles induce an increase in particle concentration and in the width of the size distribution for exosome-like vesicles stored in PBS, but not in PBS 25 mM trehalose. No signs of lysis or incomplete vesicles were observed by cryo-electron tomography in PBS and trehalose samples. In macrophage immune assays, beta-cell extracellular vesicles in trehalose show consistently higher TNF-alpha cytokine secretion stimulation indexes suggesting improved preservation of biological activity. The addition of trehalose might be an attractive means to standardize experiments in the field of exosome research and downstream applications.

Journal ArticleDOI
26 Feb 2016-Science
TL;DR: In this article, the authors argue that salinity standards for specific ions and ion mixtures, not just for total salinity, should be developed and legally enforced to protect freshwater life and ecosystem services.
Abstract: Many human activities—like agriculture and resource extraction—are increasing the total concentration of dissolved inorganic salts (i.e., salinity) in freshwaters. Increasing salinity can have adverse effects on human health ( 1 ); increase the costs of water treatment for human consumption; and damage infrastructure [e.g., amounting to $700 million per year in the Border Rivers catchment, Australia ( 2 )]. It can also reduce freshwater biodiversity ( 3 ); alter ecosystem functions ( 4 ); and affect economic well-being by altering ecosystem goods and services (e.g., fisheries collapse). Yet water-quality legislation and regulations that target salinity typically focus on drinking water and irrigation water, which does not automatically protect biodiversity. For example, specific electrical conductivities (a proxy for salinity) of 2 mS/cm can be acceptable for drinking and irrigation but could extirpate many freshwater insect species ( 3 ). We argue that salinity standards for specific ions and ion mixtures, not just for total salinity, should be developed and legally enforced to protect freshwater life and ecosystem services. We identify barriers to setting such standards and recommend management guidelines.

Journal ArticleDOI
TL;DR: Both models and experimental studies show that if phytoplankton is entrained in the turbulent flow and redistributed vertically over the entire depth, green algae and diatoms win the competition over (colonial) cyanobacteria due to a higher growth rate and reduced sedimentation losses.
Abstract: Artificial mixing has been used as a measure to prevent the growth of cyanobacteria in eutrophic lakes and reservoirs for many years In this paper, we give an overview of studies that report on the results of this remedy Generally, artificial mixing causes an increase in the oxygen content of the water, an increase in the temperature in the deep layers but a decrease in the upper layers, while the standing crop of phytoplankton (ie the chlorophyll content per m2) often increases partly due to an increase in nutrients entrained from the hypolimnion or resuspended from the sediments A change in composition from cyanobacterial dominance to green algae and diatoms can be observed if the imposed mixing is strong enough to keep the cyanobacteria entrained in the turbulent flow, the mixing is deep enough to limit light availability and the mixing devices are well distributed horizontally over the lake Both models and experimental studies show that if phytoplankton is entrained in the turbulent flow and redistributed vertically over the entire depth, green algae and diatoms win the competition over (colonial) cyanobacteria due to a higher growth rate and reduced sedimentation losses The advantage of buoyant cyanobacteria to float up to the illuminated upper layers is eradicated in a well-mixed system



Book ChapterDOI
08 May 2016
TL;DR: Two polynomial attacks on the CLT15 multilinear map are presented, which share ideas similar to the cryptanalysis of CLT13 and allow recovery of all secret parameters in timePolynomial in the security parameter, and lead to a full break of theCLT15 multi-million-dollar map for virtually all applications.
Abstract: Multilinear maps serve as a basis for a wide range of cryptographic applications. The first candidate construction of multilinear maps was proposed by Garg, Gentry, and Halevi in 2013, and soon afterwards, another construction was suggested by Coron, Lepoint, and Tibouchi CLT13, which works over the integers. However, both of these were found to be insecure in the face of so-called zeroizing attacks, by Hu and Jia, and by Cheon, Han, Lee, Ryu and Stehle. To improve on CLT13, Coron, Lepoint, and Tibouchi proposed another candidate construction of multilinear maps over the integers at Crypto 2015 CLT15. This article presents two polynomial attacks on the CLT15 multilinear map, which share ideas similar to the cryptanalysis of CLT13. Our attacks allow recovery of all secret parameters in time polynomial in the security parameter, and lead to a full break of the CLT15 multilinear map for virtually all applications.