Practical methods for witnessing genuine multi-qubit entanglement in the vicinity of symmetric states

We present general numerical methods to construct witness operators for entanglement detection and estimation of the fidelity. Our methods are applied to detecting entanglement in the vicinity of a six-qubit Dicke state with three excitations and also to further entangled symmetric states. All our witnesses are designed to keep the measurement effort small. We present also general results on the efficient local decomposition of permutationally invariant operators, which makes it possible to measure projectors to symmetric states efficientlyComment: 13 pages including 4 figures, revtex

Learning large-scale dynamic discrete choice models of spatio-temporal preferences with application to migratory pastoralism in East Africa

Understanding spatio-temporal resource preferences is paramount in the design of policies for sustainable development. Unfortunately, resource preferences are often unknown to policy-makers and have to be inferred from data. In this paper we consider the problem of inferring agents' preferences from observed movement trajectories, and formulate it as an Inverse Reinforcement Learning (IRL) problem. With the goal of informing policy-making, we take a probabilistic approach and consider generative models that can be used to simulate behavior under new circumstances such as changes in resource availability, access policies, or climate. We study the Dynamic Discrete Choice (DDC) models from econometrics and prove that they generalize the Max-Entropy IRL model, a widely used probabilistic approach from the machine learning literature. Furthermore, we develop SPL-GD, a new learning algorithm for DDC models that is considerably faster than the state of the art and scales to very large datasets. We consider an application in the context of pastoralism in the arid and semi-arid regions of Africa, where migratory pastoralists face regular risks due to resource availability, droughts, and resource degradation from climate change and development. We show how our approach based on satellite and survey data can accurately model migratory pastoralism in East Africa and that it considerably outperforms other approaches on a large-scale real-world dataset of pastoralists' movements in Ethiopia collected over 3 years

COOL down: The role of social capital in enhancing adaptation to extreme heat events in the city of Vienna (COOLCITY) : Final Report to the City of Vienna Anniversary Fund for the University of Natural Resources and Life Sciences, Vienna

The increasing number of extreme heat events in Vienna due to climate change causes negative impacts on the residents, such as heat-related mortality and morbidity. Most adaptation strategies in cities rely so far on technical solutions and on changes in individual lifestyle. However, next to financial, infrastructure and human capital, climate change adaptation also requires social capital. COOLCITY thus focused on strengthening social capital in Vienna through social innovations, particularly during extreme heat events. Two highly vulnerable areas in Vienna - 'Innerfavoriten' and 'Gründerzeitviertel/Westgürtel' - were selected based on pre-existing heat hot spots overlapped with socio-demographic data. 22 interviews with particularly vulnerable residents of the case study areas as well as eight expert interviews were conducted to investigate the relation between social capital and heat stress. Social innovations for adapting to extreme heat events were developed in two participatory citizen workshops and discussed with representatives of the City of Vienna and relevant organizations in a concluding stakeholder workshop. The COOLCITY findings show that social capital can mitigate heat stress in multiple ways: through organizing mutual help in social networks, facilitating communication between residents and administration, and sharing local knowledge. Social innovations can play a crucial role in these processes. Thus, the enhancement of social capital should be seen as a central component of a resilient city - particularly, but not exclusively during extreme heat events. COOLCITY continuously evolved in close collaboration with different administrative bodies of the City of Vienna. Such a transdisciplinary approach was followed to ensure the applicability of results and to facilitate the implementation of new policy measures increasing social capital in the City of Vienna.Die zunehmende Zahl extremer Hitzeereignisse in Wien aufgrund des Klimawandels hat negative Auswirkungen auf die Bevölkerung wie hitzebedingte Mortalität und Morbidität. Die meisten Anpassungsstrategien in Städten beruhen bislang auf technischen Lösungen und auf Änderungen im individuellen Lebensstil. Neben Finanz-, Infrastruktur- und Humankapital erfordert die Anpassung an den Klimawandel jedoch auch Sozialkapital. COOLCITY konzentrierte sich daher auf die Stärkung des Sozialkapitals in Wien durch soziale Innovationen, insbesondere bei extremen Hitzeereignissen. Zwei besonders gefährdete Gebiete in Wien - Innerfavoriten und Gründerzeitviertel/Westgürtel - wurden auf Grundlage bereits bestehender Hitze-Hotspots verschnitten mit soziodemografischen Daten ausgewählt. 22 Interviews mit besonders gefährdeten Personen in diesen Fallstudien sowie acht Expert:inneninterviews wurden durchgeführt, um den Zusammenhang zwischen Sozialkapital und Hitzestress zu untersuchen. Das Projekt entwickelte soziale Innovationen zur Anpassung an extreme Hitzeereignisse in zwei partizipativen Bürger:innenworkshops. Diese wurden zudem in einem abschließenden Stakeholder-Workshop mit der Stadt Wien und relevanten Organisationen diskutiert. Die Ergebnisse von COOLCITY zeigen, dass Sozialkapital Hitzestress auf vielfältige Weise abschwächen kann: durch die Organisation gegenseitiger Hilfe in sozialen Netzwerken, die Erleichterung der Kommunikation zwischen Bevölkerung und Verwaltung und den Austausch von lokalem Wissen. Soziale Innovationen können bei diesen Prozessen eine entscheidende Rolle spielen. Daher sollte die Stärkung des Sozialkapitals als zentraler Bestandteil einer resilienten Stadt angesehen werden - insbesondere, aber nicht ausschließlich bei extremen Hitzeereignissen. COOLCITY wurde in enger Zusammenarbeit mit verschiedenen Verwaltungsbehörden der Stadt Wien laufend weiterentwickelt. Ein derartiger transdisziplinärer Ansatz wurde verfolgt, um die Anwendbarkeit der Ergebnisse zu gewährleisten und die Umsetzung neuer politischer Maßnahmen zur Steigerung des Sozialkapitals in der Stadt Wien zu fördern

Mutations in UBA3 Confer Resistance to the NEDD8-Activating Enzyme Inhibitor MLN4924 in Human Leukemic Cells

The NEDD8-activating enzyme (NAE) initiates neddylation, the cascade of post-translational NEDD8 conjugation onto target proteins. MLN4924, a selective NAE inhibitor, has displayed preclinical anti-tumor activity in vitro and in vivo, and promising clinical activity has been reported in patients with refractory hematologic malignancies. Here, we sought to understand the mechanisms of resistance to MLN4924. K562 and U937 leukemia cells were exposed over a 6 month period to MLN4924 and populations of resistant cells (R-K562MLN, R-U937MLN) were selected. R-K562MLN and R-U937MLN cells contain I310N and Y352H mutations in the NAE catalytic subunit UBA3, respectively. Biochemical analyses indicate that these mutations increase the enzyme’s affinity for ATP while decreasing its affinity for NEDD8. These mutations effectively contribute to decreased MLN4924 potency in vitro while providing for sufficient NAE function for leukemia cell survival. Finally, R-K562MLN cells showed cross-resistance to other NAE-selective inhibitors, but remained sensitive to a pan-E1 (activating enzyme) inhibitor. Thus, our work provides insight into mechanisms of MLN4924 resistance to facilitate the development of more effective second-generation NAE inhibitors

Impact of statin therapy on coronary plaque composition: A systematic review and meta-analysis of virtual histology intravascular ultrasound studies

Background: Virtual histology intravascular ultrasound (VH-IVUS) imaging is an innovative tool for the morphological evaluation of coronary atherosclerosis. Evidence for the effects of statin therapy on VH-IVUS parameters have been inconclusive. Consequently, we performed a systematic review and meta-analysis to investigate the impact of statin therapy on plaque volume and its composition using VH-IVUS. Methods: The search included PubMed, Cochrane Library, Scopus and Embase (through 30 November 2014) to identify prospective studies investigating the effects of statin therapy on plaque volume and its composition using VH-IVUS. Results: We identified nine studies with 16 statin treatment arms and 830 participants. There was a significant effect of statin therapy in reducing plaque volume (standardized mean difference (SMD): -0.137, 95 % confidence interval (CI): -0.255, -0.019; P = 0.023), external elastic membrane volume (SMD: -0.097, 95 % CI: -0.183, -0.011; P = 0.027) but not lumen volume (SMD: -0.025, 95 % CI: -0.110, +0.061; P = 0.574). There was a significant reduction in fibrous plaque volume (SMD: -0.129, 95 % CI: -0.255, -0.003; P = 0.045) and an increase of dense calcium volume (SMD: +0.229, 95 % CI: +0.008, +0.450

Highlights of the 2nd International Symposium on Tribbles and Diseases: Tribbles tremble in therapeutics for immunity, metabolism, fundamental cell biology and cancer

The Tribbles (TRIB) family of pseudokinase proteins has been shown to play key roles in cell cycle, metabolic diseases, chronic inflammatory disease, and cancer development. A better understanding of the mechanisms of TRIB pseudokinases could provide new insights for disease development and help promote TRIB proteins as novel therapeutic targets for drug discovery. At the 2nd International Symposium on Tribbles and Diseases held on May 7‒9, 2018 in Beijing, China, a group of leading Tribbles scientists reported their findings and ongoing studies about the effects of the different TRIB proteins in the areas of immunity, metabolism, fundamental cell biology and cancer. Here, we summarize important and insightful overviews from 4 keynote lectures, 13 plenary lectures and 8 short talks that took place during this meeting. These findings may offer new insights for the understanding of the roles of TRIB pseudokinases in the development of various diseases

Expression of a Grapevine NAC Transcription Factor Gene Is Induced in Response to Powdery Mildew Colonization in Salicylic Acid-Independent Manner

Tissue colonization by grape powdery mildew (PM) pathogen Erysiphe necator (Schw.) Burr triggers a major remodeling of the transcriptome in the susceptible grapevine Vitis vinifera L. While changes in the expression of many genes bear the signature of salicylic acid (SA) mediated regulation, the breadth of PM-induced changes suggests the involvement of additional regulatory networks. To explore PM-associated gene regulation mediated by other SA-independent systems, we designed a microarray experiment to distinguish between transcriptome changes induced by E. necator colonization and those triggered by elevated SA levels. We found that the majority of genes responded to both SA and PM, but certain genes were responsive to PM infection alone. Among them, we identified genes of stilbene synthases, PR-10 proteins, and several transcription factors. The microarray results demonstrated that the regulation of these genes is either independent of SA, or dependent, but SA alone is insufficient to bring about their regulation. We inserted the promoter-reporter fusion of a PM-responsive transcription factor gene into a wild-type and two SA-signaling deficient Arabidopsis lines and challenged the resulting transgenic plants with an Arabidopsis-adapted PM pathogen. Our results provide experimental evidence that this grape gene promoter is activated by the pathogen in a SA-independent manner

The Science of Sungrazers, Sunskirters, and Other Near-Sun Comets

This review addresses our current understanding of comets that venture close to the Sun, and are hence exposed to much more extreme conditions than comets that are typically studied from Earth. The extreme solar heating and plasma environments that these objects encounter change many aspects of their behaviour, thus yielding valuable information on both the comets themselves that complements other data we have on primitive solar system bodies, as well as on the near-solar environment which they traverse. We propose clear definitions for these comets: We use the term near-Sun comets to encompass all objects that pass sunward of the perihelion distance of planet Mercury (0.307 AU). Sunskirters are defined as objects that pass within 33 solar radii of the Sun’s centre, equal to half of Mercury’s perihelion distance, and the commonly-used phrase sungrazers to be objects that reach perihelion within 3.45 solar radii, i.e. the fluid Roche limit. Finally, comets with orbits that intersect the solar photosphere are termed sundivers. We summarize past studies of these objects, as well as the instruments and facilities used to study them, including space-based platforms that have led to a recent revolution in the quantity and quality of relevant observations. Relevant comet populations are described, including the Kreutz, Marsden, Kracht, and Meyer groups, near-Sun asteroids, and a brief discussion of their origins. The importance of light curves and the clues they provide on cometary composition are emphasized, together with what information has been gleaned about nucleus parameters, including the sizes and masses of objects and their families, and their tensile strengths. The physical processes occurring at these objects are considered in some detail, including the disruption of nuclei, sublimation, and ionisation, and we consider the mass, momentum, and energy loss of comets in the corona and those that venture to lower altitudes. The different components of comae and tails are described, including dust, neutral and ionised gases, their chemical reactions, and their contributions to the near-Sun environment. Comet-solar wind interactions are discussed, including the use of comets as probes of solar wind and coronal conditions in their vicinities. We address the relevance of work on comets near the Sun to similar objects orbiting other stars, and conclude with a discussion of future directions for the field and the planned ground- and space-based facilities that will allow us to address those science topics