Proximal and distal control for ligand binding in neuroglobin: role of the CD loop and evidence for His64 gating

Neuroglobin (Ngb) is predominantly expressed in neurons of the central and peripheral nervous systems and it clearly seems to be involved in neuroprotection. Engineering Ngb to observe structural and dynamic alterations associated with perturbation in ligand binding might reveal important structural determinants, and could shed light on key features related to its mechanism of action. Our results highlight the relevance of the CD loop and of Phe106 as distal and proximal controls involved in ligand binding in murine neuroglobin. We observed the effects of individual and combined mutations of the CD loop and Phe106 that conferred to Ngb higher CO binding velocities, which we correlate with the following structural observations: the mutant F106A shows, upon CO binding, a reduced heme sliding hindrance, with the heme present in a peculiar double conformation, whereas in the CD loop mutant "Gly-loop", the original network of interactions between the loop and the heme was abolished, enhancing binding via facilitated gating out of the distal His64. Finally, the double mutant, combining both mutations, showed a synergistic effect on CO binding rates. Resonance Raman spectroscopy and MD simulations support our findings on structural dynamics and heme interactions in wild type and mutated Ngbs

The Quantum Effective Action, Wave Functions and Yang-Mills (2+1)

We explore the relationship between the quantum effective action and the ground state (and excited state) wave functions of a field theory. Applied to the Yang-Mills theory in 2+1 dimensions, we find the leading terms of the effective action from the ground state wave function previously obtained in the Hamiltonian formalism by solving the Schrodinger equation.Comment: 16 pages, expanded discussion section, added references, version accepted for Phys. Rev.

Master Integrals for the two-loop, non-planar QCD corrections to top-quark pair production in the quark-annihilation channel

We present the analytic calculation of the Master Integrals for the two-loop, non-planar topologies that enter the calculation of the amplitude for top-quark pair hadroproduction in the quark-annihilation channel. Using the method of differential equations, we expand the integrals in powers of the dimensional regulator $\epsilon$ and determine the expansion coefficients in terms of generalized harmonic polylogarithms of two dimensionless variables through to weight four.Comment: 28 pages, 2 figures, ancillary files include

Searching for superspreaders of information in real-world social media

A number of predictors have been suggested to detect the most influential spreaders of information in online social media across various domains such as Twitter or Facebook. In particular, degree, PageRank, k-core and other centralities have been adopted to rank the spreading capability of users in information dissemination media. So far, validation of the proposed predictors has been done by simulating the spreading dynamics rather than following real information flow in social networks. Consequently, only model-dependent contradictory results have been achieved so far for the best predictor. Here, we address this issue directly. We search for influential spreaders by following the real spreading dynamics in a wide range of networks. We find that the widely-used degree and PageRank fail in ranking users' influence. We find that the best spreaders are consistently located in the k-core across dissimilar social platforms such as Twitter, Facebook, Livejournal and scientific publishing in the American Physical Society. Furthermore, when the complete global network structure is unavailable, we find that the sum of the nearest neighbors' degree is a reliable local proxy for user's influence. Our analysis provides practical instructions for optimal design of strategies for "viral" information dissemination in relevant applications.Comment: 12 pages, 7 figure

c-di-GMP modulates type IV MSHA pilus retraction and surface attachment in Vibrio cholerae.

Biofilm formation by Vibrio cholerae facilitates environmental persistence, and hyperinfectivity within the host. Biofilm formation is regulated by 3',5'-cyclic diguanylate (c-di-GMP) and requires production of the type IV mannose-sensitive hemagglutinin (MSHA) pilus. Here, we show that the MSHA pilus is a dynamic extendable and retractable system, and its activity is directly controlled by c-di-GMP. The interaction between c-di-GMP and the ATPase MshE promotes pilus extension, whereas low levels of c-di-GMP correlate with enhanced retraction. Loss of retraction facilitated by the ATPase PilT increases near-surface roaming motility, and impairs initial surface attachment. However, prolonged retraction upon surface attachment results in reduced MSHA-mediated surface anchoring and increased levels of detachment. Our results indicate that c-di-GMP directly controls MshE activity, thus regulating MSHA pilus extension and retraction dynamics, and modulating V. cholerae surface attachment and colonization

Validation of Twitter opinion trends with national polling aggregates: Hillary Clinton vs Donald Trump

Measuring and forecasting opinion trends from real-time social media is a long-standing goal of big-data analytics. Despite its importance, there has been no conclusive scientific evidence so far that social media activity can capture the opinion of the general population. Here we develop a method to infer the opinion of Twitter users regarding the candidates of the 2016 US Presidential Election by using a combination of statistical physics of complex networks and machine learning based on hashtags co-occurrence to develop an in-domain training set approaching 1 million tweets. We investigate the social networks formed by the interactions among millions of Twitter users and infer the support of each user to the presidential candidates. The resulting Twitter trends follow the New York Times National Polling Average, which represents an aggregate of hundreds of independent traditional polls, with remarkable accuracy. Moreover, the Twitter opinion trend precedes the aggregated NYT polls by 10 days, showing that Twitter can be an early signal of global opinion trends. Our analytics unleash the power of Twitter to uncover social trends from elections, brands to political movements, and at a fraction of the cost of national polls

NNLL Momentum-Space Resummation for Stop-Pair Production at the LHC

If supersymmetry near the TeV scale is realized in Nature, the pair production of scalar top squarks is expected to be observable at the Large Hadron Collider. Recently, effective field-theory methods were employed to obtain approximate predictions for the cross section for this process, which include soft-gluon emission effects up to next-to-next-to-leading order (NNLO) in perturbation theory. In this work we employ the same techniques to resum soft-gluon emission effects to all orders in perturbation theory and with next-to-next-to-logarithmic (NNLL) accuracy. We analyze the effects of NNLL resummation on the stop-pair production cross section by obtaining NLO+NNLL predictions in pair invariant mass and one-particle inclusive kinematics. We compare the results of these calculations to the approximate NNLO predictions for the cross sections.Comment: 25 pages, 6 figure

Lab‐Grown Meat and Veganism: A Virtue‐Oriented Perspective

The project of growing meat artificially represents for some the next best thing to humanity. If successful, it could be the solution to several problems, such as feed- ing a growing global population while reducing the environmental impact of raising animals for food and, of course, reducing the amount and degree of animal cruelty and suffering that is involved in animal farming. In this paper, I argue that the issue of the morality of such a project has been framed only in terms of the best conse- quences for the environment, animals, and humans, or in terms of deontic princi- ples. I argue that to appreciate how deep and difficult this issue is, it is necessary to consider it in terms of a virtue-oriented approach. Such an approach will reveal aspects that are not apparent, not contemplated by typical approaches, but are essen- tial to our understanding of the morality of lab-grown meat. As I argue, evaluating the issue from a virtue-oriented perspective suggests that the project of in vitro meat should not be supported because it stems from unvirtuous motivations

Horizontal cooling towers: riverine ecosystem services and the fate of thermoelectric heat in the contemporary Northeast US

The electricity sector is dependent on rivers to provide ecosystem services that help regulate excess heat, either through provision of water for evaporative cooling or by conveying, diluting and attenuating waste heat inputs. Reliance on these ecosystem services alters flow and temperature regimes, which impact fish habitat and other aquatic ecosystem services. We demonstrate the contemporary (2000–2010) dependence of the electricity sector on riverine ecosystem services and associated aquatic impacts in the Northeast US, a region with a high density of thermoelectric power plants. We quantify these dynamics using a spatially distributed hydrology and water temperature model (the framework for aquatic modeling in the Earth system), coupled with the thermoelectric power and thermal pollution model. We find that 28.4% of thermoelectric heat production is transferred to rivers, whereas 25.9% is directed to vertical cooling towers. Regionally, only 11.3% of heat transferred to rivers is dissipated to the atmosphere and the rest is delivered to coasts, in part due to the distribution of power plants within the river system. Impacts to the flow regime are minimal, while impacts to the thermal regime include increased river lengths of unsuitable habitats for fish with maximum thermal tolerances of 24.0, 29.0, and 34.0 ° C in segments downstream of plants by 0.6%, 9.8%, and 53.9%, respectively. Our analysis highlights the interactions among electricity production, cooling technologies, aquatic impacts, and ecosystem services, and can be used to assess the full costs and tradeoffs of electricity production at regional scales

CAREFUL WHAT YOU WISH FOR: TOUGH QUESTIONS, HONEST ANSWERS, AND INNOVATIVE APPROACHES TO APPOINTIVE JUDICIAL SELECTION

This Essay, informed in significant part by personal experience, examines in greater detail some of the common features of appointive systems, and in the process raises issues, concerns, and questions. Every step of the way the goal remains the same—to devise an appointive system most likely to yield as outstanding a judiciary as possible