Cyberbiosecurity: An Emerging New Discipline to Help Safeguard the Bioeconomy

Cyberbiosecurity is being proposed as a formal new enterprise which encompasses cybersecurity, cyber-physical security and biosecurity as applied to biological and biomedical-based systems. In recent years, an array of important meetings and public discussions, commentaries and publications have occurred that highlight numerous vulnerabilities. While necessary first steps, they do not provide a systematized structure for effectively promoting communication, education and training, elucidation and prioritization for analysis, research, development, test and evaluation and implementation of scientific, technological, standards of practice, policy, or even regulatory or legal considerations for protecting the bioeconomy. Further, experts in biosecurity and cybersecurity are generally not aware of each other’s domains, expertise, perspectives, priorities, or where mutually supported opportunities exist for which positive outcomes could result. Creating, promoting and advancing a new discipline can assist with formal, beneficial and continuing engagements. Recent key activities and publications that inform the creation of Cyberbiosecurity are briefly reviewed, as is the expansion of Cyberbiosecurity to include biomanufacturing which is supported by a rigorous analysis of a biomanufacturing facility. Recommendations are provided to initialize Cyberbiosecurity and place it on a trajectory to establish a structured and sustainable discipline, forum and enterprise

Enhanced Antifibrinolytic Efficacy of a Plasmin-Specific Kunitz-Inhibitor (60-Residue Y11T/L17R with C-Terminal IEK) of Human Tissue Factor Pathway Inhibitor Type-2 Domain1

Current antifibrinolytic agents reduce blood loss by inhibiting plasmin active sites (e.g., aprotinin) or by preventing plasminogen/tissue plasminogen activator (tPA) binding to fibrin clots (e.g., ε-aminocaproic acid and tranexamic acid); however, they have adverse side effects. Here, we expressed 60-residue (NH2NAE . . . IEKCOOH) Kunitz domain1 (KD1) mutants of human tissue factor pathway inhibitor type-2 that inhibit plasmin as well as plasminogen activation. A single (KD1-L17R-KCOOH) and a double mutant (KD1-Y11T/L17R- KCOOH) were expressed in Escherichia coli as His-tagged constructs, each with enterokinase cleavage sites. KD1-Y11T/L17R-KCOOH was also expressed in Pichia pastoris. KD1-Y11T/L17R-KCOOH inhibited plasmin comparably to aprotinin and bound to the kringle domains of plasminogen/plasmin and tPA with Kd of ~50 nM and ~35 nM, respectively. Importantly, compared to aprotinin, KD1-L17R-KCOOH and KD1-Y11T/L17R-KCOOH did not inhibit kallikrein. Moreover, the antifibrinolytic potential of KD1-Y11T/L17R-KCOOH was better than that of KD1-L17R-KCOOH and similar to that of aprotinin in plasma clot-lysis assays. In thromboelastography experiments, KD1-Y11T/L17R-KCOOH was shown to inhibit fibrinolysis in a dose dependent manner and was comparable to aprotinin at a higher concentration. Further, KD1-Y11T/L17R-KCOOH did not induce cytotoxicity in primary human endothelial cells or fibroblasts. We conclude that KD1-Y11T/L17R-KCOOH is comparable to aprotinin, the most potent known inhibitor of plasmin and can be produced in large amounts using Pichia

Data assimilation in a system with two scales-combining two initialization techniques

11 pages, 11 figures, 1 tableFull-text version available Open Access at: http://clivar.iim.csic.es/?q=es/node/319An ensemble Kalman filter (EnKF) is used to assimilate data onto a non-linear chaotic model, coupling two kinds of variables. The first kind of variables of the system is characterized as large amplitude, slow, large scale, distributed in eight equally spaced locations around a circle. The second kind of variables are small amplitude, fast, and short scale, distributed in 256 equally spaced locations. Synthetic observations are obtained from the model and the observational error is proportional to their respective amplitudes. The performance of the EnKF is affected by differences in the spatial correlation scales of the variables being assimilated. This method allows the simultaneous assimilation of all the variables. The ensemble filter also allows assimilating only the large-scale variables, letting the small-scale variables to freely evolve. Assimilation of the large-scale variables together with a few small-scale variables significantly degrades the filter. These results are explained by the spurious correlations that arise from the sampled ensemble covariances. An alternative approach is to combine two different initialization techniques for the slow and fast variables. Here, the fast variables are initialized by restraining the evolution of the ensemble members, using a Newtonian relaxation toward the observed fast variables. Then, the usual ensemble analysis is used to assimilate the large-scale observationsThis study is supported by the Spanish National Science Program under contracts ESP2005–06823-C05 and ESP2007–65667-C04Peer reviewe

The IceCube Neutrino Observatory, the Pierre Auger Observatory and the Telescope Array: Joint Contribution to the 34th International Cosmic Ray Conference (ICRC 2015)

We have conducted three searches for correlations between ultra-high energy cosmic rays detected by the Telescope Array and the Pierre Auger Observatory, and high-energy neutrino candidate events from IceCube. Two cross-correlation analyses with UHECRs are done: one with 39 cascades from the IceCube `high-energy starting events' sample and the other with 16 high-energy `track events'. The angular separation between the arrival directions of neutrinos and UHECRs is scanned over. The same events are also used in a separate search using a maximum likelihood approach, after the neutrino arrival directions are stacked. To estimate the significance we assume UHECR magnetic deflections to be inversely proportional to their energy, with values $3^\circ$, $6^\circ$ and $9^\circ$ at 100 EeV to allow for the uncertainties on the magnetic field strength and UHECR charge. A similar analysis is performed on stacked UHECR arrival directions and the IceCube sample of through-going muon track events which were optimized for neutrino point-source searches.Comment: one proceeding, the 34th International Cosmic Ray Conference, 30 July - 6 August 2015, The Hague, The Netherlands; will appear in PoS(ICRC2015

Measurement of Dijet Azimuthal Decorrelations at Central Rapidities in pp-bar Collisions at sqrt(s)=1.96 TeV

Correlations in the azimuthal angle between the two largest transverse momentum jets have been measured using the D0 detector in pp-bar collisions at a center-of-mass energy sqrt(s)=1.96 TeV. The analysis is based on an inclusive dijet event sample in the central rapidity region corresponding to an integrated luminosity of 150 pb-1. Azimuthal correlations are stronger at larger transverse momenta. These are well-described in perturbative QCD at next-to-leading order in the strong coupling constant, except at large azimuthal differences where soft effects are significant.Comment: 6 pages, 3 Figures submitted to Phys. Rev. Let

The IceCube Neutrino Observatory, the Pierre Auger Observatory and the Telescope Array:Joint Contribution to the 34th International Cosmic Ray Conference (ICRC 2015)

We have conducted three searches for correlations between ultra-high energy cosmic rays detected by the Telescope Array and the Pierre Auger Observatory, and high-energy neutrino candidate events from IceCube. Two cross-correlation analyses with UHECRs are done: one with 39 cascades from the IceCube `high-energy starting events' sample and the other with 16 high-energy `track events'. The angular separation between the arrival directions of neutrinos and UHECRs is scanned over. The same events are also used in a separate search using a maximum likelihood approach, after the neutrino arrival directions are stacked. To estimate the significance we assume UHECR magnetic deflections to be inversely proportional to their energy, with values $3^\circ$, $6^\circ$ and $9^\circ$ at 100 EeV to allow for the uncertainties on the magnetic field strength and UHECR charge. A similar analysis is performed on stacked UHECR arrival directions and the IceCube sample of through-going muon track events which were optimized for neutrino point-source searches

Vacuum structure for scalar cosmological perturbations in Modified Gravity Models

We have found for the general class of Modified Gravity Models f(R,G) a new instability which can arise in vacuum for the scalar modes of the cosmological perturbations if the background is not de Sitter. In particular, the short-wavelength modes, if stable, in general have a group velocity which depends linearly in k, the wave number. Therefore these modes will be in general superluminal. We have also discussed the condition for which in general these scalar modes will be ghost-like. There is a subclass of these models, defined out of properties of the function f(R,G) and to which the f(R) and f(G) models belong, which however does not have this feature.Comment: 17 pages, 1 figure, uses RevTeX, references adde