The hyaluronan-binding serine protease from human plasma cleaves HMW and LMW kininogen and releases bradykinin

The influence of the hyaluronanbinding protease (PHBSP), a plasma enzyme with FVII- and pro-urokinase-activating potency, on components of the contact phase (kallikrein/kinin) system was investigated. No activation or cleavage of the proenzymes involved in the contact phase system was observed. The procofactor high molecular weight kininogen (HK), however, was cleaved in vitro by PHBSP in the absence of any charged surface, releasing the activated cofactor and the vasoactive nonapeptide bradykinin. Glycosoaminoglycans strongly enhanced the reaction. The cleavage was comparable to that of plasma kallikrein, but clearly different from that of coagulation factor FXIa. Upon extended incubation with PHBSP, the light chain was further processed, partially removing about 60 amino acid residues from the Nterminus of domain D5 of the light chain. These cleavage site(s) were distinct from plasma kallikrein or FXIa cleavage sites. PHBSP and, more interestingly, also plasma kallikrein could cleave low molecular weight kininogen in vitro, indicating that domains D5(H) and D6(H) are no prerequisite for kininogen cleavage. PHBSP was also able to release bradykinin from HK in plasma where the pro-cofactor circulates predominantly in complex with plasma kallikrein or FXI. In conclusion, PHBSP represents a novel kininogen-cleaving and bradykinin-releasing enzyme in plasma that shares significant catalytic similarities with plasma kallikrein. Since they are structurally unrelated in their heavy chains (propeptide), their similar in vivo catalytic activities might be directed at distinct sites where PHBSP could induce processes that are related to the kallikrein/kinin system

Effect of disorder on the electronic properties of graphene: a theoretical approach

In order to manipulate the properties of graphene, its very important to understand the electronic structure in presence of disorder. We investigate, within a tight-binding description, the effects of disorder in the on-site (diagonal disorder) term in the Hamiltonian as well as in the hopping integral (off-diagonal disorder) on the electronic dispersion and density of states by augmented space recursion method. Extrinsic off-diagonal disorder is shown to have dramatic effects on the two-dimensional Dirac-cone, including asymmetries in the band structures as well as the presence of discontinuous bands in certain limits. Disorder-induced broadening, related to the scattering length (or life-time) of electrons, is modified significantly with the increasing strength of disorder. We propose that our theory is suitable to study the effects of disorder in other 2D materials, e.g., a boron nitride monolayer.Comment: 11 pages, 8 figure

Spiritually informed not-for-profit performance measurement

Performance measurement has far-reaching implications for not-for-profit organizations because it serves to legitimize, attract resources, and preserve expectations of stakeholders. However, the existing theory and practice of not-for-profit performance measurement have fallen short, due in part, to an overuse of profit-oriented philosophies. Therefore, we examine not-for-profit performance measurement by utilizing Marques’ (J Bus Ethics 92:211–225, 2010) “five spiritual practices of Buddhism.” Marques’ spiritual practices—a pro-scientific philosophy, greater personal responsibility, healthy detachment, collaboration, and embracing a wholesome view—are the foundation of our research design. Responses from senior not-for-profit practitioners (n = 63) support the linkages between spiritual practices and not-for-profit performance measurement. We identify three essential performance measurement principles and elaborate on their capacity to generate awareness, higher meaning, and connectedness within not-for-profits

Attractor Metadynamics in Adapting Neural Networks

Slow adaption processes, like synaptic and intrinsic plasticity, abound in the brain and shape the landscape for the neural dynamics occurring on substantially faster timescales. At any given time the network is characterized by a set of internal parameters, which are adapting continuously, albeit slowly. This set of parameters defines the number and the location of the respective adiabatic attractors. The slow evolution of network parameters hence induces an evolving attractor landscape, a process which we term attractor metadynamics. We study the nature of the metadynamics of the attractor landscape for several continuous-time autonomous model networks. We find both first- and second-order changes in the location of adiabatic attractors and argue that the study of the continuously evolving attractor landscape constitutes a powerful tool for understanding the overall development of the neural dynamics

Negotiation in Multi-Agent Systems

In systems composed of multiple autonomous agents, negotiation is a key form of interaction that enables groups of agents to arrive at a mutual agreement regarding some belief, goal or plan, for example. Particularly because the agents are autonomous and cannot be assumed to be benevolent, agents must influence others to convince them to act in certain ways, and negotiation is thus critical for managing such inter-agent dependencies. The process of negotiation may be of many different forms, such as auctions, protocols in the style of the contract net, and argumentation, but it is unclear just how sophisticated the agents or the protocols for interaction must be for successful negotiation in different contexts. All these issues were raised in the panel session on negotiation

Excitons in Electrostatic Traps

We consider in-plane electrostatic traps for indirect excitons in coupled quantum wells, where the traps are formed by a laterally modulated gate voltage. An intrinsic obstacle for exciton confinement in electrostatic traps is an in-plane electric field that can lead to exciton dissociation. We propose a design to suppress the in-plane electric field and, at the same time, to effectively confine excitons in the electrostatic traps. We present calculations for various classes of electrostatic traps and experimental proof of principle for trapping of indirect excitons in electrostatic traps.Comment: 4 pages, 3 figure

Rotavirus genetic diversity, disease association, and temporal change in hospitalized rural Kenyan children

Background. The effectiveness of rotavirus vaccines will be dependent on the immunity conferred against prevalent and emergent variants causing severe diarrheal disease. Longitudinal surveillance of disease-causing strains is a prerequisite to intervention. Methods. Molecular characterization was conducted on rotavirus-positive stool samples from children admitted with diarrhea to a rural district hospital during 2002-2004. Extracted viral RNA was separated by polyacrylamide gel electrophoresis, and rotavirus VP4 (P types) and VP7 (G types) specificities were determined. Results. Among 558 investigated cases, the predominant genotype was P[8]G1 (42%), followed by P[8]G9 (15%), P[4]G8 (7%), P[6]G8 (6%), and P[8]G8 (4%), with 10% mixed strains. Overall, there were 6 different P types and 7 G types. No association was identified between genotype and child age, sex, or severity of diarrhea. The P and G genotypes and polyacrylamide gel electropherotypes showed significant temporal variation in frequency: P[8]G1 decreased from 51% (95% confidence interval [CI], 43%-58%) in 2002 to 30% (95% CI, 24%-37%) in 2004, and P[4]G8 increased from 2% (95% CI, 0%-5%) in 2002 to 13% (95% CI, 9%-19%). Quarterly data revealed seasonally endemic and emergence and/or decay patterns. Conclusions. Our study of rotavirus strains causing severe diarrhea in rural Kenyan children showed a predominance of P[8]G1 and confirms the importance of G8 and G9 strains in sub-Saharan Africa. Considerable genetic diversity of rotavirus strains was observed, including substantial mixed and unusual types, coupled with significant temporal strain variation and emergence. These results warn of variable vaccine efficacy and the need for long-term surveillance of circulating rotavirus genotypes

Numerical solution and spectrum of boundary-domain integral equation for the Neumann BVP with variable coefficient

This is the post-print version of the Article. The official published version can be accessed from the link below - Copyright @ 2012 Taylor & Francis.In this paper, a numerical implementation of a direct united boundary-domain integral equation (BDIE) related to the Neumann boundary value problem for a scalar elliptic partial differential equation with a variable coefficient is discussed. The BDIE is reduced to a uniquely solvable one by adding an appropriate perturbation operator. The mesh-based discretization of the BDIEs with quadrilateral domain elements leads to a system of linear algebraic equations (discretized BDIE). Then, the system is solved by LU decomposition and Neumann iterations. Convergence of the iterative method is discussed in relation to the distribution of eigenvalues of the corresponding discrete operators calculated numerically.The work was supported by the grant EP/H020497/1 "Mathematical analysis of localised boundary-domain integral equations for BVPs with variable coefficients" of the EPSRC, UK

The eventization of leisure and the strange death of alternative Leeds

The communicative potential of city spaces as leisure spaces is a central assumption of political activism and the creation of alternative, counter-cultural and subcultural scenes. However, such potential for city spaces is limited by the gentrification, privatization and eventization of city centres in the wake of wider societal and cultural struggles over leisure, work and identity formation. In this paper, we present research on alternative scenes in the city of Leeds to argue that the eventization of the city centre has led to a marginalization and of alternative scenes on the fringes of the city. Such marginalization has not caused the death of alternative Leeds or political activism associated with those scenes—but it has changed the leisure spaces (physical, political and social) in which alternative scenes contest the mainstream