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

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

Beyond persons: extending the personal / subpersonal distinction to non-rational animals and artificial agents

The distinction between personal level explanations and subpersonal ones has been subject to much debate in philosophy. We understand it as one between explanations that focus on an agent’s interaction with its environment, and explanations that focus on the physical or computational enabling conditions of such an interaction. The distinction, understood this way, is necessary for a complete account of any agent, rational or not, biological or artificial. In particular, we review some recent research in Artificial Life that pretends to do completely without the distinction, while using agent-centered concepts all the way. It is argued that the rejection of agent level explanations in favour of mechanistic ones is due to an unmotivated need to choose among representationalism and eliminativism. The dilemma is a false one if the possibility of a radical form of externalism is considered

Magnetic Moment Softening and Domain Wall Resistance in Ni Nanowires

Magnetic moments in atomic scale domain walls formed in nanoconstrictions and nanowires are softened which affects dramatically the domain wall resistance. We perform ab initio calculations of the electronic structure and conductance of atomic-size Ni nanowires with domain walls only a few atomic lattice constants wide. We show that the hybridization between noncollinear spin states leads to a reduction of the magnetic moments in the domain wall. This magnetic moment softening strongly enhances the domain wall resistance due to scattering produced by the local perturbation of the electronic potential.Comment: 4 pages, 5 figure

Taking the Pressure Off the Patient - Understanding Digital Rectal Examinations on a Real Subject.

Better understanding of palpation techniques during unsighted physical examinations has mostly been limited to qualitative and quantitative studies of performance of experts whilst conducting examinations on plastic benchtop models. However, little is known about their performance when conducting such examinations on real subjects. OBJECTIVE: The aim of this paper is to better understand palpation techniques of experts whilst conducting a Digital Rectal Examination on a real subject. METHODS: We recruited four consultants from relevant specialties and asked them to conduct two DREs on a Rectal Teaching Assistant whilst wearing small position and pressure sensors on their examining finger. We segmented the relevant anatomy from an MRI taken of the pelvic region, registered 3D models and analysed retrospectively performance in relation to executed tasks, supination/pronation, palpation convex hull and pressure applied. RESULTS: Primary care consultants examined the anatomy more holistically compared to secondary care experts, the maximum pressure applied across experiments is 3.3N, overall the pressure applied on the prostate is higher than that applied to rectal walls, and the urologist participant not only applied the highest pressure but also did so with the highest most prominent frequency (15.4 and 25.3 Hz). CONCLUSIONS: The results of our research allow for better understanding of experts' technical performance from relevant specialities when conducting a DRE, and suggest the range of pressure applied whilst palpating anatomy. SIGNIFICANCE: This research will be valuable in improving the design of haptics-based learning tools, as well as in encouraging reflection on palpation styles across different specialities to develop metrics of performance

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

On Predicting the Solar Cycle using Mean-Field Models

We discuss the difficulties of predicting the solar cycle using mean-field models. Here we argue that these difficulties arise owing to the significant modulation of the solar activity cycle, and that this modulation arises owing to either stochastic or deterministic processes. We analyse the implications for predictability in both of these situations by considering two separate solar dynamo models. The first model represents a stochastically-perturbed flux transport dynamo. Here even very weak stochastic perturbations can give rise to significant modulation in the activity cycle. This modulation leads to a loss of predictability. In the second model, we neglect stochastic effects and assume that generation of magnetic field in the Sun can be described by a fully deterministic nonlinear mean-field model -- this is a best case scenario for prediction. We designate the output from this deterministic model (with parameters chosen to produce chaotically modulated cycles) as a target timeseries that subsequent deterministic mean-field models are required to predict. Long-term prediction is impossible even if a model that is correct in all details is utilised in the prediction. Furthermore, we show that even short-term prediction is impossible if there is a small discrepancy in the input parameters from the fiducial model. This is the case even if the predicting model has been tuned to reproduce the output of previous cycles. Given the inherent uncertainties in determining the transport coefficients and nonlinear responses for mean-field models, we argue that this makes predicting the solar cycle using the output from such models impossible.Comment: 22 Pages, 5 Figures, Preprint accepted for publication in Ap

The s Process: Nuclear Physics, Stellar Models, Observations

Nucleosynthesis in the s process takes place in the He burning layers of low mass AGB stars and during the He and C burning phases of massive stars. The s process contributes about half of the element abundances between Cu and Bi in solar system material. Depending on stellar mass and metallicity the resulting s-abundance patterns exhibit characteristic features, which provide comprehensive information for our understanding of the stellar life cycle and for the chemical evolution of galaxies. The rapidly growing body of detailed abundance observations, in particular for AGB and post-AGB stars, for objects in binary systems, and for the very faint metal-poor population represents exciting challenges and constraints for stellar model calculations. Based on updated and improved nuclear physics data for the s-process reaction network, current models are aiming at ab initio solution for the stellar physics related to convection and mixing processes. Progress in the intimately related areas of observations, nuclear and atomic physics, and stellar modeling is reviewed and the corresponding interplay is illustrated by the general abundance patterns of the elements beyond iron and by the effect of sensitive branching points along the s-process path. The strong variations of the s-process efficiency with metallicity bear also interesting consequences for Galactic chemical evolution.Comment: 53 pages, 20 figures, 3 tables; Reviews of Modern Physics, accepte

Chiral Prediction for the πN\pi N Scattering Length a−a^- to Order O(Mπ4){\cal O}(M_\pi^4)

We evaluate the S-wave pion--nucleon scattering length $a^-$ in the framework of heavy baryon chiral perturbation theory up--to--and--including terms of order $M_\pi^4$. We show that the order $M_\pi^4$ piece of the isovector amplitude at threshold, $T^-_{\rm thr}$, vanishes exactly. We predict for the isovector scattering length, $0.088 \, M_{\pi^+}^{-1} \le a^- \le 0.096 \, M_{\pi^+}^{-1}$.Comment: 5 pp, LaTeX file, 2 figures (appended as separate compressed tar file, amin.uu

Condensation of microturbulence-generated shear flows into global modes

In full flux-surface computer studies of tokamak edge turbulence, a spectrum of shear flows is found to control the turbulence level and not just the conventional (0,0)-mode flows. Flux tube domains too small for the large poloidal scale lengths of the continuous spectrum tend to overestimate the flows, and thus underestimate the transport. It is shown analytically and numerically that under certain conditions dominant (0,0)-mode flows independent of the domain size develop, essentially through Bose-Einstein condensation of the shear flows.Comment: 5 pages, 4 figure