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

Optimal scales in weighted networks

The analysis of networks characterized by links with heterogeneous intensity or weight suffers from two long-standing problems of arbitrariness. On one hand, the definitions of topological properties introduced for binary graphs can be generalized in non-unique ways to weighted networks. On the other hand, even when a definition is given, there is no natural choice of the (optimal) scale of link intensities (e.g. the money unit in economic networks). Here we show that these two seemingly independent problems can be regarded as intimately related, and propose a common solution to both. Using a formalism that we recently proposed in order to map a weighted network to an ensemble of binary graphs, we introduce an information-theoretic approach leading to the least biased generalization of binary properties to weighted networks, and at the same time fixing the optimal scale of link intensities. We illustrate our method on various social and economic networks.Comment: Accepted for presentation at SocInfo 2013, Kyoto, 25-27 November 2013 (http://www.socinfo2013.org

Spectroscopic Observations of New Oort Cloud Comet 2006 VZ13 and Four Other Comets

Spectral data are presented for comets 2006 VZ13 (LINEAR), 2006 K4 (NEAT), 2006 OF2 (Broughton), 2P/Encke, and 93P/Lovas I, obtained with the Cerro-Tololo Inter-American Observatory 1.5-m telescope in August 2007. Comet 2006 VZ13 is a new Oort cloud comet and shows strong lines of CN (3880 angstroms), the Swan band sequence for C_2 (4740, 5160, and 5630 angstroms), C_3 (4056 angstroms), and other faint species. Lines are also identified in the spectra of the other comets. Flux measurements of the CN, C_2 (Delta v = +1,0), and C_3 lines are recorded for each comet and production rates and ratios are derived. When considering the comets as a group, there is a correlation of C_2 and C_3 production with CN, but there is no conclusive evidence that the production rate ratios depend on heliocentric distance. The continuum is also measured, and the dust production and dust-to-gas ratios are calculated. There is a general trend, for the group of comets, between the dust-to-gas ratio and heliocentric distance, but it does not depend on dynamical age or class. Comet 2006 VZ13 is determined to be in the carbon-depleted (or Tempel 1 type) class.Comment: 8 pages, 6 figures, 6 tables; Accepted by MNRA

Stationary Entangled Radiation from Micromechanical Motion

Mechanical systems facilitate the development of a new generation of hybrid quantum technology comprising electrical, optical, atomic and acoustic degrees of freedom. Entanglement is the essential resource that defines this new paradigm of quantum enabled devices. Continuous variable (CV) entangled fields, known as Einstein-Podolsky-Rosen (EPR) states, are spatially separated two-mode squeezed states that can be used to implement quantum teleportation and quantum communication. In the optical domain, EPR states are typically generated using nondegenerate optical amplifiers and at microwave frequencies Josephson circuits can serve as a nonlinear medium. It is an outstanding goal to deterministically generate and distribute entangled states with a mechanical oscillator. Here we observe stationary emission of path-entangled microwave radiation from a parametrically driven 30 micrometer long silicon nanostring oscillator, squeezing the joint field operators of two thermal modes by 3.40(37) dB below the vacuum level. This mechanical system correlates up to 50 photons/s/Hz giving rise to a quantum discord that is robust with respect to microwave noise. Such generalized quantum correlations of separable states are important for quantum enhanced detection and provide direct evidence for the non-classical nature of the mechanical oscillator without directly measuring its state. This noninvasive measurement scheme allows to infer information about otherwise inaccessible objects with potential implications in sensing, open system dynamics and fundamental tests of quantum gravity. In the near future, similar on-chip devices can be used to entangle subsystems on vastly different energy scales such as microwave and optical photons.Comment: 13 pages, 5 figure

An ensemble approach to the analysis of weighted networks

We present a new approach to the calculation of measures in weighted networks, based on the translation of a weighted network into an ensemble of edges. This leads to a straightforward generalization of any measure defined on unweighted networks, such as the average degree of the nearest neighbours, the clustering coefficient, the `betweenness', the distance between two nodes and the diameter of a network. All these measures are well established for unweighted networks but have hitherto proven difficult to define for weighted networks. Further to introducing this approach we demonstrate its advantages by applying the clustering coefficient constructed in this way to two real-world weighted networks.Comment: 4 pages 3 figure

Autowaves in a dc complex plasma confined behind a de Laval nozzle

Experiments to explore stability conditions and topology of a dense microparticle cloud supported against gravity by a gas flow were carried out. By using a nozzle shaped glass insert within the glass tube of a dc discharge plasma chamber a weakly ionized gas flow through a de Laval nozzle was produced. The experiments were performed using neon gas at a pressure of 100 Pa and melamine-formaldehyde particles with a diameter of 3.43 {\mu}m. The capturing and stable global confining of the particles behind the nozzle in the plasma were demonstrated. The particles inside the cloud behaved as a single convection cell inhomogeneously structured along the nozzle axis in a tube-like manner. The pulsed acceleration localized in the very head of the cloud mediated by collective plasma-particle interactions and the resulting wave pattern were studied in detail.Comment: 6 pages, 4 figure

Applying weighted network measures to microarray distance matrices

In recent work we presented a new approach to the analysis of weighted networks, by providing a straightforward generalization of any network measure defined on unweighted networks. This approach is based on the translation of a weighted network into an ensemble of edges, and is particularly suited to the analysis of fully connected weighted networks. Here we apply our method to several such networks including distance matrices, and show that the clustering coefficient, constructed by using the ensemble approach, provides meaningful insights into the systems studied. In the particular case of two data sets from microarray experiments the clustering coefficient identifies a number of biologically significant genes, outperforming existing identification approaches.Comment: Accepted for publication in J. Phys.

The relationship of individual comorbid chronic conditions to diabetes care quality.

ObjectiveMultimorbidity affects 26 million persons with diabetes, and care for comorbid chronic conditions may impact diabetes care quality. The aim of this study was to determine which chronic conditions were related to lack of achievement or achievement of diabetes care quality goals to determine potential targets for future interventions.Research design and methodsThis is an exploratory retrospective analysis of electronic health record data for 23 430 adults, aged 18-75, with diabetes who were seen at seven Midwestern US health systems. The main outcome measures were achievement of six diabetes quality metrics in the reporting year, 2011 (glycated haemoglobin (HbA1c) control and testing, low-density lipoprotein control and testing, blood pressure control, kidney testing). Explanatory variables were 62 chronic condition indicators. Analyses were adjusted for baseline patient sociodemographic and healthcare utilization factors.ResultsThe 62 chronic conditions varied in their relationships to diabetes care goal achievement for specific care goals. Congestive heart failure was related to lack of achievement of cholesterol management goals. Obesity was related to lack of HbA1c and BP control. Mental health conditions were related to both lack of achievement and achievement of different care goals. Three conditions were related to lack of cholesterol testing, including congestive heart failure and substance-use disorders. Of 17 conditions related to achieving control goals, 16 were related to achieving HbA1c control. One-half of the comorbid conditions did not predict diabetes care quality.ConclusionsFuture interventions could target patients at risk for not achieving diabetes care for specific care goals based on their individual comorbidities