Charging and coagulation of dust in protoplanetary plasma environments

Combining a particle-particle, particle-cluster and cluster-cluster agglomeration model with an aggregate charging model, the coagulation and charging of dust particles in various plasma environments relevant for proto-planetary disks have been investigated. The results show that charged aggregates tend to grow by adding small particles and clusters to larger particles and clusters, leading to greater sizes and masses as compared to neutral aggregates, for the same number of monomers in the aggregate. In addition, aggregates coagulating in a Lorentzian plasma (containing a larger fraction of high-energy plasma particles) are more massive and larger than aggregates coagulating in a Maxwellian plasma, for the same plasma densities and characteristic temperature. Comparisons of the grain structure, utilizing the compactness factor, {\phi}{\sigma}, demonstrate that a Lorentzian plasma environment results in fluffier aggregates, with small {\phi}{\sigma}, which exhibit a narrow compactness factor distribution. Neutral aggregates are more compact, with larger {\phi}{\sigma}, and exhibit a larger variation in fluffiness. Measurement of the compactness factor of large populations of aggregates is shown to provide information on the disk parameters that were present during aggregation

Hiding in the Shadows II: Collisional Dust as Exoplanet Markers

Observations of the youngest planets ($\sim$1-10 Myr for a transitional disk) will increase the accuracy of our planet formation models. Unfortunately, observations of such planets are challenging and time-consuming to undertake even in ideal circumstances. Therefore, we propose the determination of a set of markers that can pre-select promising exoplanet-hosting candidate disks. To this end, N-body simulations were conducted to investigate the effect of an embedded Jupiter mass planet on the dynamics of the surrounding planetesimal disk and the resulting creation of second generation collisional dust. We use a new collision model that allows fragmentation and erosion of planetesimals, and dust-sized fragments are simulated in a post process step including non-gravitational forces due to stellar radiation and a gaseous protoplanetary disk. Synthetic images from our numerical simulations show a bright double ring at 850 $\mu$m for a low eccentricity planet, whereas a high eccentricity planet would produce a characteristic inner ring with asymmetries in the disk. In the presence of first generation primordial dust these markers would be difficult to detect far from the orbit of the embedded planet, but would be detectable inside a gap of planetary origin in a transitional disk.Comment: Accepted for publication in Ap

Dependence of aptamer activity on opposed terminal extensions : improvement of light-regulation efficiency

Aptamers that can be regulated with light allow precise control of protein activity in space and time and hence of biological function in general. In a previous study, we showed that the activity of the thrombin-binding aptamer HD1 can be turned off by irradiation using a light activatable "caged" intramolecular antisense-domain. However, the activity of the presented aptamer in its ON state was only mediocre. Here we studied the nature of this loss in activity in detail and found that switching from 5'- to 3'-extensions affords aptamers that are even more potent than the unmodified HD1. In particular we arrived at derivatives that are now more active than the aptamer NU172 that is currently in phase 2 clinical trials as an anticoagulant. As a result, we present light-regulatable aptamers with a superior activity in their ON state and an almost digital ON/OFF behavior upon irradiation

Planet Formation in the Outer Solar System

This paper reviews coagulation models for planet formation in the Kuiper Belt, emphasizing links to recent observations of our and other solar systems. At heliocentric distances of 35-50 AU, single annulus and multiannulus planetesimal accretion calculations produce several 1000 km or larger planets and many 50-500 km objects on timescales of 10-30 Myr in a Minimum Mass Solar Nebula. Planets form more rapidly in more massive nebulae. All models yield two power law cumulative size distributions, N_C propto r^{-q} with q = 3.0-3.5 for radii larger than 10 km and N_C propto r^{-2.5} for radii less than 1 km. These size distributions are consistent with observations of Kuiper Belt objects acquired during the past decade. Once large objects form at 35-50 AU, gravitational stirring leads to a collisional cascade where 0.1-10 km objects are ground to dust. The collisional cascade removes 80% to 90% of the initial mass in the nebula in roughly 1 Gyr. This dust production rate is comparable to rates inferred for alpha Lyr, beta Pic, and other extrasolar debris disk systems.Comment: invited review for PASP, March 2002. 33 pages of text and 12 figure

Non-canonical proteolytic activation of human prothrombin by subtilisin from Bacillus subtilis may shift the procoagulant\ue2\u80\u93anticoagulant equilibrium toward thrombosis

Blood coagulation is a finely regulated physiological process culminating with the factor Xa (FXa)-mediated conversion of the prothrombin (ProT) zymogen to active -thrombin (T). In the prothrombinase complex on the platelet surface, FXa cleaves ProT at Arg-271, generating the inactive precursor pre-thrombin-2 (Pre2), which is further attacked at Arg-320 \u2013Ile-321 to yield mature T. Whereas the mechanism of physiological ProT activation has been elucidated in great detail, little is known about the role of bacterial proteases, possibly released in the bloodstream during infection, in inducing blood coagulation by direct proteolytic ProT activation. This knowledge gap is particularly concerning, as bacterial infections are frequently complicated by severe coagulopathies. Here, we show that addition of subtilisin (50 nM to 2 M), a serine protease secreted by the non-pathogenic bacterium Bacillus subtilis, induces plasma clotting by proteolytically converting ProT into active Pre2, a nicked Pre2 derivative with a single cleaved Ala-470 \u2013Asn-471 bond. Notably, we found that this non-canonical cleavage at Ala-470 \u2013Asn-471 is instrumental for the onset of catalysis in Pre2, which was, however, reduced about 100 \u2013200-fold compared with T. Of note, Pre2 could generate fibrin clots from fibrinogen, either in solution or in blood plasma, and could aggregate human platelets, either isolated or in whole blood. Our findings demonstrate that alternative cleavage of ProT by proteases, even by those secreted by non-virulent bacteria such as B. subtilis, can shift the delicate procoagulant\u2013anticoagulant equilibrium toward thrombosis

Platelets as mediators of Thromboinflammation in chronic Myeloproliferative Neoplasms

Chronic myeloproliferative neoplasms (MPN) are stem cell disorders driven by mutations in JAK2, CALR, or MPL genes and characterized by myeloid proliferation and increased blood cell counts. They encompass three closely related conditions, including essential thrombocythemia, polycythemia vera, and primary myelofibrosis. Elevated levels of cytokines released by clonal and non-clonal cells generate a chronic proinflammatory state that contributes to disease pathogenesis. Thrombosis represents the most common cause of morbidity and mortality in MPN, although paradoxically, patients may also present with a bleeding diathesis. The mechanisms leading to thrombosis are complex and multiple and include increased blood cells together with qualitative abnormalities of red cells, leukocytes, and platelets that favor a prothrombotic activated phenotype. The functional interplay between blood cells, the clotting cascade, and dysfunctional endothelium contributes to hypercoagulability and this process is perpetuated by the effect of inflammatory cytokines. In addition to their well-known function in hemostasis, platelets contribute to innate immunity and inflammation and play a key role in MPN thromboinflammatory state. In vivo platelet activation leads to platelet aggregate formation and exposure of adhesion molecules which favor their interaction with activated neutrophils and monocytes leading to circulating platelet-leukocyte heterotypic aggregates. Platelets are recruited to the activated endothelium further enhancing the reciprocal activation of both cell types. Crosstalk between activated cells drives cytokine production, further fuelling the self-reinforcing thromboinflammatory loop. In addition, MPN platelets provide a procoagulant scaffold which triggers the coagulation cascade and platelet-derived microparticles amplify this response. Markers of platelet, leukocyte, endothelial and coagulation activation are increased in MPN patients although prospective studies are required to determine the potential value of these parameters for identifying patients at increased thrombotic risk. Thrombosis remains the main complication of MPN patients, with a high risk of recurrence despite adequate cytoreductive and antithrombotic treatment. Deeper insight into the mechanism favoring thrombosis development in this setting may lead to novel therapeutic approaches for MPN thrombosis. Considering the critical role of inflammation in the vascular risk, concomitant targeting of inflammatory pathways could potentially impact on primary or secondary prevention strategies.Fil: Marin Oyarzún, Cecilia Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Heller, Paula Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentin