Fibrinogen-elongated Chain Inhibits Thrombin-induced Platelet Response, Hindering the Interaction with Different Receptors

The expression of the elongated fibrinogen γ chain, termed γ′, derives from alternative splicing of mRNA and causes an insertion sequence of 20 amino acids. This insertion domain interacts with the anion-binding exosite (ABE)-II of thrombin. This study investigated whether and how γ′ chain binding to ABE-II affects thrombin interaction with its platelet receptors, i.e. glycoprotein Ibα (GpIbα), protease-activated receptor (PAR) 1, and PAR4. Both synthetic γ′ peptide and fibrinogen fragment D*, containing the elongated γ′ chain, inhibited thrombin-induced platelet aggregation up to 70%, with IC50 values of 42 ± 3.5 and 0.47 ± 0.03 μm, respectively. Solid-phase binding and spectrofluorimetric assays showed that both fragment D* and the synthetic γ′ peptide specifically bind to thrombin ABE-II and competitively inhibit the thrombin binding to GpIbα with a mean Ki ≈ 0.5 and ≈35 μm, respectively. Both these γ′ chain-containing ligands allosterically inhibited thrombin cleavage of a synthetic PAR1 peptide, of native PAR1 molecules on intact platelets, and of the synthetic chromogenic peptide d-Phe-pipecolyl-Arg-p-nitroanilide. PAR4 cleavage was unaffected. In summary, fibrinogen γ′ chain binds with high affinity to thrombin and inhibits with combined mechanisms the platelet response to thrombin. Thus, its variations in vivo may affect the hemostatic balance in arterial circulation

Multi-risk assessment in a historical city

AbstractNatural hazards pose a significant threat to historical cities which have an authentic and universal value for mankind. This study aims at codifying a multi-risk workflow for seismic and flood hazards, for site-scale applications in historical cities, which provides the Average Annual Loss for buildings within a coherent multi-exposure and multi-vulnerability framework. The proposed methodology includes a multi-risk correlation and joint probability analysis to identify the role of urban development in re-shaping risk components in historical contexts. The workflow is unified by exposure modelling which adopts the same assumptions and parameters. Seismic vulnerability is modelled through an empirical approach by assigning to each building a vulnerability value depending on the European Macroseismic Scale (EMS-98) and modifiers available in literature. Flood vulnerability is modelled by means of stage-damage curves developed for the study area and validated against ex-post damage claims. The method is applied to the city centre of Florence (Italy) listed as UNESCO World Heritage site since 1982. Direct multi-hazard, multi-vulnerability losses are modelled for four probabilistic scenarios. A multi-risk of 3.15 M€/year is estimated for the current situation. In case of adoption of local mitigation measures like floodproofing of basements and installation of steel tie rods, multi-risk reduces to 1.55 M€/yr. The analysis of multi-risk correlation and joint probability distribution shows that the historical evolution of the city centre, from the roman castrum followed by rebuilding in the Middle Ages, the late XIX century and the post WWII, has significantly affected multi-risk in the area. Three identified portions of the study area with a different multi-risk spatial probability distribution highlight that the urban development of the historical city influenced the flood hazard and the seismic vulnerability. The presented multi-risk workflow could be applied to other historical cities and further extended to other natural hazards

Influence of carbon and nitrogen on electronic structure and hyperfine interactions in fcc iron-based alloys

Carbon and nitrogen austenites, modeled by Fe8N and Fe8C superstructures are studied by full-potential LAPW method. Structure parameters, electronic and magnetic properties as well as hyperfine interaction parameters are obtained. Calculations prove that Fe-C austenite can be successfully modeled by ordered Fe8C superstructure. The results show that chemical Fe-C bond in Fe8C has higher covalent part than in Fe8N. Detailed analysis of electric field gradient formation for both systems is performed. The calculation of electric field gradient allow us to carry out a good interpretation of Moessbauer spectra for Fe-C and Fe-N systems.Comment: 8 pages, 3 figures, IOP-style LaTeX, submitted to J. Phys. Condens. Matte

NSHT: New Smart Hybrid Transducer for Structural and Geotechnical Applications

This work describes the application of a new transducer prototype for continuous monitoring in both the structural and geotechnical fields. The transducer is synthetically constituted by a wire of optical fiber embedded between two fiber tapes (fiberglass or carbon fiber) and glued by a matrix of polyester resin. The fiber optical wire ends have been connected to a control unit whose detection system is based on Brillouin optical time-domain frequency analysis. Three laboratory tests were carried out to evaluate the sensor's reliability and accuracy. In each experiment, the transducer was applied to a sample of inclinometer casing sets in different configurations and with different constraint conditions. The experimental collected data were compared with theoretical models and with data obtained from the use of different measuring instruments to perform validation and calibration of the transducer at the same time. Several diagrams can compare the transducer and highlight its suitability for the monitoring and maintenance of structures. The characteristic of the transducer suggests its use as a mixed system for reinforcing and monitoring, especially in the lifetime maintenance of critical infrastructures such as transportation and service networks, and historical heritag

Combining Private Set-Intersection with Secure Two-Party Computation

Private Set-Intersection (PSI) is one of the most popular and practically relevant secure two-party computation (2PC) tasks. Therefore, designing special-purpose PSI protocols (which are more efficient than generic 2PC solutions) is a very active line of research. In particular, a recent line of work has proposed PSI protocols based on oblivious transfer (OT) which, thanks to recent advances in OT-extension techniques, is nowadays a very cheap cryptographic building block. Unfortunately, these protocols cannot be plugged into larger 2PC applications since in these protocols one party (by design) learns the output of the intersection. Therefore, it is not possible to perform secure post-processing of the output of the PSI protocol. In this paper we propose a novel and efficient OT-based PSI protocol that produces an encrypted output that can therefore be later used as an input to other 2PC protocols. In particular, the protocol can be used in combination with all common approaches to 2PC including garbled circuits, secret sharing and homomorphic encryption. Thus, our protocol can be combined with the right 2PC techniques to achieve more efficient protocols for computations of the form $z=f(X\cap Y)$ for arbitrary functions $f$

Liquid baits with Oenococcus oeni increase captures of Drosophila suzukii

The spotted-wing drosophila (SWD), Drosophila suzukii Matsumura (Diptera: Drosophilidae), native to Eastern Asia, is an invasive alien species in Europe and the Americas, where it is a severe pest of horticultural crops, including soft fruits and wine grapes. The conventional approach to controlling infestations of SWD involves the use of insecticides, but the frequency of application for population management is undesirable. Consequently, alternative strategies are urgently needed. Effective and improved trapping is important as an early risk detection tool. This study aimed to improve Droskidrink® (DD), a commercially available attractant for SWD. We focused on the chemical and behavioral effects of adding the bacterium Oenococcus oeni (Garvie) to DD and used a new trap design to enhance the effects of attractive lures. We demonstrate that microbial volatile compounds produced by O. oeni are responsible for the increase in the attractiveness of the bait and could be later utilized for the development of a better trapping system. Our results showed that the attractiveness of DD was increased up to two-fold by the addition of commercially available O. oeni when combined with an innovative trap design. The new trap-bait combination increased the number of male and especially female catches at low population densitie

SpOT-Light: Lightweight Private Set Intersection from Sparse OT Extension

We describe a novel approach for two-party private set intersection (PSI) with semi-honest security. Compared to existing PSI protocols, ours has a more favorable balance between communication and computation. Specifically, our protocol has the lowest monetary cost of any known PSI protocol, when run over the Internet using cloud-based computing services (taking into account current rates for CPU + data). On slow networks (e.g., 10Mbps) our protocol is actually the fastest. Our novel underlying technique is a variant of oblivious transfer (OT) extension that we call sparse OT extension. Conceptually it can be thought of as a communication-efficient multipoint oblivious PRF evaluation. Our sparse OT technique relies heavily on manipulating high-degree polynomials over large finite fields (i.e. elements whose representation requires hundreds of bits). We introduce extensive algorithmic and engineering improvements for interpolation and multi-point evaluation of such polynomials, which we believe will be of independent interest. Finally, we present an extensive empirical comparison of state-of-the- art PSI protocols in several application scenarios and along several dimensions of measurement: running time, communication, peak memory consumption, and — arguably the most relevant metric for practice — monetary cos

High promiscuity among females of the invasive pest species Drosophila suzukii

Drosophila suzukii (Matsumura, 1931), the spotted-wing drosophila, is a highly invasive fruit fly that spread from Southern Asia across most regions of Asia and, in the last 15 years, has invaded Europe and the Americas. It is an economically important pest of small fruits such as berries and stone fruits. Drosophila suzukii speciated by adapt ing to cooler, mountainous, and forest environments. In temperate regions, it evolved seasonal polyphenism traits which enhanced its survival during stressful winter population bottlenecks. Consequently, in these temperate regions, the populations undergo seasonal reproductive dynamics. Despite its economic importance, no data are available on the behavioural reproductive strategies of this fly. The presence of polyandry, for example, has not been determined despite the important role it might play in the reproductive dynamics of populations. We explored the presence of poly andry in an established population in Trentino, a region in northern Italy. In this area, D. suzukii overcomes the winter bottleneck and undergoes a seasonal reproductive fluctuation. We observed a high remating frequency in females during the late spring demographic explosion that led to the abundant summer population. The presence of a high degree of polyandry and shared paternity associated with the post-winter population increase raises the question of the possible evolutionary adaptive role of this reproductive behaviour in D. suzuki

HBeAg Levels Vary across the Different Stages of HBV Infection According to the Extent of Immunological Pressure and Are Associated with Therapeutic Outcome in the Setting of Immunosuppression-Driven HBV Reactivation

HBeAg is a marker of HBV-activity, and HBeAg-loss predicts a favorable clinical outcome. Here, we characterize HBeAg-levels across different phases of HBV infection, their correlation with virological/biochemical markers and the virological response to anti-HBV therapy. Quantitative HBeAg (qHBeAg, DiaSorin) is assessed in 101 HBeAg+ patients: 20 with acute-infection, 20 with chronic infection, 32 with chronic hepatitis and 29 with immunosuppression-driven HBV-reactivation (HBV-R). A total of 15/29 patients with HBV-R are monitored for > 12 months after starting TDF/ETV. qHBeAg is higher in immunosuppression-driven HBV-R (median[IQR]:930[206-1945]PEIU/mL) and declines in chronic hepatitis (481[28-1393]PEIU/mL, p = 0.03), suggesting HBeAg production, modulated by the extent of immunological pressure. This is reinforced by the negative correlation between qHBeAg and ALT in acute infection (Rho = -0.66, p = 0.006) and chronic hepatitis (Rho = -0.35; p = 0.05). Interestingly, qHBeAg strongly and positively correlates with qHBsAg across the study groups, suggesting cccDNA as a major source of both proteins in the setting of HBeAg positivity (with limited contribution of integrated HBV-DNA to HBsAg production). Focusing on 15 patients with HBV-R starting TDF/ETV, virological suppression and HBeAg-loss are achieved in 60% and 53.3%. Notably, the combination of qHBeAg > 2000 PEIU/mL + qHBsAg > 52,000 IU/mL at HBV-R is the only factor predicting no HBeAg loss (HBeAg loss: 0% with vs. 72.7% without qHBeAg > 2000 PEIU/mL + qHBsAg > 52,000 IU/mL, p = 0.03). In conclusion, qHBeAg varies over the natural course of HBV infection, according to the extent of immunological pressure. In the setting of HBV-R, qHBeAg could be useful in predicting the treatment response under immunosuppression

Lymphomononuclear cells from multiple sclerosis patients spontaneously produce high levels of oncostatin M, tumor necrosis factors a

Proinflammatory cytokines are deemed to play a pivotal role in the pathogenesis of multiple sclerosis (MS). They provide signals for T-cell activatio