2,228 research outputs found

    Hydration Water Dynamics and Instigation of Protein Structural Relaxation

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    The molecular mechanism of the solvent motion that is required to instigate the protein structural relaxation above a critical hydration level or transition temperature has yet to be determined. In this work we use quasi-elastic neutron scattering (QENS) and molecular dynamics simulation to investigate hydration water dynamics near a greatly simplified protein surface. We consider the hydration water dynamics near the completely deuterated N-acetyl-leucine-methylamide (NALMA) solute, a hydrophobic amino acid side chain attached to a polar blocked polypeptide backbone, as a function of concentration between 0.5M-2.0M, under ambient conditions. In this Communication, we focus our results of hydration dynamics near a model protein surface on the issue of how enzymatic activity is restored once a critical hydration level is reached, and provide a hypothesis for the molecular mechanism of the solvent motion that is required to trigger protein structural relaxation when above the hydration transition.Comment: 2 pages, 2 figures, Communicatio

    “NEW ROUTES FOR RISK STRATIFICATION OF PATIENTS WITH HPV-NEGATIVE ORAL SQUAMOUS CELL CARCINOMA – EXPLORING THE TUMOR-MICROENVIRONMENT INTERFACE”

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    Head and Neck Cancers (HNCs) comprise a wide range of neoplasms originating from the lining epithelium of head and neck district, mainly squamous cell carcinomas of the oral cavity (OSCC). OSCC is mostly associated to tobacco and to alcohol abuse and recently to persistent Human Papillomavirus (HPV) infection (in particular, restricted to the oropharyngeal region). Whereas HPV-related OSCC are characterized by a significantly slow progression and high response to chemo- and radiotherapy, the “HPV-unrelated OSCC are intrinsically highly aggressive and almost always chemo- and radio resistant. To date, there is still an urgent need for new prognostic and predictive biomarkers, for these deadly cancers. In fact, oppositely to that occurring in HPV-positive oropharyngeal squamous cell cancer, there are no reliable prognostic or predictive biomarkers for non-oropharyngeal SCC. Recently, we demonstrated that the native (full-length) form of the FKBP51 protein may have a role in biological aggressiveness of skin melanoma and OSCC. FKBP51 is a member of the FK506 binding proteins, a family of immunophilins, that is targetable by immunosuppressive drugs such as rapamycin and tacrolimus. For this reason, this protein is emerging as a very interesting new target for cancer immunotherapy. The present study has been focused on the possible biological significance of the tissue immunohistochemical expression of the short splice variant of the gene FKBP5 (FKBP5s), in immunoediting and biological behavior of OSCC. Our OSCC study population included 49 cases, 20 males and 29 females (mean age 64.5 years, median 66 years). The statistical analysis of the expression of FKBP51s evidenced that 93.3% (14/15) of cancers with poor outcome registered at follow-up showed significantly strong immunostaining on the tumor invasion front. By converse, all the pre-neoplastic lesional areas with medium degree dysplasia were found negative for FKBP51s, whereas in the case of severe dysplasia and in situ carcinomas we found an exclusively nuclear staining for the protein, progressively shifting toward cytoplasm exclusively in micro invasive areas. These results support the hypothesis of a role for either FKBP51 and FKBP51s as new progression markers, easily detectable by immunohistochemistry at the time of the first diagnosis. In addition, they can significantly contribute to the better risk stratification of patients with OSCC. Finally, our results lead us to postulate that the introduction of selective FKBP51 inhibitors (either for FKBP51 and FKBP51s) may directly counteract tumor aggressiveness of OSCC and provide also new useful tools for new immunotherapy regimens

    The evolution of clearing and central counterparty services for exchange-traded derivatives in the United States and Europe - a comparison

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    This paper is organised as follows. Section 1 explains why issues concerning central counterparty clearing houses are of direct concern to central banks and why a comparison of the European and the US situation is of interest. Section 2 provides a comparative overview of the organisation of derivatives exchanges in the United States and in Europe. Section 3 focuses on the organisation of clearing, covering a broad range of aspects. Section 4 analyses operational developments in international risk management practices and arrangements. Section 5 discusses various forms of structural consolidation in the clearing and settlement infrastructure by highlighting the different approaches taken in the United States and in Europe. Section 6 is devoted to the roles of central banks and financial market regulators regarding clearing and to the challenges they face as a result of current innovations in clearing arrangements. Finally, Section 7 summarises some of the main findings.

    Governance of securities clearing and settlement systems

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    In the context of securities clearing and settlement systems, the nature of governance arrangements acquires a dimension that goes beyond their traditional function in corporate law. They constitute a tool for regulators and central banks to achieve their respective policy goals relating to market operation, market integrity, and systemic stability. In the light of the analysis of this paper, and pending a further evolution in the regulation of securities clearing and settlement in the Community, the following conclusions can be drawn. Whatever the model of corporate governance used in a jurisdiction, securities clearing and settlement systems should adopt and ensure effective implementation of the highest corporate governance standards or best practices adopted or recommended for companies in the jurisdiction in which it operates as such standards or practices evolve over time. Generally, this would imply that securities clearing and settlement systems at minimum should adopt and implement the best practices recommended for listed companies. Additionally, a securities clearing or settlement system should adopt corporate governance mechanisms adequate to address the interests of users and the public in the operation of the system. Such mechanisms should be organized so that the criteria followed to select participants on the board or on specialized committees are established ex ante. Board members should also take into account the interests of users and the public in board decisions, in particular, those relating to qualifications for system access, fair pricing, the integrity of the risk management system, innovation and efficiency, and the achievement of the policy objectives of competent authorities. Securities clearing and settlement systems should make adequate disclosures regarding their corporate governance arrangements so that users and the public can ascertain the manner in which conflicts of interest among owners, the board, users and the public interest are prevented, resolved or mitigated. Corporate governance arrangements of securities clearing and settlement systems should be the subject of adequate regulation and oversight to ensure that services are provided at fair prices to users under fair and equitable conditions of access; that the risk management programs of system operators are effective; that risk management decisions are not affected by considerations extraneous to the risk management function; and that, to the maximum extent possible, functional service providers compete in equivalent conditions of competition. Looking forward, the adoption of a harmonized regulatory regime for securities clearing and settlement systems should be considered to complete the internal market within the Community and to better achieve the policy goals identified in this paper relating to the governance of those systems.clearing, settlement, governance, risk management, oversight.

    Policymakers, researchers, and practitioners discuss the role of central counterparties

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    This article summarizes a conference, titled “Issues Related to Central Counterparty Clearing,” cosponsored by the Federal Reserve Bank of Chicago and the European Central Bank on April 3–4, 2006. The conference brought together industry executives, policymakers, and research economists to evaluate current public policy issues involving central counterparties.Banks and banking, Central ; Risk management ; Clearinghouses (Banking)

    The securities custody industry

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    Custody is, in essence, a service consisting in holding (and normally administering) securities on behalf of third parties. In step with the growth of sophisticated financial markets, custody has evolved into a complex industry no longer characterised by physical safekeeping but by a range of information and banking services. Given the multi-tier structure of the industry, custody services are provided by a variety of intermediaries. This paper describes the development of the custody industry and the structure of the custody services market. It also discusses the risks involved in custody and the challenges the industry is facing, particularly in the European context. JEL Classification: G15, G21, L22.Custody industry, securities settlement, systemic risk, custodian banks, global custodians.

    NEW APPROACHES FOR VERY SHORT-TERM STEADY-STATE ANALYSIS OF AN ELECTRICAL DISTRIBUTION SYSTEM WITH WIND FARMS

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    Distribution networks are undergoing radical changes due to the high level of penetration of dispersed generation. Dispersed generation systems require particular attention due to their incorporation of uncertain energy sources, such as wind farms, and due to the impacts that such sources have on the planning and operation of distribution networks. In particular, the foreseeable, extensive use of wind turbine generator units in the future requires that distribution system engineers properly account for their impacts on the system. Many new technical considerations must be addressed, including protection coordination, steady-state analysis, and power quality issues. This paper deals with the very short-term, steady-state analysis of a distribution system with wind farms, for which the time horizon of interest ranges from one hour to a few hours ahead. Several wind-forecasting methods are presented in order to obtain reliable input data for the steady-state analysis. Both deterministic and probabilistic methods were considered and used in performing deterministic and probabilistic load-flow analyses. Numerical applications on a 17-bus, medium-voltage, electrical distribution system with various wind farms connected at different busbars are presented and discusse

    La filiera automotive in Emilia-Romagna

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    In questo capitolo utilizziamo la metodologia sviluppata da Pavone e Russo (2017) per classificare le specializzazioni produttive della filiera automotive. Tale metodologia utilizza un\u2019analisi automatica delle descrizioni testuali delle attivit\ue0 delle imprese contenute nel database della popolazione statistica utilizzata nell\u2019Osservatorio automotive 2017. Il capitolo presenta un quadro dell\u2019industria metalmeccanica dell\u2019Emilia-Romagna e delle specializzazioni nella filiera automotive della regione. Sono commentati i risultati relativi all\u2019indagine dell\u2019Osservatorio ed un approfondimento realizzato grazie alle interviste condotte dagli studenti dell\u2019Universit\ue0 di Modena e Reggio Emilia. Le conclusioni del capitolo propongono uno sviluppo dell'indagine empirica sui temi della digitalizzazione

    Influence of sonication on co-precipitation synthesis of copper oxide catalyst for CO2 electroreduction

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    The need to reduce greenhouse gas emissions and increase our energy supply makes the electrochemical reduction of CO2 (CO2R) a very attractive alternative to produce non-fossil-based fuels or chemicals. Copper-based catalysts is one of the catalyst that most efficiently promote the formation of species with one or more carbon-carbon bonds from the electrochemical reduction of CO2 [1]. Because the catalyst preparation method has an influence on the physicochemical properties and on the electrocatalytic performance[2], in this work, it was decided to evaluate the effect of the ultrasound application (US) on the shape and size of the particles obtained, its electrocatalytic activity and its selectivity to products of interest. For this purpose, sonication was carried out at different percentage amplitudes of ultrasonic power (23, 30 and 37%) during the aging time of the synthesis. Physical characterization was carried out by using different techniques including X-ray diffraction, BET and filed-emission scanning electron microscopy (FESEM). Electrochemical tests for CO2 reduction were done under ambient conditions. Regarding the physical characteristics, we found that pore size distribution is narrower by increasing the US amplitude. On the other hand, there is no significant difference in morphology and dimension of particles. However, the surface area increased with the use of ultrasound, this is attributed to a better dispersion created by acoustic cavitation. Ultrasound has also an effect on Copper-based catalysts performance; in this case, the selectivity towards H2 and C1 products (CO and formate) was enhanced. In addition, an increase in productivity of CO2R products was obtained with respect to the synthesized catalysts that were not assisted by ultrasound (> 3-fold). These results motivate us to further explore in what other ways acoustic cavitation phenomenon can influence the physical characteristics of the catalysts and, in turns, their performance for the electrochemical reduction of CO2
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