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Recent findings support the hypothesis that inhibition of SMYD3 methyltransferase may be a therapeutic avenue for some of the deadliest cancer types. Herein, active site-selective covalent SMYD3 inhibitors were designed by introducing an appropriate reactive cysteine trap into reversible first-generation SMYD3 inhibitors. The 4-aminopiperidine derivative EM127 (11C) bearing a 2-chloroethanoyl grou
Objectives.: To assess the comparability of the Tandem-R and IMx serumprostate-specific antigen (PSA) assays across levels of the ratio of free-to-total serum PSA found in a community-based population of healthy men. Methods.: Banked serum samples from the baseline component of the Olmsted CountyStudy of Urinary Symptoms and Health Status Among Men were thawed and analyzed using the Tandem-R and I
The expansion of the European Union’s (EU) regulatory sphere creates conflicts of sovereignty between the EU and its member states, and third countries that lack a possibility to participate in the making of those laws and policies. The conflict is epitomised in the concept of the Union’s decision-making autonomy. Albeit stringently applied, the concept is ambiguous and undefined. This article end
Recent observations of the gamma-ray source HAWC J2227+610 by Tibet AS+MD and LHAASO confirm the special interest of this source as a galactic PeVatron candidate in the northern hemisphere. HAWC J2227+610 emits Very High Energy (VHE) gamma-rays up to 500 TeV, from a region coincident with molecular clouds and significantly displaced from the nearby pulsar J2229+6114. Even if this morphology favour
OBJECTIVE: To investigate gastrointestinal infection episodes (GIEs) in relation to the appearance of islet autoantibodies in The Environmental Determinants of Diabetes in the Young (TEDDY) cohort.RESEARCH DESIGN AND METHODS: GIEs on risk of autoantibodies against either insulin (IAA) or GAD (GADA) as the first-appearing autoantibody were assessed in a 10-year follow-up of 7,867 children. Stool vi
In this position paper we argue for a radical departure from today's approach to software engineering, centered on target-specific tools and general processes such as modeling and agile practices. The old principle of right tool for each problem shall be applied to software engineering as well: to address ever higher complexity, we need to raise dramatically the level of abstraction; as general so
The strong negative relationship between geographical distance and trade is not well understood. I use the liberalization of the Soviet airspace to estimate the causal impact of business travel cost on trade. The liberalization radically reduced travel time between Europe and East Asia and was followed by a significant increase in trade. I find that the cost of business travel can account for a la
After many years of preclinical development, cell and gene therapies have advanced from research tools in the lab to clinical-grade products for patients, and today they constitute more than a quarter of all new Phase I clinical trials for Parkinson's disease. Whereas efficacy has been convincingly proven for many of these products in preclinical models, the field is now entering a new phase where
The thesis explores the ‘missing link’ in the study of priority-setting for research, development, and innovation (RDI), namely the processes of implementing RDI priorities, and the consequences of these processes. It does so by focusing on how choices, actions, and motivations of implementers of RDI priorities established elsewhere in the policy system enact, or carry out, the priorities, resulti
Population ageing is a fact of all advanced economies. Fewer people are born all the while current members live longer. The support which old people have come to depend on, for example through elderly care and pensions, thus becomes increasingly expensive. This accentuates an assurance problem. Although it has been and still is the case that the young are willing to support the currently old, this
The ATLAS physics program at the High Luminosity LHC (HL-LHC) calls for a precision in the luminosity measurement of ±1%. A larger uncertainty would represent the dominant systematic error in some precision measurements, including the Higgs sector. To fulfil such requirement in an environment characterized by up to 140 simultaneous interactions per bunch crossing (200 in the ultimate scenario), AT
For many decades the CERN North Area facility at the Super Proton Synchrotron (SPS) has delivered secondary beams to various fixed target experiments and test beams. In 2018, two new tertiary extensions of the existing beam lines, designated "H2-VLE" and "H4-VLE", have been constructed and successfully commissioned. These beam lines have been designed to provide charged particles of both polaritie
The device or the formulation? Which one governs drug dispersibility from the inhaler? To address this question, three budesonide-containing reservoir DPIs: Novopulmon Novolizer®, Giona Easyhaler® and DuoResp Spiromax®, were analyzed using the Next Generation Impactor, NGI. Thereafter, the devices were carefully opened, emptied, and formulations were switched between devices. Finally, three ‘proto
In this paper, the authors present the characterization experiments of a 20 fs vacuum ultraviolet beam from a high harmonic generation source. The beam hits a silicon sample and passes a triple reflection gold polarizer located inside an ultrahigh vacuum chamber. The polarizer's Malus curve was obtained; the total acquisition time for each point of the curve was 30 s. This aims to be the first vac
