Measurement of the Permanent Electric Dipole Moment of the 129^{129}Xe Atom

We report on a new measurement of the CP-violating permanent Electric Dipole Moment (EDM) of the neutral $^{129}$Xe atom. Our experimental approach is based on the detection of the free precession of co-located nuclear spin-polarized $^3$He and $^{129}$Xe samples. The EDM measurement sensitivity benefits strongly from long spin coherence times of several hours achieved in diluted gases and homogeneous weak magnetic fields of about 400~nT. A finite EDM is indicated by a change in the precession frequency, as an electric field is periodically reversed with respect to the magnetic guiding field. Our result, $\left(-4.7\pm6.4\right)\cdot 10^{-28}$ ecm, is consistent with zero and is used to place a new upper limit on the $^{129}$Xe EDM: $|d_\text{Xe}|<1.5 \cdot 10^{-27}$ ecm (95% C.L.). We also discuss the implications of this result for various CP-violating observables as they relate to theories of physics beyond the standard model

The Influence of the effect of solute on the thermodynamic driving force on grain refinement of Al alloys

Grain refinement is known to be strongly affected by the solute in cast alloys. Addition of some solute can reduce grain size considerably while others have a limited effect. This is usually attributed to the constitutional supercooling which is quantified by the growth restriction factor, Q. However, one factor that has not been considered is whether different solutes have differing effects on the thermodynamic driving force for solidification. This paper reveals that addition of solute reduces the driving force for solidification for a given undercooling, and that for a particular Q value, it is reduced more substantially when adding eutectic-forming solutes than peritectic-forming elements. Therefore, compared with the eutectic-forming solutes, addition of peritectic-forming solutes into Al alloys not only possesses a higher initial nucleation rate resulted from the larger thermodynamic driving force for solidification, but also promotes nucleation within the constitutionally supercooled zone during growth. As subsequent nucleation can occur at smaller constitutional supercoolings for peritectic-forming elements, a smaller grain size is thus produced. The very small constitutional supercooling required to trigger subsequent nucleation in alloys containing Ti is considered as a major contributor to its extraordinary grain refining efficiency in cast Al alloys even without the deliberate addition of inoculants.The Australian Research Council (ARC DP10955737)

European Integration and Democratic Consolidation: Spain, Poland and Turkey in Comparative Perspective

The study explored when, under what conditions, and to what extent did European integration, particularly the European Union’s requirement for democratic conditionality, contribute to democratic consolidation in Spain, Poland, and Turkey? On the basis of a four-part definition, the dissertation examined the democratizing impact of European integration process on each of the following four components of consolidation: (i) holding of fair, free and competitive elections, (ii) protection of fundamental rights, including human and minority rights, (iii) high prospects of regime survival and civilian control of the military, and (iv) legitimacy, elite consensus, and stateness. To assess the relative significance of EU’s democratizing leverage, the thesis also examined domestic and non-EU international dynamics of democratic consolidation in the three countries. By employing two qualitative methods (case study and process-tracing), the study focused on three specific time frames: 1977-1986 for Spain, 1994-2004 for Poland, and 1999-present for Turkey. In addition to official documents, newspapers, and secondary sources, face-to-face interviews made with politicians, academics, experts, bureaucrats, and journalists in the three countries were utilized. The thesis generated several conclusions. First of all, the EU’s democratizing impact is not uniform across different components of democratic consolidation. Moreover, the EU’s democratizing leverage in Spain, Poland, and Turkey involved variations over time for three major reasons: (i) the changing nature of EU’s democratic conditionality over time (ii) varying levels of the EU’s credible commitment to the candidate country’s prospect for membership, and (iii) domestic dynamics in the candidate countries. Furthermore, the European integration process favors democratic consolidation but its magnitude is shaped by the candidate country’s prospect for EU membership and domestic factors in the candidate country. Finally, the study involves a major policy implication for the European Union: unless the EU provides a clear prospect for membership, its democratizing leverage will be limited in the candidate countries

Development of a planar multi-body model of the human knee joint

The aim of this work is to develop a dynamic model for the biological human knee joint. The model is formulated in the framework of multibody systems methodologies, as a system of two bodies, the femur and the tibia. For the purpose of describing the formulation, the relative motion of the tibia with respect to the femur is considered. Due to their higher stiffness compared to that of the articular cartilages, the femur and tibia are considered as rigid bodies. The femur and tibia cartilages are considered to be deformable structures with specific material characteristics. The rotation and gliding motions of the tibia relative to the femur can not be modeled with any conventional kinematic joint, but rather in terms of the action of the knee ligaments and potential contact between the bones. Based on medical imaging techniques, the femur and tibia profiles in the sagittal plane are extracted and used to define the interface geometric conditions for contact. When a contact is detected, a continuous non-linear contact force law is applied which calculates the contact forces developed at the interface as a function of the relative indentation between the two bodies. The four basic cruciate and collateral ligaments present in the knee are also taken into account in the proposed knee joint model, which are modeled as non-linear elastic springs. The forces produced in the ligaments, together with the contact forces, are introduced into the system’s equations of motion as external forces. In addition, an external force is applied on the center of mass of the tibia, in order to actuate the system mimicking a normal gait motion. Finally, numerical results obtained from computational simulations are used to address the assumptions and procedures adopted in this study.Fundação para a Ciência e a Tecnologia (FCT

Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen

The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca's large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells

An overview of the cutaneous porphyrias

This is an overview of the cutaneous porphyrias. It is a narrative review based on the published literature and my personal experience; it is not based on a formal systematic search of the literature. The cutaneous porphyrias are a diverse group of conditions due to inherited or acquired enzyme defects in the porphyrin–haem biosynthetic pathway. All the cutaneous porphyrias can have (either as a consequence of the porphyria or as part of the cause of the porphyria) involvement of other organs as well as the skin. The single commonest cutaneous porphyria in most parts of the world is acquired porphyria cutanea tarda, which is usually due to chronic liver disease and liver iron overload. The next most common cutaneous porphyria, erythropoietic protoporphyria, is an inherited disorder in which the accumulation of bile-excreted protoporphyrin can cause gallstones and, rarely, liver disease. Some of the porphyrias that cause blistering (usually bullae) and fragility (clinically and histologically identical to porphyria cutanea tarda) can also be associated with acute neurovisceral porphyria attacks, particularly variegate porphyria and hereditary coproporphyria. Management of porphyria cutanea tarda mainly consists of visible-light photoprotection measures while awaiting the effects of treating the underlying liver disease (if possible) and treatments to reduce serum iron and porphyrin levels. In erythropoietic protoporphyria, the underlying cause can be resolved only with a bone marrow transplant (which is rarely justifiable in this condition), so management consists particularly of visible-light photoprotection and, in some countries, narrowband ultraviolet B phototherapy. Afamelanotide is a promising and newly available treatment for erythropoietic protoporphyria and has been approved in Europe since 2014