Useful topologies and separable systems

[EN] Let X be an arbitrary set. A topology t on X is said to be useful if every continuous linear preorder on X is representable by a continuous real valued order preserving function. Continuous linear preorders on X are induced by certain families of open subsets of X that are called (linear) separable systems on X. Therefore, in a first step useful topologies on X will be characterized by means of (linear) separable systems on X. Then, in a second step particular topologies on X are studied that do not allow the construction of (linear) separable systems on X that correspond to non representable continuous linear preorders. In this way generalizations of the Eilenberg Debreu theorems which state that second countable or separable and connected topologies on X are useful and of the theorem of Estévez and Hervés which states that a metrizable topology on X is useful, if and only if it is second countable can be proved.Herden, G.; Pallack, A. (2000). Useful topologies and separable systems. Applied General Topology. 1(1):61-81. doi:10.4995/agt.2000.3024.SWORD61811

Shallow BF2 implants in Xe-bombardment-preamorphized Si: the interaction between Xe and F

Si(100) samples, preamorphized to a depth of ~30 nm using 20 keV Xe ions to a nominal fluence of 2×1014 cm-2 were implanted with 1 and 3 keV BF2 ions to fluences of 7×1014 cm-2. Following annealing over a range of temperatures (from 600 to 1130 °C) and times the implant redistribution was investigated using medium-energy ion scattering (MEIS), secondary ion mass spectrometry (SIMS), and energy filtered transmission electron microscopy (EFTEM). MEIS studies showed that for all annealing conditions leading to solid phase epitaxial regrowth, approximately half of the Xe had accumulated at depths of 7 nm for the 1 keV and at 13 nm for the 3 keV BF2 implant. These depths correspond to the end of range of the B and F within the amorphous Si. SIMS showed that in the preamorphized samples, approximately 10% of the F migrates into the bulk and is trapped at the same depths in a ~1:1 ratio to Xe. These observations indicate an interaction between the Xe and F implants and a damage structure that becomes a trapping site. A small fraction of the implanted B is also trapped at this depth. EXTEM micrographs suggest the development of Xe agglomerates at the depths determined by MEIS. The effect is interpreted in terms of the formation of a volume defect structure within the amorphized Si, leading to F stabilized Xe agglomerates or XeF precipitates

Open questions in utility theory

Throughout this paper, our main idea is to explore different classical questions arising in Utility Theory, with a particular attention to those that lean on numerical representations of preference orderings. We intend to present a survey of open questions in that discipline, also showing the state-of-art of the corresponding literature.This work is partially supported by the research projects ECO2015-65031-R, MTM2015-63608-P (MINECO/ AEI-FEDER, UE), and TIN2016-77356-P (MINECO/ AEI-FEDER, UE)

EnGraft: a multicentre, open-label, randomised, two-arm, superiority study protocol to assess bioavailability and practicability of Envarsus® versus Advagraf™ in liver transplant recipients

Background Graft rejection and chronic CNI toxicity remain obstacles to organ transplant success. Current formulations of tacrolimus, such as Prograf® and Advagraf™, exhibit limitations in terms of pharmacokinetics and tolerability, related in part to suboptimal bioavailability. As dosing non-compliance can result in graft rejection, the once daily formulation of tacrolimus, Advagraf™, was developed (vs 2x/day Prograf®). Benefits of Advagraf™ are counterbalanced by delayed achievement of therapeutic trough levels and need for up to 50% higher doses to maintain Prograf®-equivalent troughs. Envarsus® is also a prolonged-release once-daily tacrolimus formulation, developed using MeltDose™ drug-delivery technology to increase drug bioavailability; improved bioavailability results in low patient drug absorption variability and less pronounced peak-to-trough fluctuations. In phase III de novo kidney transplant studies, Envarsus® proved non-inferior to twice-daily tacrolimus; however, no phase IV studies show superiority of Envarsus® vs Advagraf™ in de novo liver transplant (LTx) recipients. Methods The EnGraft compares bioavailability and tests superiority of Envarsus® (test arm) versus Advagraf™ (comparator arm) in de novo LTx recipients. A total of 268 patients from 15 German transplant centres will be randomised 1:1 within 14 days post-LTx. The primary endpoint is dose-normalised trough level (C/D ratio) measured 12 weeks after randomisation. Secondary endpoints include the number of dose adjustments, time to reach first defined trough level and incidence of graft rejections. Additionally, clinical and laboratory parameters will be assessed over a 3-year period. Discussion C/D ratio is an estimate for tacrolimus bioavailability. Improving bioavailability and increasing C/D ratio using Envarsus could reduce renal dysfunction and other tacrolimus-related toxicities; previous trials have shown that a higher C/D ratio (i.e. slower tacrolimus metabolism) is not only associated with improved renal function but also linked to reduced neurotoxic side effects. A higher C/D ratio could improve clinical outcomes for LTx recipients; EnGraft has begun, with one third of patients recruited by January 2022

Glucocortiocoid Treatment of MCMV Infected Newborn Mice Attenuates CNS Inflammation and Limits Deficits in Cerebellar Development

Infection of the developing fetus with human cytomegalovirus (HCMV) is a major cause of central nervous system disease in infants and children; however, mechanism(s) of disease associated with this intrauterine infection remain poorly understood. Utilizing a mouse model of HCMV infection of the developing CNS, we have shown that peripheral inoculation of newborn mice with murine CMV (MCMV) results in CNS infection and developmental abnormalities that recapitulate key features of the human infection. In this model, animals exhibit decreased granule neuron precursor cell (GNPC) proliferation and altered morphogenesis of the cerebellar cortex. Deficits in cerebellar cortical development are symmetric and global even though infection of the CNS results in a non-necrotizing encephalitis characterized by widely scattered foci of virus-infected cells with mononuclear cell infiltrates. These findings suggested that inflammation induced by MCMV infection could underlie deficits in CNS development. We investigated the contribution of host inflammatory responses to abnormal cerebellar development by modulating inflammatory responses in infected mice with glucocorticoids. Treatment of infected animals with glucocorticoids decreased activation of CNS mononuclear cells and expression of inflammatory cytokines (TNF-α, IFN-β and IFNγ) in the CNS while minimally impacting CNS virus replication. Glucocorticoid treatment also limited morphogenic abnormalities and normalized the expression of developmentally regulated genes within the cerebellum. Importantly, GNPC proliferation deficits were normalized in MCMV infected mice following glucocorticoid treatment. Our findings argue that host inflammatory responses to MCMV infection contribute to deficits in CNS development in MCMV infected mice and suggest that similar mechanisms of disease could be responsible for the abnormal CNS development in human infants infected in-utero with HCMV