Оцінювання за зашумленними спостереженнями невідомих даних лінійних еліптичних рівнянь, що допускають змішане варіаційне формулювання

Получен новый класс систем вариационных уравнений через решения которых выражаются минимаксные оценки значений функционалов от неизвестных правых частей линейных эллиптических уравнений 2-го порядка.Одержаний новий клас систем варіаційних рівнянь через розв'язки яких виражаються мінімаксні оцінки значень функционалів від невідомих правих частин лінійних еліптичних рівнянь 2-го порядку.We obtain a new class of systems of variational equations via whose solutions the minimax estimates of values of functionals from unknown right-hand sides of the second order linear elliptic equations are expressed

Gene-Environment Interaction Research and Transgenic Mouse Models of Alzheimer's Disease

The etiology of the sporadic form of Alzheimer's disease (AD) remains largely unknown. Recent evidence has suggested that gene-environment interactions (GxE) may play a crucial role in its development and progression. Whereas various susceptibility loci have been identified, like the apolipoprotein E4 allele, these cannot fully explain the increasing prevalence of AD observed with aging. In addition to such genetic risk factors, various environmental factors have been proposed to alter the risk of developing AD as well as to affect the rate of cognitive decline in AD patients. Nevertheless, aside from the independent effects of genetic and environmental risk factors, their synergistic participation in increasing the risk of developing AD has been sparsely investigated, even though evidence points towards such a direction. Advances in the genetic manipulation of mice, modeling various aspects of the AD pathology, have provided an excellent tool to dissect the effects of genes, environment, and their interactions. In this paper we present several environmental factors implicated in the etiology of AD that have been tested in transgenic animal models of the disease. The focus lies on the concept of GxE and its importance in a multifactorial disease like AD. Additionally, possible mediating mechanisms and future challenges are discussed

Symmetry Breaking and Finite Size Effects in Quantum Many-Body Systems

We consider a quantum many-body system on a lattice with a continuous symmetry which exhibits a spontaneous symmetry breaking in its infinite volume ground states, but in which the order operator does not commute with the Hamiltonian. A typical example is the Heisenberg antiferromagnet with a Neel order. In the corresponding finite system, the symmetry breaking is usually "obscured" by "quantum fluctuation" and one gets a symmetric ground state with a long range order. In such a situation, we prove that there exist ever increasing numbers of low-lying eigenstates whose excitation energies are bounded by a constant times 1/N, where N denotes the number of sites. By forming linear combinations of these low-lying states and the (finite-volume) ground state, and by taking infinite volume limits, we construct infinite volume ground states with explicit symmetry breaking. Our general theorems do not only shed light on the nature ofsymmetry breaking in quantum many-body systems, but provide indispensable information for numerical approaches to these systems. We also discuss applications of our general results to a variety of examples. The present paper is intended to be accessible to the readers without background in mathematical approaches to quantum many-body systems.Comment: LaTeX, 58 pages, no figures. Notes about Bose-Einstein condenstaion are added after the publicatio

Polarity in GaN and ZnO: Theory, measurement, growth, and devices

This article may be downloaded for personal use only. Any other use requires prior permission of the author and AIP Publishing. This article appeared in Appl. Phys. Rev. 3, 041303 (2016) and may be found at https://doi.org/10.1063/1.4963919.The polar nature of the wurtzite crystalline structure of GaN and ZnO results in the existence of a spontaneous electric polarization within these materials and their associated alloys (Ga,Al,In)N and (Zn,Mg,Cd)O. The polarity has also important consequences on the stability of the different crystallographic surfaces, and this becomes especially important when considering epitaxial growth. Furthermore, the internal polarization fields may adversely affect the properties of optoelectronic devices but is also used as a potential advantage for advanced electronic devices. In this article, polarity-related issues in GaN and ZnO are reviewed, going from theoretical considerations to electronic and optoelectronic devices, through thin film, and nanostructure growth. The necessary theoretical background is first introduced and the stability of the cation and anion polarity surfaces is discussed. For assessing the polarity, one has to make use of specific characterization methods, which are described in detail. Subsequently, the nucleation and growth mechanisms of thin films and nanostructures, including nanowires, are presented, reviewing the specific growth conditions that allow controlling the polarity of such objects. Eventually, the demonstrated and/or expected effects of polarity on the properties and performances of optoelectronic and electronic devices are reported. The present review is intended to yield an in-depth view of some of the hot topics related to polarity in GaN and ZnO, a fast growing subject over the last decade

CERTL reduces C16 ceramide, amyloid-β levels, and inflammation in a model of Alzheimer's disease

BACKGROUND: Dysregulation of ceramide and sphingomyelin levels have been suggested to contribute to the pathogenesis of Alzheimer's disease (AD). Ceramide transfer proteins (CERTs) are ceramide carriers which are crucial for ceramide and sphingomyelin balance in cells. Extracellular forms of CERTs co-localize with amyloid-β (Aβ) plaques in AD brains. To date, the significance of these observations for the pathophysiology of AD remains uncertain. METHODS: A plasmid expressing CERTL, the long isoform of CERTs, was used to study the interaction of CERTL with amyloid precursor protein (APP) by co-immunoprecipitation and immunofluorescence in HEK cells. The recombinant CERTL protein was employed to study interaction of CERTL with amyloid-β (Aβ), Aβ aggregation process in presence of CERTL, and the resulting changes in Aβ toxicity in neuroblastoma cells. CERTL was overexpressed in neurons by adeno-associated virus (AAV) in a mouse model of familial AD (5xFAD). Ten weeks after transduction, animals were challenged with behavior tests for memory, anxiety, and locomotion. At week 12, brains were investigated for sphingolipid levels by mass spectrometry, plaques, and neuroinflammation by immunohistochemistry, gene expression, and/or immunoassay. RESULTS: Here, we report that CERTL binds to APP, modifies Aβ aggregation, and reduces Aβ neurotoxicity in vitro. Furthermore, we show that intracortical injection of AAV, mediating the expression of CERTL, decreases levels of ceramide d18:1/16:0 and increases sphingomyelin levels in the brain of male 5xFAD mice. CERTL in vivo over-expression has a mild effect on animal locomotion, decreases Aβ formation, and modulates microglia by decreasing their pro-inflammatory phenotype. CONCLUSION: Our results demonstrate a crucial role of CERTL in regulating ceramide levels in the brain, in amyloid plaque formation and neuroinflammation, thereby opening research avenues for therapeutic targets of AD and other neurodegenerative diseases

Spectroscopic scanning tunneling microscopy insights into Fe-based superconductors

In the first three years since the discovery of Fe-based high Tc superconductors, scanning tunneling microscopy (STM) and spectroscopy have shed light on three important questions. First, STM has demonstrated the complexity of the pairing symmetry in Fe-based materials. Phase-sensitive quasiparticle interference (QPI) imaging and low temperature spectroscopy have shown that the pairing order parameter varies from nodal to nodeless s\pm within a single family, FeTe1-xSex. Second, STM has imaged C4 -> C2 symmetry breaking in the electronic states of both parent and superconducting materials. As a local probe, STM is in a strong position to understand the interactions between these broken symmetry states and superconductivity. Finally, STM has been used to image the vortex state, giving insights into the technical problem of vortex pinning, and the fundamental problem of the competing states introduced when superconductivity is locally quenched by a magnetic field. Here we give a pedagogical introduction to STM and QPI imaging, discuss the specific challenges associated with extracting bulk properties from the study of surfaces, and report on progress made in understanding Fe-based superconductors using STM techniques.Comment: 36 pages, 23 figures, 229 reference

Transanal minimally invasive surgery (TAMIS) versus endoscopic submucosal dissection (ESD) for resection of non-pedunculated rectal lesions (TRIASSIC study):study protocol of a European multicenter randomised controlled trial

BACKGROUND: In the recent years two innovative approaches have become available for minimally invasive en bloc resections of large non-pedunculated rectal lesions (polyps and early cancers). One is Transanal Minimally Invasive Surgery (TAMIS), the other is Endoscopic Submucosal Dissection (ESD). Both techniques are standard of care, but a direct randomised comparison is lacking. The choice between either of these procedures is dependent on local expertise or availability rather than evidence-based. The European Society for Endoscopy has recommended that a comparison between ESD and local surgical resection is needed to guide decision making for the optimal approach for the removal of large rectal lesions in Western countries. The aim of this study is to directly compare both procedures in a randomised setting with regard to effectiveness, safety and perceived patient burden. METHODS: Multicenter randomised trial in 15 hospitals in the Netherlands. Patients with non-pedunculated lesions > 2 cm, where the bulk of the lesion is below 15 cm from the anal verge, will be randomised between either a TAMIS or an ESD procedure. Lesions judged to be deeply invasive by an expert panel will be excluded. The primary endpoint is the cumulative local recurrence rate at follow-up rectoscopy at 12 months. Secondary endpoints are: 1) Radical (R0-) resection rate; 2) Perceived burden and quality of life; 3) Cost effectiveness at 12 months; 4) Surgical referral rate at 12 months; 5) Complication rate; 6) Local recurrence rate at 6 months. For this non-inferiority trial, the total sample size of 198 is based on an expected local recurrence rate of 3% in the ESD group, 6% in the TAMIS group and considering a difference of less than 6% to be non-inferior. DISCUSSION: This is the first European randomised controlled trial comparing the effectiveness and safety of TAMIS and ESD for the en bloc resection of large non-pedunculated rectal lesions. This is important as the detection rate of these adenomas is expected to further increase with the introduction of colorectal screening programs throughout Europe. This study will therefore support an optimal use of healthcare resources in the future. TRIAL REGISTRATION: Netherlands Trial Register, NL7083 , 06 July 2018

Openness in participation, assessment, and policy making upon issues of environment and environmental health: a review of literature and recent project results

Issues of environment and environmental health involve multiple interests regarding e.g. political, societal, economical, and public concerns represented by different kinds of organizations and individuals. Not surprisingly, stakeholder and public participation has become a major issue in environmental and environmental health policy and assessment. The need for participation has been discussed and reasoned by many, including environmental legislators around the world. In principle, participation is generally considered as desirable and the focus of most scholars and practitioners is on carrying out participation, and making participation more effective. In practice also doubts regarding the effectiveness and importance of participation exist among policy makers, assessors, and public, leading even to undermining participatory practices in policy making and assessment