Dynamic and combinatorial control of gene expression by nuclear retinoic acid receptors (RARs)

Nuclear retinoic acid receptors (RARs) are transcriptional regulators controlling the expression of specific subsets of genes in a ligand-dependent manner. The basic mechanism for switching on transcription of cognate target genes involves RAR binding at specific response elements and a network of interactions with coregulatory protein complexes, the assembly of which is directed by the C-terminal ligand-binding domain of RARs. In addition to this scenario, new roles for the N-terminal domain and the ubiquitin-proteasome system recently emerged. Moreover, the functions of RARs are not limited to the regulation of cognate target genes, as they can transrepress other gene pathways. Finally, RARs are also involved in nongenomic biological activities such as the activation of translation and of kinase cascades. Here we will review these mechanisms, focusing on how kinase signaling and the proteasome pathway cooperate to influence the dynamics of RAR transcriptional activity

High fidelity numerical fracture mechanics assisted by RBF mesh morphing

The study and design of cyclically loaded structures cannot neglect the evaluation of their fatigue behavior. Today numerical prediction tools allow adopting, in various industrial fields, refined and consolidated procedures for the assessment of cracked parts through analyses based on fracture mechanics. An high level of detail can be obtained through the use of well consolidated FEM methods, allowing an accurate and reliable calculation of the flaw Stress Intensity Factor (SIF) and its resulting prediction in terms of crack propagation. A challenging step for this computational workflow remains, however, the generation and update of the computational grid during crack evolution. It is in this context that radial basis functions (RBF) mesh morphing is emerging as a viable solution to replace the complex and time-consuming remeshing operation. The flaw front is updated, according to its propagation, by automatically deforming the numerical grid obtaining an evolutionary workflow suitable to be used for industrially-sized numerical meshes (many millions of nodes). A review of applications, obtained by exploiting FEA (Ansys Mechanical) and mesh morphing (RBF Morph) state of-the-art tools, is presented in this work. At first the proposed workflow is applied on a circular notched bar with a defect controlled by a two-parameters evolution. The same approach is then refined and demonstrated for a Multi Degree of Freedom (MDoF) case on the same geometry and on the vacuum vessel port stub from the fusion nuclear reactor Iter

Magnetic properties of tektites and other related impact glasses

© 2015 Elsevier B.V. We present a comprehensive overview of the magnetic properties of the four known tektite fields and related fully melted impact glasses (Aouelloul, Belize, Darwin, Libyan desert and Wabar glasses, irghizites, and atacamaites), namely magnetic susceptibility and hysteresis properties as well as properties dependent on magnetic grain-size. Tektites appear to be characterized by pure Fe2+ paramagnetism, with ferromagnetic traces below 1 ppm. The different tektite fields yield mostly non-overlapping narrow susceptibility ranges. Belize and Darwin glasses share similar characteristics. On the other hand the other studied glasses have wider susceptibility ranges, with median close to paramagnetism (Fe2+ and Fe3+) but with a high-susceptibility population bearing variable amounts of magnetite. This signs a fundamental difference between tektites (plus Belize and Darwin glasses) and other studied glasses in terms of oxygen fugacity and heterogeneity during formation, thus bringing new light to the formation processes of these materials. It also appears that selecting the most magnetic glass samples allows to find impactor-rich material, opening new perspectives to identify the type of impactor responsible for the glass generation

Linking forest cover, soil erosion and mire hydrology to late-Holocene human activity and climate in NW Spain

This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 3.0 License (http://www.creativecommons.org/licenses/by-nc/3.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (http://www.uk.sagepub.com/aboutus/openaccess.htm).This article has been made available through the Brunel Open Access Publishing Fund.Forest clearance is one of the main drivers of soil erosion and hydrological changes in mires, although climate may also play a significant role. Because of the wide range of factors involved, understanding these complex links requires long-term multi-proxy approaches and research on the best proxies to focus. A peat core from NW Spain (Cruz do Bocelo mire), spanning the last ~3000 years, has been studied at high resolution by physical (density and loss on ignition (LOI)), geochemical (elemental composition) and palynological (pollen and non-pollen palynomorphs) analyses. Proxies related to mineral matter fluxes from the catchment (lithogenic tracers, Glomus and Entorrhiza), rainfall (Bromine), mire hydrology (HdV-18), human pressure (Cerealia-type, nitrophilous taxa and coprophilous fungi) and forest cover (mesophilous tree taxa) were the most useful to reconstruct the evolution of the mire and its catchment. Forest clearance for farming was one of the main drivers of environmental change from at least the local Iron Age (~2685 cal. yr BP) onwards. The most intense phase of deforestation occurred during Roman and Germanic times and the late Middle Ages. During these phases, the entire catchment was affected, resulting in enhanced soil erosion and severe hydrological modifications of the mire. Climate, especially rainfall, may have also accelerated these processes during wetter periods. However, it is noteworthy that the hydrology of the mire seems to have been insensitive to rainfall variations when mesophilous forest dominated. Abrupt changes were only detected once intense forest clearance commenced during the Iron Age/Roman transition (~2190 cal. yr BP) phase, which represented a tipping point in catchment's ability to buffer impacts. Overall, our findings highlight the importance of studying ecosystems' long-term trajectories and catchment-wide processes when implementing mire habitat protection measures.This work was funded by the projects CGL2010-20672 (Plan Nacional I+D+i, Spanish Ministry of Science and Innovation) and 10PXIB200182PR (General Directorate of I+D, Xunta de Galicia). N Silva-Sánchez and L López-Merino are currently supported by a FPU predoctoral scholarship (AP2010-3264) funded by the Spanish Government and a MINT postdoctoral fellowship funded by the Brunel Institute for the Environment, respectively

Rochechouart 2017-Drilling Campaign: First Results

No abstract available

A digital shadow cloud-based application to enhance quality control in manufacturing

In Industry 4.0 era, rapid changes to the global landscape of manufacturing are transforming industrial plants in increasingly more complex digital systems. One of the most impactful innovations generated in this context is the "Digital Twin", a digital copy of a physical asset, which is used to perform simulations, health predictions and life cycle management through the use of a synchronized data flow in the manufacturing plant. In this paper, an innovative approach is proposed in order to contribute to the current collection of applications of Digital Twin in manufacturing: a Digital Shadow cloud-based application to enhance quality control in the manufacturing process. In particular, the proposal comprises a Digital Shadow updated on high performance computing cloud infrastructure in order to recompute the performance prediction adopting a variation of the computer-aided engineering model shaped like the actual manufactured part. Thus, this methodology could make possible the qualification of even not compliant parts, and so shift the focus from the compliance to tolerance requirements to the compliance to usage requirements. The process is demonstrated adopting two examples: the structural assessment of the geometry of a shaft and the one of a simplified turbine blade. Moreover, the paper presents a discussion about the implications of the use of such a technology in the manufacturing context in terms of real-time implementation in a manufacturing line and lifecycle management. Copyright (C) 2020 The Authors

Uncovering treatment burden as a key concept for stroke care: a systematic review of qualitative research

<b>Background</b> Patients with chronic disease may experience complicated management plans requiring significant personal investment. This has been termed ‘treatment burden’ and has been associated with unfavourable outcomes. The aim of this systematic review is to examine the qualitative literature on treatment burden in stroke from the patient perspective.<p></p> <b>Methods and findings</b> The search strategy centred on: stroke, treatment burden, patient experience, and qualitative methods. We searched: Scopus, CINAHL, Embase, Medline, and PsycINFO. We tracked references, footnotes, and citations. Restrictions included: English language, date of publication January 2000 until February 2013. Two reviewers independently carried out the following: paper screening, data extraction, and data analysis. Data were analysed using framework synthesis, as informed by Normalization Process Theory. Sixty-nine papers were included. Treatment burden includes: (1) making sense of stroke management and planning care, (2) interacting with others, (3) enacting management strategies, and (4) reflecting on management. Health care is fragmented, with poor communication between patient and health care providers. Patients report inadequate information provision. Inpatient care is unsatisfactory, with a perceived lack of empathy from professionals and a shortage of stimulating activities on the ward. Discharge services are poorly coordinated, and accessing health and social care in the community is difficult. The study has potential limitations because it was restricted to studies published in English only and data from low-income countries were scarce.<p></p> <b>Conclusions</b> Stroke management is extremely demanding for patients, and treatment burden is influenced by micro and macro organisation of health services. Knowledge deficits mean patients are ill equipped to organise their care and develop coping strategies, making adherence less likely. There is a need to transform the approach to care provision so that services are configured to prioritise patient needs rather than those of health care systems

Climate change mitigation and adaptation in the land use sector: from complementarity to synergy

Currently, mitigation and adaptation measures are handled separately, due to differences in priorities for the measures and segregated planning and implementation policies at international and national levels. There is a growing argument that synergistic approaches to adaptation and mitigation could bring substantial benefits at multiple scales in the land use sector. Nonetheless, efforts to implement synergies between adaptation and mitigation measures are rare due to the weak conceptual framing of the approach and constraining policy issues. In this paper, we explore the attributes of synergy and the necessary enabling conditions and discuss, as an example, experience with the Ngitili system in Tanzania that serves both adaptation and mitigation functions. An in-depth look into the current practices suggests that more emphasis is laid on complementarity—i.e., mitigation projects providing adaptation co-benefits and vice versa rather than on synergy. Unlike complementarity, synergy should emphasize functionally sustainable landscape systems in which adaptation and mitigation are optimized as part of multiple functions. We argue that the current practice of seeking co-benefits (complementarity) is a necessary but insufficient step toward addressing synergy. Moving forward from complementarity will require a paradigm shift from current compartmentalization between mitigation and adaptation to systems thinking at landscape scale. However, enabling policy, institutional, and investment conditions need to be developed at global, national, and local levels to achieve synergistic goals

Preparation of amino-substituted indenes and 1,4-dihydronaphthalenes using a one-pot multireaction approach: total synthesis of oxybenzo[c]phenanthridine alkaloids

Allylic trichloroacetimidates bearing a 2-vinyl or 2-allylaryl group have been designed as substrates for a one-pot, two-step multi-bond-forming process leading to the general preparation of aminoindenes and amino-substituted 1,4-dihydronaphthalenes. The synthetic utility of the privileged structures formed from this one-pot process was demonstrated with the total synthesis of four oxybenzo[c]phenanthridine alkaloids, oxychelerythrine, oxysanguinarine, oxynitidine, and oxyavicine. An intramolecular biaryl Heck coupling reaction, catalyzed using the Hermann–Beller palladacycle was used to effect the key step during the synthesis of the natural products