Topology optimization of nonlinear periodically microstructured materials for tailored homogenized constitutive properties

A topology optimization method is presented for the design of periodic microstructured materials with prescribed homogenized nonlinear constitutive properties over finite strain ranges. The mechanical model assumes linear elastic isotropic materials, geometric nonlinearity at finite strain, and a quasi-static response. The optimization problem is solved by a nonlinear programming method and the sensitivities computed via the adjoint method. Two-dimensional structures identified using this optimization method are additively manufactured and their uniaxial tensile strain response compared with the numerically predicted behavior. The optimization approach herein enables the design and development of lattice-like materials with prescribed nonlinear effective properties, for use in myriad potential applications, ranging from stress wave and vibration mitigation to soft robotics

How installers select and explain domestic heating controls

Though central heating controls have the potential to reduce the energy consumed through domestic space heating, their installation does not guarantee savings. End users do not always understand their controls, or operate them in an energy-efficient way, but there is little appreciation of why this is. Drawing on an ethnographic study, this paper investigates how installers select and explain central heating controls. With reference to the concept of technology scripting, which suggests that the assumptions made about users during the design of devices can influence their eventual use, it shows how heating installers also draw on certain user scripts. Through these means the paper illuminates the significant role that heating installers play in influencing the control products fitted into homes, and how they might be used. Though their use of these scripts is understandable, it is not always conducive to ensuring that central heating systems are operated in the most energy-efficient way. It is suggested that industry and policy-makers might engage with how installers understand users and revise current guidelines to foster better communication between them

Expert consensus document: Clinical and molecular diagnosis, screening and management of Beckwith-Wiedemann syndrome: an international consensus statement.

Beckwith-Wiedemann syndrome (BWS), a human genomic imprinting disorder, is characterized by phenotypic variability that might include overgrowth, macroglossia, abdominal wall defects, neonatal hypoglycaemia, lateralized overgrowth and predisposition to embryonal tumours. Delineation of the molecular defects within the imprinted 11p15.5 region can predict familial recurrence risks and the risk (and type) of embryonal tumour. Despite recent advances in knowledge, there is marked heterogeneity in clinical diagnostic criteria and care. As detailed in this Consensus Statement, an international consensus group agreed upon 72 recommendations for the clinical and molecular diagnosis and management of BWS, including comprehensive protocols for the molecular investigation, care and treatment of patients from the prenatal period to adulthood. The consensus recommendations apply to patients with Beckwith-Wiedemann spectrum (BWSp), covering classical BWS without a molecular diagnosis and BWS-related phenotypes with an 11p15.5 molecular anomaly. Although the consensus group recommends a tumour surveillance programme targeted by molecular subgroups, surveillance might differ according to the local health-care system (for example, in the United States), and the results of targeted and universal surveillance should be evaluated prospectively. International collaboration, including a prospective audit of the results of implementing these consensus recommendations, is required to expand the evidence base for the design of optimum care pathways

Lead and its isotopes in the sediment of three sites on the Lebanese coast: Identification of contamination sources and mobility

Lead concentrations and isotopic composition of sediment samples collected from three sites within the Lebanese coastal zones were measured: at Akkar, Dora and Selaata. Akkar is located far from any direct source of contamination, while Dora and Selaata receive urban and industrial wastes, respectively. Low Pb concentrations (6-16 mu g g(-1)) were detected in the Akkar sediments, and high concentrations of Pb (70-101 mu g g(-1)) were detected in the Dora sediments. Measuring stable isotope ratios of Pb makes it possible to identify the principal sources of Pb in the Akkar sediments as Pb emitted from gasoline combustion and Pb originating from natural sources. On the other hand, Pb stable isotopic ratios in Dora sediments indicate that they are more highly influenced by anthropogenic sources. Isotopic Pb ratios in the Selaata deposits, where Pb concentrations range between 5 and 35 mu g g(-1), have an exceptional radiogenic signature for marine sediments 1.25 60%) after 24 h of extraction, and that the extracted Pb is less radiogenic than the residual Pb

Engineering of a target site-specific recombinase by a combined evolution- and structure-guided approach.

Site-specific recombinases (SSRs) can perform DNA rearrangements, including deletions, inversions and translocations when their naive target sequences are placed strategically into the genome of an organism. Hence, in order to employ SSRs in heterologous hosts, their target sites have to be introduced into the genome of an organism before the enzyme can be practically employed. Engineered SSRs hold great promise for biotechnology and advanced biomedical applications, as they promise to extend the usefulness of SSRs to allow efficient and specific recombination of pre-existing, natural genomic sequences. However, the generation of enzymes with desired properties remains challenging. Here, we use substrate-linked directed evolution in combination with molecular modeling to rationally engineer an efficient and specific recombinase (sTre) that readily and specifically recombines a sequence present in the HIV-1 genome. We elucidate the role of key residues implicated in the molecular recognition mechanism and we present a rationale for sTre's enhanced specificity. Combining evolutionary and rational approaches should help in accelerating the generation of enzymes with desired properties for use in biotechnology and biomedicine

Unexpected central role of the androgen receptor in the spontaneous regeneration of myelin

Lost myelin can be replaced after injury or during demyelinating diseases in a regenerative process called remyelination. In the central nervous system (CNS), the myelin sheaths, which protect axons and allow the fast propagation of electrical impulses, are produced by oligodendrocytes. The abundance and widespread distribution of oligodendrocyte progenitors (OPs) within the adult CNS account for this remarkable regenerative potential. Here, we report a key role for the male gonad, testosterone, and androgen receptor (AR) in CNS remyelination. After lysolecithin-induced demyelination of the male mouse ventral spinal cord white matter, the recruitment of glial fibrillary acidic protein-expressing astrocytes was compromised in the absence of testes and testosterone signaling via AR. Concomitantly, the differentiation of OPs into oligodendrocytes forming myelin basic protein (MBP)$^{+}$ and proteolipid protein-positive myelin was impaired. Instead, in the absence of astrocytes, axons were remyelinated by protein zero (P0)$^{+}$ and peripheral myelin protein 22-kDa (PMP22)$^{+}$ myelin, normally only produced by Schwann cells in the peripheral nervous system. Thus, testosterone favors astrocyte recruitment and spontaneous oligodendrocyte-mediated remyelination. This finding may have important implications for demyelinating diseases, psychiatric disorders, and cognitive aging. The testosterone dependency of CNS oligodendrocyte remyelination may have roots in the evolutionary history of the AR, because the receptor has evolved from an ancestral 3-ketosteroid receptor through gene duplication at the time when myelin appeared in jawed vertebrates.We thank Wendy B. Macklin (University of Colorado) for sharing Plp-EGFP mice and René Habert for providing Tfm mice (University Paris-Diderot and French Atomic Energy Commission). B.B. was successively supported by the European Leukodystrophy Association (ELA) Foundation (France) and by the Mattern Foundation. The fellowship of S.J. was funded by the Higher Education Commission of Pakistan and the French Embassy in Pakistan. This work was supported by grants from the ELA, French Multiple Sclerosis Foundation (ARSEP), and UK Multiple Sclerosis Society

Spatial Laplace transform for complex wavenumber recovery and its application to the analysis of attenuation in acoustic systems

International audienc

Spatial Laplace transform for complex wavenumber recovery and its application to the analysis of attenuation in acoustic systems

International audienceWe present a method for the recovery of complex wavenumber information via spatial Laplace transforms of spatiotemporal wave propagation measurements. The method aids in the analysis of acoustic attenuation phenomena and is applied in three different scenarios: (i) Lamb-like modes in air-saturated porous materials in the low kHz regime, where the method enables the recovery of viscoelastic parameters; (ii) Lamb modes in a Duralumin plate in the MHz regime, where the method demonstrates the effect of leakage on the splitting of the forward S-1 and backward S-2 modes around the Zero-Group Velocity point; and (iii) surface acoustic waves in a two-dimensional microscale granular crystal adhered to a substrate near 100 MHz, where the method reveals the complex wave-numbers for an out-of-plane translational and two in-plane translational-rotational resonances. This method provides physical insight into each system and serves as a unique tool for analyzing spatiotemporal measurements of propagating waves