Size effects in elastic-plastic functionally graded materials

We develop a strain gradient plasticity formulation for composite materials with spatially varying volume fractions to characterize size effects in functionally graded materials (FGMs). The model is grounded on the mechanism-based strain gradient plasticity theory and effective properties are determined by means of a linear homogenization scheme. Several paradigmatic boundary value problems are numerically investigated to gain insight into the strengthening effects associated with plastic strain gradients and geometrically necessary dislocations (GNDs). The analysis of bending in micro-size functionally graded foils shows a notably stiffer response with diminishing thickness. Micro-hardness measurements from indentation reveal a significant increase with decreasing indenter size. And large dislocation densities in the vicinity of the crack substantially elevate stresses in cracked FGM components. We comprehensively assess the influence of the length scale parameter and material gradation profile to accurately characterize the micro-scale response and identify regimes of GNDs relevance in FGMs.Ministry of Economy and Competitiveness of Spain through Grant MAT2014-58738-C3 People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007–2013) under REA Grant agreement n 609405 (COFUNDPostdocDTU

Engineered swift equilibration of a Brownian particle

A fundamental and intrinsic property of any device or natural system is its relaxation time relax, which is the time it takes to return to equilibrium after the sudden change of a control parameter [1]. Reducing $tau$ relax , is frequently necessary, and is often obtained by a complex feedback process. To overcome the limitations of such an approach, alternative methods based on driving have been recently demonstrated [2, 3], for isolated quantum and classical systems [4--9]. Their extension to open systems in contact with a thermostat is a stumbling block for applications. Here, we design a protocol,named Engineered Swift Equilibration (ESE), that shortcuts time-consuming relaxations, and we apply it to a Brownian particle trapped in an optical potential whose properties can be controlled in time. We implement the process experimentally, showing that it allows the system to reach equilibrium times faster than the natural equilibration rate. We also estimate the increase of the dissipated energy needed to get such a time reduction. The method paves the way for applications in micro and nano devices, where the reduction of operation time represents as substantial a challenge as miniaturization [10]. The concepts of equilibrium and of transformations from an equilibrium state to another, are cornerstones of thermodynamics. A textbook illustration is provided by the expansion of a gas, starting at equilibrium and expanding to reach a new equilibrium in a larger vessel. This operation can be performed either very slowly by a piston, without dissipating energy into the environment, or alternatively quickly, letting the piston freely move to reach the new volume

Physics of Neutron Star Crusts

The physics of neutron star crusts is vast, involving many different research fields, from nuclear and condensed matter physics to general relativity. This review summarizes the progress, which has been achieved over the last few years, in modeling neutron star crusts, both at the microscopic and macroscopic levels. The confrontation of these theoretical models with observations is also briefly discussed.Comment: 182 pages, published version available at <http://www.livingreviews.org/lrr-2008-10

Pressure induced enhancement of the magnetic ordering temperature in rhenium(IV) monomers

Materials that demonstrate long-range magnetic order are synonymous with information storage and the electronics industry, with the phenomenon commonly associated with metals, metal alloys or metal oxides and sulfides. A lesser known family of magnetically ordered complexes are the monometallic compounds of highly anisotropic d-block transition metals; the ‘transformation’ from isolated zero-dimensional molecule to ordered, spin-canted, three-dimensional lattice being the result of through-space interactions arising from the combination of large magnetic anisotropy and spin-delocalization from metal to ligand which induces important intermolecular contacts. Here we report the effect of pressure on two such mononuclear rhenium(IV) compounds that exhibit long-range magnetic order under ambient conditions via a spin canting mechanism, with Tc controlled by the strength of the intermolecular interactions. As these are determined by intermolecular distance, ‘squeezing’ the molecules closer together generates remarkable enhancements in ordering temperatures, with a linear dependence of Tc with pressure

Genetic Dissection of the Canq1 Locus Governing Variation in Extent of the Collateral Circulation

<div><h3>Background</h3><p>Native (pre-existing) collaterals are arteriole-to-arteriole anastomoses that interconnect adjacent arterial trees and serve as endogenous bypass vessels that limit tissue injury in ischemic stroke, myocardial infarction, coronary and peripheral artery disease. Their extent (number and diameter) varies widely among mouse strains and healthy humans. We previously identified a major quantitative trait locus on chromosome 7 (<em>Canq1</em>, LOD = 29) responsible for 37% of the heritable variation in collateral extent between C57BL/6 and BALB/c mice. We sought to identify candidate genes in <em>Canq1</em> responsible for collateral variation in the cerebral pial circulation, a tissue whose strain-dependent variation is shared by similar variation in other tissues.</p> <h3>Methods and Findings</h3><p>Collateral extent was intermediate in a recombinant inbred line that splits <em>Canq1</em> between the C57BL/6 and BALB/c strains. Phenotyping and SNP-mapping of an expanded panel of twenty-one informative inbred strains narrowed the <em>Canq1</em> locus, and genome-wide linkage analysis of a SWRxSJL-F2 cross confirmed its haplotype structure. Collateral extent, infarct volume after cerebral artery occlusion, bleeding time, and re-bleeding time did not differ in knockout mice for two vascular-related genes located in <em>Canq1</em>, <em>IL4ra</em> and <em>Itgal</em>. Transcript abundance of 6 out of 116 genes within the 95% confidence interval of <em>Canq1</em> were differentially expressed >2-fold (p-value<0.05÷150) in the cortical <em>pia mater</em> from C57BL/6 and BALB/c embryos at E14.5, E16.5 and E18.5 time-points that span the period of collateral formation.</p> <h3>Conclusions</h3><p>These findings refine the <em>Canq1</em> locus and identify several genes as high-priority candidates important in specifying native collateral formation and its wide variation.</p> </div

Exchange of functional domains between a bacterial conjugative relaxase and the integrase of the human adeno-associated virus

Endonucleases of the HUH family are specialized in processing single-stranded DNA in a variety of evolutionarily highly conserved biological processes related to mobile genetic elements. They share a structurally defined catalytic domain for site-specific nicking and strand-transfer reactions, which is often linked to the activities of additional functional domains, contributing to their overall versatility. To assess if these HUH domains could be interchanged, we created a chimeric protein from two distantly related HUH endonucleases, containing the N-terminal HUH domain of the bacterial conjugative relaxase TrwC and the C-terminal DNA helicase domain of the human adeno-associated virus (AAV) replicase and site-specific integrase. The purified chimeric protein retained oligomerization properties and DNA helicase activities similar to Rep68, while its DNA binding specificity and cleaving-joining activity at oriT was similar to TrwC. Interestingly, the chimeric protein could catalyse site-specific integration in bacteria with an efficiency comparable to that of TrwC, while the HUH domain of TrwC alone was unable to catalyze this reaction, implying that the Rep68 C-terminal helicase domain is complementing the TrwC HUH domain to achieve site-specific integration into TrwC targets in bacteria. Our results illustrate how HUH domains could have acquired through evolution other domains in order to attain new roles, contributing to the functional flexibility observed in this protein superfamily.This work was supported by the Medical Research Council (MRC) grant MR/N022890/1 to EH and grant 1001764 to RML; National Institutes of Health (NIH) grant RO1-GM09285 to CRE; Spanish Ministry of Economy and competitiveness (MINECO) grant BIO2013-46414-P to ML and AFM is supported by a Doc.Mobility fellowship from the Swiss National Science Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Technical aspects and clinical limitations of sperm DNA fragmentation testing in male infertility: a global survey, current guidelines, and expert recommendations.

PURPOSE: Sperm DNA fragmentation (SDF) is a functional sperm abnormality that can impact reproductive potential, for which four assays have been described in the recently published sixth edition of the WHO laboratory manual for the examination and processing of human semen. The purpose of this study was to examine the global practices related to the use of SDF assays and investigate the barriers and limitations that clinicians face in incorporating these tests into their practice. MATERIALS AND METHODS: Clinicians managing male infertility were invited to complete an online survey on practices related to SDF diagnostic and treatment approaches. Their responses related to the technical aspects of SDF testing, current professional society guidelines, and the literature were used to generate expert recommendations via the Delphi method. Finally, challenges related to SDF that the clinicians encounter in their daily practice were captured. RESULTS: The survey was completed by 436 reproductive clinicians. Overall, terminal deoxynucleotidyl transferase deoxyuridine triphosphate Nick-End Labeling (TUNEL) is the most commonly used assay chosen by 28.6%, followed by the sperm chromatin structure assay (24.1%), and the sperm chromatin dispersion (19.1%). The choice of the assay was largely influenced by availability (70% of respondents). A threshold of 30% was the most selected cut-off value for elevated SDF by 33.7% of clinicians. Of respondents, 53.6% recommend SDF testing after 3 to 5 days of abstinence. Although 75.3% believe SDF testing can provide an explanation for many unknown causes of infertility, the main limiting factors selected by respondents are a lack of professional society guideline recommendations (62.7%) and an absence of globally accepted references for SDF interpretation (50.3%). CONCLUSIONS: This study represents the largest global survey on the technical aspects of SDF testing as well as the barriers encountered by clinicians. Unified global recommendations regarding clinician implementation and standard laboratory interpretation of SDF testing are crucial

An Internal Ribosome Entry Site Directs Translation of the 39-Gene from Pelargonium Flower Break Virus Genomic RNA: Implications for Infectivity

[EN] Pelargonium flower break virus (PFBV, genus Carmovirus) has a single-stranded positive-sense genomic RNA (gRNA) which contains five ORFs. The two 59-proximal ORFs encode the replicases, two internal ORFs encode movement proteins, and the 39-proximal ORF encodes a polypeptide (p37) which plays a dual role as capsid protein and as suppressor of RNA silencing. Like other members of family Tombusviridae, carmoviruses express ORFs that are not 59-proximal from subgenomic RNAs. However, in one case, corresponding to Hisbiscus chlorotic ringspot virus, it has been reported that the 39-proximal gene can be translated from the gRNA through an internal ribosome entry site (IRES). Here we show that PFBV also holds an IRES that mediates production of p37 from the gRNA, raising the question of whether this translation strategy may be conserved in the genus. The PFBV IRES was functional both in vitro and in vivo and either in the viral context or when inserted into synthetic bicistronic constructs. Through deletion and mutagenesis studies we have found that the IRES is contained within a 80 nt segment and have identified some structural traits that influence IRES function. Interestingly, mutations that diminish IRES activity strongly reduced the infectivity of the virus while the progress of the infection was favoured by mutations potentiating such activity. These results support the biological significance of the IRES-driven p37 translation and suggest that production of the silencing suppressor from the gRNA might allow the virus to early counteract the defence response of the host, thus facilitating pathogen multiplication and spread.This research was supported by grants BFU2006-11230 and BFU2009-11699 from the Spanish Ministerio de Ciencia e Innovacion (MICINN) and by grants ACOM/2006/210 and ACOMP/2009/040 (to CH) and GVPRE/2008/121 (to OF-M) from the Generalitat Valenciana. The latter was the recipient of an I3P postdoctoral contract from the Spanish Consejo Superior de Investigaciones Cientificas and an additional contract from MICINN. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Fernandez Miragall, O.; Hernandez Fort, C. (2011). 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Virology, 413(2), 310-319. doi:10.1016/j.virol.2011.03.001Martinez-Turino, S., & Hernandez, C. (2009). Inhibition of RNA silencing by the coat protein of Pelargonium flower break virus: distinctions from closely related suppressors. Journal of General Virology, 90(2), 519-525. doi:10.1099/vir.0.006098-0Rico, P., & Hernández, C. (2009). Characterization of the subgenomic RNAs produced by Pelargonium flower break virus: Identification of two novel RNAs species. Virus Research, 142(1-2), 100-107. doi:10.1016/j.virusres.2009.01.018Koh, D. C.-Y., Wong, S.-M., & Liu, D. X. (2003). Synergism of the 3′-Untranslated Region and an Internal Ribosome Entry Site Differentially Enhances the Translation of a Plant Virus Coat Protein. Journal of Biological Chemistry, 278(23), 20565-20573. doi:10.1074/jbc.m210212200Hellen, C. U. T. (2001). Internal ribosome entry sites in eukaryotic mRNA molecules. Genes & Development, 15(13), 1593-1612. doi:10.1101/gad.891101Martínez-Salas, E. (1999). Internal ribosome entry site biology and its use in expression vectors. Current Opinion in Biotechnology, 10(5), 458-464. doi:10.1016/s0958-1669(99)00010-5Dobrikova, E., Florez, P., Bradrick, S., & Gromeier, M. (2003). Activity of a type 1 picornavirus internal ribosomal entry site is determined by sequences within the 3’ nontranslated region. Proceedings of the National Academy of Sciences, 100(25), 15125-15130. doi:10.1073/pnas.2436464100Belsham, G. J. (2009). Divergent picornavirus IRES elements. Virus Research, 139(2), 183-192. doi:10.1016/j.virusres.2008.07.001Fernández-Miragall, O., Quinto, S. L. de, & Martínez-Salas, E. (2009). Relevance of RNA structure for the activity of picornavirus IRES elements. Virus Research, 139(2), 172-182. doi:10.1016/j.virusres.2008.07.009Pestova, T. V., Kolupaeva, V. G., Lomakin, I. B., Pilipenko, E. V., Shatsky, I. N., Agol, V. I., & Hellen, C. U. T. (2001). Molecular mechanisms of translation initiation in eukaryotes. Proceedings of the National Academy of Sciences, 98(13), 7029-7036. doi:10.1073/pnas.111145798FERNANDEZ-MIRAGALL, O. (2003). Structural organization of a viral IRES depends on the integrity of the GNRA motif. RNA, 9(11), 1333-1344. doi:10.1261/rna.5950603ROBERTSON, M. E. M., SEAMONS, R. A., & BELSHAM, G. J. (1999). A selection system for functional internal ribosome entry site (IRES) elements: Analysis of the requirement for a conserved GNRA tetraloop in the encephalomyocarditis virus IRES. RNA, 5(9), 1167-1179. doi:10.1017/s1355838299990301Dorokhov, Y. L., Skulachev, M. V., Ivanov, P. A., Zvereva, S. D., Tjulkina, L. G., Merits, A., … Atabekov, J. G. (2002). Polypurine (A)-rich sequences promote cross-kingdom conservation of internal ribosome entry. Proceedings of the National Academy of Sciences, 99(8), 5301-5306. doi:10.1073/pnas.082107599Xia, X., & Holcik, M. (2009). Strong Eukaryotic IRESs Have Weak Secondary Structure. 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C.-Y., Wang, X., Wong, S.-M., & Liu, D. X. (2006). Translation initiation at an upstream CUG codon regulates the expression of Hibiscus chlorotic ringspot virus coat protein. Virus Research, 122(1-2), 35-44. doi:10.1016/j.virusres.2006.06.008Castaño, A., Ruiz, L., & Hernández, C. (2009). Insights into the translational regulation of biologically active open reading frames of Pelargonium line pattern virus. Virology, 386(2), 417-426. doi:10.1016/j.virol.2009.01.017Fraser, C. S., & Doudna, J. A. (2006). Structural and mechanistic insights into hepatitis C viral translation initiation. Nature Reviews Microbiology, 5(1), 29-38. doi:10.1038/nrmicro1558LÓPEZ-LASTRA, M., RIVAS, A., & BARRÍA, M. I. (2005). Protein synthesis in eukaryotes: The growing biological relevance of cap-independent translation initiation. Biological Research, 38(2-3). doi:10.4067/s0716-97602005000200003Pacheco, A., & Martinez-Salas, E. (2010). 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Specific interference between two unrelated internal ribosome entry site elements impairs translation efficiency. FEBS Letters, 579(30), 6803-6808. doi:10.1016/j.febslet.2005.11.015Ishitani, M., Xiong, L., Stevenson, B., & Zhu, J. K. (1997). Genetic analysis of osmotic and cold stress signal transduction in Arabidopsis: interactions and convergence of abscisic acid-dependent and abscisic acid-independent pathways. The Plant Cell, 9(11), 1935-1949. doi:10.1105/tpc.9.11.1935Knoester, M., van Loon, L. C., van den Heuvel, J., Hennig, J., Bol, J. F., & Linthorst, H. J. M. (1998). Ethylene-insensitive tobacco lacks nonhost resistance against soil-borne fungi. Proceedings of the National Academy of Sciences, 95(4), 1933-1937. doi:10.1073/pnas.95.4.1933Mathews, D. H., Sabina, J., Zuker, M., & Turner, D. H. (1999). Expanded sequence dependence of thermodynamic parameters improves prediction of RNA secondary structure. 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Systematic Review of Potential Health Risks Posed by Pharmaceutical, Occupational and Consumer Exposures to Metallic and Nanoscale Aluminum, Aluminum Oxides, Aluminum Hydroxide and Its Soluble Salts

Aluminum (Al) is a ubiquitous substance encountered both naturally (as the third most abundant element) and intentionally (used in water, foods, pharmaceuticals, and vaccines); it is also present in ambient and occupational airborne particulates. Existing data underscore the importance of Al physical and chemical forms in relation to its uptake, accumulation, and systemic bioavailability. The present review represents a systematic examination of the peer-reviewed literature on the adverse health effects of Al materials published since a previous critical evaluation compiled by Krewski et al. (2007). Challenges encountered in carrying out the present review reflected the experimental use of different physical and chemical Al forms, different routes of administration, and different target organs in relation to the magnitude, frequency, and duration of exposure. Wide variations in diet can result in Al intakes that are often higher than the World Health Organization provisional tolerable weekly intake (PTWI), which is based on studies with Al citrate. Comparing daily dietary Al exposures on the basis of “total Al”assumes that gastrointestinal bioavailability for all dietary Al forms is equivalent to that for Al citrate, an approach that requires validation. Current occupational exposure limits (OELs) for identical Al substances vary as much as 15-fold. The toxicity of different Al forms depends in large measure on their physical behavior and relative solubility in water. The toxicity of soluble Al forms depends upon the delivered dose of Al+ 3 to target tissues. Trivalent Al reacts with water to produce bidentate superoxide coordination spheres [Al(O2)(H2O4)+ 2 and Al(H2O)6 + 3] that after complexation with O2•−, generate Al superoxides [Al(O2•)](H2O5)]+ 2. Semireduced AlO2• radicals deplete mitochondrial Fe and promote generation of H2O2, O2 • − and OH•. Thus, it is the Al+ 3-induced formation of oxygen radicals that accounts for the oxidative damage that leads to intrinsic apoptosis. In contrast, the toxicity of the insoluble Al oxides depends primarily on their behavior as particulates. Aluminum has been held responsible for human morbidity and mortality, but there is no consistent and convincing evidence to associate the Al found in food and drinking water at the doses and chemical forms presently consumed by people living in North America and Western Europe with increased risk for Alzheimer\u27s disease (AD). Neither is there clear evidence to show use of Al-containing underarm antiperspirants or cosmetics increases the risk of AD or breast cancer. Metallic Al, its oxides, and common Al salts have not been shown to be either genotoxic or carcinogenic. Aluminum exposures during neonatal and pediatric parenteral nutrition (PN) can impair bone mineralization and delay neurological development. Adverse effects to vaccines with Al adjuvants have occurred; however, recent controlled trials found that the immunologic response to certain vaccines with Al adjuvants was no greater, and in some cases less than, that after identical vaccination without Al adjuvants. The scientific literature on the adverse health effects of Al is extensive. Health risk assessments for Al must take into account individual co-factors (e.g., age, renal function, diet, gastric pH). Conclusions from the current review point to the need for refinement of the PTWI, reduction of Al contamination in PN solutions, justification for routine addition of Al to vaccines, and harmonization of OELs for Al substances