A finite strain kinematic hardening constitutive model based on Hencky strain: general framework, solution algorithm and application to shape memory alloys

The logarithmic or Hencky strain measure is a favored measure of strain due to its remarkable properties in large deformation problems. Compared with other strain measures, e.g., the commonly used Green–Lagrange measure, logarithmic strain is a more physical measure of strain. In this paper, we present a Hencky-based phenomenological finite strain kinematic hardening, non-associated constitutive model, developed within the framework of irreversible thermodynamics with internal variables. The derivation is based on the multiplicative decomposition of the deformation gradient into elastic and inelastic parts, and on the use of the isotropic property of the Helmholtz strain energy function. We also use the fact that the corotational rate of the Eulerian Hencky strain associated with the socalled logarithmic spin is equal to the strain rate tensor (symmetric part of the velocity gradient tensor). Satisfying the second law of thermodynamics in the Clausius–Duhem inequality form, we derive a thermodynamically-consistent constitutive model in a Lagrangian form. In comparison with the available finite strain models in which the unsymmetric Mandel stress appears in the equations, the proposed constitutive model includes only symmetric variables. Introducing a logarithmic mapping, we also present an appropriate form of the proposed constitutive equations in the time-discrete frame. We then apply the developed constitutive model to shape memory alloys and propose a well-defined, non-singular definition for model variables. In addition, we present a nucleation-completion condition in constructing the solution algorithm. We finally solve several boundary value problems to demonstrate the proposed model features as well as the numerical counterpart capabilities

Lamotrigine versus valproic acid as first-line monotherapy in newly diagnosed typical absence seizures: an open-label,randomized, parallel-group study

Purpose: To compare the efficacy of lamotrigine (LTG) and valproic acid (VPA) in newly diagnosed children and adolescents with typical absence seizures. Methods: A randomized, open-label parallel-group design was used. After undergoing an awake video-EEG recording, which included one to two trials of 3 min of hyperventilation and intermittent photic stimulation, eligible patients were randomized to receive LTG or VPA. LTG was initiated at a daily dose of 0.5 mg/kg for 2 weeks in two divided doses, followed by 1.0 mg/kg/day for an additional 2 weeks. Thereafter, doses were increased in 1-mg/kg/day increments every 5 days until seizures were controlled, intolerable adverse effects occurred, or a maximum dose of 12 mg/kg/day had been reached. VPA was equally uptitrated according to clinical response, starting at 10 mg/kg and increasing by 5 mg/kg/24 h every 3 days, if required, to a maximum of 30 mg/kg/day in three divided doses. Patients were seen in the clinic every month for ≤12 months.The primary efficacy end point at each visit was seizure freedom, defined as lack of clinically observed seizures since the previous visit and lack of electroclinical seizures during ambulatory 24-h EEG testing and a video-EEG session with hyperventilation. Results: Thirty-eight children (17 boys, 21 girls), aged from 3 to 13 years (mean, 7.5 years), all newly diagnosed with childhood or juvenile typical absence seizures, were enrolled. After 1 month of treatment, 10 (52.6%) of 19 children taking VPA and one (5.3%) of 19 taking LTG were seizure free (p = 0.004). By the 3-month follow-up, 12 (63.1%) children taking VPA and seven (36.8%) taking LTG were controlled (p = 0.19). After 12 months, 13 children taking VPA (dose range, 20–30 mg/kg/day; mean serum level, 76.8 mg/L; range, 51.4–91 mg/L) and 10 taking LTG (dose range, 2–11 mg/kg/day; mean serum level, 8.1 mg/L; range, 1.1–18 mg/L) were seizure free (p=0.51). Side effects were mostly mild and transient and were recorded in two (10.6%) children treated with VPA and in six (31.8%) treated with LTG. Conclusions: Both VPA and LTG can be efficacious against absence seizures, although VPA shows a much faster onset of action, at least in part because of its shorter titration schedule. KeyWords: Lamotrigine—Valproic acid—Typical absences— Monotherapy. Valproic acid (VPA) and ethosuximide (ESM) have been shown to be equally effective as monotherapy for typical absence seizures (1,2), and, at present, they are generally considered first-choice drugs for this seizure type. VPA controls absences in∼75% of patients, in addition to being effective against generalized tonic–clonic seizures (70%) and myoclonic seizures (75%). However, its use may involve safety risks for postmenarchal women (3). ESM produces complete control of absences in 70% of treated patients (4,5), but it is unsuitable as monotherapy Accepted Ma

Precision medicine and machine learning towards the prediction of the outcome of potential celiac disease

Potential Celiac Patients (PCD) bear the Celiac Disease (CD) genetic predisposition, a significant production of antihuman transglutaminase antibodies, but no morphological changes in the small bowel mucosa. A minority of patients (17%) showed clinical symptoms and need a gluten free diet at time of diagnosis, while the majority progress over several years (up to a decade) without any clinical problem neither a progression of the small intestine mucosal damage even when they continued to assume gluten in their diet. Recently we developed a traditional multivariate approach to predict the natural history, on the base of the information at enrolment (time 0) by a discriminant analysis model. Still, the traditional multivariate model requires stringent assumptions that may not be answered in the clinical setting. Starting from a follow-up dataset available for PCD, we propose the application of Machine Learning (ML) methodologies to extend the analysis on available clinical data and to detect most influent features predicting the outcome. These features, collected at time of diagnosis, should be capable to classify patients who will develop duodenal atrophy from those who will remain potential. Four ML methods were adopted to select features predictive of the outcome; the feature selection procedure was indeed capable to reduce the number of overall features from 85 to 19. ML methodologies (Random Forests, Extremely Randomized Trees, and Boosted Trees, Logistic Regression) were adopted, obtaining high values of accuracy: all report an accuracy above 75%. The specificity score was always more than 75% also, with two of the considered methods over 98%, while the best performance of sensitivity was 60%. The best model, optimized Boosted Trees, was able to classify PCD starting from the selected 19 features with an accuracy of 0.80, sensitivity of 0.58 and specificity of 0.84. Finally, with this work, we are able to categorize PCD patients that can more likely develop overt CD using ML. ML techniques appear to be an innovative approach to predict the outcome of PCD, since they provide a step forward in the direction of precision medicine aimed to customize healthcare, medical therapies, decisions, and practices tailoring the clinical management of PCD children

Multi-material 3D printed shape memory polymer with tunable melting and glass transition temperature activated by heat or light

Shape memory polymers are attractive smart materials that have many practical applications and academic interest. Three-dimensional (3D) printable shape memory polymers are of great importance for the fabrication of soft robotic devices due to their ability to build complex 3D structures with desired shapes. We present a 3D printable shape memory polymer, with controlled melting and transition temperature, composed of methacrylated polycaprolactone monomers and N-Vinylcaprolactam reactive diluent. Tuning the ratio between the monomers and the diluents resulted in changes in melting and transition temperatures by 20, and 6 °C, respectively. The effect of the diluent addition on the shape memory behavior and mechanical properties was studied, showing above 85% recovery ratio, and above 90% fixity, when the concentration of the diluent was up to 40 wt %. Finally, we demonstrated multi-material printing of a 3D structure that can be activated locally, at two different temperatures, by two different stimuli; direct heating and light irradiation. The remote light activation was enabled by utilizing a coating of Carbon Nano Tubes (CNTs) as an absorbing material, onto sections of the printed objects

Development status of the LAUE project

We present the status of LAUE, a project supported by the Italian Space Agency (ASI), and devoted to develop Laue lenses with long focal length (up to 100 meters), for hard X--/soft gamma--ray astronomy (80-600 keV). Thanks to their focusing capability, the design goal is to improve the sensitivity of the current instrumention in the above energy band by 2 orders of magnitude, down to a few times $10^{-8}$ photons/(cm$^2$ s keV).Comment: 9 pages, 9 figures, presented at the Space Telescopes and Instrumentation Symposium in Amsterdam, 2012: Ultraviolet to Gamma Ray Conference. Published in the Proceedings of the SPIE, Volume 8443, id. 84430B-84430B-9 (2012

Scientific prospects in soft gamma-ray astronomy enabled by the LAUE project

This paper summarizes the development of a successful project, LAUE, supported by the Italian Space Agency (ASI) and devoted to the development of long focal length (up to 100 m) Laue lenses for hard X--/soft gamma--ray astronomy (80-600 keV). The apparatus is ready and the assembling of a prototype lens petal is ongoing. The great achievement of this project is the use of bent crystals. From measurements obtained on single crystals and from simulations, we have estimated the expected Point Spread Function and thus the sensitivity of a lens made of petals. The expected sensitivity is a few $\times10^{-8}$ photons cm$^{-2}$ s$^{-1}$ keV$^{-1}$. We discuss a number of open astrophysical questions that can settled with such an instrument aboard a free-flying satellite.Comment: 17 pages, 18 figures, published in Proceedings of the SPIE, Volume 8861, id. 886106 17 pp. (2013

Allele-specific editing ameliorates dominant retinitis pigmentosa in a transgenic mouse model

Retinitis pigmentosa (RP) is a group of progressive retinal degenerations of mostly monogenic inheritance, which cause blindness in about 1:3,500 individuals worldwide. Heterozygous variants in the rhodopsin (RHO) gene are the most common cause of autosomal dominant RP (adRP). Among these, missense variants at C-terminal proline 347, such as p.Pro347Ser, cause severe adRP recurrently in European affected individuals. Here, for the first time, we use CRISPR/Cas9 to selectively target the p.Pro347Ser variant while preserving the wild-type RHO allele in vitro and in a mouse model of adRP. Detailed in vitro, genomic, and biochemical characterization of the rhodopsin C-terminal editing demonstrates a safe downregulation of p.Pro347Ser expression leading to partial recovery of photoreceptor function in a transgenic mouse model treated with adeno-associated viral vectors. This study supports the safety and efficacy of CRISPR/Cas9-mediated allele-specific editing and paves the way for a permanent and precise correction of heterozygous variants in dominantly inherited retinal diseases

Systematic review: early infant feeding and the prevention of coeliac disease.

BACKGROUND: PREVENTCD, Prevent Coeliac Disease, is an international project investigating the hypothesis of possible induction of tolerance to gluten in genetically predisposed children through introducing small quantities of gluten during the period of breastfeeding. AIM: To summarise current knowledge on the possible relationship between early feeding practices and the risk of coeliac disease (CD). METHODS: The Cochrane Library, MEDLINE, and EMBASE databases were searched in May 2011, and the search was updated in January 2012, and again in July 2012. RESULTS: Breastfeeding (BF) and CD: some studies show a protective effect of BF, while others show no effect. No studies have shown a long-term preventive effect. BF at the time of gluten introduction and CD: Results from a meta-analysis of five observational case-control studies suggest that BF at gluten introduction is associated with a lower risk of CD compared with formula feeding. It is unclear whether BF provides a permanent protection or only delays the onset of CD. Timing of gluten introduction: The data suggest that both early (≤4 months) and late (≥7 months) introduction of gluten may increase the risk of CD. Amount of gluten at weaning (and later) and CD: One incident case-referent study documented that the introduction of gluten in large amounts compared with small or medium amounts increased the risk of CD. CONCLUSIONS: In the absence of clear evidence, in order to decrease the risk of later coeliac disease, it is reasonable to avoid both early (<4 months) and late (≥7 months) introduction of gluten, and to introduce gluten while the infant is still being breastfed. Future studies may clarify the remaining uncertainties

Natural antisense transcripts associated with genes involved in eye development

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