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Pronounced temporal and spatial variation in the availability of food resources can produce energetic deficits in organisms. Fruit-dependent Bornean orangutans face extreme variation in fruit availability and experience negative energy and protein balance during episodes of fruit scarcity. We evaluate the possibility that orangutans of different sexes and ages catabolize muscle tissue when the availability of fruit is low. We assess variation in muscle mass by examining the relationship between urinary creatinine and specific gravity and use the residuals as a non-invasive measure of estimated lean body mass (ELBM). Despite orangutans having a suite of adaptations to buffer them from fruit scarcity and associated caloric deficits, ELBM was lower during low fruit periods in all age-sex classes. As predicted, adult male orangutans had higher ELBM than adult females and immatures. Contrary to expectation, flanged and unflanged males did not differ significantly in ELBM. These findings highlight the precarity of orangutan health in the face of rapid environmental change and add to a growing body of evidence that orangutans are characterized by unique metabolic traits shaped by their unpredictable forest environment.

Incidence and mortality figures are needed to get a comprehensive overview of cancer burden. In many countries, cancer mortality figures are routinely recorded by statistical offices, whereas incidence depends on regional cancer registries. However, due to the complexity of updating cancer registries, incidence numbers become available 3 or 4 years later than mortality figures. It is, therefore, necessary to develop reliable procedures to predict cancer incidence at least until the period when mortality data are available. Most of the methods proposed in the literature are designed to predict total cancer (except nonmelanoma skin cancer) or major cancer sites. However, less frequent lethal cancers, such as brain cancer, are generally excluded from predictions because the scarce number of cases makes it difficult to use univariate models. Our proposal comes to fill this gap and consists of modeling jointly incidence and mortality data using spatio-temporal models with spatial and age shared components. This approach allows for predicting lethal cancers improving the performance of individual models when data are scarce by taking advantage of the high correlation between incidence and mortality. A fully Bayesian approach based on integrated nested Laplace approximations is considered for model fitting and inference. A validation process is also conducted to assess the performance of alternative models. We use the new proposals to predict brain cancer incidence rates by gender and age groups in the health units of Navarre and Basque Country (Spain) during the period 2005-2008. Spanish Reseach Agency, Grant/Award Number: PID2020-113125RBI-00/MCIN/AEI/10.13039/50110001103; Universidad Publica de Navarra, Grant/Award Number: PJUPNA2018-11

Valves are mechanical devices for controlling fluid-flow in pipes of different diameter and service pressures used in several industry sectors. Most demanding industry sectors add custom design requirements and require product validation reports many times even before placing valve purchase orders of varying quantities. Therefore, customer and valve developer requirements must be made compatible, design reliably completed and a design validation report created, all as soon as possible. In order to respond to these market constraints, complete valve design process from product planning to product design and validation delivery must be optimized. This paper reports a 96% time reduction in Simulation Based Design validation and reporting tasks obtained by applying Design Automation in a company that develops valves for this market. Additionally, the architecture and most remarkable features of the Simulation Based Design validation and reporting automation are described.

Indexación: Scopus. Synaptic abnormalities have been described in individuals with autism spectrum disorders (ASD). The cell-adhesion molecule Neuroligin-3 (Nlgn3) has an essential role in the function and maturation of synapses and NLGN3 ASD-associated mutations disrupt hippocampal and cortical function. Here we show that Wnt/β-catenin signaling increases Nlgn3 mRNA and protein levels in HT22 mouse hippocampal cells and primary cultures of rat hippocampal neurons. We characterized the activity of mouse and rat Nlgn3 promoter constructs containing conserved putative T-cell factor/lymphoid enhancing factor (TCF/LEF)-binding elements (TBE) and found that their activity is significantly augmented in Wnt/β-catenin cell reporter assays. Chromatin immunoprecipitation (ChIP) assays and site-directed mutagenesis experiments revealed that endogenous β-catenin binds to novel TBE consensus sequences in the Nlgn3 promoter. Moreover, activation of the signaling cascade increased Nlgn3 clustering and co-localization with the scaffold PSD-95 protein in dendritic processes of primary neurons. Our results directly link Wnt/β-catenin signaling to the transcription of the Nlgn3 gene and support a functional role for the signaling pathway in the dysregulation of excitatory/inhibitory neuronal activity, as is observed in animal models of ASD. https://www.nature.com/articles/s41398-018-0093-y.pdf

[EN] Universities are one of the fundamental actors to guarantee the dissemination of knowledge and the development of competences related to the Industry of the Future (IoF) or Industry 4.0. Computer Aided (CAX) and Product Lifecycle Management (PLM) technologies are key part in the IoF. With this aim, it was launch a project focused on Manufacturing and partially funded by La Fondation Dassault Systèmes. This communication presents a review on CAX-PLM training, four initiatives already in place in universities participating in the project, the project scope, the approach to integrate with the industrial context, the working method to consider different competence profiles and the development framework., The authors express their gratitude to the other project colleagues and to La Fondation Dassault Systèmes for its funding support.

BACKGROUND Despite computer-aided design and computer-aided manufacturing (CAD/CAM) technology improving prosthesis fit, errors inherent to digital workflow still exist. PURPOSE To measure scanning/milling errors, and identify factors influencing marginal (MD) and internal discrepancy (ID). MATERIALS AND METHODS After scanning, 22 conical abutments in 5 master casts, 6 suprastructures with more than 2 implants (3, 4, and 6) were CAD designed. Angular deviation and errors in the vertical/horizontal planes were analyzed using a coordinate measuring machine (CMM). CAD suprastructures were milled and MD/ID evaluated with micro-computed tomography (CT) and optic microscopy (OM) at one screw test (OST) and final fit test (FFT). RESULTS Mean scanning errors, at the vertical/horizontal planes, and angulation error were 3 μm ± 13, 44 μm ± 34, 0.3° ± 0.2°, respectively. Angulation errors nearly double in structures >3 abutments (0.26°vs 0.4°). OM MD in FFT/OST was 57.7 μm ± 13.9/100.7 μm ± 34.6, respectively. Micro-CT FFT-MD was 38.9 μm ± 12.8. Lineal/perimetral ID was 49.6 μm ± 11.9 and 108.2° ± 41.8, respectively. Structures >3-implants were 2.3 times more likely to present higher MD (CI95%:0.4-13.6). Nearly all the internal horizontal gap was due to scanning errors (44 of 49.6 μm). Horizontal scanning errors were three times more likely to present greater ID (CI95%:0.5-17.4). CONCLUSION Horizontal plane scanning errors are greater than vertical errors. Scanning angulation/milling errors are higher for suprastructures>3implants. Scanning/milling errors are associated with ID/MD, respectively, leading to micro-gap formation. A CMM reduces scanning errors in >3-implant-frameworks before milling the final piece.

Two distantly located promoter regions regulate the dynamic expression of RUNX genes during development: distal P1 and proximal P2 promoters. We have recently described that β-catenin increases total Runx1 mRNA levels in human CD34(+) hematopoietic progenitors and enhances spatial proximity with its translocation partner ETO. Here, we report that induction of Wnt/β-catenin signaling in HL60 and Jurkat leukemia-derived cell lines and CD34(+) progenitors selectively activate the production of the longer distal P1-Runx1 mRNA isoform. Gain- and loss-of-function experiments revealed that the differential increase in P1-Runx1 expression is accomplished through a minimal β-catenin responsive region that includes a highly conserved TCF/LEF-binding element, located -20/-16 bp upstream of the canonical distal P1-Runx1 transcription start site. We conclude that the distal P1-Runx1 promoter is a direct transcriptional target of Wnt/β-catenin signaling that may be important in normal hematopoiesis or its transition into malignant stem cells during the onset or progression of leukemia.

Tensile residual stress (RS) peaks near the weld toe accelerate crack generation and propagation stages reducing dramatically the life of welded components. In order to relief RS, components are typically heat-treated. However, heat treatments can affect the microstructure compromising mechanical properties. In addition, their application in big structures is complex due to size limitations. As an alternative, mechanical treatments such as shot peening can be locally applied. Moreover, they generate local compressive stresses in the treated surfaces, which present beneficial effect in the fatigue strength of treated components. In the present work, the contribution of shot peening in the fatigue strength of multipass welded joints is numerically evaluated. For that purpose, first the RS stress pattern of a 3 pass butt weld of 10mm thick, 50mm length S275JR plates is calculated. Following, the application of shot peening in the tensile RS area is modelled and the evolution of RS pattern is analyzed. Finally, the fatigue strength of treated and non-treated butt welds is evaluated.

Latin Americans and Chilean Amerindians have the highest prevalence of gallstone disease (GSD) and gallbladder cancer (GBC) in the world. A handful of loci have been associated with GSD in populations of predominantly European ancestry, however, they only explain a small portion of the genetic component of the disease. Here, we performed a genome-wide association study (GWAS) for GSD in 1,095 admixed Chilean Latinos with Mapuche Native American ancestry. Disease status was assessed by cholecystectomy or abdominal ultrasonography. Top-10 candidate variants surpassing the suggestive cutoff of P −5 in the discovery cohort were genotyped in an independent replication sample composed of 1,643 individuals. Variants with positive replication were further examined in two European GSD populations and a Chilean GBC cohort. We consistently replicated the association of ABCG8 gene with GSD (rs11887534, P = 3.24 × 10−8, OR = 1.74) and identified TRAF3 (rs12882491, P = 1.11 × 10−7, OR = 1.40) as a novel candidate gene for the disease in admixed Chilean Latinos. ABCG8 and TRAF3 variants also conferred risk to GBC. Gene expression analyses indicated that TRAF3 was significantly decreased in gallbladder (P = 0.015) and duodenal mucosa (P = 0.001) of GSD individuals compared to healthy controls, where according to GTEx data in the small intestine, the presence of the risk allele contributes to the observed effect. We conclude that ABCG8 and TRAF3 genes are associated with GSD and GBC in admixed Latinos and that decreased TRAF3 levels could enhance gallbladder inflammation as is observed in GSD and GSD-associated GBC.

BackgroundLatin Americans and Chilean Amerindians have the highest prevalence of cholesterol gallstone disease (GSD) and gallbladder cancer (GBC) in the world. A handful of loci have been associated with GSD in populations of predominantly European ancestry, however they only explain a small portion of the population-attributable risk of the disease.MethodsWe performed a genome-wide association study (GWAS) for GSD in 1,095 admixed Latinos with Mapuche Native American Ancestry, followed by a replication analysis of 10 candidate single nucleotide polymorphisms (SNPs) with suggestive genome-wide significance (P−5) in 1,643 individuals. Disease status was assessed by cholecystectomy or abdominal ultrasonography. Logistic regression analyses were adjusted for age, sex, BMI, Type 2 Diabetes and Amerindian ancestry. Associated variants were further examined in two large GSD European populations and in a Chilean gallbladder cancer (GBC) cohort. We determined the expression levels of a novel GSD-candidate gene in normal and GSD-tissue samples.ResultsWe consistently replicated theABCG8gene (rs11887534; P=3.24×10−8, OR=1.74) associated with GSD in admixed Latinos and identified a novel candidate signal within theTRAF3gene on chromosome 14 (rs12882491; P=1.11×10−7, OR=1.40).ABCG8andTRAF3variants also conferred risk to GBC. Gene expression analyses indicated thatTRAF3levels were significantly decreased in the gallbladder (P=0.015) and the duodenal mucosa (P=0.001) of affected GSD individuals compared to healthy controls.ConclusionsWe confirmedABCG8and identifiedTRAF3both associated with GSD and GBC in admixed Latinos. Decreased TRAF3 expression levels could enhance gallbladder inflammation as is observed in GSD and GSD-associated GBC.

Ponència presentada a 7th Manufacturing Engineering Society International Conference (MESIC 2017) celebrada a Vigo, del 28 al 30 de juny de 2017 Training and learning methods for engineering students, in the disciplines of product design and manufacturing, are becoming more difficult and complex since they have to integrate theoretical technical knowledge, skills in computer-aided applications (CAx) and skills in collaborative work practices. Product Lifecycle Management (PLM) tools support structured collaborative practices and CAx supports engineering content creation. Both types of software applications are key in the Industry 4.0 development. They also evolve over time, incorporate new functionalities, and change their graphical user interface (GUI), adding complexity to the learning process. Traditionally, engineering education addresses the learning of CAx and PLM tools separately, hindering a holistic learning experience to the students. This communication presents a structured integrated vision of these tools and their learning. Project-Based Learning (PBL) is proposed as a learning approach suitable to provide a learning experience that facilitates the development of Industry 4.0 skills and competences.

Gas metal arc welding (GMAW) is one of the most used joining method in the industry. However, one of the main problems of this process is the generation of residual stresses which have direct impact on the fatigue life of welded components. Nevertheless, residual stress pattern prediction is complex and requires the simulation of the welding process. Currently, there are different numerical methods to predict the residual stresses generated in GMAW process, being Goldak’s method one of the most widely used model. However, the main limitation of these methods is that they require defining many parameters experimentally and, consequently, this method is not valid during design process. Alternatively, in this work, it is developed a procedure where the heat source is defined based on the welding physics for spray transfer welding. The developed procedure has been validated for a spray transfer multipass butt weld case. Results have shown good correspondence with an average deviation of 9.16 % in thermal field and 42 MPa in the final residual stress field. Thus, the developed procedure has been validated as a cost-effective alternative method to estimate residual stress pattern in spray transfer multipass welding. Furthermore, the developed method does not require any welding experimental characterization once the efficiency of the used welding machine is defined. The proposed method can be used as a valid tool to optimize the welding process in order to minimize the residual stress field and, consequently, improve the fatigue life.

Residual stress (RS) pattern of thick T-joint welds, which directly affects fatigue life, varies considerably depending on the thickness and number of passes. Nowadays, most approaches to predict fatigue life do not consider RS real value due to the difficulty of estimating them, hence, they tend to be conservatives. However, recent works have demonstrated that considering RS the conservative error in life prediction can be reduced down to around 15%. In the present work, the fatigue performance of multipass T-joints of S275JR plates for a thickness range from 20 to 60mm is evaluated considering RS. It is observed that maximum RS value for thick plates decreases progressively (down to 66% of yield stress). Consequently, fatigue performance of different thickness T-joint samples subjected to the same stress load cycles varies considerably in the HCF regime.

Modelling of anatomical parts is usually tackled through triangulated models with specialised Bio-CAD applications. If features beyond anatomy are required, geometry is usually translated into NURBS geometry for further modification in parametric feature based design CAD systems. But, they remain quite unmanageable yet. The authors present, validate and implement into a knowledge feature a methodology that generates an anatomically personalised trachea stent based a point cloud data extracted from a Computerised Axial Tomography with an open-source medical data visualisation application.

O objetivo deste estudo foi avaliar a rugosidade superficial (µm) do cimento Biodentine (M1) e do cimento de ionômero de vidro – Fuji IX (M2) submetidos a diferentes enxaguatórios bucais. Foram confeccionados 54 corpos de prova (cps) por meio de uma matriz de teflon (6mm x 2mm), distribuídos aleatoriamente em 6 grupos de acordo com a solução utilizada: água destilada (S1), enxaguatório com álcool – Listerine Cool Mint (S2) e enxaguatório sem álcool – Colgate Plax (S3). Todos os cps foram mantidos em umidade relativa de 100%, em estufa 37±1°C durante todo o experimento, exceto nos períodos de imersão nos enxaguatórios estabelecidos. Os cps foram colocados individualmente em um frasco contendo 8mL do enxaguatório específico para cada grupo, durante 2 minutos, sob vibração, duas vezes ao dia, por um período de 21 dias. As leituras foram realizadas nos tempos de 48 horas (T0), 7 dias (T1), 14 dias (T2) e 21 dias (T3). Os dados obtidos foram submetidos aos testes estatísticos Kolmogorov-Smirnov, Anova e Teste de Tukey. Verificou-se que os fatores Tempo (T), Solução (S) e Material (M) isoladamente e a interação TxM e SxM tiveram efeito estatisticamente significante na rugosidade superficial. Isoladamente, T3 (0,92±0,02) e M1 (0,87±0,01) apresentaram maior média e S3 (0,72±0,02) a menor média de rugosidade. Para MxT e SXM, respectivamente o M1T3 (1,10±0,03) e M1S1 (1,03±0,03) apresentaram maiores médias de rugosidade. De acordo com a metodologia pode-se concluir que o M1 apresentou maior rugosidade superficial nos tempos T1, T2 e T3 do que o M2.Palavras-chave: Materiais Dentários. Cimentos de Ionômeros de Vidro. Antissépticos Bucais.

Residual Stress (RS) pattern changes considerably depending on the width of the plates and the welding parameters, having effect on the fatigue strength. Most of the standards do not consider them and in some works, yield stress is taken as residual stress value. It results in a very conservative estimation of fatigue life. Authors developed recently a numerical model to predict more properly the value of RS pattern depending on the plate thickness. In a welded joint, considering the RS and alternating axial loads, the evolution of the stresses is multiaxial, becoming necessary its study. Therefore, the aim of this work is to analyse different fatigue indicator parameters (Smith-Watson-Topper, Fatemi-Socie, and Critical Plane implementation of the Basquin equation) in order to predict the fatigue behaviour of butt-weld components. For that purpose, the numerical model to predict the RS pattern in welded joint developed by this research group is used.

Finite Element Modeling (FEM) of chip formation has proved great sensitivity to tool/chip friction coefficient. This parameter cannot be adequately identified through conventional tests, because thermal and mechanical loadings during these tests are far from those encountered during machining. In this study, the inadequacy of using constant Coulomb's friction coefficient in FEM is showed. Although a good agreement is found for cutting force and chip thickness variables, significant differences can be found for feed force and tool–chip contact length. Differences of more than 50% are observed in some cases for those variables when FEM results are compared with experimental ones. A new approach to identify a friction model after experimental tests will be detailed. This new approach involves application of a variable friction coefficient at the tool–chip interface, which allows obtaining a better agreement between numerical results (differences close to 10%) regarding the feed force.

Two distantly located promoter regions regulate the dynamic expression of RUNX genes during development: distal P1 and proximal P2 promoters. We have recently described that β-catenin increases total Runx1 mRNA levels in human CD34(+) hematopoietic progenitors and enhances spatial proximity with its translocation partner ETO. Here, we report that induction of Wnt/β-catenin signaling in HL60 and Jurkat leukemia-derived cell lines and CD34(+) progenitors selectively activate the production of the longer distal P1-Runx1 mRNA isoform. Gain- and loss-of-function experiments revealed that the differential increase in P1-Runx1 expression is accomplished through a minimal β-catenin responsive region that includes a highly conserved TCF/LEF-binding element, located -20/-16 bp upstream of the canonical distal P1-Runx1 transcription start site. We conclude that the distal P1-Runx1 promoter is a direct transcriptional target of Wnt/β-catenin signaling that may be important in normal hematopoiesis or its transition into malignant stem cells during the onset or progression of leukemia.

Chromosomal translocations are frequently associated with a wide variety of cancers, particularly hematologic malignancies. A recurrent chromosomal abnormality in acute myeloid leukemia is the reciprocal translocation t(8;21) that fuses RUNX1 and ETO genes. We report here that Wnt/β-catenin signaling increases the expression of ETO and RUNX1 genes in human hematopoietic progenitors. We found that β-catenin is rapidly recruited into RNA polymerase II transcription factories (RNAPII-Ser5) and that ETO and RUNX1 genes are brought into close spatial proximity upon Wnt3a induction. Notably, long-term treatment of cells with Wnt3a induces the generation a frequent RUNX1-ETO translocation event. Thus, Wnt/β-catenin signaling induces transcription and translocation of RUNX1 and ETO fusion gene partners, opening a novel window to understand the onset/development of leukemia.

Mortality counts are usually aggregated over age groups assuming similar effects of both time and region, yet the spatio-temporal evolution of cancer mortality rates may depend on changing age structures. In this paper, mortality rates are analyzed by region, time period and age group, and models including space-time, space-age, and age-time interactions are considered. The integrated nested Laplace approximation method, known as INLA, is adopted for model fitting and inference in order to reduce computing time in comparison with Markov chain Monte Carlo (McMC) methods. The methodology provides full posterior distributions of the quantities of interest while avoiding complex simulation techniques. The proposed models are used to analyze prostate cancer mortality data in 50 Spanish provinces over the period 1986-2010. The results reveal a decline in mortality since the late 1990s, particularly in the age group [65,70), probably because of the inclusion of the PSA (prostate-specific antigen) test and better treatment of early-stage disease. The decline is not clearly observed in the oldest age groups. Copyright © 2016 John WileySons, Ltd.

Metallic nanowires (NWs) have been intensily investigated in the past years, but details on their formation are still not completely understood. In this work we report high resolution transmission electron microscopy data and molecular dynamics simulation results for gold NW elongation. Our results show that different initial crystallographic orientations lead to very differentiated linear atomic suspended chain (LAC) formations and strongly support that kinetic aspects are the dominant mechanisms determining the LAC morphologies.

A method to quantify the resolution of atomic force microscopy (AFM) probes using Fourier analysis of the AFM images is proposed. The maximum detectable spatial frequency obtained from the power spectrum was used to estimate the lateral resolution. Carbon nanotube tips were successfully used to study very dense arrays of semiconductor nanostructures. In particular, accurate measurements of shallow facet angles were obtained, which are in perfect agreement with results obtained by two complementary techniques - High Resolution Transmission Electron Microscopy and Reflection High-Energy Electron Diffraction.

We have studied structural and electrical behavior of nanowires generated by mechanical elongation using in situ High Resolution Transmission Electron Microscopy and ultra-high-vacuum Mechanically Controllable Break Junction. It has been observed that the narrowest region of metal constriction is crystalline and defect-free. In particular, gold nanowires adopt only three types of atomic arrangement; a model correlating these three structures and the quantum conductance behavior is proposed, which showed a remarkable agreement with electrical transport measurements.

Nanometric materials present interesting properties due to size reduction effects and have potential applications in new and sophisticated technologies. However, a deep understanding of the phenomena involved is still required to allow their full exploitation in the generation of systems with pre-established properties. For this, a complete set of powerful and modern characterization tools is necessary, such as those available at the Brazilian National Synchrotron Laboratory (LNLS), Campinas, Brazil. Here, a brief description is presented of the LNLS facilities as well as a few examples of the local research activities under development in the field of nanoscience (nanoparticles, semiconductor quantum dots and nanowires). Open facilities, managing complex and large-scale equipment, such as those at LNLS, are extremely important in the development of competitive research in this area.

We have used high resolution transmission electron microscopy and mechanically controllable break junction technique to study metal NW structure and electrical transport properties. In the last stages just before rupture, gold and platinum nanowires are crystalline and defect-free. In particular, gold NWs assume merely three kinds of atomic arrangements, which were correlated to observed conductance behaviors.

Optical and structural properties of In0.15Ga0.85As/GaAs quantum wells (100, 200 and 300 A wide), grown by molecular beam epitaxy on nominal and vicinal GaAs(0 0 1) substrates, have been investigated by low-temperature photoluminescence, high-resolution X-ray diffraction and transmission electron microscopy. All the experimental data pointed out towards the presence of step bunching on vicinal substrate. The blueshift of the optical emissions observed in the semiconductor structure grown on the vicinal substrate was explained in terms of a simple model that includes both indium segregation and strain modulation.

Genome-wide association studies (GWAS) have successfully identified several risk loci for Alzheimer's disease (AD). Nonetheless, these loci do not explain the entire susceptibility of the disease, suggesting that other genetic contributions remain to be identified. Here, we performed a meta-analysis combining data of 4,569 individuals (2,540 cases and 2,029 healthy controls) derived from three publicly available GWAS in AD and replicated a broad genomic region (>248,000 bp) associated with the disease near the APOE/TOMM40 locus in chromosome 19. To detect minor effect size contributions that could help to explain the remaining genetic risk, we conducted network-based pathway analyses either by extracting gene-wise p-values (GW), defined as the single strongest association signal within a gene, or calculated a more stringent gene-based association p-value using the extended Simes (GATES) procedure. Comparison of these strategies revealed that ontological sub-networks (SNs) involved in glutamate signaling were significantly overrepresented in AD (p

In the present work, we investigated the influence of step bunching on the optical properties of InGaAs/GaAs quantum wells (QWs) grown by molecular beam epitaxy (MBE) on vicinal surfaces. Photoluminescence (PL) measurements showed a larger full width at half maximum (FWHM) of the emission coming from the QWs grown on the vicinal surfaces with respect to the nominal sample. Transmission-electron-microscopy (TEM) measurements revealed the presence of step bunches that clearly roughen the interfaces of the heterostructures and worsen the optical properties of the samples.

Size-dependent inter-atomic distance contraction was investigated by Extended X-ray Absorption Fine Structure in thiol-capped gold nanoparticles. A slight nearest-neighbor distance reduction was observed as a function of particle diameter (2–4 nm range) but, for all samples, it was less than 1%. This value contrasts with the larger effect expected and found in other systems, especially for the smallest particles (2 nm) where it is twice as small. Our analysis also points out a short metal–ligand bond, suggesting a rather strong surface interaction. We interpreted these results as a passivant effect where the metal–ligand interaction partially compensates the expected lattice contraction.

We report a structural study of gold nanoparticle supercrystals formed by a few layers and of micrometer size, where the long-range order has been stimulated by a soft thermal annealing. We have clearly identified an expansion of the first layer lying on amorphous carbon substrate and an ordered second layer sitting on twofold saddle points. The third nanoparticle layer recovers the conventional close-packed stacking. This anomalous packing has been explained by means of a simple theoretical model based on dispersional forces.

Transient Receptor Potential Vanilloid type 1 channel (TRPV1) is an important endogenous transducer of noxious heat and chemical stimuli and is required during development of inflammatory hypersensitivity. The transcription factor Runx1 is known to play a relevant role in sensory neuron differentiation as it controls the expression of several sensory nociceptive receptors, including TRPV1. Here, we show that Runx1 up-regulates TRPV1 transcription activity by interacting directly with the proximal TRPV1 gene promoter sequence. Importantly, C/EBPβ a well-established heterodimer partner of Runx1 also binds to the TRPV1 promoter and cooperates with Runx1 to further stimulate TRPV1 transcription. Our results support a mechanism where Runx1-C/EBPβ-containing transcription regulatory complexes are recruited to the TRPV1 gene promoter to modulate TRPV1 expression in dorsal root ganglia neurons. J. Cell. Physiol. 228: 860–870, 2013. © 2012 Wiley Periodicals, Inc.

This paper presents a Knowledge Based Engineering (KBE) application developed for the aeronautical sector. Specifically, this paper describes a KBE application that aids on the definition of the contact interface between turbine discs and blades of low pressure turbines, namely the firtree. Designing firtrees requires more than 60 different entry parameters, a check for static stresses, de-featuring for fatigue finite element analysis and as cast design for manufacturing and weight management purposes. The application delivered at first the typical benefits of KBE applications: significant time savings, error reduction and standardization. However, the challenges posed by the aeronautical industry, quickly pushed designers out of the standard agreed topology for the firtree. This raised the typical issue on development time and maintainability of KBE applications. The challenge was partially solved through designer knowledge capture and reuse in the form of a User Defined Feature library integrated in to the original KBE application.

Current cancer mortality data are available with a delay of roughly three years due to the administrative procedure necessary to create the registries. Therefore, health agencies rely on forecast cancer deaths. In this context, statistical procedures providing mortality/incidence risk predictions for different regions or health areas are very useful. These predictions are essential for defining priorities for cancer prevention and treatment. The main objective of this work is to evaluate the predictive performance of alternative spatio-temporal models for short-term cancer risk/counts prediction in small areas. All the models analyzed here are presented under a general-mixed model framework, providing a unified structure of presentation and facilitating the use of similar tools for computing the prediction mean squared error. Prostate cancer mortality data are used to illustrate the behavior of the different models in Spanish provinces.

We previously found that single nucleotide polymorphisms in the low-density lipoprotein receptor-related protein 6 (LRP6) gene are associated with Alzheimer's disease (AD). Here, we studied the posttranscriptional metabolism of the LRP6 message scanning sequentially the 23 LRP6 exons in human tissues and found a novel LRP6 isoform that completely skips exon 3 (LRP6Δ3) in all tissues examined and was also conserved in mice. Expression levels of the LRP6 isoforms were determined in 47 cortical brain messenger (m)RNA samples including 22 AD cases, 11 control subjects, and 14 individuals with other neurological disorders. LRP6Δ3 mRNA levels were significantly augmented in AD brains compared with controls (1.6-fold; p = 0.037) or other pathological samples (2-fold; p = 0.007). Functional analysis in Wnt/β-catenin signaling assays revealed that skipping of exon 3 reduced significantly the signaling activity of the LRP6 coreceptor. We conclude that the LRP6Δ3 isoform is a novel splice variant, which shows diminished Wnt/β-catenin signaling activity and might have a functional role in individuals with AD.

In Spain, an increase in the incidence of colorectal cancer (CRC) has been observed in both sexes in recent years, probably due to an improved diagnostic, the westernization of dietary habits, and worse obesity levels, among others factors. In this work, the CRC incidence rate trends in different health areas in Navarre (northern Spain) are studied during the 1990-2005 period.An estimated incidence trend curve for each health area and the corresponding confidence bands were obtained for each gender using P-spline models.These results show an increasing trend of CRC in most of the areas in both sexes, being less pronounced in women than in men. In the central area of Pamplona (the capital) a decreasing trend has been observed for men during the period studied.Primary prevention is the best strategy to change the increasing trend observed in most areas of the province of Navarre. However, a healthy lifestyle has long-term results, so it is important to have an early detection program that would serve as a short-term prevention strategy.

Recent evidence indicates that transcription factor Runx1 modulates the expression of several phenotypic markers in dorsal root ganglia (DRGs) neurons, including the pain-related P2X3 receptor. In several cell lineages C/EBP transcription factors interact with the Runx factor family members to jointly bind and activate transcription of target genes. Here, we examine whether these two transcription factors directly regulate P2X3 gene expression. Through in silico analyses of the first 2 kb of the P2X3 gene promoter we identified putative consensus-binding sites for both Runx1 and C/EBPβ transcription factors. Transient over-expression in PC12 cells of either Runx1 or C/EBPβ increases P2X3 gene promoter activity and co-expression of both factors results in an additive stimulatory effect on the promoter function. Accordingly, chromatin immunoprecipitation assays demonstrate that both Runx1 and C/EBPβ bind to the P2X3 promoter in PC12 cells expressing this gene. Site-directed mutagenesis of the proximal Runx1 and C/EBPβ consensus elements in the P2X3 promoter decrease Runx1- and C/EBPβ-mediated transcriptional activity. Moreover, C/EBPβ-mediated enhancement of the P2X3 promoter requires a functional Runx1 binding site. Altogether our results support a functional and coordinated role for Runx1 and C/EBPβ transcription factors during activation of P2X3 gene transcription.

It is very important to perform studies to evaluate micro-hardness and curation level at different depths to refine the clinical indications and orientations that the odontologist gives to the patients, helping to achieve more durable treatments when using resin-modified glass ionomers. This in vitro study evaluated knoop micro-hardness in 2 different brands of resin-modified glass ionomers: Ketac ™ N100 (M1) and Fuji II LC (M2).Tests were performed at three depths: surface (P1), 2 mm (P2) and 3 mm (P3). A total of 40 samples where made (20 of each type of resin), half of these measuring 5 x 2 mm and the other half with 5 x3 mm. To evaluate micro-hardness at different depths, 24 hours after the manufacture of samples, tests where made on both top and bottom surfaces. These tests were performed using an HMV-200 Micro Hardness Tester (Shimadzu brand). For statistical analysis data were collected and used first for ANOVA variance analysis (P≤0.01) followed then by Turkey's test.It also shows that the effect is not significant for the interaction between material and depth. Micro-hardness on P1 (34.7) is statistically greater than with P2 (29.2) and P3 (29.0) and these last two are statistically equal between them. M1 (27.8) presented less micro-hardness than M2 (34.2).Surface micro-hardness is greater than micro-hardness at other depths and M2 presented better results than M1.

Medical applications of rapid manufacturing are being used to develop and manufacture medical devices and instrumentation. One important point of this process is the design that can be helped via 3D modeling. Using digitalized patient data, this process of modeling can improve the customization process. This paper provides a new methodology for the customization process of a tracheal stent.

Raman spectra of annealed carbon soot reveal strong structural changes. Downshifts of the graphite-like phonon bands to lower energies after annealing are suggested to be related to strained or curved graphitic planes. The effect of curvature on the energy of the in-plane optical phonon mode is quantitatively estimated by applying the semi-empirical interatomic Tersoff potential. A weighted average curvature corresponding to a bond bending of 2.1° is deduced for spherical shells with 20.6 A radius. These findings are consistent with high-resolution electron microscopy images which reveal closed-shell carbon particles in the same size range.

We present direct imaging of carbon clusters using high-resolution electron microscopy. We find the stable form of carbon particles, obtained after electron irradiation, to be a spherical, concentric-shelled graphitic structure, rather than a hollow cage, icosahedral or tubular. The shells of these onionlike particles are remarkably well crystallized. They are stable under an intense electron beam, even when formed of only a few shells (2 ÷ 5). We suggest that the canonical form of large carbon clusters, containing more than a hundred atoms, is the spheroidal, concentric-shelled graphitic structure.

We report on experiments aimed at producing three-dimensional self-organization in InAs quantum-dot multilayers embedded in GaAs. These InAs/GaAs quantum-dot multilayers have been grown by molecular beam epitaxy. Employing atomic force microscopy, we have analyzed the island density in samples with different number of periods of InAs/GaAs bilayers The results reveals a decrease and a tendency to saturation of the island density with an increase in the number of periods, as a three-dimensional self-organization characteristic of these samples. Optical properties of the samples are examined via photoluminescence spectroscopy. The evolution of the quantum-dot photoluminescence peak position indicates an increment in the mean size of the buried islands and a relative homogenization in size of the quantum dots, as the number of periods increases. The results of the optical measurements agree with the morphological data, and characterize a spatial process of self-organization, related to the increment of the nu...

The effect of particle size distribution on the magnetic properties of nanocrystalline Fe/sub 86/Zr/sub 7/Cu/sub 1/B/sub 6/ samples is studied in detail. The analysis applies a realistic particle size distribution, obtained from transmission electron microscopy images, to the recently developed extended Random Anisotropy Model. The effect of a broad size distribution is found to be more relevant when the tail of the distribution is larger than 20 nm.