Gold surface with gold nitride–a surface enhanced Raman scattering active substrate

The nitration of gold surfaces is a nonpolluting method, which can lead to large scale production of substrates with remarkable properties and applications. We present a topographical study of the nanoscale structure of the gold nitride surfaces produced by radio frequency (rf) nitrogen plasma etching of thin gold films. Atomic force microscopy images taken after rf etching reveal the striking appearance of the cluster assembly with large clusters surrounded by small clusters (7.9±1.4 and 2.3±0.9 nm, respectively) appearing to exhibit an attractive interaction. We discuss the possible mechanism for this attraction based on a colloid model by Messina et al. [Phys. Rev. Lett. 85, 872 (2000) ]. This surface exhibits a notable surface enhanced Raman scattering effect demonstrated with L-alanine and rhodamine-6G. The significance of this work is that we found that this SERS active gold nitride surface can be prepared in just one step: by nitrogen plasma etching a thin gold film. Until now most SERS active gold cluster covered surfaces have been prepared in several steps very often requiring complex lithography

Low-density lipoprotein receptor mutational analysis in diagnosis of familial hypercholesterolemia

PURPOSE OF REVIEW: To present up to date evidence on the pathogenicity of low-density lipoprotein receptor (LDLR) variants and to propose a strategy that is suitable for implementation in the clinical work-up of familial hypercholesterolaemia. RECENT FINDINGS: More than 1800 variants have been described in the LDLR gene of patients with a clinical diagnosis of familial hypercholesterolaemia; however, less than 15% have functional evidence of pathogenicity. SUMMARY: The spectrum of variants in the LDLR identified in patients with clinical familial hypercholesterolaemia is increasing as novel variants are still being reported. However, over 50% of all LDLR variants need further evidence before they can be confirmed as mutations causing disease. Even with applying the recent American College of Medical Genetics variant classification, a large number of variants are still considered variants of unknown significance. Before obtaining an undisputable confirmation of the effect on the expression and activity of the LDLR, reporting these variants as part of a clinical diagnosis to the patient holds the risk that it might need to be withdrawn in a later stage. An investment should be made to develop functional assays to characterize LDLR variants of unknown significance for a better patient diagnosis and to prevent confusion in the physician's office.The MB research has been supported by grants from the Portuguese Cardiology Society, Science and Technology Foundation and BioISI, centre grant UID/MULTI/ 04046/2013, from FCT/MCTES/PIDDAC, Portugal.info:eu-repo/semantics/publishedVersio

Conjugate Cooling of a Discrete Heater in Laminar Channel Flow

Electronic components are usually assembled on printed circuit boards cooled by forced airflow. When the spacing between the boards is small, there is no room to employ a heat sink on critical components. Under these conditions, the components? thermal control may depend on the conductive path from the heater to the board in addition to the direct convective heat transfer to the airflow.The conjugate forced convection-conduction heat transfer from a two-dimensional strip heater flush mounted to a finite thickness wall of a parallel plates channel cooled by a laminar airflow was investigated numerically. A uniform heat flux was generated along the strip heater surface. Under steady state conditions, a fraction of the heat generation was transferred by direct convection to the airflow in the channel and the remaining fraction was transferred by conduction to the channel wall. The lower surface of the channel wall was adiabatic, so that the heat conducted from the heater to the plate eventually returned to the airflow. A portion of it returned upstream of the heater, preheating the airflow before it reached the heater surface. Due to this, it was convenient to treat the direct convection from the heater surface to the airflow by the adiabatic heat transfer coefficient. The flow was developed from the channel entrance, with constant properties.The conjugate problem was solved numerically within a single solution domain comprising both the airflow region and the solid wall of the channel. The results were obtained for the channel flow Reynolds number ranging from about 600 to 1900, corresponding to average airflow velocities from 0.5 m/s to 1.5 m/s. The effects of the solid wall to air thermal conductivities ratio were investigated in the range from 10 to 80, typical of circuit board materials. The wall thickness influence was verified from 1 mm to 5 mm. The results indicated that within these ranges, the conductive substrate wall provided a substantial enhancement of the heat transfer from the heater, accomplished by an increase of its average adiabatic surface temperature.278286Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Micropropagation Of Agapanthus Umbellatus Var. Minor By Using Two Systems Of Multiplication

For conventional micropropagation methods, semisolidified medium (SM) is used; the use of this medium requires intense manipulation of the cultures and skilled labor. Systems that use liquid medium show equal or better efficiency of the multiplication process, besides reducing the cost for the elimination of agar. In this study, we evaluated the mass propagation of Agapanthus umbellatus var. minor two in vitro multiplication systems (SM system and temporary immersion system [SIT]). The plant material was grown in MS medium supplemented with 6-benzylaminopurine (6-BA; 0.0, 8.9, 17.8, and 35.6 μM). The data obtained in this study demonstrate that the two systems used were efficient for the multiplication phase of this species. However, we recommend SIT in view of its reuse in the process of multiplication and rooting. Moreover, simple construction, low cost of the culture medium, and low cost of the bioreactors and the fact that agar is not required qualify this system as an efficient alternative for large-scale micropropagation of Agapanthus umbellatus var. minor. We recommend 17.8 μM 6-BA for the SM system and 8.9 μM 6-BA for SIT.3752923293

Estudo Português de Hipercolesterolemia Familiar

A Hipercolesterolemia Familiar (FH) é uma doença autossómica dominante que se caracteriza, a nível clínico, por níveis elevados de colesterol LDL, levando ao aparecimento prematuro de doenças cardiovasculares (DCV). A nível genético esta doença caracteriza-se, principalmente, por mutações em três genes: LDLR, APOB e PCSK9. Estima-se que em Portugal existam cerca de 20 000 doentes com FH. A identificação clínica de FH é possível mas apenas o estudo molecular confirma a presença da doença. O Estudo Português de Hipercolesterolemia Familiar (EPFH) tem como objectivo principal identificar a causa genética da dislipidémia em doentes com diagnóstico clínico de FH. O EPHF recebeu desde 1999, para realização do estudo molecular, 486 casos-index com diagnóstico clínico de FH e 858 familiares. O estudo molecular é realizado em 3 fases. Fase I: Identificação de mutações nos genes APOB e LDLR. Fase II: Pesquisa de grandes rearranjos no gene LDLR por MLPA. Fase III: Pesquisa de mutações no gene PCSK9. A pesquisa de mutações nos genes APOB e PCSK9 é realizada por amplificação dos fragmentos a estudar e sequenciação directa. No gene LDLR os 18 exões são amplificados dos 18 exôes por PCR e analisados por DHPLC e sequenciação. Até à data foram identificados um total de 504 doentes com um defeito genético num dos três genes estudados: 3 doentes com mutação no gene PCSK9, 12 doentes com mutação no gene APOB e 438 doentes com mutação no gene LDLR (7 dos quais em homozigotia ou heterozigotia composta). No gene LDLR foram encontradas 89 mutações diferentes, que incluem 43 mutações missense,17 delecções/inserções, 6 nonsense, 12 mutações de splicing, 4 grandes delecções e 2 no promotor e 1no codão stop. As mutações mais comuns na população portuguesa são: p.A431T (11%), p.D224N (6,9%) e p.R406W (6,2%). Foram efectuados funcionais em algumas mutações de splicing e comprovou-se a sua patogeneicidade em 6 alterações (c.-135C>G; c.-190+4insTG; c.313+6T>C; c.818-2A>G; c.2389G>T (V776L); c.2547+1G>A). Foram também efectuados estudos funcionais para 5 alterações missense não descritas anteriormente (p.V429L, p.W490R, p.S648P, p.P685S e p.V859M), verificou-se que apenas a alteração p.V859M não é patogenica. No gene APOB foi identificada a mutação mais comum (p.Arg3527Gln) e também a mutação p.Tyr3560Cys. No gene PCSK9 foi encontrada uma única alteração, p.Asp374His. A FH esta sub-diagnosticada no nosso País, esforços têm de ser conduzidos para identificar estes doentes, ainda em idade jovem, de modo a que seja evitado o aparecimento da DCV prematura, e no caso mais extremo a morte prematura como observado em algumas famílias. O diagnóstico e aconselhamento genético da FH é importante para a correcta percepção e prevenção do risco familiar de DCV. O estudo molecular fundamenta a instituição de terapêutica farmacológica adequada e a adopção de um estilo de vida saudável reduzindo substancialmente o risco cardiovascular. Nas crianças e adolescentes o diagnóstico genético é ainda mais importante, uma vez que se sabe que o risco cardiovascular é elevado, mas evitável, se medidas preventivas forem colocadas em prática. O futuro passa pela prevenção em vez da resolução tardia das complicações cardiovasculares inerentes a esta patologia

Invertebrados Associados A Bromélias Em Fragmentos De Mata Atlântica

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Forest fragments in the state of Minas Gerais contain a large number of Bromeliaceae genera, whose cisterns accumulate water and organic matter, providing shelter and food for a wide range of organisms. However, these fragments often consist only of small patches of vegetation, making the species more vulnerable to the effects of this landscape changes. This study aimed to test the effect of the distance to the edge and of the matrix type on the structure of aquatic invertebrate communities in four morphospecies of bromeliads. Samples were collected in Atlantic Forest fragments adjacent to pasture and planted forest areas, in a region of Serra da Mantiqueira, Brazil. Of the 147 bromeliads investigated, we found 35 taxa, among which the most abundant groups were Ostracoda (4,962 individuals), Culicidae (2,358), Tanypodinae (1,164) and Scirtidae (1,043). The richness of taxa and Shannon diversity of invertebrates were similar at different distances from the edge, with variation of richness between 17 and 23 taxa and diversity between 1.25 and 1.52. The composition of the fauna in the cisterns changed between some collection sections (A vs. C, C vs. D and D vs. F), irrespective of being close to or far from the edge. There was no variation of richness (t=-1.145, df=106, p= 0.341) and diversity (t= 1.376, df= 106, p= 0.429) among samples collected from fragments next to planted forest and pasture, likely because the bromeliads studied were located on hillsides above the canopy of planted forests, and subject to similar conditions to those found in the fragments next to pastures. The results demonstrate the importance of bromeliads in maintaining the richness and diversity of the invertebrates they harbor, even in altered landscapes exposed to extreme conditions such as fragment edges. © 2017, Universidade Estadual de Campinas UNICAMP. All rights reserved.171CAPES, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior303156/2012-0, CNPq, Conselho Nacional de Desenvolvimento Científico e TecnológicoFAPEMIG, Fundação de Amparo à Pesquisa do Estado de Minas GeraisCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Complex phenotype of hypercholesterolaemia in a family with both ABCG8 and APOB mutations

Familial Hypercholesterolemia (FH) is the most common of all genetic hypercholesterolaemias with defects in LDLR, APOB and PCSK9 accounting for the majority of cases. However, there are other rare disorders like sitosterolaemia that can present the same phenotype. Both can cause premature atherosclerosis but have distinctive dietetic and therapeutic intervention.N/

Conceptual multi-agent system design for distributed scheduling systems

With the progressive increase in the complexity of dynamic environments, systems require an evolutionary configuration and optimization to meet the increased demand. In this sense, any change in the conditions of systems or products may require distributed scheduling and resource allocation of more elementary services. Centralized approaches might fall into bottleneck issues, becoming complex to adapt, especially in case of unexpected events. Thus, Multi-agent systems (MAS) can extract their automatic and autonomous behaviour to enhance the task effort distribution and support the scheduling decision-making. On the other hand, MAS is able to obtain quick solutions, through cooperation and smart control by agents, empowered by their coordination and interoperability. By leveraging an architecture that benefits of a collaboration with distributed artificial intelligence, it is proposed an approach based on a conceptual MAS design that allows distributed and intelligent management to promote technological innovation in basic concepts of society for more sustainable in everyday applications for domains with emerging needs, such as, manufacturing and healthcare scheduling systems.This work has been supported by FCT - Fundação para a Ciência e a Tecnologia within the R&D Units Projects Scope: UIDB/00319/2020 and UIDB/05757/2020. Filipe Alves is supported by FCT Doctorate Grant Reference SFRH/BD/143745/2019.info:eu-repo/semantics/publishedVersio

Genetic diagnosis of familial hypercholesterolaemia: the importance of functional analysis of potential splice-site mutations

Familial hypercholesterolemia (FH) results from defective low-density lipoprotein receptor (LDLR) activity, mainly due to LDLR gene defects. Of the many different LDLR mutations found in patients with FH, about 6% of single base substitutions are located near or within introns, and are predicted to result in exon skipping, retention of an intron, or activation of cryptic sites during mRNA splicing. This paper reports on the Portuguese FH Study, which found 10 such mutations, 6 of them novel. For the mutations that have not been described before or those whose effect on function have not been analysed, their effect on splicing was investigated, using reverse transcriptase PCR analysis of LDLR mRNA from freshly isolated blood mononuclear cells. Two of these variants (c.313+6 T-->C, c.2389G-->T (p.V776L)) caused exon skipping, and one caused retention of an intron (c.1359-5C-->G), whereas two others (c.2140+5 G-->A and c.1061-8T-->C) had no apparent effect. Any effect of c.1185G-->C (p.V374V) on splicing could not be determined because it was on an allele with a promoter mutation (-42C-->G) that was probably not transcribed. Variants in four patients lost to follow-up could not be tested experimentally, but they almost certainly affect splicing because they disrupt the invariant AG or GT in acceptor (c.818-2A-->G) or donor (c.1060+1G-->A, c.1845+1delG and c.2547+1G-->A) spice sites. These findings emphasise that care must be taken before reporting the presence or absence of a splice-site mutation in the LDLR gene for diagnostic purposes. The study also shows that relatively simple, quick and inexpensive RNA assays can evaluate putative splicing mutations that are not always predictable by available software, thereby reducing genetic misdiagnosis of patients with FH

Diagnóstico molecular de hipercolesterolemia familiar: uma ferramenta importante para a estratificação do risco cardiovascular

Familial hypercholesterolemia (FH) is associated with an increased risk of premature coronary heart disease. Molecular identification of these patients can reduce the burden of mortality from cardiovascular disorders simply by the correct identification of the disease early in life, followed by counseling and appropriate lifestyle modifications, and therapeutic measures when required. Recent studies show that, in Portugal, this disease is severely under-diagnosed. After more than 10 years of research through the Portuguese FH Study, it is now possible to translate the original research results into clinical application. AIMS: The main aims of the present work were to determine whether clinical characterization is sufficient to identify these individuals at high risk of developing CHD and to evaluate the clinical applicability of molecular diagnosis for FH. METHODS: All patients described in this study were recruited for the Portuguese FH Study. The diagnostic criteria used to select the index patients were adapted from the Simon Broome Heart Research Trust. To analyze the usefulness of the molecular diagnosis, graphs of total and LDL cholesterol values by age were constructed for 622 possible FH patients. The lipid profile of patients genetically identified as having FH, before and under medication, were analyzed to assess whether these patients were receiving appropriate treatment. The data are shown separately for children and adults and for female and male propositi (index cases and hypercholesterolemic relatives), both with and without a detectable mutation in the LDLR gene. RESULTS: The Portuguese FH Study has already genetically identified 404 individuals (171 index patients and 233 relatives) among more than one thousand individuals sent for study. A total of 78 different mutations in the LDLR gene were found in 171 index patients, 2 different mutations were found in the apoB gene of 4 patients and 2 patients had a unique PCSK9 mutation. Statistical analysis revealed that there are significant differences between total cholesterol (p < 0.001) and apoB (p = 0.026) values in the group of children (male and female) with and without a mutation in LDLR. For female children LDL values were also significantly different (p < 0.001) between subgroups but for male children this difference did not reach statistical significance. In adult women there is a statistically significant difference for total cholesterol (p = 0.049), LDL cholesterol (p = 0.031) and apoB (p = 0.003) values in the subgroups with and without a LDLR mutation. In adult males there is a statistical difference for total cholesterol (p = 0.002). LDL cholesterol (p = 0.003) and apoB (p = 0.0023) in subgroups with and without an LDLR mutation. Nevertheless there was considerable dispersion of values and individually it is not possible to distinguish between patients with and without a mutation in the LDLR gene, based only on lipid profile. CONCLUSIONS: By analysis of the clinical data of 696 possible FH patients, the present report shows evidence that clinical characterization is not sufficient to distinguish between patients with genetic or environmental dyslipidemia, and so molecular diagnosis is useful in clinical practice, allowing correct identification of FH patients and their relatives, and the early implementation of therapeutic measures to reduce the elevated cardiovascular risk of these patients. In general, molecular diagnosis of FH is feasible and could be obtained in 1-2 months if the technology is available. In Portugal the test will be offered to the population by our Institute at a cost of about 500 euros, like many other genetic tests or exams such as nuclear magnetic resonance