Classification and biomarker selection in lower-grade glioma using robust sparse logistic regression applied to RNA-seq data

Funding Information: This work was supported by national funds through Fundação para a Ciência e a Tecnologia (FCT) with references CEECINST/00102/2018, UIDB/00297/2020 and UIDB/00297/2020 (NOVA MATH, Center for Mathematics and Applications), UIDB/04516/2020 (NOVA LINCS), and the research project “MONET – Multi-omic networks in gliomas” (PTDC/CCI-BIO/4180/2020). The results presented are based upon data generated by the TCGA Research Network: https://www.cancer. gov/tcga. Publisher Copyright: © Brazilian Journal of Biometrics.Effective diagnosis and treatment in cancer is a barrier for the development of personalized medicine, mostly due to tumor heterogeneity. In the particular case of gliomas, highly heterogeneous brain tumors at the histological, cellular and molecular levels, and exhibiting poor prognosis, the mechanisms behind tumor heterogeneity and progression remain poorly understood. The recent advances in biomedical high-throughput technologies have allowed the generation of large amounts of molecular information from the patients that combined with statistical and machine learning techniques can be used for the definition of glioma subtypes and targeted therapies, an invaluable contribution to disease understanding and effective management. In this work sparse and robust sparse logistic regression models with the elastic net penalty were applied to glioma RNA-seq data from The Cancer Genome Atlas (TCGA), to identify relevant tran-scriptomic features in the separation between lower-grade glioma (LGG) subtypes and identify putative outlying observations. In general, all classification models yielded good accuracies, selecting different sets of genes. Among the genes selected by the models, TXNDC12, TOMM20, PKIA, CARD8 and TAF12 have been reported as genes with relevant role in glioma development and progression. This highlights the suitability of the present approach to disclose relevant genes and fosters the biological validation of non-reported genes.publishersversionpublishe

Experimental research on structural concrete masonry walls subjected to fire

The construction in masonry is one of the oldest ways of construction. However, the knowledge regarding its structural behavior is still not well consolidated, especially regarding extreme conditions, such as fire. Although the few available studies regarding structural masonry under fire conditions show some promising results, still the available normative documents seem to have some limitations regarding the topic, which highlights the need for further research, especially experimental, in this field. This paper presents the results of a study on the behavior of structural masonry walls subjected to simulated fire conditions. The specimens were built with three cells concrete blocks, which are common in European and US construction. In the fire resistance tests the walls were subjected to the action of a serviceability in-plane load and the ISO 834 fire curve. Temperatures were measured in the furnace, while temperatures and displacements were measured in the specimens. The obtained results were also compared with the Eurocode 6 part 1.2 predictions, for similar cases

A survey of potential insect vectors of the plant pathogenic bacterium Xylella fastidiosa in three regions of Spain

The emergence of a rapid-spreading olive disease associated with Xylella fastidiosa in southern Italy represents a high risk to susceptible crops in other countries of the Mediterranean basin, if insect vectors occur in the region. The goal of this study was to identify xylem-feeding Auchenorrhyncha that could potentially act as vectors of X. fastidiosa in three regions of Spain (Andalucía, Murcia and Madrid). Samplings with sweep net and stem tap were carried out in October/2004 on grapevines and adjacent crops (olives, nectarine, citrus, Prunus spp.), ornamental trees and herbaceous weeds. Yellow sticky cards were placed in ten vineyards located across 100 km in Andalucía and in three vineyards distant 10-15 km apart in Murcia. Specimens of frequently-trapped species were tested by nested- or multiplex-PCR for the presence of X. fastidiosa. The Typhlocybinae leafhopper, Austroasca (Jacobiasca) lybica (Hemiptera: Cicadellidae) was the most abundant species in vineyards and citrus orchards. Planthoppers (Hemiptera: Fulgoroidea) and psyllids (Hemiptera: Psylloidea) were prevalent on olives. Cicadellinae leafhoppers (known as sharpshooters), which are major vectors of X. fastidiosa in the Americas, were not found in the samples. The only potential vectors were spittlebugs (Hemiptera: Cercopoidea) collected on Populus sp., herbaceous and on conifer trees (Pinus halepense); the spittlebug Neophileanus sp. was common on conifer trees adjacent to a vineyard in Jumilla. None of the insect samples tested positive for X. fastidiosa by PCR assays. However, spittlebugs already associated with susceptible crops in Spain may allow fast spread of X. fastidiosa in case this pathogen is introduced.We also acknowledge financial support from the CNPq-CSIC bilateral grant no. 2004BR0004 and EU grant ICA4-CT-2001-10005.Peer Reviewe

AS INFLUÊNCIAS DO PLANEJAMENTO DAS AÇÕES NA GESTÃO INSTITUCIONAL DA UFPEL

O crescente desenvolvimento das telecomunicações e da informática tem produzido relevantes mudanças nas estruturas sociais, econômicas e organizacionais, porém essa evolução também tem mostrado entraves para a gestão das organizações. Um dos problemas mais críticos é a falta de informações úteis para o processo decisório. Logo, o gerenciamento da informação passa a ser uma questão estratégica no processo de gestão nestes novos tempos de rapidez na tomada de decisão. As informações mostram-se inadequadas pela sua falta, ou por seu excesso desnecessário. Também podem estar defasadas e com acesso limitado, o que, invariavelmente, leva o gestor a tomar decisões baseadas na intuição, sem o adequado suporte da informação. Adaptar-se às contingências e às pressões do ambiente externo tornou-se um desafio constante nas organizações, onde a informação aparece como uma peça fundamental para subsidiar planos nesse complexo cenário organizacional da atualidade. As instituições federais de ensino superior não estão isentas das influências do ambiente externo. Na verdade, as universidades vivem um paradoxo. Ao mesmo tempo em que delas emergem novas tecnologias de informação e a capacitação de pessoas nas diversas extensões dessa área percebe-se a precariedade das informações e do planejamento das ações na gestão administrativa, em parte justificada pela estrutura burocrática pesada, pela resistência a mudanças, pela dependência econômica do Estado, pelo corporativismo, além de precariedade na avaliação dos resultados institucionais, dentre outros aspectos. Muitos são os impactos das mudanças sociais, políticas e econômicas nas organizações universitárias. As dificuldades, em administrar burocracias como as universidades públicas, sem uma cultura de captação de recursos extragoverno federal, demonstram a inércia da própria instituição frente a um ambiente cada vez mais incerto, e a intervenção normativa do Estado também contribuiu para restringir o desenvolvimento de planos de ações para o funcionamento e desenvolvimento das universidades. Entretanto, acredita-se que a tecnologia da informação, por sua vez, aparece como um meio facilitador para a elaboração de estratégias que atendam os objetivos institucionais, e como tal deve ser usada como um recurso interno da organização a ser tratado com o mesmo grau de importância dos demais recursos que constituem as variáveis a serem analisadas na formulação da estratégia organizacional. O planejamento e a informação têm uma relação de sinergia e integração total. A informação, para buscar resultados qualitativos, tem que ser coerente em todos os níveis de planejamento, visto que está presente em toda a organização, bem como, no ambiente externo. Maximiano (2000) destaca que em “qualquer nível de administração o planejamento compreende o processo que define as ações necessárias para enfrentar situações futuras e atingir metas” (p.395), sendo a informação a base de qualquer nível de planejamento visando uma relação mais eficaz entre organização e ambiente. Contudo, apesar das profundas mudanças tecnológicas e organizacionais, grande parte do setor público ainda permanece incapaz de dar respostas rápidas e de implantar políticas públicas que possam corresponder a um modelo renovado de relação Estado-Sociedade, no qual busca-se a melhor equalização da cidadania. Para que o Estado possa cumprir seu papel é necessária a utilização de sistemas de informação que propiciem apoio ao processo decisório, permitam a formulação de políticas adequadas e possibilitem a avaliação sistemática dos resultados. As formas de se administrar as organizações, assim como as adaptações destas ao ambiente externo e interno é uma discussão perene na esfera pública. Debater acerca da performance da universidade perpassa por propostas de mudança, de inovação, de adaptação às novas demandas por parte da comunidade universitária e da sociedade em geral, num efervescente espaço de questionamentos e descobertas que é a universidade. No intuito de mudar o cenário atual, ou seja, de propor alternativas para a elaboração e execução de um planejamento tático e operacional coerente com a realidade da universidade procurou-se, a partir deste estudo, compreender as influências do planejamento das ações da UFPel na percepção de diretores de unidades acadêmicas e administrativas, e da contribuição de técnicos da área de planejamento e de um representante da administração superior da UFPel. Para tanto, os dados foram coletados a partir da análise documental e, num segundo momento buscaram-se informações por meio de visitas às unidades acadêmicas e administrativas que, na época, estavam elaborando o Plano de Ação 2002. A análise foi feita de forma descritivo-interpretativa

Experimental and numerical analysis on the structural fire behaviour of three-cell hollowed concrete masonry walls

Preprint versionMasonry is one of the oldest and most traditional materials in building construction. Nevertheless, the knowledge on the structural fire behaviour of masonry elements is not yet well consolidated. The literature on the load-bearing capacity of masonry walls in case of fire showed an enhanced performance of these elements, however the lack of normative documents, characterization of material properties at high temperatures and experimental results, for calibrating and validating the numerical models, indicates the need of further research. A research study on the structural fire behaviour of three-cell hollowed concrete masonry walls subjected to fire is presented based on results of experimental and numerical studies. First, several loadbearing capacity tests at high temperatures and fire resistance tests on the walls, were carried out in order to assess their behaviour, critical times, failure modes and temperature distribution. The specimens were built with three cell concrete blocks and M10 mortar and were then subjected to an in-plane serviceability load during test. The temperatures, loads and displacements were measured. Second, finite element models were developed and validated with the experimental results. The experimental and numerical results were also compared with the ones given by EN1996-1–2 provisions.European Union (European Commission), Marie Skłodowska-Curie Actions Innovative Training Networks in the frame of the project ATHOR - Advanced THermomechanical multiscale modelling of Refractory linings 764987 Gran

Electronic doping of graphene by deposited transition metal atoms

We perform a phenomenological analysis of the problem of the electronic doping of a graphene sheet by deposited transition metal atoms, which aggregate in clusters. The sample is placed in a capacitor device such that the electronic doping of graphene can be varied by the application of a gate voltage and such that transport measurements can be performed via the application of a (much smaller) voltage along the graphene sample, as reported in the work of Pi et al. [Phys. Rev. B 80, 075406 (2009)]. The analysis allows us to explain the thermodynamic properties of the device, such as the level of doping of graphene and the ionisation potential of the metal clusters in terms of the chemical interaction between graphene and the clusters. We are also able, by modelling the metallic clusters as perfect conducting spheres, to determine the scattering potential due to these clusters on the electronic carriers of graphene and hence the contribution of these clusters to the resistivity of the sample. The model presented is able to explain the measurements performed by Pi et al. on Pt-covered graphene samples at the lowest metallic coverages measured and we also present a theoretical argument based on the above model that explains why significant deviations from such a theory are observed at higher levels of coverage.Comment: 16 pages, 10 figure

Combined use of a new SNP-based assay and multilocus SSR markers to assess genetic diversity of Xylella fastidiosa subsp. pauca infecting citrus and coffee plants

Two haplotypes of Xylella fastidiosa subsp. pauca (Xfp) that correlated with their host of origin were identified in a collection of 90 isolates infecting citrus and coffee plants in Brazil, based on a single-nucleotide polymorphism in the gyrB sequence. A new single-nucleotide primer extension (SNuPE) protocol was designed for rapid identification of Xfp according to the host source. The protocol proved to be robust for the prediction of the Xfp host source in blind tests using DNA from cultures of the bacterium, infected plants, and insect vectors allowed to feed on Xfp- infected citrus plants. AMOVA and STRUCTURE analyses of microsatellite data separated most Xfp populations on the basis of their host source, indicating that they were genetically distinct. The combined use of the SNaPshot protocol and three previously developed multilocus SSR markers showed that two haplotypes and distinct isolates of Xfp infect citrus and coffee in Brazil and that multiple, genetically different isolates can be present in a single orchard or infect a single tree. This combined approach will be very useful in studies of the epidemiology of Xfp- induced diseases, host specificity of bacterial genotypes, the occurrence of Xfp host jumping, vector feeding habits, etc., in economically important cultivated plants or weed host reservoirs of Xfp in Brazil and elsewhere [Int Microbiol 2015; 18(1):13-24].We acknowledge financial support from the EU grant ICA4-CT-2001-10005 and an ‘Intramural Project’ to B. B. Landa from the Spanish National Research Council (CSIC), as well as CNPq for a scholarship to J. R. S. Lopes in Brazil.Peer reviewe

Human phenylalanine hydroxylase as the case study

Funding Information: Authors acknowledge Sofarimex, Indústria Química e Farmacêutica SA, Portugal, for all the support concerning freeze-drying studies. This work was supported by FEDER and Fundação para a Ciência e a Tecnologia, I. P. through iMED.ULisboa (Projects UIDB/04138/2020 and UIDP/04138/2020), iNOVA4Health (UIDB/04462/2020, UIDP/04462/2020) and LS4FUTURE Associated Laboratory (LA/P/0087/2020) and research project PTDC/EBB-BIO/101237/2008 and research grant SFRH/BD/47946/2008 (to Paulo R. Lino). This work has also received funding from the National PKU Alliance, USA. The authors would like to thank Luís Miguel Ramos and Cátia Nascimento who contributed to the exploratory research that culminated in the work herein presented. Funding Information: Authors acknowledge Sofarimex, Indústria Química e Farmacêutica SA, Portugal, for all the support concerning freeze-drying studies. This work was supported by FEDER and Fundação para a Ciência e a Tecnologia, I. P. through iMED.ULisboa (Projects UIDB/04138/2020 and UIDP/04138/2020), iNOVA4Health (UIDB/04462/2020, UIDP/04462/2020) and LS4FUTURE Associated Laboratory (LA/P/0087/2020) and research project PTDC/EBB-BIO/101237/2008 and research grant SFRH/BD/47946/2008 (to Paulo R. Lino). This work has also received funding from the National PKU Alliance, USA. Publisher Copyright: © 2023 The Author(s)The structural maintenance of therapeutic proteins during formulation and/or storage is a critical aspect, particularly for multi-domain and/or multimeric proteins which usually exhibit intrinsic structural dynamics leading to aggregation with concomitant loss-of-function. Protein freeze-drying is a widely used technique to preserve protein structure and function during storage. To minimize chemical/physical stresses occurring during this process, protein stabilizers are usually included, their effect being strongly dependent on the target protein. Therefore, they should be screened for on a time-consuming case-by-case basis. Herein, differential scanning fluorimetry (DSF) and isothermal denaturation fluorimetry (ITDF) were employed to screen, among different classes of freeze-drying additives, for the most effective stabilizer of the model protein human phenylalanine hydroxylase (hPAH). Correlation studies among retrieved DSF and ITDF parameters with recovered enzyme amount and activity indicated ITDF as the most appropriate screening method. Biochemical and biophysical characterization of hPAH freeze-dried with ITDF-selected stabilizers and a long-term storage study (12 months, 5 ± 3 °C) showed that the selected compounds prevented protein aggregation and preserved hPAH structural and functional properties throughout time storage. Our results provide a solid basis towards the choice of ITDF as a high-throughput screening step for the identification of protein freeze-drying protectors.publishersversionpublishe

Gestational protein restriction induces CA3 dendritic atrophy in dorsal hippocampal neurons but does not alter learning and memory performance in adult offspring

Studies have demonstrated that nutrient deficiency during pregnancy or in early postnatal life results in structural abnormalities in the offspring hippocampus and in cognitive impairment. In an attempt to analyze whether gestational protein restriction might induce learning and memory impairments associated with structural changes in the hippocampus, we carried out a detailed morphometric analysis of the hippocampus of male adult rats together with the behavioral characterization of these animals in the Morris water maze (MWM). Our results demonstrate that gestational protein restriction leads to a decrease in total basal dendritic length and in the number of intersections of CA3 pyramidal neurons whereas the cytoarchitecture of CA1 and dentate gyrus remained unchanged. Despite presenting significant structural rearrangements, we did not observe impairments in the MWM test. Considering the clear dissociation between the behavioral profile and the hippocampus neuronal changes, the functional significance of dendritic remodeling in fetal processing remains undisclosed

Structure of full-length wild-type human phenylalanine hydroxylase by small angle X-ray scattering reveals substrate-induced conformational stability

Human phenylalanine hydroxylase (hPAH) hydroxylates l-phenylalanine (l-Phe) to l-tyrosine, a precursor for neurotransmitter biosynthesis. Phenylketonuria (PKU), caused by mutations in PAH that impair PAH function, leads to neurological impairment when untreated. Understanding the hPAH structural and regulatory properties is essential to outline PKU pathophysiological mechanisms. Each hPAH monomer comprises an N-terminal regulatory, a central catalytic and a C-terminal oligomerisation domain. To maintain physiological l-Phe levels, hPAH employs complex regulatory mechanisms. Resting PAH adopts an auto-inhibited conformation where regulatory domains block access to the active site. l-Phe-mediated allosteric activation induces a repositioning of the regulatory domains. Since a structure of activated wild-type hPAH is lacking, we addressed hPAH l-Phe-mediated conformational changes and report the first solution structure of the allosterically activated state. Our solution structures obtained by small-angle X-ray scattering support a tetramer with distorted P222 symmetry, where catalytic and oligomerisation domains form a core from which regulatory domains protrude, positioning themselves close to the active site entrance in the absence of l-Phe. Binding of l-Phe induces a large movement and dimerisation of regulatory domains, exposing the active site. Activated hPAH is more resistant to proteolytic cleavage and thermal denaturation, suggesting that the association of regulatory domains stabilises hPAH.publishe