Network conduciveness with application to the graph-coloring and independent-set optimization transitions

We introduce the notion of a network's conduciveness, a probabilistically interpretable measure of how the network's structure allows it to be conducive to roaming agents, in certain conditions, from one portion of the network to another. We exemplify its use through an application to the two problems in combinatorial optimization that, given an undirected graph, ask that its so-called chromatic and independence numbers be found. Though NP-hard, when solved on sequences of expanding random graphs there appear marked transitions at which optimal solutions can be obtained substantially more easily than right before them. We demonstrate that these phenomena can be understood by resorting to the network that represents the solution space of the problems for each graph and examining its conduciveness between the non-optimal solutions and the optimal ones. At the said transitions, this network becomes strikingly more conducive in the direction of the optimal solutions than it was just before them, while at the same time becoming less conducive in the opposite direction. We believe that, besides becoming useful also in other areas in which network theory has a role to play, network conduciveness may become instrumental in helping clarify further issues related to NP-hardness that remain poorly understood

Do reciprocal relationships between academic workload and self-regulated learning predict medical freshmen's achievement? A longitudinal study on the educational transition from secondary school to medical school

One of the most important factors that makes the transition from secondary school to medical school challenging is the inability to put in the study time that a medical school curriculum demands. The implementation of regulated learning is essential for students to cope with medical course environment and succeed. This study aimed to investigate the reciprocal relationships between self-regulated learning skills (SRLS) and academic workload (AW) across secondary school to medical school transition. Freshmen enrolled in medical school (N = 102) completed questionnaires at the beginning and at the end of their academic year, assessing AW (measured as study time hours and perceived workload), SRLS (planning and strategies for learning assessment, motivation and action to learning and self-directedness) and academic achievement. An exploratory factor analysis (EFA) and a longitudinal path analysis were performed. According to the EFA, study time and perceived workload revealed two factors of AW: students who had a high perceived workload also demonstrated increased study time (tandem AW); and those who had a low perceived workload also demonstrated increased study time (inverse AW). Only a longitudinal relationship between SRLS and AW was found in the path analysis: prior self-directedness was related to later tandem AW. Moreover, success during the first year of medical school is dependent on exposure to motivation, self-directedness and high study time without overload during secondary school and medical school, and prior academic achievement. By better understanding these relationships, teachers can create conditions that support academic success during the first year medical school

O lineamento transbrasiliano na Bacia do Paraná : compartimentação crustal do embasamento e reativações fanerozóicas

Tese (doutorado)—Universidade de Brasília, Instituto de Geociências, 2015.A Plataforma Sul Americana inclui dois importantes componentes geológicos de escala continental e com raízes estruturais em comum: o Lineamento Transbrasiliano (LTB) e a Bacia do Paraná. Importante relação entre os dois ocorre na região entre o Arco Magmático de Goiás e a Faixa Paraguai, que impõem particularidades estruturais obscurecidas pela cobertura sedimentar da Bacia do Paraná. A área, alvo desse estudo, é recoberta por dados aerogeofísicos, magnéticos e gravimétricos, adquiridos com diferentes resoluções. Sua integração permitiu gerar mapas de anomalias magnéticas e anomalias Bouguer, este incluindo dados terrestres.Técnicas de processamento e modelagem geofísica foram utilizadas com objetivo de esclarecer a disposição de compartimentos crustais e estruturas do embasamento da bacia em diferentes níveis de profundidade. Três grandes descontinuidades magnéticas do LTB limitam compartimentos crustais na área, de leste para oeste: lineamentos Serra Negra, Baliza e General Carneiro, com direções gerais N30°E, N60°E e N70°E, respectivamente, que separam mudanças significativas no background gravimétrico, ainda subdividido por lineamento adicional N50°W, São Vicente. Análise de lineamentos de 1ª, 2ª e 3ª ordens aponta a predominância de orientações NE, interpretadas como originalmente brasilianas e reativadas no Jurássico-Cretáceo, e direções NW, bem marcadas nas unidades sedimentares da bacia e com caráter distensivo, atribuído a reativação mesozóica. Análise do matched-filter aplicada a dados magnéticos e gravimétricos, com suporte da deconvolução de Euler e tilt-depth, aponta estimativas de profundidades importantes: (i) 2,5 km, relacionado ao topo do embasamento da Bacia do Paraná; (ii) 6 km, atribuído ao topo do embasamento da bacia neoproterozóica (Grupo Cuiabá); (iii) 20 km, possivelmente associado à interface crosta superior/inferior; e (iv) 33-39 e 43 km, relativos às espessuras crustais a oeste e sudeste do lineamento Serra Negra, respectivamente. A crosta a leste é formada pelo o Arco Magmático de Arenópolis e o limite noroeste do Bloco Paranapanema e a oeste é constituída por zona de transição crustal e o paleocontinente Amazônico. A modelagem geofísica conjunta 2D com dados gravimétricos e magnéticos esclarece a geometria assimétrica do embasamento da bacia, configurando pelo menos três meiográbens formados ao longo de estruturas reativadas do LTB. A região entre os lineamentos Serra Negra e General Carneiro caracteriza-se por menor espessura e maior fraqueza crustal, onde importantes estruturas se desenvolveram no Mesozóico: desde reativações com direção NW, vinculadas a soerguimento crustal e à implantação de pequenas bacias cretáceas alinhadas a NE. Dois depocentros importantes ocorrem: a norte do lineamento General Carneiro, com direção N70°E, e a leste da falha Serra Negra, com direção N30°E – NS.The South American Platform includes two major geological components of continental scale with common structural roots: the Transbrasiliano Lineament (LTB) and the Paraná Basin. An important relationship between the two is observed in the region between the Goiás Magmatic Arc and the Paraguay Belt, which impose structural features concealed by the sedimentary cover of the Paraná Basin. This region comprises our study area, and is covered by airborne magnetic and gravity surveys, acquired with different resolutions. These data were integrated to generate maps of magnetic and Bouguer anomalies, the latter included ground data. Data processing and geophysical modeling techniques were used in order to reveal the disposition of crustal compartments and the basin basement structures at different depths. Three large magnetic discontinuities limit crustal compartments in the area, from east to west: Serra Negra, Baliza and General Carneiro lineaments, with N30°E, N60°E and N70°E trending alignments, respectively, which separate significant changes in the gravity background, still subdivided by the additional Sao Vicente lineament, N50°W. Analyses of 1st, 2nd and 3rd order lineaments indicate predominance of NE trending directions, which were interpreted as Brasiliano structures, reactivated in the Jurassic-Cretaceous. NW directions, well-marked in the sedimentary units of the basin and with extensional character, were attributed to Mesozoic reactivation. Matched-filter analysis applied to magnetic and gravity data, supported by the Euler deconvolution and tiltdepth, yielded important depths estimates: (i) 2.5 km to the top of the Paraná Basin basement; (ii) 6 km to the top of the Neoproterozoic Basin basement (Cuiabá Group); (iii) 20 km, possibly associated with the upper/lower crust interface; and (iv) 33-39 and 43 km related to crustal thicknesses west and southeast of the Serra Negra lineament, respectively. To the east, the crust is formed by the Arenópolis Magmatic Arc and the northwest boundary of Paranapanema Block, while to the west it consists of a crustal transition zone and the Amazon paleocontinent. The 2D geophysical modeling based on gravity and magnetic data sheds light on the asymmetric geometry of the basement of the basin, with at least three half-grabens formed by LTB reactivated structures. The region between the Serra Negra and General Carneiro lineaments is characterized by thinner crust and higher crustal weakness, where important structures have developed in the Mesozoic, including NW trending reactivations, linked to crustal uplift and deployment of small NE-aligned Cretaceous basins. Important depocenters occur: the first, to the north of General Carneiro lineament, and the second, to the east of the Serra Negra fault, with N70ºE and N30°E – NS trending directions, respectively

Broadly conserved roles of TMEM131 family proteins in intracellular collagen assembly and secretory cargo trafficking.

Collagen is the most abundant protein in animals. Its dysregulation contributes to aging and many human disorders, including pathological tissue fibrosis in major organs. How premature collagen proteins in the endoplasmic reticulum (ER) assemble and route for secretion remains molecularly undefined. From an RNA interference screen, we identified an uncharacterized Caenorhabditis elegans gene tmem-131, deficiency of which impairs collagen production and activates ER stress response. We find that amino termini of human TMEM131 contain bacterial PapD chaperone-like domains, which recruit premature collagen monomers for proper assembly and secretion. Carboxy termini of TMEM131 interact with TRAPPC8, a component of the TRAPP tethering complex, to drive collagen cargo trafficking from ER to the Golgi. We provide evidence that previously undescribed roles of TMEM131 in collagen recruitment and secretion are evolutionarily conserved in C. elegans, Drosophila, and humans

Genetically engineered-MSC therapies for non-unions, delayed unions and critical-size bone defects

The normal bone regeneration process is a complex and coordinated series of events involving different cell types and molecules. However, this process is impaired in critical-size/large bone defects, with non-unions or delayed unions remaining a major clinical problem. Novel strategies are needed to aid the current therapeutic approaches. Mesenchymal stem/stromal cells (MSCs) are able to promote bone regeneration. Their beneficial effects can be improved by modulating the expression levels of specific genes with the purpose of stimulating MSC proliferation, osteogenic differentiation or their immunomodulatory capacity. In this context, the genetic engineering of MSCs is expected to further enhance their pro-regenerative properties and accelerate bone healing. Herein, we review the most promising molecular candidates (protein-coding and non-coding transcripts) and discuss the different methodologies to engineer and deliver MSCs, mainly focusing on in vivo animal studies. Considering the potential of the MSC secretome for bone repair, this topic has also been addressed. Furthermore, the promising results of clinical studies using MSC for bone regeneration are discussed. Finally, we debate the advantages and limitations of using MSCs, or genetically-engineered MSCs, and their potential as promoters of bone fracture regeneration/repair.This project is supported by Fundação para a Ciência e a Tecnologia (FCT)—in the framework of the project POCI-01-0145-FEDER-031402-R2Bone, under the PORTUGAL 2020 Partnership Agreement, through ERDF, co-funded by FEDER/FNR, and national funding (through FCT – Fundação para a Ciência e a Tecnologia, I.P., provided by the contract-program and according to numbers 4, 5 and 6 of art. 23 of Law No. 57/2016 of 29 August 2016, as amended by Law No. 57/2017 of 19 July 2017). RG, JHT, and MIA are supported by FCT, through the FCT Investigator Program (IF/00638/2014), SFRH/BD/112832/2015, and DL 57/2016/CP1360/CT0008, respectively

Long noncoding RNAs: a missing link in osteoporosis

Osteoporosis is a systemic disease that results in loss of bone density and increased fracture risk, particularly in the vertebrae and the hip. This condition and associated morbidity and mortality increase with population ageing. Long noncoding (lnc) RNAs are transcripts longer than 200 nucleotides that are not translated into proteins, but play important regulatory roles in transcriptional and post-transcriptional regulation. Their contribution to disease onset and development is increasingly recognized. Herein, we present an integrative revision on the studies that implicate lncRNAs in osteoporosis and that support their potential use as therapeutic tools. Firstly, current evidence on lncRNAs involvement in cellular and molecular mechanisms linked to osteoporosis and its major complication, fragility fractures, is reviewed. We analyze evidence of their roles in osteogenesis, osteoclastogenesis, and bone fracture healing events from human and animal model studies. Secondly, the potential of lncRNAs alterations at genetic and transcriptomic level are discussed as osteoporosis risk factors and as new circulating biomarkers for diagnosis. Finally, we conclude debating the possibilities, persisting difficulties, and future prospects of using lncRNAs in the treatment of osteoporosis.This project has been supported by Portuguese funds through FCT—Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior in the framework of the project POCI-01-0145-FEDER-031402—R2Bone, under the PORTUGAL 2020 Partnership Agreement, through ERDF. Authors would like to thank to FCT DL 57/2016/CP1360/CT0008 (M.I.A.) and SFRH/BD/112832/2015 (J.H.T)

The inflammatory response in the regression of lumbar disc herniation

Lumbar disc herniation (LDH) is highly associated with inflammation in the context of low back pain. Currently, inflammation is associated with adverse symptoms related to the stimulation of nerve fibers that may lead to pain. However, inflammation has also been indicated as the main factor responsible for LDH regression. This apparent controversy places inflammation as a good prognostic indicator of spontaneous regression of LDH. This review addresses the molecular and cellular mechanisms involved in LDH regression, including matrix remodeling and neovascularization, in the scope of the clinical decision on conservative versus surgical intervention. Based on the evidence, a special focus on the inflammatory response in the LDH context is given, particularly in the monocyte/macrophage role. The phenomenon of spontaneous regression of LDH, extensively reported in the literature, is therefore analyzed here under the perspective of the modulatory role of inflammation.This work was financed by project “Bioengineered Therapies for infectious diseases and tissue regeneration” (NORTE-01-0145-FEDER-000012), supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), by FEDER/COMPETE 2020 (POCI), Portugal 2020, and by Portuguese funds through FCT/MCTES in the framework of the project "Institute for Research and Innovation in Health Sciences" (POCI-01- 0145-FEDER-007274). Cunha C and Gonçalves RM acknowledge FCT by their postdoc fellowship (SFRH/BDP/87071/2012) and FCT Investigator Grant (IF/ 00638/2014), respectively. Silva AJ acknowledges her fellowship under the framework of the project Norte-01-0145-FEDER-000012

Peripheral biomarkers for first-episode psychosis-opportunities from the neuroinflammatory hypothesis of schizophrenia

Objective Schizophrenia is a disabling disorder of unknown aetiology, lacking definite diagnostic method and cure. A reliable biological marker of schizophrenia is highly demanded, for which traceable immune mediators in blood could be promising candidates. We aimed to gather the best findings of neuroinflammatory markers for first-episode psychosis (FEP). Methods We performed an extensive narrative review of online literature on inflammation-related markers found in human FEP patients only. Results Changes to cytokine levels have been increasingly reported in schizophrenia. The peripheral levels of IL-1 (or its receptor antagonist), soluble IL-2 receptor, IL-4, IL-6, IL-8, and TNF-a have been frequently reported as increased in FEP, in a suggestive continuum from high-risk stages for psychosis. Microglia and astrocytes establish the link between this immune signalling and the synthesis of noxious tryptophan catabolism products, that cause structural damage and directly hamper normal neurotransmission. Amongst these, only 3-hydroxykynurenine has been consistently described in the blood of FEP patients. Conclusion Peripheral molecules stemming from brain inflammation might provide insightful biomarkers of schizophrenia, as early as FEP or even prodromal phases, although more timeand clinically-adjusted studies are essential for their validation.This work has been conducted with the support of the Portuguese Foundation for Science and Technology

High-resolution mass spectrometry applied to the study of metabolome modifications in various chicken tissues after amoxicillin administration

The performance of high resolution accurate mass spectrometry (HRMS) operating in full scan MS mode was investigated for the quantitative determination of amoxicillin (AMX) as well as qualitative analysis of metabolomic profiles in tissues of medicated chickens. The metabolomic approach was exploited to compile analytical information on changes in the metabolome of muscle, kidney and liver from chickens subjected to a pharmacological program with AMX. Data consisting of m/z features taken throughout the entire chromatogram were extracted and filtered to be treated by Principal Component Analysis. As a result, it was found that medicated and non-treated animals were clearly clustered in distinct groups. Besides, the multivariate analysis revealed some relevant mass features contributing to this separation. In this context, recognizing those potential markers of each chicken class was a priority research for both metabolite identification and, obviously, evaluation of food quality and health effects associated to food consumption

Trigonometric Parallaxes of Massive Star Forming Regions: III. G59.7+0.1 and W 51 IRS2

We report trigonometric parallaxes for G59.7+0.1 and W 51 IRS2, corresponding to distances of 2.16^{+0.10}_{-0.09} kpc and 5.1^{+2.9}_{-1.4} kpc, respectively. The distance to G59.7+0.1 is smaller than its near kinematic distance and places it between the Carina-Sagittarius and Perseus spiral arms, probably in the Local (Orion) spur. The distance to W 51 IRS2, while subject to significant uncertainty, is close to its kinematic distance and places it near the tangent point of the Carina-Sagittarius arm. It also agrees well with a recent estimate based on O-type star spectro/photometry. Combining the distances and proper motions with observed radial velocities gives the full space motions of the star forming regions. We find modest deviations of 5 to 10 km/s from circular Galactic orbits for these sources, both counter to Galactic rotation and toward the Galactic center.Comment: 16 pages, 6 figures; to appear in the Astrophysical Journa