Updated Big Bang Nucleosynthesis Bounds on Long-lived Particles from Dark Sectors

As electromagnetic showers may alter the abundance of Helium, Lithium, and Deuterium, we can place severe constraints on the lifetime and amount of electromagnetic energy injected by long-lived particles. Considering up-to-date measurements of the light element abundances that point to $Y_p=0.245\pm 0.003$,$({\rm D/H})= (2.527\pm 0.03)\times 10^{-5}$,$(^7{\rm Li/H})=1.58 ^{+0.35}_{-0.28} \times 10^{-10}$, $(^6{\rm Li/^7 Li})=0.05$, and the baryon-to-photon ratio obtained from the Cosmic Microwave Background data, $\eta=6.104 \times 10^{-10}$, we derive upper limits on the fraction of electromagnetic energy produced by long-lived particles. Our findings apply to decaying dark matter models, long-lived gravitinos, and other non-thermal processes that occurred in the early universe between $10^2-10^{10}$ seconds.Comment: 7 pages, 3 figure

A methodology to design a domotics human-machine interface for visually impaired people

According to the World Health Organization (WHO), more than one billion people in the world have some disability. A 2017 report of the Brazilian Geography and Statistics Institute (IBGE) shows that 45.6 million Brazilians have an impairment, among which 18.8 million declare vision issues not fixed by glasses or contact lenses. So a significant population lead to the creation of many legal mechanisms to guarantee their quality-of-life. Potentially, these mechanisms should regulate many aspects of urban design to assure the accessibility of any environment. However, there are several design challenges to be overcome. In this paper, we address the problem of developing Human-Machine Interfaces (HMI) for visually impaired people, focusing on residential automation systems (domotics). The efficient development of such interfaces needs a link among two accessibility areas: domotics and HMI. We used pre-tests, human-computer interaction (HCI) techniques, and the user's emotional state identification to determine the user's profile. We must highlight that the design is intended to be used by any user, visually impaired or not. That is, the system should be universal. The methodology described can be used to assess the efficiency and quality metrics of accessibility in domotic systems.According to the World Health Organization (WHO), more than one billion people in the world have some disability. A 2017 report of the Brazilian Geography and Statistics Institute (IBGE) shows that 45.6 million Brazilians have an impairment, among which 18.8 million declare vision issues not fixed by glasses or contact lenses. So, a significant population leads to developing many legal mechanisms to guarantee their quality-of-life. Potentially, these mechanisms should regulate many aspects of urban design to assure the accessibility of any environment. However, there are several design challenges to be overcome. In this paper, we address the problem of developing Human-Machine Interfaces (HMI) for visually impaired people, focusing on residential automation systems (domotics). The efficient development of such interfaces needs a link among two accessibility areas: domotics and HMI. We used pre-tests, human-computer interaction (HCI) techniques, and the user's emotional state identification to determine the user's profile. We must highlight that the design is intended to be used by any user, visually impaired or not. That is, the system should be universal. The methodology described can be used to assess the efficiency and quality metrics of accessibility in domotics systems

Análise da atividade antimicobacteriana de 36 extratos vegetais da Mata Atlântica brasileira

Trinta e seis extratos vegetais originários da Mata Atlântica foram testados quanto à sua atividade antimicobacteriana frente ao M. tuberculosis H37Rv e M. kansasii, utilizando o método REMA em concentrações seriadas de 100 a 0,20 µg/mL. Dentre os trinta e seis extratos testados, cinco mostraram atividade frente ao M. tuberculosis, e destes apenas, três mostraram atividade ao M. kansasii, que apresentou susceptibilidade a outros dez. O teste de citotoxicidade com células VERO foi realizado com os cinco extratos ativos frente ao M. tuberculosis em que identificou-se a não toxicidade em apenas um extrato (Peschiera affinis) na concentração de 100 µg/mL.Thirty-six plant extracts from the brazilian Atlantic Forest were tested for their antimycobacterial activity against Mycobacterium tuberculosis H37Rv and M. kansasii, using the method REMA in seriate concentrations of 100 to 0.20 µg/mL. Among the thirty six extracts tested, five were active against M. tuberculosis, and three of these extracts also showed activity against M. kansasii. Cytotoxicity test with VERO cells was performed with the five extracts active against M. tuberculosis. Only the extract of Peschiera affinis was identified as non-toxic in the concentration of 100µg/mL

Effects of starch/polycaprolactone-based blends for spinal cord injury regeneration in neurons/glial cells viability and proliferation

Spinal cord injury (SCI) leads to drastic alterations on the quality of life of afflicted individuals. With the advent of Tissue Engineering and Regenerative Medicine where approaches combining biomaterials, cells and growth factors are used, one can envisage novel strategies that can adequately tackle this problem. The objective of this study was to evaluate a blend of starch with poly(ε-caprolactone) (SPCL) aimed to be used for the development of scaffolds spinal cord injury (SCI) repair. SPCL linear parallel filaments were deposited on polystyrene coverslips and assays were carried out using primary cultures of hippocampal neurons and glial cells. Light and fluorescence microscopy observations revealed that both cell populations were not negatively affected by the SPCL-based biomaterial. MTS and total protein quantification indicated that both cell viability and proliferation rates were similar to controls. Both neurons and astrocytes occasionally contacted the surface of SPCL filaments through their dendrites and cytoplasmatic processes, respectively, while microglial cells were unable to do so. Using single cell [Ca2+ ]i imaging, hippocampal neurons were observed growing within the patterned channels and were functional as assessed by the response to a 30 mM KCl stimulus. The present data demonstrated that SPCL-based blends are potentially suitable for the development of scaffolds in SCI regenerative medicine.Portuguese Foundation for Science and Technology through funds from POCTI and/or FEDER programs (Funding to ICVS, 3B's Research Group and post doctoral fellowship to A.J. Salgado-SFRH/BPD/17595/2004)

Dynamic culture of osteogenic cells in biomimetically coated poly(caprolactone) nanofibre mesh constructs

In our previous work, biomimetic calcium phosphate-coated poly(caprolactone) nanofibre meshes (BCP-NMs) were demonstrated to be more effective for supporting cell attachment and proliferation under static conditions, when compared with poly(caprolactone) nanofibre meshes (PCL-NMs). In many applications, in vitro cultivation of constructs using bioreactors that support efficient nutrition of cells has appeared as an important step toward the development of functional grafts. This work aimed at studying the effects of dynamic culture conditions and biomimetic coating on bone cells grown on the nanofibre meshes. BCP-NM and PCL-NM were seeded with osteoblast-like cells (MG63--human osteosarcoma-derived cell line). The cell-seeded constructs were cultured within a rotating bioreactor that simulated microgravity, at a fixed rotating speed, for different time periods, and then characterized. Cell morphology, viability, and phenotype were assessed. PCL-NM constructs presented a higher number of dead cells than BCP-NM constructs. Under dynamic conditions, the production of proteins associated with the extracellular matrix of bone was higher on BCP-NM constructs than in the PCL-NM ones, which indicates that coated samples may provide cells with a better environment for tissue growth. It is suggested that improved mass transfer in the bioreactor in combination with the appropriate substrate were decisive factors for this highly positive outcome for generating bone.This work was developed under the scope of the EU Project Network of Excellence "Expertissues'' (NMP3-CT-2004-500283) and supported by Alea jacta est Marie Curie Actions (MEST-CT-2004-008104). M. Alves da Silva would like to acknowledge the Portuguese Foundation for Science and Technology for her grant (SFRH-BD-28708-2006). Jose V. Araujo is grateful to S. Rathbone, H. Sura, I. Wimpenny, I. Dublon, G. Jones, and E. D. Pinho for useful technical discussions

EGF functionalized polymer-coated gold nanoparticles promote EGF photostability and EGFR internalization for photothermal therapy

The application of functionalized nanocarriers on photothermal therapy for cancer ablation has wide interest. The success of this application depends on the therapeutic efficiency and biocompatibility of the system, but also on the stability and biorecognition of the conjugated protein. This study aims at investigating the hypothesis that EGF functionalized polymer -coated gold nanoparticles promote EGF photostability and EGFR internalization, making these conjugated particles suitable for photothermal therapy. The conjugated gold nanoparticles (100-200 nm) showed a plasmon absorption band located within the near infrared range (650-900 nm), optimal for photothermal therapy applications. The effects of temperature, of polymer-coated gold nanoparticles and of UVB light (295nm) on the fluorescence properties of EGF have been investigated with steady-state and time-resolved fluorescence spectroscopy. The fluorescence properties of EGF, including the formation of Trp and Tyr photoproducts, is modulated by temperature and by the intensity of the excitation light. The presence of polymeric-coated gold nanoparticles reduced or even avoided the formation of Trp and Tyr photoproducts when EGF is exposed to UVB light, protecting this way the structure and function of EGF. Cytotoxicity studies of conjugated nanoparticles carried out in normal-like human keratinocytes showed small, concentration dependent decreases in cell viability (0-25%). Moreover, conjugated nanoparticles could activate and induce the internalization of overexpressed Epidermal Growth Factor Receptor in human lung carcinoma cells. In conclusion, the gold nanoparticles conjugated with Epidermal Growth Factor and coated with biopolymers developed in this work, show a potential application for near infrared photothermal therapy, which may efficiently destroy solid tumours, reducing the damage of the healthy tissue.Support was provided by: Fundacao para a Ciencia e Tecnologia (FCT) for the financial support under the project reference PTDC/BBB-BMC/0611/2012 [https://www.fct.pt/apoios/projectos)]. The work at CBMA was supported by the strategic programme UID/BIA/04050/2013 (POCI-01-0145-FEDER-007569) funded by national funds through the FCT I.P. and by the ERDF through the COMPETE2020 - Programa Operacional Competitividade e Internacionalizacao (POCI) [https://www.fct.pt/apoios/projectos]; European Commission through the project H2020-644242-SAPHELY (https://saphely.eu/project.php) and the project H2020-634013-2-PHOCNOSIS [http://cordis.europa.eu/project/rcn/193268_en.html].The authors would like to thank Fundacao para a Ciencia e Tecnologia (FCT) for the financial support under the project reference PTDC/BBB-BMC/0611/2012. The work at CBMA was supported by the strategic programme UID/BIA/04050/2013 (POCI-01-0145-FEDER-007569) funded by national funds through the FCT I.P. and by the ERDF through the COMPETE2020 - Programa Operacional Competitividade e Internacionalizacao (POCI). The authors acknowledge the funding from the European Commission through the project H2020-644242-SAPHELY and the project H2020-634013-2-PHOCNOSIS. Finally, the authors would also like to thank the master student Joao Lopes from Universidade Lusofona (Portugal) for the help with in vitro cytotoxic assays. Isabel Correia acknowledges FCT for Investigator FCT contract.info:eu-repo/semantics/publishedVersio

Cellular localization, accumulation and trafficking of double-walled carbon nanotubes in human prostate cancer cells

Carbon nanotubes (CNTs) are at present being considered as potential nanovectors with the ability to deliver therapeutic cargoes into living cells. Previous studies established the ability of CNTs to enter cells and their therapeutic utility, but an appreciation of global intracellular trafficking associated with their cellular distribution has yet to be described. Despite the many aspects of the uptake mechanism of CNTs being studied, only a few studies have investigated internalization and fate of CNTs inside cells in detail. In the present study, intracellular localization and trafficking of RNA-wrapped, oxidized double-walled CNTs (oxDWNT–RNA) is presented. Fixed cells, previously exposed to oxDWNT–RNA, were subjected to immunocytochemical analysis using antibodies specific to proteins implicated in endocytosis; moreover cell compartment markers and pharmacological inhibitory conditions were also employed in this study. Our results revealed that an endocytic pathway is involved in the internalization of oxDWNT–RNA. The nanotubes were found in clathrin-coated vesicles, after which they appear to be sorted in early endosomes, followed by vesicular maturation, become located in lysosomes. Furthermore, we observed co-localization of oxDWNT–RNA with the small GTP-binding protein (Rab 11), involved in their recycling back to the plasma membrane via endosomes from the trans-golgi network

Postembryonic establishment of megabase-scale gene silencing in nucleolar dominance

Nucleolar dominance is an epigenetic phenomenon in plant and animal genetic hybrids that describes the expression of 45S ribosomal RNA genes (rRNA genes) inherited from only one progenitor due to the silencing of the other progenitor’s rRNA genes. rRNA genes are tandemly arrayed at nucleolus organizer regions (NORs) that span millions of basepairs, thus gene silencing in nucleolar dominance occurs on a scale second only to X-chromosome inactivation in female mammals. In Arabidopsis suecica, the allotetraploid hybrid of A. thaliana and A. arenosa, theA. thaliana –derived rRNA genes are subjected to nucleolar dominance and are silenced via repressive chromatin modifications. However, the developmental stage at which nucleolar dominance is established in A. suecica is currently unknown. We show that nucleolar dominance is not apparent in seedling cotyledons formed during embryogenesis but becomes progressively established during early postembryonic development in tissues derived from both the shoot and root apical meristems. The progressive silencing of A. thaliana rRNA genes correlates with the transition of A. thaliana NORs from a decondensed euchromatic state associated with histone H3 that is trimethylated on lysine 4 (H3K4me3) to a highly condensed heterochromatic state in which the NORs are associated with H3K9me2 and 5-methylcytosine-enriched chromocenters. In RNAi-lines in which the histone deacetylases HDA6 and HDT1 are knocked down, the developmentally regulated condensation and inactivation of A. thaliana NORs is disrupted. Collectively, these data demonstrate that HDA6 and HDT1 function in the postembryonic establishment of nucleolar dominance, a process which recurs in each generatio

Integrative multi-kinase approach for the identification of potent antiplasmodial hits

Malaria is a tropical infectious disease that affects over 219 million people worldwide. Due to the constant emergence of parasitic resistance to the current antimalarial drugs, the discovery of new antimalarial drugs is a global health priority. Multi-target drug discovery is a promising and innovative strategy for drug discovery and it is currently regarded as one of the best strategies to face drug resistance. Aiming to identify new multi-target antimalarial drug candidates, we developed an integrative computational approach to select multi-kinase inhibitors for Plasmodium falciparum calcium-dependent protein kinases 1 and 4 (CDPK1 and CDPK4) and protein kinase 6 (PK6). For this purpose, we developed and validated shape-based and machine learning models to prioritize compounds for experimental evaluation. Then, we applied the best models for virtual screening of a large commercial database of drug-like molecules. Ten computational hits were experimentally evaluated against asexual blood stages of both sensitive and multi-drug resistant P. falciparum strains. Among them, LabMol-171, LabMol-172, and LabMol-181 showed potent antiplasmodial activity at nanomolar concentrations (EC50 15 folds. In addition, LabMol-171 and LabMol-181 showed good in vitro inhibition of P. berghei ookinete formation and therefore represent promising transmission-blocking scaffolds. Finally, docking studies with protein kinases CDPK1, CDPK4, and PK6 showed structural insights for further hit-to-lead optimization studies.7CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP405996/2016-0; 400760/2014-2Sem informação2018/05926-2; 2017/02353-9; 2012/16525-2; 2017/18611-7; 2018/07007-4; 2013/13119-6; 2018/24878-9; 2015/20774-