Several studies have shown that diverse components of the bone marrow (BM) microenvironment play a central role in the progression, pathophysiology, and drug resistance in multiple myeloma (MM). In ...particular, the dynamic interaction between BM mesenchymal stem cells (BM-MSC) and MM cells has shown great relevance. Here we showed that inhibiting both PKC and NF-κB signalling pathways in BM-MSC reduced cell survival in the MM cell line H929 and increased its susceptibility to the proteasome inhibitor bortezomib. PKC-mediated cell survival inhibition and bortezomib susceptibility induction were better performed by the chimeric peptide HKPS than by the classical enzastaurin inhibitor, probably due to its greatest ability to inhibit cell adhesion and its increased capability to counteract the NF-κB-related signalling molecules increased by the co-cultivation of BM-MSC with H929 cells. Thus, inhibiting two coupled signalling molecules in BM-MSC was more effective in blocking the supportive cues emerging from the mesenchymal stroma. Considering that H929 cells were also directly susceptible to PKC and NF-κB inhibition, we showed that treatment of co-cultures with the HKPS peptide and BAY11-7082, followed by bortezomib, increased H929 cell death. Therefore, targeting simultaneously connected signalling elements of BM-MSC responsible for MM cells support with compounds that also have anti-MM activity can be an improved treatment strategy.
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The introduction of biocompatible coatings onto nanoparticle surfaces can be synthetically challenging. In this work, calcium phosphate (brushite, CaHPO4⋅2H2O), iron oxide (hematite, ...α-Fe2O3), zinc oxide (ZnO), and CaHPO4@ZnO and α-Fe2O3@ZnO nanoparticles were synthesized and treated with the biocompatible, biodegradable, polysaccharide inulin {(2R,3S,4S,5R)-2-(2R,3S,4S,5R)-3,4-dihydroxy-2,5-bis(hydroxymethyl)oxolan-2-yloxymethyl-5-(hydroxymethyl)oxolane-2,3,4-triol} under mild conditions. The products were fully characterized by Fourier transforms infrared (FTIR) spectroscopy, energy dispersive spectroscopy (EDS), dynamic light scattering (DLS), differential thermogravimetric/differential thermal analysis (TGA/DTA), transmission electron microscopy (TEM) and powder X-ray diffraction (XRD). Surface interactions among hematite and brushite with inulin are weak, but coating the nanoparticle surface with ZnO increased the affinity toward the polysaccharide. Inulin adsorption on the nanoparticle surface was confirmed by thermal and spectroscopic analyses. The nanoparticles had diameters ranging from 50 to 80nm, with nearly spherical morphology. The nanoparticles sizes, stability and solubility in water could make them useful as components for enriched foods.
Abstract Faced with the uncertainty of whether the vaccines against Covid-19 are effective or not and faced with living or dying, it is important to know the perception and expectation of their ...acceptance. The main aim of the study to analyze the perception and expectation of the vaccine against Covid- 19 that South American families have in an urban area of De Pasco. Descriptive, cross-sectional study, simple random sampling of 197 families. The participants were recruited digitally through a neighborhood leadership and an online survey was applied with prior consent. The logistic regression analysis was performed in EPIDAT 4.1 with a significance level of 5%. Regarding the desire to be vaccinated, it is worth noting that a family member died from the coronavirus, hence the health personnel must continue with the preventive promotional work of vaccination in order to obtain favorable results in the entire population. The majority (100%) have a favorable perception and expectation about the vaccine against Covid- 19 ( X c 2=132.83) and the p-value (0.00); As regards the desire to be vaccinated, it is worth noting having had a family member die from the coronavirus, hence the health personnel must continue with the preventive promotional work of vaccination in order to obtain favorable results in the entire population.
Resumo Diante da incerteza quanto à eficácia das vacinas contra a Covid-19 e diante da possibilidade de viver ou morrer, é importante conhecer a percepção e a expectativa de sua aceitação por parte da população. O objetivo principal do presente estudo é analisar a como a vacina contra a Covid-19 é vista pela população estudada e quais são as expectativas que famílias sul-americanas de uma área urbana de Pasco têm em relação a esta vacina. Este é um estudo descritivo, transversal, usando uma amostragem aleatória simples de 197 famílias. Os participantes foram selecionados digitalmente através do contato com uma liderança local e uma pesquisa online foi aplicada com o consentimento prévio dos indivíduos. A análise de regressão logística foi realizada no EPIDAT 4.1 com nível de significância de 5%. Acerca do desejo de se vacinar, é válido enfatizar que há falecimentos de familiares devido ao coronavírus e, portanto, é necessário que a equipe assistencial continue com o trabalho preventivo de incentivo à vacinação para obter resultados favoráveis para toda a população. De acordo com os resultados encontrados no presente estudo, a maioria (100%) dos participantes demonstrou ter uma percepção e expectativa favoráveis sobre a vacina contra a Covid-19 ( X c 2=132,83), com valor-p (0,00).
In this paper, we study the dynamical behavior of a linear control system on
R
2
when the associated matrix has real eigenvalues. Different from the complex case, we show that the position of the ...control zero relative to the control range can have a strong interference in such dynamics if the matrix is not invertible. In the invertible case, we explicitly construct the unique control set with a nonempty interior.
ABSTRACT
Supernova remnants are the nebular leftover of defunct stellar environments, resulting from the interaction between a supernova blastwave and the circumstellar medium shaped by the ...progenitor throughout its life. They display a large variety of non-spherical morphologies such as ears that shine non-thermally. We have modelled the structure and the non-thermal emission of the supernova remnant G1.9 + 0.3 through 3D magnetohydrodynamic numerical simulations. We propose that the peculiar ear-shaped morphology of this supernova remnant results from the interaction of its blast wave with a magnetized circumstellar medium, which was previously asymmetrically shaped by the past stellar wind emanating from the progenitor star or its stellar companion. We created synthetic non-thermal radio and X-ray maps from our simulated remnant structure, which are in qualitative agreement with observations, forming ears on the polar directions. Our synthetic map study explains the discrepancies between the measured non-thermal radio and X-ray surface brightness distributions assuming that the inverse Compton process produces the observed X-ray emission.
Results are reported from an improved measurement of ν_{μ}→ν_{e} transitions by the NOvA experiment. Using an exposure equivalent to 6.05×10^{20} protons on target, 33 ν_{e} candidates are observed ...with a background of 8.2±0.8 (syst.). Combined with the latest NOvA ν_{μ} disappearance data and external constraints from reactor experiments on sin^{2}2θ_{13}, the hypothesis of inverted mass hierarchy with θ_{23} in the lower octant is disfavored at greater than 93% C.L. for all values of δ_{CP}.
Technological development is key for national strategies to cope with the Paris Agreement’s goals. Technology Needs Assessments (TNAs) aim to identify, prioritize, and diffuse climate change ...mitigation and/or adaptation technologies in developing countries. Their methodology includes a multi-criteria decision analysis (MCDA) framework but, although many countries already conducted a TNA, literature lacks discussions on country-specific processes for a TNA, as it usually follows a one-size-fits-all approach. This paper provides empirical evidence on the importance of country-driven processes that help shaping international programmes into country-specific needs and capabilities. It presents lessons learned from a tailored process for identification, prioritization, and selection of mitigation technologies in the scope of a TNA project for Brazil, an exceptional case of a developing country with strong capacity in integrated assessment modelling (IAM) scenarios for guiding its climate strategies. A previous IAM scenario result allowed pre-selecting technologies in six key economic sectors, while other TNAs prioritized no more than three. This allowed the elaboration of an overall ranking from the MCDA, in contrast to sectoral rankings that are mostly employed in other countries’ TNAs. The overall ranking serves not only as a basis for the selection of priority technologies but also provides information on the integrated innovations framework for climate technologies in the country. Further specific findings of the tailored Brazilian TNA approach are discussed in the paper in order to call for the importance that a technology transfer project should not only be country-driven but also conducted through a country-specific process.
Industrial waste fired clay materials, which are good pozzolans, can be used in place of cement in the manufacture of precast concrete products. This paper analyzes the use of industrial waste fired ...clay as pozzolanic materials for the manufacture of concrete roofing tiles, exploring the microstructure and morphology of the resulting concrete and their impact on product properties and performance. All trials and measurements were taken on an industrial ceramic product subsequently used in a second industrial process to manufacture concrete tiles, which were found to meet market standards. Porosity was observed to be greater in the waste fired clay product in only one trial, while the proportion of pores with larger diameters was found to decline. The microstructural studies revealed the existence of pozzolanic reaction products and an incomplete cement reaction, as in the control specimens, due to the processing conditions. This effect caused an increase in flexural strength after 28 days.
► This paper compares the standard methods C and E (new) to predict the frost resistance of clay tiles. ► It deals with the effect of clay, microstructure and manufacturing on the frost durability. ► ...Microstructure was studied by DRX, FRX and mercury porosimetry. ► It leads on clay characterisation and industrial process control to improve frost durability.
Clay roofing tiles are sensitive to frost action and require testing by repeated freezing and thawing cycles. The research purpose is to predict frost durability, taking into account the effect of clay mineralogy, microstructure (studied by DRX, FRX and mercury porosimetry) and manufacturing parameters, drawing an empirical comparison between methods C and E suggested by the European Standard. Method E is more severe and selective than method C, showing earlier failure and smaller dispersion, which may be explained due to the different saturation process, cooling kinetic and the presence of cloth. The damage increased with the number of cycles, it is substantially affected by the fired clay porosity and calcium content, being consistent with the thermodynamics and kinetics of the mechanisms that lead to failure. The findings provide guidance to improve frost durability based on clay characterisation and industrial process control.
Abstract Introduction Previous reports have shown that CD24 gene polymorphisms have an important role in the risk of development and progression of multiple sclerosis (MS). Objective To investigate ...the association between P226 polymorphisms (T/C), P1056 (A/G), P1527 (TG/del) and P1626 (A/G) of the CD24 gene and MS, comparing allele and genotype frequencies of patients versus controls. Materials and methods We analyzed DNA samples from 102 MS patients and from 205 unrelated healthy individuals. DNA was extracted from peripheral blood and polymorphic regions were amplified by nested PCR. Genotyping was performed by restriction fragments length polymorphisms. Time from disease onset to reach EDSS 6 and time to conversion to secondary progressive phase (SP) were used as variables of survival as well as percentage of patients that reached those endpoints. We used the log Rank test for data comparison (significant p ≤ 0.05). Results We found no differences between cases and controls in frequency of polymorphisms at the CD24 gene. 44.6% of patients with the AA genotype (P1626) reached an EDSS 6 vs 16% of patients with other genotypes (p < 0.001, HR 3.2, 95% CI 1.4 to 7.4). 45.8% of patients with the AA genotype reached SPMS vs 16.7% without this genotype (p < 0.001, HR 3.4, 95% CI 1.5 to 7.8). Conclusions This study showed a strong association between the presence of AA genotype in the 1626 polymorphism of the CD24 gene and the risk of disease progression in MS patients.
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