Bifurcation of limit cycle from a n-dimensional linear center inside a class of piecewise linear differential systems

Agraïments: The two first authors are partially supported by a FAPESP-BRAZIL grant 2007/07957-8 and grant 2007/08707-5 respec- tively.Let n be an even integer. We study the bifurcation of limit cycles from the periodic orbits of the n-dimensional linear center given by the differential system x˙ 1 = −x2, x˙ 2 = x1, . . . , x˙ n−1 = −xn, x˙ n = xn−1, perturbed inside a class of piecewise linear differential systems. Our main result shows that at most (4n − 6)n/2−1 limit cycles can bifurcate up to first-order expansion of the displacement function with respect to a small parameter. For proving this result we use the averaging theory in a form where the differentiability of the system is not needed

Multiself-loop Lackadaisical Quantum Walk with Partial Phase Inversion

Quantum walks are the quantum counterpart of classical random walks and provide an intuitive framework for building new quantum algorithms. The lackadaisical quantum walk, which is a quantum analog of the lazy random walk, is obtained by adding a self-loop transition to each state allowing the walker to stay stuck in the same state, being able to improve the performance of the quantum walks as search algorithms. However, the high dependence of a weight $l$ makes it a key parameter to reach the maximum probability of success in the search process. Although many advances have been achieved with search algorithms based on quantum walks, the number of self-loops can also be critical for search tasks. Believing that the multiple self-loops have not yet been properly explored, this article proposes the quantum search algorithm Multiself-loop Lackadaisical Quantum Walk with Partial Phase Inversion, which is based on a lackadaisical quantum walk with multiple self-loops where the target state phase is partially inverted. Each vertex has $m$ self-loops, with weights $l' = l/m$, where $l$ is a real parameter. The phase inversion is based on Grover's algorithm and acts partiality, modifying the phase of a given quantity $s \leqslant m$ of self-loops. On a hypercube structure, we analyzed the situation where $s=1$ and $1 \leqslant m \leqslant 30$ and investigated its effects in the search for 1 to 12 marked vertices. Based on two ideal weights $l$ used in the literature, we propose two new weight values. As a result, with the proposal of the Multiself-loop Lackadaisical Quantum Walk with partial phase inversion of target states and the new weight values for the self-loop, this proposal improved the maximum success probabilities to values close to 1. This article contributes with a new perspective on the use of quantum interferences in the construction of new quantum search algorithms.Comment: 16 pages, 4 figures, 3 table

Potential of silicon fertilization in the resistance of chestnut plants toink disease(Phytophthora cinnamomi)

The European chestnut (Castanea sativa Mill.) is a specie with great economic importance in Europe that have been present for thousands of years. In Portugal, the chestnut helps to maintain a positive trade balance, by contributing to the gross national product (GDP). One of the biggest threats for the chestnut is the ink disease caused by Phytophthoracinnamomi, this disease is problematic to chestnut crop with a damaging impact. Silicon (Si) is classified as a beneficial nutrient, having the ability to make plants more resistant to attacks by pathogens. Studies on the effect of silicon on chestnut are practically non-existent, so the aim of this study was to evaluate the impact of silicon in the resistance of chestnut plants to P. cinnamomi. The plants were treated by 0 mM, 5 mM, 7.5mM and 10 mM SiK® with the analyzed mad at 0, 15 and 30 days after inoculation by P. cinnamomi. These findings showed that the Si-treated plants had higher survival rate resulted from the presence of phytoliths in root tissues, that acted as a mechanical barrier reducing the development of pathogenic structures and they arealso associated with the improvement on antioxidant activity through the increase of CAT and SOD, higher values of total phenols compounds and less oxidative damage. The presence of Si in PDA medium reduced the growth of P. cinnamomi all over the time, presenting high PI. This work shows that the Si fertilization in chestnut plants contributes to increase the resistance against P. cinnamomi infection

Investigation of cell adhesion in chitosan membranes for peripheral nerve regeneration

Peripheral nerve injuries have produced major concerns in regenerative medicine for several years, as the recovery of normal nerve function continues to be a significant clinical challenge. Chitosan (CHT), because of its good biocompatibility, biodegradability and physicochemical properties, has been widely used as a biomaterial in tissue engineering scaffolding. In this study, CHT membranes were produced with three different Degrees of Acetylation (DA), envisioning its application in peripheral nerve regeneration. The three CHT membranes (DA I: 1%, DA II: 2%, DA III: 5%) were extensively characterized and were found to have a smooth and flat surface, with DA III membrane having slightly higher roughness and surface energy. All the membranes presented suitable mechanical properties and did not show any signs of calcification after SBF test. Biodegradability was similar for all samples, and adequate to physically support neurite outgrowth. The in vitro cell culture results indicate selective cell adhesion. The CHT membranes favoured Schwann cells invasion and proliferation, with a display of appropriate cytoskeletal morphology. At the same time they presented low fibroblast infiltration. This fact may be greatly beneficial for the prevention of fibrotic tissue formation, a common phenomenon impairing peripheral nerve regeneration. The great deal of results obtained during this work permitted to select the formulation with the greatest potential for further biological tests.This work has received funding from the European Community's Seventh Framework Programme (FP7-HEALTH-2011) under grant agreement no 278612 (BIOHYBRID). This study was also funded by European Union's FP7 Programme under grant agreement no REGPOT-CT2012-316331-POLARIS.The authors thank the chitosan raw material provided by Altakitin S.A., (Lisboa, Portugal). We are further thankful to Silke Fischer, Natascha Heidrich, Kerstin Kuhlemann, Jennifer Metzen, Hildegard Streich and Maike Wesemann (all from the Institute of Neuroanatomy, Hannover Medical School) for their technical support

Bioprocess integration for human mesenchymal stem cells: from up to downstream processing scale-up to cell proteome characterization

Human mesenchymal stem cells (hMSC) are relevant cell-based products for autologous and allogeneic therapies. To deliver the required cell numbers and doses to therapy, scaling up production and purification processes (at least to the liter-scale) while ensuring high purity, viability and maintaining cells’ critical quality attributes (CQA) and functionality is essential [1]. Therefore, the aim of this work was to prove scalability of an integrated streamlined bioprocess compatible with current good manufacturing practices (cGMP) comprised by cell expansion, harvesting and volume reduction unit operations using human mesenchymal stem cells (hMSC) isolated from bone marrow (BM-MSC) and adipose tissues (AT-MSC). BM-MSC and AT-MSC expansion and harvesting steps were scaled-up from spinner flasks to 2 L scale stirred tank single-use bioreactor using synthetic microcarriers and xeno-free medium, ensuring high cellular volumetric productivities (50 x 106 cell.L-1.day-1), expansion factors (14 - 16 fold) and cell recovery yields (80%). For the concentration step, flat sheet cassettes (FSC) and hollow fiber cartridges (HF) were compared showing a fairly linear scale-up, with a need to slightly decrease the permeate flux (30 - 50 LMH, respectively) to maximize cell recovery yield. Nonetheless, FSC allowed to recover 18% more cells after a volume reduction factor of 50. Overall, at the end of the entire bioprocess more than 65% of viable (\u3e 95%) hMSC could be recovered without compromising cell’s CQA of viability, identity and differentiation potential. “Omic” tools in combination with standard analytical assays allow for a better cell characterization, increasing product and process understanding [2] and are thus fundamental for process development. Thus, alongside the standard quality assays for evaluating hMSC’s CQA, a proteomics workflow based on mass spectrometry tools was established to characterize the impact of processing on hMSC’ CQA. Overall, through sensitivity, robustness and throughput, this type of workflow provided the identification of specific signatures of the final product. Therefore, it proves to be essential to understand the cells’ final quality as well as to evaluate the impact of manufacturing at different stages of processing. References: [1] Pattasseril J et al, BioProcess Int. 2013, 3, 38–46. [2] Campbell A et al, Stem Cells Transl. Med. 2015, 4, 1155–1163. The authors acknowledge UniMS – Mass Spectrometry Unit team (ITQB-NOVA/iBET, Oeiras, Portugal), iNOVA4Health Research Unit (LISBOA-01-0145-FEDER-007344), and Fundação para a Ciência e Tecnologia (FCT, Portugal) for funding the project CARDIOSTEM (MITP-TB/ECE/0013/2013), and the grants SFRH/BD/51940/2012 (MIT-Portugal), SFRH/BD/52302/2013, SFRH/BD/52481/2014, SFRH/BPD/86513/201

Engineering scalable manufacturing of high-quality human MSC for cell therapy: From up to downstream processing integration to cell proteome characterization

Human mesenchymal stem cells (hMSC) are relevant cell therapy products for autologous and allogeneic therapies. To deliver the required cell numbers and doses to therapy, scaling up production and purification processes (at least to the liter-scale) while ensuring high purity, viability and maintaining cells’ critical quality attributes (CQA) and functionality is essential. Therefore, the aim of this work was to prove scalability of an integrated streamlined bioprocess compatible with current good manufacturing practices (cGMP) comprised by cell expansion, harvesting, volume reduction and washing unit operations using human mesenchymal stem cells (hMSC) isolated from bone marrow (BM-MSC) and adipose tissues (AT-MSC). Single-use technologies were adopted at different steps of the manufacturing workflow to support process integration and scale-up. BM-MSC and AT-MSC expansion and harvesting steps were scaled-up from spinner flasks to 2 L single-use stirred tank bioreactor using synthetic microcarriers and xeno-free medium, ensuring high cellular volumetric productivities (50 x 106 cell.L-1.day-1), expansion factors (14 - 16 fold) and cell recovery yields (\u3e80%). For the volume reduction and washing steps, flat sheet cassettes (FSC) and hollow fiber cartridges (HF) were compared showing a fairly linear scale-up, with a need to slightly decrease the permeate flux (30 - 50 LMH, respectively) to maximize cell recovery yield. Nonetheless, FSC performed better allowing recovering 18% more cells after a volume reduction factor of 50 without compromising cell’s CQA of viability, identity and differentiation potential. “Omic” tools in combination with standard analytical assays allow for a better cell characterization, increasing product and process understanding and are thus fundamental for process development. Thus, alongside the standard quality assays for evaluating hMSC’s CQA, a proteomics workflow based on mass spectrometry tools was established to characterize the impact of processing on hMSC’ CQA. Overall, through sensitivity, robustness and throughput, this type of workflow provided the identification of specific signatures of the final product. Therefore, it proves to be essential to understand the cells’ final quality as well as to evaluate the impact of manufacturing at different stages of processing. The authors acknowledge UniMS – Mass Spectrometry Unit team (ITQB-NOVA/iBET, Oeiras, Portugal), iNOVA4Health Research Unit (LISBOA-01-0145-FEDER-007344), and Fundação para a Ciência e Tecnologia (FCT, Portugal) for funding the project CARDIOSTEM (MITP-TB/ECE/0013/2013), and the grants SFRH/BD/51940/2012 (MIT-Portugal), SFRH/BD/52302/2013, SFRH/BD/52481/2014, SFRH/BPD/86513/2012

2-(4-Methyl­phen­yl)-1H-anthraceno[1,2-d]imidazole-6,11-dione: a fluorescent chemosensor

In the title compound, C22H14N2O2, the five rings of the mol­ecule are not coplanar. There is a significant twist between the four fused rings, which have a slightly arched conformation, and the pendant aromatic ring, as seen in the dihedral angle of 13.16 (8)° between the anthraquinonic ring system and the pendant aromatic ring plane

Selection and phenotypic divergence in pau de balsa of different origins.

Abstract: Pau de balsa is a forest species that is native to the Amazon and stands out for its rapid growth, being an option for a productive and profitable activity. The objective of this study was to select phenotypically superior pau de balsa trees and verify the dissimilarity between them and their respective origins in order to identify individuals for wood production. Three distinct populations trees in plantations of pau de balsa implanted in January 2011 in the municipality of Guarantã do Norte, Mato Grosso, Brazil, were evaluated as to their characteristics of commercial importance. Among the trees evaluated, highlight the genotype A09 as a candidate for the matrix in breeding programs of the species due to its superiority in the characteristics of diameter at breast height and total height. Genotypes A09 and IF03 are the most genetically distant and S02 and S09 the most similar. The principal component analysis explained 81.24% of all the variance of the characteristics analyzed in the first two variables. With the results obtained, it was possible to identify the superior characteristics of the Ecuadorian genotypes A01, A09 and A14; the first two present good characteristics for wood production, and the third presents the lowest basic density of wood. | Resumo: O pau de balsa é uma espécie florestal nativa da Amazônia, e destaca-se pelo rápido crescimento e, portanto, considerada como uma opção de atividade produtiva e rentável. Objetivou-se neste estudo selecionar árvores de pau de balsa superiores fenotipicamente e verificar a dissimilaridade entre elas e suas respectivas origens, afim de identificar indivíduos para a produção de madeira. Foram avaliadas as árvores de plantios de pau de balsa implantado em janeiro de 2011 no município de Guarantã do Norte, Mato Grosso, Brasil, em três populações distintas e avaliadas características de importância comercial. Entre as árvores avaliadas podemos destacar o genótipo A09 como um candidato à matriz em programas de melhoramento da espécie, devido à superioridade nas características de diâmetro à altura do peito e altura total. Os genótipos A09 e IF03 são os mais distantes geneticamente e S02 e S09 os mais similares. A análise de componentes principais explicou 81,24% de toda a variância das características analisadas logo nas duas primeiras variáveis. Com os resultados obtidos foi possível selecionar os genótipos equatorianos A01, A09 e A14, os dois primeiros por apresentar boas características para a produção de madeira, e o terceiro por apresentar a menor densidade básica da madeira