Improved magnetic charged system search optimization algorithm with application to satellite formation flying

This paper is devoted to the implementation and application of an improved version of the metaheuristic algorithm called magnetic charged system search. Some modifications and novelties are introduced and tested. Firstly, the authors’ attempt is to develop a self-adaptive and user-friendly algorithm which can automatically set all the preliminary parameters (such as the numbers of particles, the maximum iterations number) and the internal coefficients. Indeed, some mathematical laws are proposed to set the parameters and many coefficients can dynamically change during the optimization process based on the verification of internal conditions. Secondly, some strategies are suggested to enhance the performances of the proposed algorithm. A chaotic local search is introduced to improve the global best particle of each iteration by exploiting the features of ergodicity and randomness. Moreover, a novel technique is proposed to handle bad-defined boundaries; in fact, the possibility to self-enlarge the boundaries of the optimization variables is considered, allowing to achieve the global optimum even if it is located on the boundaries or outside. The algorithm is tested through some benchmark functions and engineering design problems, showing good results, followed by an application regarding the problem of time-suboptimal manoeuvres for satellite formation flying, where the inverse dynamics technique, together with the B-splines, is employed. This analysis proves the ability of the proposed algorithm to optimize control problems related to space engineering, obtaining better results with respect to more common and used algorithms in literature

Estudio experimental comparativo de la estabilidad de distintos tutores externos

Se investigó la rigidez de 11 diferentes montajes de tutores externos usando un modelo experimental con tibias cadavéricas a las cuales se realizaba una osteotomía transversal mediodiafisaria perpendicular al eje longitudinal del hueso, creando entre ambos segmentos una brecha de 35 mm, simulando una fractura. Mediante dispositivos de medición diseñados y construidos especialmente para este estudio se logró cuantificar los desplazamientos que se producen en el foco de fractura ante cargas de compresión axial, torsión y flexiones anteroposterior y mediolateral. Se determinó en cada ensayo la carga segura y carga máxima previamente definidas. La mayor rigidez a la compresión axial se observó en el tutor Orthofix a la torsión y a la flexión anteroposterior en el Kronner biplanar y a la flexión mediolateral en el tutor AO triangulado. Se determina la rigidez total porcentual de cada montaje como índice que representa el funcionamiento promedio del mismo en todas las modalidades de carga. Se consideran las indicaciones, ventajas, complicaciones y fundamentalmente la biología de la consolidación ósea en referencia a los fijadores externos. Se concluye sobre el cuidado con que debe ser conducida la carga de un miembro con fractura inestable, ya que la mayoría de los montajes permiten más de 1 mm de movimiento en la brecha de la fractura con una carga axial baja.The stiffness of 11 different device configurations of external fixation was investigated in an experimental model using human cadaveric tibia. After application of the different devices, a diaphyseal osteotomy allowing removal of a 35 mm bone segment was performed in the specimens. Displacements of the bone fragments at the osteotomy site induced by compresion loading, torsion, and both anteroposterior and mediolateral flexion were measured with dispositives designed for this experiment. Maximal load and that required for inducing 1 mm displacement were recorded. The higher stiffness corresponded to the Orthofix fixator in axial compression, the Kronner biplanar device in anteroposterior flexion, and the triangular configuration of the AO device in mediolateral flexion. A total stiffness index of each configuration as an average of the behavior against all loading modahties was obtained. The indications, advantages, complications and the biology of bone consolidation wien regards to external fixation are considered. As conclusion, progressive loading of the extremity with unstable fracture requires a close monitorization, since most of the device configurations analyzed allow more than 1 mm displacement of bone fragments at the fracture site, even with low axial loading

Emerging bone marrow microenvironment‐driven mechanisms of drug resistance in acute myeloid leukemia: Tangle or chance?

Acute myeloid leukemia (AML) has been considered for a long time exclusively driven by critical mutations in hematopoietic stem cells. Recently, the contribution of further players, such as stromal and immune bone marrow (BM) microenvironment components, to AML onset and progression has been pointed out. In particular, mesenchymal stromal cells (MSCs) steadily remodel the leukemic niche, not only favoring leukemic cell growth and development but also tuning their responsiveness to treatments. The list of mechanisms driven by MSCs to promote a leukemia drug-resistant phenotype has progressively expanded. Moreover, the relative proportion and the activation status of immune cells in the BM leukemic microenvironment may vary by influencing their reactivity against leukemic cells. In that, the capacity of the stroma to re‐program immune cells, thus promoting and/or hampering therapeutic efficacy, is emerging as a crucial aspect in AML biology, adding an extra layer of complexity. Current treatments for AML have mainly focused on eradicating leukemia cells, with little consideration for the leukemia‐damaged BM niche. Increasing evidence on the contribution of stromal and immune cells in response to therapy underscores the need to hold the mutual interplay, which takes place in the BM. A careful dissection of these interactions will help provide novel applications for drugs already under experimentation and open a wide array of opportunities for new drug discovery

Endothelialization of a New Dacron Graft in an Experimental Model: Light Microscopy, Electron Microscopy and Immunocytochemistry

Two types of synthetic vascular grafts, Dacron Triaxial and Dacron Gelseal Triaxial, were implanted into both the common carotids of sheep. The animals were sacrificed 1, 2, 8, and 16 weeks after surgery. Multiple specimens, obtained from grafts and anastomoses, were studied by light microscopy, transmission and scanning electron microscopy. A parallel immunocytochemical analysis was performed on some specimens. Dacron Triaxial grafts failed to develop a complete neointimal coverage. Myofibroblasts and fibroblasts were the dominant cells in such synthetic graft. Moreover, focal areas of stripping, platelet deposition, and thrombosis were observed at 8 and 16 weeks. In contrast, a stable endothelial coverage developed on the Gelseal Triaxial grafts after 16 weeks

Healing of Prosthetic Arterial Grafts

Numerous synthetic biomaterials have been developed as vascular substitutes. In vitro, ex vivo and in vivo studies have demonstrated that in animals, selected materials, i.e., Dacron and ePTFE (expanded polytetrafluoroethylene) grafts, are successfully incorporated in both the large and the small caliber host arteries through a process which is generally referred to as graft healing. Morphologically, this process consists of a series of complex events including fibrin deposition and degradation, monocyte-macrophage recruitment and flow-oriented cell-layer generation, this last event being the complete endothelialization of the arterial substitute. In contrast to experimental animals, the flow surface of synthetic vascular grafts remains unhealed in humans, particularly in the small caliber conduits. Healing in man consists of graft incorporation by the perigraft fibrous tissue response with a surface covered by more or less compacted, cross-linked fibrin. It is therefore obvious that: i) marked differences in graft healing exist between animals and man; and ii) the usual mechanisms of graft endothelialization are partially ineffective in man. In order to guarantee the patency of synthetic vascular grafts for human small artery bypass, new strategies and approaches have recently been attempted. In particular, the endothelial cell seeding approach has been successfully accomplished in animals and is being experimented in human clinical studies. The problems and results of this biological approach are outlined in this paper

PGE2-Induced IDO1 Inhibits the Capacity of Fully Mature DCs to Elicit an In Vitro Antileukemic Immune Response.

In the last years, dendritic cells (DC) have been evaluated for antitumor vaccination. Although DC-based vaccines have raised great expectations, their clinical translation has been largely disappointing. For these results, several explanations have been proposed. In particular, the concomitant expression by DCs of tolerogenic pathways, such as the immunosuppressive agent indoleamine 2,3-dioxygenase-1 (IDO1), has been demonstrated. The aim of this study is to evaluate both the stimulatory and the tolerogenic feature of monocyte-derived DCs (Mo-DCs) after maturation with PGE2. In particular, the role of IDO1 expression in PGE2-matured Mo-DCs has been addressed. Here we show that PGE2, which is required for full maturation of DCs, is one mediator of DC tolerance by enhancing IDO1. PGE2-mediated expression of IDO1 results in the production of kynurenine, in the generation of Tregs, and in the inhibition of either the allogeneic or the autologous antigen-specific stimulatory capacity of DCs. When pulsed with leukemic lysates and matured with PGE2, DCs are impaired in the induction of IFN-γ secreting CD4(+) and CD8(+) T cells due to IDO1 upregulation. Moreover, the inhibition of IDO1 enhances the antileukemic response. Overall, these results point toward the use of IDO1 inhibitors to enhance the vaccination capacity of DCs, matured with PGE2

Sunitinib Exerts In Vitro Immunomodulatory Activity on Sarcomas via Dendritic Cells and Synergizes With PD-1 Blockade

Background: High-grade sarcomas are a heterogeneous group of aggressive tumors arising in bone and soft tissues. After relapse, treatment options are limited. The multi-targeted receptor tyrosine kinase inhibitors (TKIs) sunitinib and inhibitor of PD-1 (anti-PD-1) nivolumab have shown antitumor activity in selected subtypes. In this study, we examine the role of TKIs and PD-1 based therapy in in vitro cocultures of sarcoma. Methods: The human osteosarcoma (SaOS-2) and synovial sarcoma (SYO-1) cell lines were treated with sunitinib. After cell death and proliferation assessment, expression of PD-L1 was analyzed by flow cytometry. Sunitinib-treated sarcoma cells were cocultured with dendritic cells (DCs), and the phenotype of mature DCs was determined by flow cytometry. Mature DCs were cultured with autologous T cells. PD-1 expression on T cells, their proliferation, T regulatory cell (Tregs) induction and IFN-γ production, before and after nivolumab exposure, were analyzed. Results: Along with its anti-proliferative and direct pro-apoptotic effect on sarcoma cell lines, sunitinib prompted PD-L1 upregulation on sarcoma cells. Interestingly, sunitinib-treated sarcoma cells drive DCs to full maturation and increase their capacity to induce sarcoma-reactive T cells to produce IFN-γ. Conversely, no effect on T cell proliferation and T cell subpopulation composition was observed. Moreover, both bone and synovial sarcoma cell lines induced Tregs through DCs but sunitinib treatment completely abrogated Treg induction. Finally, sarcoma cell lines induced PD-1 upregulation on both effector T cells and Tregs when loaded into DCs, providing a rationale for using PD-1 blockade. Indeed, PD-1 blockade by nivolumab synergized with sunitinib in inducing IFN-γ-producing effector T cells. Conclusions: Taken together, our in vitro data indicate that the treatment of sarcoma cells with sunitinib can exert significant changes on immune cell subsets toward immune activation, leading to DC-based cross-priming of IFN-γ-producing effector T cells and reduced Treg induction. PD-1 blockade with nivolumab has a synergistic effect with sunitinib, supporting the use of TKI and anti-PD-1 approach in sarcomas, and perhaps in other cancers. DC-targeted drugs, including toll-like receptor 3 inhibitors and CD47 inhibitors, are under development and our preclinical model might help to better design their clinical application

Characterization of symbolic play in deaf children: case and control studies

BACKGROUND: children with hearing loss do not acquire language at the same time nor at the same rate of normal hearing children because the learning process of oral language is essentially auditory. Child development consists in gradually acquiring motor and psychocognitive abilities. Entering the symbolic world is decisive for the child to reach higher levels of linguistic complexity. AIM: to correlate symbolic play and aspects of child development in deaf children and in hearing children. METHOD: participants of this study were 32 children, of both genders, with ages between 2 and 6 years, age matched. All participants were submitted to the Evaluation of Symbolic Maturation and to the Denver Developmental Screening Test II. Sixteen participants presented moderate to profound sensory-neural hearing loss and composed the research group (RG); the remaining 16 children had normal hearing and composed the control group (CG). RESULTS: symbolism was observed in the play of 81.25% of RG and in 87.5% of CG. In the Denver Developmental Screening Test II, 100% of the RG was classified as being at risk. As for the CG, 94% of the children were classified as normal and the remaining 6% as being at risk (p<0.001). CONCLUSION: a similar performance was observed between the groups for symbolic play. However, in a qualitative analysis, the RG presented less complex symbolic play than the CG. It was observed that the RG presented a performance in the symbolic play compatible to its performance in aspects of personal-social, refined motor and gross motor control in the Denver Developmental Screening Test II.TEMA: crianças deficientes auditivas não adquirem linguagem no mesmo período e velocidade de uma criança normo-ouvinte, pois o aprendizado da linguagem oral é um evento essencialmente auditivo. O desenvolvimento da criança consiste na aquisição progressiva de habilidades motoras e psicocognitivas, e a entrada no mundo simbólico é fator preponderante para que a criança possa atingir os níveis de maior complexidade no domínio da linguagem. OBJETIVO: relacionar o jogo simbólico e aspectos do desenvolvimento infantil em crianças deficientes auditivas com seus pares ouvintes. MÉTODO: 32 crianças, de ambos os sexos, de 2 a 6 anos de idade, pareadas por idade, foram submetidas à Avaliação da Maturidade Simbólica e ao Teste de Triagem do Desenvolvimento de Denver II, sendo 16 deficientes auditivas neurossensorial de grau moderado a profundo (grupo pesquisa - GP) e 16 normo-ouvintes (grupo controle - GC). RESULTADOS: observou-se simbolismo na brincadeira de 81,25% do GP, enquanto que no GC isto ocorreu em 87,5%. No Teste de Denver II 100% do GP foi classificado como risco, e o GC apresentou 94% de crianças normais e 6% de risco (p < 0,001). CONCLUSÃO: observou-se desempenho semelhante nos dois grupos quanto ao jogo simbólico. Entretanto, numa análise qualitativa, o GP apresentou brincadeiras menos complexas que o GC. Observou-se que o GP apresentou desempenho no jogo simbólico compatível ao seu desempenho nos aspectos pessoal-social, motor fino-adaptativo e motor grosseiro do Teste de Denver II.Universidade de São PauloCentro de Estudos da VozUniversidade Federal do Rio Grande do SulUNIFESP-EPM Departamento de Fonoaudiologia da Disciplina de Distúrbios da Comunicação HumanaUNIFESP, EPM, Depto. de Fonoaudiologia da Disciplina de Distúrbios da Comunicação HumanaSciEL

Prediction of vascular aging based on smartphone acquired PPG signals

Photoplethysmography (PPG) measured by smartphone has the potential for a large scale, non-invasive, and easy-to-use screening tool. Vascular aging is linked to increased arterial stiffness, which can be measured by PPG. We investigate the feasibility of using PPG to predict healthy vascular aging (HVA) based on two approaches: machine learning (ML) and deep learning (DL). We performed data preprocessing, including detrending, demodulating, and denoising on the raw PPG signals. For ML, ridge penalized regression has been applied to 38 features extracted from PPG, whereas for DL several convolutional neural networks (CNNs) have been applied to the whole PPG signals as input. The analysis has been conducted using the crowd-sourced Heart for Heart data. The prediction performance of ML using two features (AUC of 94.7%) \u2013 the a wave of the second derivative PPG and tpr, including four covariates, sex, height, weight, and smoking \u2013 was similar to that of the best performing CNN, 12-layer ResNet (AUC of 95.3%). Without having the heavy computational cost of DL, ML might be advantageous in finding potential biomarkers for HVA prediction. The whole workflow of the procedure is clearly described, and open software has been made available to facilitate replication of the results

Development of a Rotation Device for Microvascular Endothelial Cell Seeding

A rotation device (RD) specifically designed to achieve sterile endothelial cell (EC) seeding of vascular grafts has been developed. The basic characteristics of the RD include: small dimensions, fully autoclavable components, and perfectly sealed graft holders. These features make it possible to maintain sterility during all the steps of EC seeding. This was documented by negativity of all bacteriological assays performed . Moreover, the RD can simultaneously support three vascular grafts with different lengths (20, 40, and 60 cm) and diameters (4-8 mm). EC seeding is performed in the climatized chamber (37 °C; 5 % C02) with constant rotation (0.1 -3 rpm). The rotation cycle can be completed automatically. The practical efficacy of the RD was investigated by seeding 2 x 105/cm2 of human microvascular EC on 20 cm length, 4 mm internal diameter (ID) fibronectin- coated polytetrafluoroethylene (ePTFE) grafts for 24 and 48 hours respectively . Further, the effect of a highly viscous plasma expander, i.e., haemagel, on cell retention was also evaluated. Results were not as favorable as expected. However, it should be emphasized that after 48 hours of eel! incubation by using the RD, 42 % of the initially seeded EC were still present and approximately 15 % were fully spread over the graft surface. Moreover, the 10 minute perfusion with haemagel did not decrease the number of adherent microvascular EC