Adaptive multibeam phased array design for a Spacelab experiment

The parametric tradeoff analyses and design for an Adaptive Multibeam Phased Array (AMPA) for a Spacelab experiment are described. This AMPA Experiment System was designed with particular emphasis to maximize channel capacity and minimize implementation and cost impacts for future austere maritime and aeronautical users, operating with a low gain hemispherical coverage antenna element, low effective radiated power, and low antenna gain-to-system noise temperature ratio

Comparison of pure and mixed gas permeation of the highly fluorinated polymer of intrinsic microporosity PIM-2 under dry and humid conditions: Experiment and modelling

This manuscript describes the gas separation performance of PIM-2, a partially fluorinated linear copolymer synthesized from 5,5',6,6'-tetrahydroxy-3,3,3',3'-tetramethylspirobisindane (TTSBI) and decafluorobiphenyl (DFBP). As one of the early members of the family of polymers of intrinsic microporosity, it had never been tested as a gas separation membrane because of insufficient mechanical resistance. This has been solved only recently, allowing the preparation of robust self-standing films. Molecular modelling studies demonstrated a high fractional free volume (34%) and an elevated surface area (642 m2 g-1), and the latter is in good agreement with experimental BET results. Pure gas permeabilities measured on a fixed-volume time-lag instrument at 1 bar compare well with the results of mixed separation tests on a variable volume setup from 1-6 bar(a). Molecular modelling and independent sorption measurements on a gravimetric sorption balance both show strong dual-mode sorption behaviour, especially for CO2 and to a lesser extent for CH4. Temperature-dependent pure gas permeation measurements show typical Arrhenius behaviour, with a clear increase in the activation energy for diffusion with the increasing molecular size of the gas, indicating high size-selectivity. This is in agreement with the highly rigid PIM structure, determined by AFM force spectroscopy measurements. The dual-mode behaviour results in a moderate pressure dependence of the CO2 permeability and the CO2/N2 and CO2/CH4 selectivity, all slightly decreasing with increasing pressure. The presence of humidity in the gas stream has a remarkable small effect on the membrane performance, which is probably due to the high fluorine content and the consequently low water vapour solubility in the polymer, as confirmed by gravimetric sorption measurements. The manuscript describes an extensive study on the structure-property relationships in PIM-2. © 2019 Elsevier B.V.European Commission, EC Grantová Agentura Ceské Republiky, GA Ä?R: 18-05484S --Research on biogas upgrading presented in this work was supported by EU structural funding in the frame of Operational Programme Research, Development and Education, project No. CZ.02.1.01./0.0/0.0/17_049/0008419 “COOPERATION”. This work was further supported by the CNR-CAS bilateral agreement 2016–2018 “Innovative polymeric membranes for pervaporation and advanced gas and vapour separations” and by the Czech Science Foundation (grant no. 18-05484S ). Appendix A -

Determination of carbonyl compounds in exhaled breath by on-sorbent derivatization coupled with thermal desorption and gas chromatography-tandem mass spectrometry

A reliable method for the determination of carbonyl compounds in exhaled breath based on on-sorbent derivatization coupled with thermal desorption and gas chromatography-tandem mass spectrometry is described. The analytical performances were optimized for a mixture of C2-C9 aldehydes and C3-C9 ketones, particularly interesting for clinical applications, by using an internal standard and applying a 2^3 full factorial design. A volume of sample (250 ml) was loaded at 50 ml min-1 into a Tenax GR sorbent tube containing 130 nmol of O-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine hydrochloride. All compounds showed a limit of detection lower than 200 pptv. The yield of the derivatization procedure was normalized by adding to the sample a known amount of 6D-acetone as an internal standard. This allowed halving the relative standard deviation to 10% and 15% for the mono-and di-carbonyl compounds, respectively, thus improving reliability. The optimized method was applied to the determination of carbonyl compounds in 12 breath samples collected from four patients suffering from heart failure during hospitalization

Adipogenesis of skeletal muscle fibro/adipogenic progenitors is affected by the WNT5a/GSK3/β-catenin axis

Fibro/Adipogenic Progenitors (FAPs) are muscle-interstitial progenitors mediating pro-myogenic signals that are critical for muscle homeostasis and regeneration. In myopathies, the autocrine/paracrine constraints controlling FAP adipogenesis are released causing fat infiltrates. Here, by combining pharmacological screening, high-dimensional mass cytometry and in silico network modeling with the integration of single-cell/bulk RNA sequencing data, we highlighted the canonical WNT/GSK/β-catenin signaling as a crucial pathway modulating FAP adipogenesis triggered by insulin signaling. Consistently, pharmacological blockade of GSK3, by the LY2090314 inhibitor, stabilizes β-catenin and represses PPARγ expression abrogating FAP adipogenesis ex vivo while limiting fatty degeneration in vivo. Furthermore, GSK3 inhibition improves the FAP pro-myogenic role by efficiently stimulating, via follistatin secretion, muscle satellite cell (MuSC) differentiation into mature myotubes. Combining, publicly available single-cell RNAseq datasets, we characterize FAPs as the main source of WNT ligands inferring their potential in mediating autocrine/paracrine responses in the muscle niche. Lastly, we identify WNT5a, whose expression is impaired in dystrophic FAPs, as a crucial WNT ligand able to restrain the detrimental adipogenic differentiation drift of these cells through the positive modulation of the β-catenin signaling

Inter and intra-tumor heterogeneity of paediatric type diffuse high-grade gliomas revealed by single-cell mass cytometry

Paediatric-type diffuse high-grade gliomas (PDHGG) are aggressive tumors affecting children and young adults, with no effective treatment. These highly heterogeneous malignancies arise in different sites of the Central Nervous System (CNS), carrying distinctive molecular alterations and clinical outcomes (inter-tumor heterogeneity). Moreover, deep cellular and molecular profiling studies highlighted the coexistence of genetically and phenotypically different subpopulations within the same tumor mass (intra-tumor heterogeneity). Despite the recent advances made in the field, the marked heterogeneity of PDHGGs still impedes the development of effective targeted therapies and the identification of suitable biomarkers. In order to fill the existing gap, we used mass cytometry to dissect PDHGG inter- and intra-heterogeneity. This is one of the most advanced technologies of the “-omics” era that, using antibodies conjugated to heavy metals, allows the simultaneous measurement of more than 40 markers at single-cell level. To this end, we analyzed eight PDHGG patient-derived cell lines from different locational and molecular subgroups. By using a panel of 15 antibodies, directly conjugated to metals or specifically customized to detect important histone variants, significant differences were highlighted in the expression of the considered antigens. The single-cell multiparametric approach realized has deepened our understanding of PDHGG, confirming a high degree of intra- and inter-tumoral heterogeneity and identifying some antigens that could represent useful biomarkers for the specific PDHGG locational or molecular subgroups

A GNR e as Operações de Apoio à Paz: Legitimidade e limites de actuação

O presente trabalho de investigação aplicada está subordinado ao tema: ―A GNR e as Operações de Apoio à Paz: Legitimidade e Limites de Actuação‖. As operações de apoio à paz são uma realidade do mundo actual e a participação da GNR nestas operações tem sido uma constante. Neste sentido, a legitimidade desta participação tem sido ao longo dos anos questionada, tese esta que é debatida neste trabalho. Para além da legitimidade, são também aqui debatidos quais são os limites de actuação desta força militar em operações deste tipo. Neste contexto, desenvolve-se um estudo através da pergunta de partida: "De que forma a participação nas OAP é importante para a GNR? E para o País?." Os principais objectivos do trabalho são responder às perguntas supra mencionadas, verificar a legitimidade da participação da GNR neste tipo de operações, compreender o conceito das regras de empenhamento e a sua criação e, finalmente , identificar a importância destas regras para a decisão de um comandante. O trabalho iniciou-se com uma fase exploratória, procedendo-se em seguida à pesquisa com particular incidência em livros, legislação e textos relacionados com o tema, tendo sido tam bém utilizada a internet como fontes de informação sobre as operações de apoio à paz. A investigação de campo baseou-se na análise de conteúdo das entrevistas efectuadas, o que permitiu responder às perguntas de investigação através da verificação das hipó teses formuladas. Após a análise dos dados, conclui-se que a GNR tem legitimidade para participar nestas operações, o que está contemplado na sua lei orgânica, e que, em simultâneo, estas participações revelam elevada importância não só para a GNR como para o País. No entanto, para que exista uma melhor preparação das forças que executam estas missões será necessário que o novo Centro de Treino e Aprontamento para Forças de Missões Internacionais entre em funcionamento com uma estrutura diferente da planeada. O presente trabalho foi realizado entre Janeiro e Março de 2009.Abstract This investigation project was developed under the theme: ―The GNR (Portuguese Republican National Guard) and the Peace Operations: Legitimacy and Action Limits. The peace-support operations are a reality in our contemporary world and the GNR's participation in these operations has been a constant. Considering this, the legitimacy of such participations has been questioned over the years, fact that led to the thesis discussed along this work. In addition to legitimacy, the limits of military force in such operations are also debated. In this context, this project was based on two former question s: "What is the meaning of the GNR participation in the peace operations? And for the country?". The main goals of the project are answering the questions above, confirming the legitimacy of GNR's participation in such operations, understanding the rules of engagement and its creation and, at last, identifying the rules importance for a commander’s decision. The project began with an exploratory phase, followed by a research work supported by books, legislation and texts on the subject as well as the Internet as sources of information on peace-support operations. The field research was developed by analysing the conducted interviews, which allowed the research to answer the questions while checking the assumptions previously made. After analyzing the data, it is concluded that the GNR is entitled to participate in these operations, which is included in its organic law, and, simultaneously, these actions reveal high importance not only for the GNR but for the country also. Nevertheless, in order to get a better preparation of the forces that will carry out these missions, changes in structure and functioning of the new Training Centre are needed. This work was developed from January to March 2009

Ejection of damaged mitochondria and their removal by macrophages ensure efficient thermogenesis in brown adipose tissue

Recent findings have demonstrated that mitochondria can be transferred between cells to control metabolic homeostasis. Although the mitochondria of brown adipocytes comprise a large component of the cell volume and undergo reorganization to sustain thermogenesis, it remains unclear whether an intercellular mitochondrial transfer occurs in brown adipose tissue (BAT) and regulates adaptive thermogenesis. Herein, we demonstrated that thermogenically stressed brown adipocytes release extracellular vesicles (EVs) that contain oxidatively damaged mitochondrial parts to avoid failure of the thermogenic program. When re-uptaken by parental brown adipocytes, mitochondria-derived EVs reduced peroxisome proliferator-activated receptor-γ signaling and the levels of mitochondrial proteins, including UCP1. Their removal via the phagocytic activity of BAT-resident macrophages is instrumental in preserving BAT physiology. Depletion of macrophages in vivo causes the abnormal accumulation of extracellular mitochondrial vesicles in BAT, impairing the thermogenic response to cold exposure. These findings reveal a homeostatic role of tissue-resident macrophages in the mitochondrial quality control of BAT

Decellularised skeletal muscles allow functional muscle regeneration by promoting host cell migration

Pathological conditions affecting skeletal muscle function may lead to irreversible volumetric muscle loss (VML). Therapeutic approaches involving acellular matrices represent an emerging and promising strategy to promote regeneration of skeletal muscle following injury. Here we investigated the ability of three different decellularised skeletal muscle scaffolds to support muscle regeneration in a xenogeneic immune-competent model of VML, in which the EDL muscle was surgically resected. All implanted acellular matrices, used to replace the resected muscles, were able to generate functional artificial muscles by promoting host myogenic cell migration and differentiation, as well as nervous fibres, vascular networks, and satellite cell (SC) homing. However, acellular tissue mainly composed of extracellular matrix (ECM) allowed better myofibre three-dimensional (3D) organization and the restoration of SC pool, when compared to scaffolds which also preserved muscular cytoskeletal structures. Finally, we showed that fibroblasts are indispensable to promote efficient migration and myogenesis by muscle stem cells across the scaffolds in vitro. This data strongly support the use of xenogeneic acellular muscles as device to treat VML conditions in absence of donor cell implementation, as well as in vitro model for studying cell interplay during myogenesis

Measurement of Warfarin in the Oral Fluid of Patients Undergoing Anticoagulant Oral Therapy

BACKGROUND: Patients on warfarin therapy undergo invasive and expensive checks for the coagulability of their blood. No information on coagulation levels is currently available between two controls. METHODOLOGY: A method was developed to determine warfarin in oral fluid by HPLC and fluorimetric detection. The chromatographic separation was performed at room temperature on a C-18 reversed-phase column, 65% PBS and 35% methanol mobile phase, flow rate 0.7 mL/min, injection volume 25 µL, excitation wavelength 310 nm, emission wavelength 400 nm. FINDINGS: The method was free from interference and matrix effect, linear in the range 0.2-100 ng/mL, with a detection limit of 0.2 ng/mL. Its coefficient of variation was <3% for intra-day measurements and <5% for inter-day measurements. The average concentration of warfarin in the oral fluid of 50 patients was 2.5±1.6 ng/mL (range 0.8-7.6 ng/mL). Dosage was not correlated to INR (r = -0.03, p = 0.85) but positively correlated to warfarin concentration in the oral fluid (r = 0.39, p = 0.006). The correlation between warfarin concentration and pH in the oral fluid (r = 0.37, p = 0.009) confirmed the importance of pH in regulating the drug transfer from blood. A correlation between warfarin concentration in the oral fluid and INR was only found in samples with pH values ≥7.2 (r = 0.84, p = 0.004). CONCLUSIONS: Warfarin diffuses from blood to oral fluid. The method allows to measure its concentration in this matrix and to analyze correlations with INR and other parameters