Design and stability study of a paediatric oral solution of methotrexate 2mg/ml

International audience

The scientific rationale, design and implementation plan for a Biogeochemical-Argo float array

Biogeochemical-Argo is the extension of the Argo array of profiling floats to include floats that are equipped with biogeochemical sensors for pH, oxygen, nitrate, chlorophyll, suspended particles, and downwelling irradiance. Argo is a highly regarded, international program that measures the changing ocean temperature (heat content) and salinity with profiling floats distributed throughout the ocean. Newly developed sensors now allow profiling floats to also observe biogeochemical properties with sufficient accuracy for climate studies. This extension of Argo will enable an observing system that can determine the seasonal to decadal-scale variability in biological productivity, the supply of essential plant nutrients from deep-waters to the sunlit surface layer, ocean acidification, hypoxia, and ocean uptake of CO2. Biogeochemical-Argo will drive a transformative shift in our ability to observe and predict the effects of climate change on ocean metabolism, carbon uptake, and living marine resource management. Presently, vast areas of the open ocean are sampled only once per decade or less, with sampling occurring mainly in summer. Our ability to detect changes in biogeochemical processes that may occur due to the warming and acidification driven by increasing atmospheric CO2, as well as by natural climate variability, is greatly hindered by this undersampling. In close synergy with satellite systems (which are effective at detecting global patterns for a few biogeochemical parameters, but only very close to the sea surface and in the absence of clouds), a global array of biogeochemical sensors would revolutionize our understanding of ocean carbon uptake, productivity, and deoxygenation. The array would reveal the biological, chemical, and physical events that control these processes. Such a system would enable a new generation of global ocean prediction systems in support of carbon cycling, acidification, hypoxia and harmful algal blooms studies, as well as the management of living marine resources. In order to prepare for a global Biogeochemical-Argo array, several prototype profiling float arrays have been developed at the regional scale by various countries and are now operating. Examples include regional arrays in the Southern Ocean (SOCCOM ), the North Atlantic Sub-polar Gyre (remOcean ), the Mediterranean Sea (NAOS ), the Kuroshio region of the North Pacific (INBOX ), and the Indian Ocean (IOBioArgo ). For example, the SOCCOM program is deploying 200 profiling floats with biogeochemical sensors throughout the Southern Ocean, including areas covered seasonally with ice. The resulting data, which are publically available in real time, are being linked with computer models to better understand the role of the Southern Ocean in influencing CO2 uptake, biological productivity, and nutrient supply to distant regions of the world ocean. The success of these regional projects has motivated a planning meeting to discuss the requirements for and applications of a global-scale Biogeochemical-Argo program. The meeting was held 11-13 January 2016 in Villefranche-sur-Mer, France with attendees from eight nations now deploying Argo floats with biogeochemical sensors present to discuss this topic. In preparation, computer simulations and a variety of analyses were conducted to assess the resources required for the transition to a global-scale array. Based on these analyses and simulations, it was concluded that an array of about 1000 biogeochemical profiling floats would provide the needed resolution to greatly improve our understanding of biogeochemical processes and to enable significant improvement in ecosystem models. With an endurance of four years for a Biogeochemical-Argo float, this system would require the procurement and deployment of 250 new floats per year to maintain a 1000 float array. The lifetime cost for a Biogeochemical-Argo float, including capital expense, calibration, data management, and data transmission, is about $100,000. A global Biogeochemical-Argo system would thus cost about $25,000,000 annually. In the present Argo paradigm, the US provides half of the profiling floats in the array, while the EU, Austral/Asia, and Canada share most the remaining half. If this approach is adopted, the US cost for the Biogeochemical-Argo system would be ~$12,500,000 annually and ~$6,250,000 each for the EU, and Austral/Asia and Canada. This includes no direct costs for ship time and presumes that float deployments can be carried out from future research cruises of opportunity, including, for example, the international GO-SHIP program (http://www.go-ship.org). The full-scale implementation of a global Biogeochemical-Argo system with 1000 floats is feasible within a decade. The successful, ongoing pilot projects have provided the foundation and start for such a system.

Design and synthesis of novel quinolones directed to the Plasmodium falciparum bc1 protein complex

Tese de Doutoramento, Química, Especialização em Química Orgânica, Faculdade de Ciências e Tecnologia, Universidade do Algarve, 2016

Design And Synthesis Of N-acylated Aza-goniothalamin Derivatives And Evaluation Of Their In Vitro And In Vivo Antitumor Activity.

Herein we describe the synthesis of a focused library of compounds based on the structure of goniothalamin (1) and the evaluation of the potential antitumor activity of the compounds. N-Acylation of aza-goniothalamin (2) restored the in vitro antiproliferative activity of this family of compounds. 1-(E)-But-2-enoyl-6-styryl-5,6-dihydropyridin-2(1H)-one (18) displayed enhanced antiproliferative activity. Both goniothalamin (1) and derivative 18 led to reactive oxygen species generation in PC-3 cells, which was probably a signal for caspase-dependent apoptosis. Treatment with derivative 18 promoted Annexin V/7-aminoactinomycin D double staining, which indicated apoptosis, and also led to G2 /M cell-cycle arrest. In vivo studies in Ehrlich ascitic and solid tumor models confirmed the antitumor activity of goniothalamin (1), without signs of toxicity. However, derivative 18 exhibited an unexpectedly lower in vivo antitumor activity, despite the treatments being administered at the same site of inoculation. Contrary to its in vitro profile, aza-goniothalamin (2) inhibited Ehrlich tumor growth, both on the ascitic and solid forms. Our findings highlight the importance of in vivo studies in the search for new candidates for cancer treatment.

Influence of specimens' design and manufacturing process on microtensile bond strength to enamel: laboratory and FEA comparison

This study evaluated the effect of specimens' design and manufacturing process on microtensile bond strength, internal stress distributions (Finite Element Analysis - FEA) and specimens' integrity by means of Scanning Electron Microscopy (SEM) and Laser Scanning Confocal Microscopy (LCM). Excite was applied to flat enamel surface and a resin composite build-ups were made incrementally with 1-mm increments of Tetric Ceram. Teeth were cut using a diamond disc or a diamond wire, obtaining 0.8 mm² stick-shaped specimens, or were shaped with a Micro Specimen Former, obtaining dumbbell-shaped specimens (n = 10). Samples were randomly selected for SEM and LCM analysis. Remaining samples underwent microtensile test, and results were analyzed with ANOVA and Tukey test. FEA dumbbell-shaped model resulted in a more homogeneous stress distribution. Nonetheless, they failed under lower bond strengths (21.83 ± 5.44 MPa)c than stick-shaped specimens (sectioned with wire: 42.93 ± 4.77 MPaª; sectioned with disc: 36.62 ± 3.63 MPa b), due to geometric irregularities related to manufacturing process, as noted in microscopic analyzes. It could be concluded that stick-shaped, nontrimmed specimens, sectioned with diamond wire, are preferred for enamel specimens as they can be prepared in a less destructive, easier, and more precise way.

Design and characterization of bridged loop-gap resonators for use in electron paramagnetic resonance measurements

This paper revisits the design of L and S band bridged loop-gap resonators (BLGRs) for electron paramagnetic resonance applications. A novel configuration is described and extensively characterized for resonance frequency and quality factor as a function of the geometrical parameters of the device. The obtained experimental results indicate higher values of the quality factor (Q) than previously reported in the literature, and the experimental analysis data should provide useful guidelines for BLGR design.

Hypotheses, rationale, design, and methods for prognostic evaluation in type 2 diabetic patients with angiographically normal coronary arteries. The MASS IV-DM Trial

Background: The MASS IV-DM Trial is a large project from a single institution, the Heart Institute (InCor), University of Sao Paulo Medical School, Brazil to study ventricular function and coronary arteries in patients with type 2 diabetes mellitus. Methods/Design: The study will enroll 600 patients with type 2 diabetes who have angiographically normal ventricular function and coronary arteries. The goal of the MASS IV-DM Trial is to achieve a long-term evaluation of the development of coronary atherosclerosis by using angiograms and coronary-artery calcium scan by electron-beam computed tomography at baseline and after 5 years of follow-up. In addition, the incidence of major cardiovascular events, the dysfunction of various organs involved in this disease, particularly microalbuminuria and renal function, will be analyzed through clinical evaluation. In addition, an effort will be made to investigate in depth the presence of major cardiovascular risk factors, especially the biochemical profile, metabolic syndrome inflammatory activity, oxidative stress, endothelial function, prothrombotic factors, and profibrinolytic and platelet activity. An evaluation will be made of the polymorphism as a determinant of disease and its possible role in the genesis of micro- and macrovascular damage. Discussion: The MASS IV-DM trial is designed to include diabetic patients with clinically suspected myocardial ischemia in whom conventional angiography shows angiographically normal coronary arteries. The result of extensive investigation including angiographic follow-up by several methods, vascular reactivity, pro-thrombotic mechanisms, genetic and biochemical studies may facilitate the understanding of so-called micro- and macrovascular disease of DM.

Design and fabrication of microcavity-array superhydrophobic surfaces

We have modeled, fabricated, and characterized superhydrophobic surfaces with a morphology formed of periodic microstructures which are cavities. This surface morphology is the inverse of that generally reported in the literature when the surface is formed of pillars or protrusions, and has the advantage that when immersed in water the confined air inside the cavities tends to expel the invading water. This differs from the case of a surface morphology formed of pillars or protrusions, for which water can penetrate irreversibly among the microstructures, necessitating complete drying of the surface in order to again recover its superhydrophobic character. We have developed a theoretical model that allows calculation of the microcavity dimensions needed to obtain superhydrophobic surfaces composed of patterns of such microcavities, and that provides estimates of the advancing and receding contact angle as a function of microcavity parameters. The model predicts that the cavity aspect ratio (depth-to-diameter ratio) can be much less than unity, indicating that the microcavities do not need to be deep in order to obtain a surface with enhanced superhydrophobic character. Specific microcavity patterns have been fabricated in polydimethylsiloxane and characterized by scanning electron microscopy, atomic force microscopy, and contact angle measurements. The measured advancing and receding contact angles are in good agreement with the predictions of the model. (C) 2010 American Institute of Physics. [doi:10.1063/1.3466979]

Design and fabrication of superhydrophobic surfaces formed of microcavities

We have developed a theoretical model for superhydrophobic surfaces that are formed from an extended array of microcavities, and have fabricated specific microcavity patterns to form superhydrophobic surfaces of the kind modeled. The model shows that the cavity aspect ratio can be significantly less than unity, indicating that the microcavities do not need to be deep in order to enhance the superhydrophobic character of the surface. We have fabricated surfaces of this kind and measured advancing contact angle as high as 153 degrees, in agreement with predictions of the model.

Power imbalance application region method for distributed synchronous generator anti-islanding protection design and evaluation

This paper presents a novel graphical approach to adjust and evaluate frequency-based relays employed in anti-islanding protection schemes of distributed synchronous generators, in order to meet the anti-islanding and abnormal frequency variation requirements, simultaneously. The proposed method defines a region in the power mismatch space, inside which the relay non-detection zone should be located, if the above-mentioned requirements must be met. Such region is called power imbalance application region. Results show that this method can help protection engineers to adjust frequency-based relays to improve the anti-islanding capability and to minimize false operation occurrences, keeping the abnormal frequency variation utility requirements satisfied. Moreover, the proposed method can be employed to coordinate different types of frequency-based relays, aiming at improving overall performance of the distributed generator frequency protection scheme. (C) 2011 Elsevier B.V. All rights reserved.

Design and assembly of an experimental laboratory for the study of atmosphere-plant interactions in the system of fumigation chambers

An experimental laboratory was designed and assembled at the Botanical Institute of So Paulo, Brazil, in order to research atmosphere-plant interactions through the use of a system of fumigation chambers. A system of three ""closed"" fumigation chambers was designed to be used inside or outside the laboratory. The system was built to be used with a single pollutant or a mix of them. The innovation in this system is to allow chemical reactions inside the chambers that simulate atmospheric chemistry, especially photochemical processes involving high levels of ozone. Assessment of the performance and applicability of the system was based on the response of Nicotiana tabacum Bel W3 exposed to ozone produced alternatively by a generator and inside the chamber by reactions of its precursors. The results showed that the system can be well applied to the study of atmospheric chemistry interactions and the effects on plants.

Design and Characterization of Novel Wear Resistant Multilayer CVD Coatings with Improved Adhesion Between Al(2)O(3) and Ti(C,N)

Multilayer CVD coatings for high speed cutting applications were designed to achieve high wear and heat resistance during machining of steel alloys. In this work the microstructure and cutting performance of these novel multilayer CVD coatings are investigated and compared with standard CVD multilayer coatings. 3D-FIB tomography is used to characterize the microstructure of the layers, especially the transition between the Ti(C,N) and the Al(2)O(3) layer. The 3D reconstruction of the surface of the Ti(C,N) layer shows the formation of protruded Ti(C,N) grains with a very particular architecture, which penetrate into the Al(2)O(3) top-layer, providing a mechanical anchoring between both layers. Cemented carbides coated with the novel CVD multilayer present reduced crater and flank wear as well as improved adherence between the Al(2)O(3) top-layer and the Ti(C,N) layer leading to a dramatic improvement of cutting performance.

Adaptable Strut-and-Tie Model for Design and Verification of Four-Pile Caps

A large percentage of pile caps support only one column, and the pile caps in turn are supported by only a few piles. These are typically short and deep members with overall span-depth ratios of less than 1.5. Codes of practice do not provide uniform treatment for the design of these types of pile caps. These members have traditionally been designed as beams spanning between piles with the depth selected to avoid shear failures and the amount of longitudinal reinforcement selected to provide sufficient flexural capacity as calculated by the engineering beam theory. More recently, the strut-and-tie method has been used for the design of pile caps (disturbed or D-region) in which the load path is envisaged to be a three-dimensional truss, with compressive forces being supported by concrete compressive struts between the column and piles and tensile forces being carried by reinforcing steel located between piles. Both of these models have not provided uniform factors of safety against failure or been able to predict whether failure will occur by flexure (ductile mode) or shear (fragile mode). In this paper, an analytical model based on the strut-and-tie approach is presented. The proposed model has been calibrated using an extensive experimental database of pile caps subjected to compression and evaluated analytically for more complex loading conditions. It has been proven to be applicable across a broad range of test data and can predict the failures modes, cracking, yielding, and failure loads of four-pile caps with reasonable accuracy.

Design and Characterization of a Biomimetic Piezoelectric Pump Inspired on Group Fish Swimming Effect

Flow pumps are important tools in several engineering areas, such as in the fields of bioengineering and thermal management solutions for electronic devices. Nowadays, many of the new flow pump principles are based on the use of piezoelectric actuators, which present some advantages such as miniaturization potential and lower noise generation. In previous work, authors presented a study of a novel pump configuration based on placing an oscillating bimorph piezoelectric actuator in water to generate flow. It was concluded that this oscillatory behavior (such as fish swimming) yields vortex interaction, generating flow rate due to the action and reaction principle. Thus, following this idea the objective of this work is to explore this oscillatory principle by studying the interaction among generated vortex from two bimorph piezoelectric actuators oscillating inside the same pump channel, which is similar to the interaction of vortex generated by frontal fish and posterior ones when they swim together in a group formation. It is shown that parallel-series configurations of bimorph piezoelectric actuators inside the same pump channel provide higher flow rates and pressure for liquid pumping than simple parallel-series arrangements of corresponding single piezoelectric pumps, respectively. The scope of this work includes structural simulations of bimorph piezoelectric actuators, fluid flow simulations, and prototype construction for result validation.