Controlling instabilities along a 3DVar analysis cycle by assimilating in the unstable subspace: a comparison with the EnKF

A hybrid scheme obtained by combining 3DVar with the Assimilation in the Unstable Subspace (3DVar-AUS) is tested in a QG model, under perfect model conditions, with a fixed observational network, with and without observational noise. The AUS scheme, originally formulated to assimilate adaptive observations, is used here to assimilate the fixed observations that are found in the region of local maxima of BDAS vectors (Bred vectors subject to assimilation), while the remaining observations are assimilated by 3DVar. The performance of the hybrid scheme is compared with that of 3DVar and of an EnKF. The improvement gained by 3DVar-AUS and the EnKF with respect to 3DVar alone is similar in the present model and observational configuration, while 3DVar-AUS outperforms the EnKF during the forecast stage. The 3DVar-AUS algorithm is easy to implement and the results obtained in the idealized conditions of this study encourage further investigation toward an implementation in more realistic contexts

Detecting unstable structures and controlling error growth by assimilation of standard and adaptive observations in a primitive equation ocean model

International audienceOceanic and atmospheric prediction is based on cyclic analysis-forecast systems that assimilate new observations as they become available. In such observationally forced systems, errors amplify depending on their components along the unstable directions; these can be estimated by Breeding on the Data Assimilation System (BDAS). Assimilation in the Unstable Subspace (AUS) uses the available observations to estimate the amplitude of the unstable structures (computed by BDAS), present in the forecast error field, in order to eliminate them and to control the error growth. For this purpose, it is crucial that the observational network can detect the unstable structures that are active in the system. These concepts are demonstrated here by twin experiments with a large state dimension, primitive equation ocean model and an observational network having a fixed and an adaptive component. The latter consists of observations taken each time at different locations, chosen to target the estimated instabilities, whose positions and features depend on the dynamical characteristics of the flow. The adaptive placement and the dynamically consistent assimilation of observations (both relying upon the estimate of the unstable directions of the data-forced system), allow to obtain a remarkable reduction of errors with respect to a non-adaptive setting. The space distribution of the positions chosen for the observations allows to characterize the evolution of instabilities, from deep layers in western boundary current regions, to near-surface layers in the eastward jet area

Developing a dynamically based assimilation method for targeted and standard observations

International audienceIn a recent study, a new method for assimilating observations has been proposed and applied to a small size nonlinear model. The assimilation is obtained by confining the analysis increment in the unstable subspace of the Observation-Analysis-Forecast (OAF) cycle system, in order to systematically eliminate the dynamically unstable components, present in the forecast error, which are responsible for error growth. Based on the same ideas, applications to more complex models and different, standard and adaptive, observation networks are in progress. Observing System Simulation Experiments (OSSE), performed with an atmospheric quasi-geostrophic model, with a restricted "land" area where vertical profiles are systematically observed, and a wider "ocean" area where a single supplementary observation is taken at each analysis time, are reviewed. The adaptive observation is assimilated either with the proposed method or, for comparison, with a 3-D VAR scheme. The performance of the dynamic assimilation is very good: a reduction of the error of almost an order of magnitude is obtained in the data void region. The same method is applied to a primitive equation ocean model, where "satellite altimetry" observations are assimilated. In this standard observational configuration, preliminary results show a less spectacular but significant improvement obtained by the introduction of the dynamical assimilation

Uptake and cytotoxicity of citrate-coated gold nanospheres : comparative studies on human endothelial and epithelial cells

The use of gold nanoparticles (AuNPs) for diagnostic applications and for drug and gene-delivery is currently under intensive investigation. For such applications, biocompatibility and the absence of cytotoxicity of AuNPs is essential. Although generally considered as highly biocompatible, previous in vitro studies have shown that cytotoxicity of AuNPs in certain human epithelial cells was observed. In particular, the degree of purification of AuNPs (presence of sodium citrate residues on the particles) was shown to affect the proliferation and induce cytotoxicity in these cells. To expand these studies, we have examined if the effects are related to nanoparticle size (10, 11 nm, 25 nm), to the presence of sodium citrate on the particles' surface or they are due to a varying degree of internalization of the AuNPs. Since two cell types are present in the major barriers to the outside in the human body, we have also included endothelial cells from the vasculature and blood brain barrier. Results Transmission electron microscopy demonstrates that the internalized gold nanoparticles are located within vesicles. Increased cytotoxicity was observed after exposure to AuNPs and was found to be concentration-dependent. In addition, cell viability and the proliferation of both endothelial cells decreased after exposure to gold nanoparticles, especially at high concentrations. Moreover, in contrast to the size of the particles (10 nm, 11 nm, 25 nm), the presence of sodium citrate on the nanoparticle surface appeared to enhance these effects. The effects on microvascular endothelial cells from blood vessels were slightly enhanced compared to the effects on brain-derived endothelial cells. A quantification of AuNPs within cells by ICP-AES showed that epithelial cells internalized a higher quantity of AuNPs compared to endothelial cells and that the quantity of uptake is not correlated with the amount of sodium citrate on the nanoparticles’ surface. Conclusions In conclusion the higher amount of citrate on the particle surface resulted in a higher impairment of cell viability, but did not enhance or reduce the uptake behavior in endothelial or epithelial cells. In addition, epithelial and endothelial cells exhibited different uptake behaviors for citrate-stabilized gold nanoparticles, which might be related to different interactions occurring at the nanoparticle-cell-surface interface. The different uptake in epithelial cells might explain the higher reduction of proliferation of these cells after exposure to AuNPs treatment although more detailed investigations are necessary to determine subcellular events. Nevertheless an extrinsic effect of sodium-citrate stabilized particles could not be excluded. Thus, the amount of sodium citrate should be reduced to a level on which the stability of the particles and the safety for biomedical applications are guaranteed

Retentive device for intravesical drug delivery based on water-induced shape memory response of poly(vinyl alcohol): design concept and 4D printing feasibility

The use of shape memory polymers exhibiting water-induced shape recovery at body temperature and water solubility was proposed for the development of indwelling devices for intravesical drug delivery. These could be administered via catheter in a suitable temporary shape, retained in the bladder for a programmed period of time by recovery of the original shape and eliminated with urine following dissolution/erosion. Hot melt extrusion and fused deposition modeling 3D printing were employed as the manufacturing techniques, the latter resulting in 4D printing because of the shape modifications undergone by the printed item over time. Pharmaceutical-grade poly(vinyl alcohol) was selected based on its hot-processability, availability in different molecular weights and on preliminary data showing water-induced shape memory behavior. Specimens having various original and temporary geometries as well as compositions, successfully obtained, were characterized by differential scanning calorimetry and dynamic-mechanical thermal analysis as well as for fluid uptake, mass loss, shape recovery and release behavior. The samples exhibited the desired ability to recover the original shape, consistent in kinetics with the relevant thermo-mechanical properties, and concomitant prolonged release of a tracer. Although preliminary in scope, this study indicated the viability of the proposed approach to the design of retentive intravesical delivery systems

Monoclonal antibodies to human low density lipoprotein identify distinct areas on apolipoprotein B-100 relevant to the low density lipoprotein-receptor interaction.

We have characterized the epitopes for ten murine monoclonal antibodies (Mabs) to human low density lipoprotein (LDL) and studied their ability to interfere with the LDL-receptor interaction. The epitopes for the antibodies were defined by using the following approaches: 1) interaction with apoB-48; 2) interaction with apoB-100 thrombolytic fragments; and 3) interaction with beta-galactosidase-apoB fusion proteins spanning different areas of the apoB-100 sequence. The results obtained are consistent with the following map of epitopes: Mab 6E, amino acids (aa) 1-1297, Mabs 5A and 6B, aa 1480-1693, Mabs 2A, 7A, 3B, and 4B, aa 2152-2377, Mabs 8A and 9A, aa 2657-3248 and 3H, aa 4082-4306. Four Mabs (2A, 5A, 7A, and 9A) whose epitopes are located in three different areas of apoB, dramatically reduced (up to 95%) the LDL-receptor interaction on cultured human fibroblasts; Fab fragments were as effective as the whole antibodies. Mab 3H, on the other hand, increased LDL binding up to threefold. These findings are consistent with the hypothesis that several areas of apoB-100 are involved independently or in concert in modulating the apoprotein B conformation required for interaction with the LDL receptor

Comparative mapping of the fragile histidine triad (FHIT) gene in cattle, river buffalo, sheep and goat by FISH and assignment to BTA22 by RH-mapping: a comparison with HSA3

Common fragile sites can be damaged by exposure to a variety of carcinogens. The fragile histidine triad (FHIT) gene, including the most active human chromosomal fragile site (FRA3B) at chromosome band HSA3p14.2,1 has been proposed as a tumour suppressor gene for a variety of tumours.2 The most common response to carcinogen exposure is deletions at the FHIT locus that alter the gene structure and function. In this study we assign the FHIT gene in cattle, river buffalo, sheep and goat chromosomes by comparative fluorescence in situ hybridization (FISH)-mapping. In addition, the assignment to BTA22 was confirmed by typing the marker across a bovine radiation hybrid (RH) panel

Effect of Polyethylene Glycol Content and Molar Mass on Injection Molding of Hydroxypropyl Methylcellulose Acetate Succinate-Based Gastroresistant Capsular Devices for Oral Drug Delivery

Capsular devices for oral drug delivery were recently proposed and manufactured by injection molding (IM) as an evolution of traditional reservoir systems comprising a core and a functional coating. IM allowed the fabrication of capsule shells with release-controlling features based on the employed materials and the design characteristics. These features are independent of the drug, with significant savings in development time and costs. In previous work, IM was used to produce enteric-soluble capsules from blends of hydroxypropyl methylcellulose acetate succinate, with polyethylene glycol (PEG) as the plasticizer. In this work, the range of plasticizer concentrations and molar mass was broadened to evaluate in-depth how those parameters affect material processability and capsule performance over time. As expected, increasing the amount of the low molar mass plasticizer decreased the viscosity and modulus of the material. This simplified the molding process and enhanced the mechanical resistance of the shell, as observed during assembly. However, some samples turned out translucent, depending on several factors including storage conditions. This was attributed to plasticizer migration issues. Such results indicate that higher molar mass PEGs, while not significantly impacting on processability, lead to capsular devices with consistent performance in the investigated time lapse

Treatment of primary shoulder stiffness: Results of a survey on surgeon practice patterns in Italy

Objectives Shoulder stiffness is a condition of restricted glenohumeral range of motion (ROM), which can arise spontaneously or as consequence of a known cause. Several treatment options are available and currently no consensus has been obtained on which treatment algorithm represents the best choice for the patient. The aim of this study was to investigate surgeon practice patterns in Italy regarding treatment of primary shoulder stiffness. Methods A literature review was performed to identify randomized controlled trials reporting results of shoulder stiffness treatment. The following controversial or critical points in the treatment of primary shoulder stiffness were identified: modalities of physical therapy; indication for oral corticosteroid; indication and frequency for injective corticosteroid; technique and site of injection; and indication, timing, and technique for surgery. A survey composed by 14 questions was created and adminis-trated to the members of a national association specialized in orthopaedics and sports traumatology (SIGASCOT at the time of survey completion, recently renamed SIA-GASCOT after the fusion of the societies SIGASCOT and SIA). Results A total of 204 completed questionnaires were collected. Physical therapy was recommended by 98% of the interviewed. The use of oral corticosteroids was considered by 51%, and injections of corticosteroids by 72%. The posterior injection approach was the one preferred and a number of three was considered the upper limit for repeated injections. Injective therapy with local anesthetics and hyaluronic acid was considered by more than 20% of the interviewed. Thirty percent of the interviewed did not treat shoulder stiffness surgically. Conclusion Several approaches to shoulder stiffness have been proposed and high-level evidence is available to analyze and discuss their results. Several controversial points emerged both from a literature review and from this national survey. Treatment of shoulder stiffness should be tailored to the patient’s clinical situation and the stage of its pathology and should aim at pain reduction, ROM restoration, functional regain, and shortening of symptoms duration, with conservative therapy remaining the mainstay of treatment