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

534 SIX-MONTH EFFICACY OF INTRA-ARTICULAR HYALURONIC ACID FOR CARPOMETACARPAL JOINT OSTEOARTHRITIS

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Identification of domains in apoA-I susceptible to proteolysis by mast cell chymase. Implications for HDL function.

When stimulated, rat serosal mast cells degranulate and secrete a cytoplasmic neutral protease, chymase. We studied the fragmentation of apolipoprotein (apo) A-I during proteolysis of HDL(3) by chymase, and examined how chymase-dependent proteolysis interfered with the binding of eight murine monoclonal antibodies (Mabs) against functional domains of apoA-I. Size exclusion chromatography of HDL(3) revealed that proteolysis for up to 24 h did not alter the integrity of the alpha-migrating HDL, whereas a minor peak containing particles of smaller size with prebeta mobility disappeared after as little as 15 min of incubation. At the same time, generation of a large (26 kDa) polypeptide containing the N-terminus of apoA-I was detected. This large fragment and other medium-sized fragments of apoA-I produced after prolonged treatment with chymase were found to be associated with the alphaHDL; meanwhile, small lipid-free peptides were rapidly produced. Incubation of HDL(3) with chymase inhibited binding of Mab A-I-9 (specific for prebeta(1)HDL) most rapidly (within 15 min) of the eight studied Mabs. This rapid loss of binding was paralleled by a similar reduction in the ability of HDL(3) to induce high-affinity efflux of cholesterol from macrophage foam cells, indicating that proteolysis had destroyed an epitope that is critical for this function. In sharp contrast, prolonged degradation of HDL(3) by chymase failed to reduce the ability of HDL(3) to activate LCAT, even though it led to modification of three epitopes in the central region of apoA-I that are involved in lecithin cholesterol acyltransferase (LCAT) activation. This differential sensitivity of the two key functions of HDL(3) to the proteolytic action of mast cell chymase is compatible with the notion that, in reverse cholesterol transport, intactness of apoA-I is essential for prebeta(1)HDL to promote the high-affinity efflux of cellular cholesterol, but not for the alpha-migrating HDL particles to activate LCAT

Localization of apolipoprotein A-I epitopes involved in the activation of lecithin: Cholesterol acyltransferase

Eight murine monoclonal antibodies (Mab) to apolipoprotein A-I were characterized for their epitopes and for their ability to interfere with lecithin:cholesterol acyltransferase (LCAT) activation mediated by apo apoA-I using a synthetic substrate. Using overlapping synthetic peptides we have identified six continuous epitopes that span amino acids 1-10 (Mab A-I-19), 96-101 (Mab A-I-15), 133-141 (Mab A-I-5), 140-145 (Mab A-I-9), 144-148 (Mab A-I-8), and 167-174 (Mab A-I-57). Furthermore, antibodies A-I-11 and A-I-16 recognized discontinuous epitopes, namely amino acids 124-128 and 144-148. When antibodies were tested for their ability to inhibit LCAT activation, an inhibitory effect was observed with those whose epitopes covered the area of apoA-I encompassing amino acids 96-174. From these data we conclude that several areas of apoA-I spanning the middle region of the apolipoprotein act in concert to stimulate LCAT activity, possibly by cooperative interaction with the enzyme

Extracting low energy signals from raw LArTPC waveforms using deep learning techniques -- A proof of concept

We investigate the feasibility of using deep learning techniques, in the form of a one-dimensional convolutional neural network (1D-CNN), for the extraction of signals from the raw waveforms produced by the individual channels of liquid argon time projection chamber (LArTPC) detectors. A minimal generic LArTPC detector model is developed to generate realistic noise and signal waveforms used to train and test the 1D-CNN, and evaluate its performance on low-level signals. We demonstrate that our approach overcomes the inherent shortcomings of traditional cut-based methods by extending sensitivity to signals with ADC values below their imposed thresholds. This approach exhibits great promise in enhancing the capabilities of future generation neutrino experiments like DUNE to carry out their low-energy neutrino physics programs

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

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

Cost of Bordetella pertussis illness in tertiary hospitals in Argentina

La Comisión Nacional de Inmunizaciones y el ProNaCEI (Programa Nacional de Control de Enfermedades Inmunoprevenibles) actualizaron la política de vacunación por Bordetella pertussis (BP) a partir del año 2009 con el objetivo de optimizar el control de esta enfermedad, de acuerdo con las recomendaciones internacionales. Para evaluar el impacto económico de esta nueva política de vacunación resulta necesario conocer inicialmente el costo que implica para el sistema de salud un niño internado o ambulatorio con infección por BP. El objetivo de este estudio fue describir el perfl de costos en niños internados o tratados ambulatoriamente, con infección confrmada por laboratorio de BP en tres hospitales de la Argentina. Estudio prospectivo de costo de la enfermedad durante el período diciembre de 2010 a marzo de 2012. Resultados. El costo total para toda la cohorte fue de 1 170 663,32 pesos (236 497,64 dólares); los costos médicos directos, de 1 124 052,31 pesos (227 081,27 dólares); los costos indirectos y gastos de bolsillo, de 46611 pesos (9 416,36 dólares), lo que permite inferir un costo total promedio por paciente de 10 546,52 pesos (IC 95% 9009 a 13 840) (2130,60 dólares, IC 95% 1820 a 2795), costos médicos directos por paciente de 10 126,6 pesos (IC 95% 8607 a 13 171) (2045,77 dólares, IC 95%1738 a 2660) y costos indirectos más de bolsillo (viajes y extras) de 419,92 pesos (IC 95% 344,7 a 565,3), (84 dólares, IC 95% 69 a 115). Conclusión. El costo de un caso confrmado hospitalizado por BP es 10 546,52 pesos (IC 95% 9009 a 13 840) (2130,60 dólares, IC 95% 1820 a 2795). Los costos directos no médicos y costos indirectos constituyen el 4% del total, lo que corresponde a 419,91 pesos por familia (84 dólares, IC 95% 69 a 115), un 8% del salario promedio.Fil: Gentile, Angela. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "ricardo Gutierrez"; ArgentinaFil: Salgueiro, Ana L.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "ricardo Gutierrez"; ArgentinaFil: Garcia Bournissen, Facundo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "r. Gutierrez". Servicio de Parasitología y Chagas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Romanin, Viviana. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "ricardo Gutierrez"; ArgentinaFil: Bulgheroni, Sonia. Hospital Materno Infantil de San Isidro "Dr. Gianantonio"; ArgentinaFil: Gaiano, Alejandra. Hospital Materno Infantil de San Isidro "Dr. Gianantonio"; ArgentinaFil: Benegas, Liliana. Hospital de Niños "Víctor J. Vilela"; ArgentinaFil: Uboldi, Andrea. Hospital de Niños "Víctor J. Vilela"; ArgentinaFil: Giglio, Norberto. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "ricardo Gutierrez"; Argentin

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

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