Function of lanGT3, a glycosyltransferase gene involved in landomycin A biosynthesis

The glycosyltransferase gene lanGT3, involved in the biosynthesis of the angucyclic antibiotic landomycin A, has been characterised by targeted gene deletion. A lanGT3 mutant was shown to produce landomycin E, which consists of a trisaccharide side chain attached to the polyketide moiety. Expression of lanGT3 in the mutant restored landomycin A production. Our results indicate that LanGT3 is responsible for the transfer of the fourth sugar during landomycin A biosynthesis.     

Reconstruction of cloud geometry from multi-view satellite images

Reflected solar radiances measured by the pushbroom cameras of the Multiangle Imaging SpectroRadiometer (MISR) on the Terra satellite at nine viewing angles are combined to give eight stereo pairs. These are analyzed with stereo-photogrammetric methods to measure the geometry of a convective cloud system. Both cloud-top heights and cloud sides are retrieved with a precision of about 200-300 m. Two case studies of deep, convective clouds over ocean are considered. The accuracy of the MISR retrieval is tested in the first case study by reference to coincident, higher resolution stereo data from ASTER, showing how the accuracy of the cloud-top height retrieval is improved using the oblique MISR views. In the second case study, the entire cross-section of the cloud aligned with the viewing azimuthal direction is measured, using all nine cameras. The methodology presented is an important step towards more routine retrievals of the 3D geometrical reconstruction of isolated, deep-convective clouds. Such reconstructions are a necessary prerequisite to the subsequent 3D radiative transfer modeling used to aid the remote sensing of the elusive microphysical properties of such clouds.     

Application-specific multiprocessor Systems-on-Chip

It often happens that designers have to integrate different instruction-set processors on a single chip. Typical applications are wireless, image processing, xDSL, network and game processors. This paper deals with the three main problems that make the design of application-specific heterogeneous multiprocessor Systems-on-Chip very hard and expensive:

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higher level specification;

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software support packages design;

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on-chip HW/SW communication design.

     

Immunological effects of yogurt addition to a re-nutrition diet in a malnutrition experimental model

The therapeutic and preventive effects of yogurt and lactic acid bacteria on diseases such as cancer, infection and gastrointestinal disorders are well ocumented. The aim of this research was to study the effects of different doses of yogurt addition after milk re-nutrition diet, on the recovery of the intestinal barrier and mucosal immune function. Experiments were performed on groups of mice, malnourished and re-nourished with milk during 7 d, and mice with diet supplemented with yogurt for 2, 5 and 7 consecutive d. Nutritional parameters such as weight gain, serum total protein, and the number of IgA, IgM and IgG B cells of the small intestine were determined. We also quantified intraepithelial leukocytes, mastocytes and goblet cells, and performed structural and ultrastructural studies on the small intestine. We observed that 5 d of yogurt feeding was the optimal dose for improving gut barrier function and mucosal immune system in a malnutrition model. This effect was not observed with milk re-nutrition. Although the results were better for 5 d of yogurt, addition for 7 d also showed beneficial effects. Yogurt feeding in our model did not impair any gut functions. These results suggest that yogurt addition after a re-nutrition diet gives better recovery of intestinal function than the re-nutrition diet usually recommended. Although these results were obtained in an animal model, they indicate that consumption of yogurt by malnourished children might accelerate the restoration of gut function.     

Enhanced osteoinductive capacity and decreased variability by enrichment of demineralized bone matrix with a bone protein extract

Osteoinductive capacity of demineralized bone matrix (DBM) is sometimes insufficient or shows high variability between different batches of DBM. Here, we tried to improve its osteoinductive activity by alkali-urea or trypsin treatment but this strategy was unsuccessful. Then, we tested the enrichment of DBM with a bone protein extract (BPE) containing osteogenic growth factors comparing two sources: cortical bone powder and DBM. The osteoinductive capacity (alkaline phosphatase activity) of the obtained BPEs was evaluated in vitro in C2C12 cells. Specific protein levels present in the different BPE was determined by enzyme-linked immunosorbent assay or by a multiplex assay. BPE from cortical bone powder showed a lack of osteoinductive effect, in agreement with the low content on osteoinductive factors. In contrast, BPE from DBM showed osteoinductive activity but also high variability among donors. Thus, we decided to enrich DBM with BPE obtained from a pool of DBM from different donors. Following this strategy, we achieved increased osteoinductive activity and lower variability among donors. In conclusion, the use of a BPE obtained from a pool of demineralized bone to enrich DBM could be used to increase its osteoinductive effect and normalize the differences between donors.

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Freeze drying optimization of polymeric nanoparticles for ocular flurbiprofen delivery: effect of protectant agents and critical process parameters on long-term stability

Context: The stabilization of flurbiprofen loaded poly-?-caprolactone nanoparticles (FB-P?CL-NPs) for ocular delivery under accurate freeze-drying (FD) process provides the basis for a large-scale production and its commercial development.

Objective: Optimization of the FD to improve long-term stability of ocular administration’s FB-P?CL-NPs.

Methods: FB-P?CL-NPs were prepared by solvent displacement method with poloxamer 188 (P188) as stabilizer. Freezing and primary drying (PD) were studied and optimized through freeze-thawing test and FD microscopy. Design of experiments was used to accurate secondary drying (SD) conditions and components concentration. Formulations were selected according to desired physicochemical properties. Furthermore, differential scanning calorimetry (DSC) and X-ray diffraction (XRD) were used to study interactions components.

Results: Optimized FB-P?CL-NPs, stabilized with 3.5% (w/w) P188 and protected with 8% (w/w) poly(ethylene glycol), was submitted to precooling at +10?°C for 1?h, freezing at ?50?°C for 4?h, PD at +5?°C and 0.140 mbar for 24?h and a SD at +45?°C during 10?h. These conditions showed 188.4?±?1.3?nm, 0.087?±?0.014, 85.5?±?1.4%, 0.61?±?0.12%, ?16.4?±?0.1?mV and 325?±?7 mOsm/kg of average size, polydispersity index, entrapment efficiency, residual moisture, surface charge and osmolality, respectively. It performed a long-term stability >12 months. DSC and XRD spectra confirmed adequate chemical interaction between formulation components and showed a semi-crystalline state after FD.

Conclusions: An optimal freeze dried ocular formulation was achieved. Evidently, the successful design of this promising colloidal system resulted from rational cooperation between a good formulation and the right conditions in the FD process.     

Albendazole solution formulation via vesicle-to-micelle transition of phospholipid-surfactant aggregates

Objective: To reveal the physicochemical mechanisms governing the solubilization of albendazole in surfactant and phospholipid-surfactant solutions and, on this basis, to formulate clinically relevant dose of albendazole in solution suitable for parenteral delivery.

Significance: (1) A new drug delivery system for parenteral delivery of albendazole is proposed, offering high drug solubility and low toxicity of the materials used; (2) New insights on the role of surface curvature on albendazole solubilization in surfactant and surfactant-phospholipid aggregates are provided.

Methods: The effect of 17 surfactants and 6 surfactant-phospholipid mixtures on albendazole solubility was studied. The size of the colloidal aggregates was determined by light-scattering. The dilution stability of the proposed formulation was assessed by experiments with model human serum.

Results: Anionic surfactants increased very strongly drug solubility at pH?=?3 (up to 4?mg/mL) due to strong electrostatic attraction between the oppositely charged (at this pH) drug and surfactant molecules. This effect was observed with all anionic surfactants studied, including sodium dodecyl sulfate, double chain sodium dioctylsulfosuccinate (AOT), and the bile salt sodium taurodeoxycholate. The phospholipid-surfactant mixture of 40% sodium dipalmitoyl-phosphatidylglycerol +60% AOT provided highest albendazole solubilization (4.4?mg/mL), smallest colloidal aggregate size (11?nm) and was stable to dilution with model human serum at (and above) 1:12 ratio.

Conclusions: A new albendazole delivery system with high drug load and low toxicity of the materials used was developed. The high solubility of albendazole was explained with vesicle-to-micelle transition due to the larger interfacial curvature preferred for albendazole solubilization locus.     

Whey protein active films incorporated with a blend of essential oils: Characterization and effectiveness

Whey protein concentrate (WPC) films incorporated with a blend of Cinnamomum cassia, Cinnamomum zeylanicum, and Rosmarinus officinalis essential oils were characterized and evaluated for their effectiveness as an antioxidant for food applications. The effect of the incorporation of essential oils (EOs) at different concentrations (1, 2, 2.7, and 5% w/w) in WPC were studied by measuring their physical, optical, mechanical, and microstructural properties, in order to evaluate their behavior as a food packaging. The effectiveness of these active WPC films as a packaged was evaluated using a fatty food model (salami). The state of the salami oxidation was measured by the TBARs and hexanal assays during 180 days of storage. A yellowish characteristic color and opacity of WPC‐based films tend to increase with the increase of the EO concentration in the film formulation. While films containing 1 and 2% of EOs showed to be the most hydrophobic and present the lowest moisture content and solubility in water, films with higher EOs % (2, 2.7, and 5%, w/w) presented the highest water vapor transmission rate. The developed WPC active films showed to be heterogeneous, presenting cracks and pores due to the weakening of the polymer chain interaction forces by the EOs, which affected their mechanical behavior. WPC films incorporated with EOs may retard lipid oxidation induced by UV light in food. Besides, they showed to be very effective in the reduction of lipid oxidation in a previous assay with salami, with a longer storage time.     

Simultaneous optimization of production planning and inventory management of polyurethane foam plant

In this work, the management of a polyurethane foam plant is tackled through a mixed integer linear programming model that simultaneously solves production and inventory planning problems. The production process considers the foaming stage where large polyurethane blocks are produced as well as the curing step where the blocks are dried. The proposed formulation takes into account several tradeoffs involved in the overall production process. The daily production planning is tightly related to production requirements, available space for the curing and stored elements. Moreover, the required time to dry blocks introduces a delay that must be appropriately considered in order to allow an adequate operation of downstream operations. Thus, an integrated approach where all these problems are jointly addressed is proposed using a mathematical programming model. Several study cases provided by a local company are tested to demonstrate the model performance.