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To assess efficacy, safety, pharmacokinetics, and immunogenicity of pegloticase plus methotrexate (MTX) versus pegloticase plus placebo cotreatment for uncontrolled gout in a randomized, placebo-controlled, double-blind trial.This study included adults with uncontrolled gout, defined as serum urate ≥7 mg/dl, oral urate-lowering therapy failure or intolerance, and presence of ongoing gout symptoms including ≥1 tophus, ≥2 flares in the past 12 months, or gouty arthritis. Key exclusion criteria included MTX contraindication, current immunosuppressant use, G6PDH deficiency, and estimated glomerular filtration rate40 ml/minute/1.73 mA total of 152 patients were randomized, 100 to receive pegloticase plus MTX, 52 to receive pegloticase plus placebo. Significantly higher treatment response occurred during month 6 in the MTX group versus the placebo group (71.0% [71 of 100 patients] versus 38.5% [20 of 52 patients], respectively; between-group difference 32.3% [95% confidence interval 16.3%, 48.3%]) (P 0.0001 for between-group difference). During the first 6 months of pegloticase plus MTX or pegloticase plus placebo treatment, 78 (81.3%) of 96 MTX patients versus 47 (95.9%) of 49 placebo patients experienced ≥1 adverse event (AE), most commonly gout flare (64 [66.7%] of 96 MTX patients and 34 [69.4%] of 49 placebo patients). Reports of AEs and serious AEs were comparable between groups, but the infusion reaction rate was considerably lower with MTX cotherapy (4.2% [4 of 96 MTX patients, including 1 patient who had anaphylaxis]) than with placebo cotherapy (30.6% [15 of 49 placebo patients, 0 who had anaphylaxis]) (P 0.001). Antidrug antibody positivity was also lower in the MTX group.MTX cotherapy markedly increased pegloticase response rate over placebo (71.0% versus 38.5%) during month 6 with no new safety signals. These findings verify higher treatment response rate, lower infusion reaction incidence, and lower immunogenicity when pegloticase is coadministered with MTX.

Adsorption is a highly versatile separation technique that can be used both for product separation and waste purification, involving selective interaction of one or more compounds from the liquid phase on a solid called adsorbent. In literature, several models have been proposed to describe both the kinetics and the equilibrium data of different systems. These models are relevant for fluid-solid adsorption and fluid-solid reactions. Kinetic models can be classified in either pseudo-kinetic or diffusive models. Most of them cannot be applied directly in simulating the behavior of continuous columns, while others are applicable only in a narrow range of experimental conditions. The performances of a general continuous adsorption model have been tested by performing a dedicated parametric investigation with the aim to give an overview of how the parameters affect the continuous operation.

The aim of this study was to determine the isotopic-turnover rate (RIT ) and trophic-discrimination factor (FTD ) in muscle tissues of Lebranche mullet Mugil liza fed an experimental diet (δ13 C = -27·1‰; δ15 N = 1·0‰). Juvenile M. liza exhibited a relatively fast RIT , with a half-life (t50 ) of only 16 and 14 days for δ13 C and δ15 N respectively and a nearly complete isotopic turnover (t95 ) of 68 and 60 days for δ13 C and δ15 N.

Strongyloides stercoralis (SS) hyperinfection is a well-documented condition. However, SS eggs in stool samples are not commonly observed during routine analysis. Here, we report a case on SS hyperinfection where both larvae and eggs were observed in the stool sample of an immunossupressed liver allograft transplanted patient.

The intermediates for the production of nonionic surfactants can be derived from petrochemicals and/or from renewable raw materials. In both, the role of catalysis is fundamental. In this paper the main results reported in the literature related with the catalysis for ethoxylation of fatty esters will be reviewed. The main open challenges for these technologies will be outlined.

The world production of epoxidized vegetable oil, mainly epoxidized soybean oil, is continuously increasing because this product can have a wide range of applications. Non-edible vegetable oils, recovered by the plants growing on marginal and polluted lands, represent a possible answer to industry versus food chain debate. Cardoon (Cynara cardunculus L.) seed oil can be considered as an interesting and sustainable alternative to edible soybean oil to make plasticizers. In this work, a comparison between different epoxidation methods of cardoon oil is depicted and argued, focusing on strong points and weaknesses for each of them. It is found that cardoon seed oil can be successfully epoxidized through feasible existing technologies, by peracids and hydrogen peroxide equally. Moreover, it is demonstrated that a “greener” cardoon oil epoxidation process is possible, by using hydrogen peroxide in the presence of commercial γ-alumina as heterogeneous solid catalyst. Practical Applications: The paper analyzes the advantages and the problems of different epoxidation methods in order to obtain a final product with high quality and answer the environmental, social, and economic sustainability requirements.

Osteosarcomas (OS) are the most common malignant bone tumors, and the identification of useful tumor biomarkers and target proteins is required to predict the clinical outcome of patients and therapeutic response as well as to develop novel therapeutic strategies. In our previous study, MAPK7 has been identified as a candidate oncogene, and a promising prognostic marker for OS. Sequential activation of protein kinases within the mitogen-activated protein kinase (MAPK) cascades is a common mechanism of signal transduction in many cellular processes. In this study, we investigated the behavior of MAPK7 gene in OS cell lines. Technical viability, proliferation, migration, invasion, and apoptosis were used to evaluate the function of the MAPK7 gene. We evaluated the behavior of the OS cells with MAPK7 gene silenced, not silenced, and exposed to the main chemotherapy drugs used in OS treatment. We found that silenced MAPK7 gene is effective at suppressing cell proliferation, inhibiting cell migration, and invasion. Furthermore, MAPK7 is an important activator of transcription factors and is the main expression modulator of other key genes in the MAPK pathway. In summary, our study suggests that MAPK7 might be a promising therapeutic target for OS. © 2015 Wiley Periodicals, Inc.

Polymeric foams are widely used both as structural and as thermal insulating material. Few detailed data about the process of foam growth are reported in the literature, especially for recently developed polyurethane formulations that involve the use of a volatile organic compound instead of the banned chlorofluorocarbons (CFCs). In this work, a dedicated device was realized that allows experimental data collection for polymeric foams growth in terms of temperature and density profiles. For modeling and simulation purposes, a model reported in the literature was modified by improving, in particular, the description of the vapor–liquid phase equilibrium for the system blowing agent/polymer mixture. Simulation of the collected experimental data was performed by this model after the determination of the kinetic parameters for the occurring reaction between polyol and isocyanate. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 92: 1875–1886, 2004

The aim of this study was to evaluate the effects of temperature on survival and growth of juvenile marine pejerrey, Odontesthes argentinensis. Juveniles were randomly distributed into plastic tanks (100 L) with 50 juveniles per tank. The growth experiment was carried out at four temperatures: 20, 23, 26, and 29 C with triplicate tanks for each treatment. Survival was not affected in the range of 20–26 C, but it was significantly reduced at 29 C. Pejerrey reared at 23 C showed significantly higher total length compared with the other treatments. Fish maintained at 29 C grew significantly slower than fish reared at all other temperatures, while weight of pejerrey reared at either 20 or 26 C did not differ after 28 d (P > 0.05); they were both significantly smaller than fish kept at 23 C (P < 0.05). Feed consumption increased significantly from 20 to 29 C. The relationships between specific growth rate and temperature, and feed conversion ratio and temperature were adequately fitted with a second-order polynomial equation. The results of this study show that juvenile pejerrey should be reared at around 23 C to maximize growth and food conversion.

Finite-difference methods are commonplace in High Performance Computing applications. Despite their apparent regularity, they often exhibit load imbalance that damages their efficiency. We characterize the spatial and temporal load imbalance of Ondes3D, a typical finite-differences application dedicated to earthquake mod-eling. Our analysis reveals imbalance originating from the structure of the input data, and from low-level CPU optimizations. Ondes3D was successfully ported to AMPI/CHARM++ using over-decomposition and MPI process migration techniques to dynamically rebalance the load. However, this approach requires careful selection of the over-decomposition level, the load balancing algorithm, and its activation frequency. These choices are usually tied to application structure and platform characteristics. In this article, we propose a workflow that leverages the capabilities of SimGrid to conduct such study at low experimental cost. We rely on a combination of emulation, simulation, and application modeling that requires minimal code modification and manages to capture both spatial and temporal load imbalance to faithfully predict the performance of dynamic load balancing. We evaluate the quality of our simulation by comparing simulation results with the outcome of real executions and demonstrate how this approach can be used to quickly find the optimal load balancing configuration for a given application/hardware configuration.

The syntheses of four ACTH-analogues: [Orn15-18]-, [DSer1, Orn15-18]-, [Orn11-15-18]- and [DSer1, Orn11,15-18]-β-corticotropin-(1-18)-octadecapeptide amide** are described. The last mentioned compound exhibits an unexpected, strongly prolonged, biological activity. A possible explanation is given.

Various 2-[Ar(alk)ylsulfonyl]ethanols were prepared and subsequently converted into the corresponding phosphorodichloridites in almost quantitative yield via a convenient synthetic route. The versatility of the method, which obviates the necessity of a distillation step, is demonstrated by the preparation of other Ar(alk)yl phosphorodichloridites, including the unstable benzyl phosphorodichloridite.

This article describes the synthesis of two analogues of β-corticotropin-(l-24)-tetracosapeptide, in which the amidine function in one or in all three arginyl residues has been replaced by hydrogen. In connection with previous work, the weak biological) activity of both analogues proves the essentiality of a guanidine function in position 8 for hormonal activity.

Phthaloyl amino acids can be synthesized from N-carboethoxy phthalimide and amino acid salts under very mild conditions in water. The preparation of 11 of these phthaloyl derivatives is described, some of which are new. Up to the present the method has only failed with tryptophane. Retention of the optical configuration during the reaction is shown.

The stability of the ester bond in phthalimidomethyl benzoate has been tested under a wide variety of circumstances, applied for the removal of protecting groups from amino acids. The chemical properties of the ester (table I) warranted the expectation that the phthalimidomethyl group would be useful for the protection of carboxyl functions in peptide syntheses. Several amino acid esters of phthalimidomethanol (table III) have been prepared by simple methods. Some of these compounds have been converted into peptides by conventional routes (table IV). No racemization was observed during these reactions. The usefulness of the phthalimidomethyl esters in peptide syntheses has been investigated further with amino acid and peptide esters containing also amino or other carboxyl protecting groups (benzyloxycarbonyl, benzyl, p-nitrobenzyl or tert.-butyl). In all cases the phthalimidomethyl group as well as the other substituents could be removed separately and very specifically, giving pure products in satisfactory or good yields (see e.g. schemes A and B).

A synthesis is described of a protected pentapeptide, in which the amino-acid sequence L-alanyl-D-glutamyl-L-lysyl-D-alanyl-D-alanine, found in bacterial cell wall substances, is present. By the nature of its amino- and carboxyl-protecting groups it seems suitable for condensation with N-acetylmuramic acid, which is intended.

Esters can be prepared from N-hydroxyphthalimide and N-carbobenzoxy- or N-phthaloyl-amino acids using dicyclohexylcarbodi-imide as condensing agent. The compounds are suitable for the stepwise synthesis of peptides without racemization. With methanol the N-hydroxyphthalimide ester of N-phthaloylglycine can be converted into the methyl ester of N-phthaloylglycine.

A number of phosphorodichloridites (1) carrying various β-functionalized ethyl protective groups were converted into their corresponding phosphoromorpholido chloridites (2). These were then reacted with 5′-O-(dimethoxytrityl)thymidine to give the pertinent phosphoromorpholidites (3). The applicability of these compounds in the synthesis of oligodeoxynucleotides on a solid support has been evaluated using the synthesis of the thymidine decamer.

This report describes the formation of a non-covalent complex between two tryptic peptides of horse heart cytochrome-c. All amino functions of cytochrome-c were completely protected with the methylsulfonylethyloxycarbonyl (Msc) group. Trypsin split the protected product specifically at Arg38. After separation the fragments were deprotected by a very short treatment with a base. The complex resulting from the deprotected peptides, exhibited a completely developed 695 nm band, and an enhanced oxidase but diminished reductase activity in comparison with native horse heart cytochrome-c.

Modification of the methyl group in 2-(methylsulphonyl)ethanol gave alcohols which could be used to introduce amino-protective groups of the urethane type, which are labile in alkaline media. The cleavage involves β-elimination. Exchange of the methyl group by a phenyl group bearing a function with a negative inductive effect (NO2 or MeSO2) afforded protecting groups with a higher sensitivity to base. The recommended function is a disulphone: 2-[4-(methylsulphonyl)phenylsulphonyl]ethanol. The function has a somewhat better stability than the Fmoc group, resists catalytic hydrogenolysis, is highly stable in acidic medium and its elimination product does not polymerize spontaneously. The suggested designation of the new protective group is Mpc.

As a model study for the usefulness of the synthetic action of a proteinase in the semisynthesis of large polypeptides, a heme peptide, comprising the residues 1-38 of horse heart cytochrome-c and bearing protective functions on the ϵ-amino groups, was incubated with trypsin in the presence of H-Orn(Msc)-Trp-NHCH3 in a mixture of water and organic solvents. We found that the proteolytic enzyme catalysed the formation of a peptide bond between the fragment and the dipeptide derivative.

When performing the seismic risk assessment of new or existing buildings, the definition of compact indexes able to measure the damaging and safety level of structures is essential, also in view of the economic considerations on buildings rehabilitation. This paper proposes two series of indexes, named, respectively, Global Damage Indexes (GDIs), which are representative of the overall structure performance, and Section Damage Indexes (SDIs), which assess the conditions of reinforced concrete (RC) beam-column sections. Such indexes are evaluated by means of an efficient numerical model able to perform nonlinear analyses of the RC frame, based on the continuum damage mechanics theory and fiber approach. An improvement of a two-parameter damage model for concrete, developed by some of the authors, which guarantees a better correlation between the Local Damage Indexes (LDIs) and the material's mechanical characteristics, is also presented. For the reinforcement, a specific LDI, named ‘steel damage index’, which takes into account the plastic strain development and the bar buckling effect, is proposed. The numerical model has been employed to simulate several experimental tests, in order to verify the accuracy of the proposed approach in predicting the RC member's behavior. Nonlinear static and dynamic analyses of two RC frames are carried out. The robustness of the method, as well as the effectiveness of the GDIs in assessing the structural conditions, are demonstrated here. Finally, comparisons between the evolution of GDIs and the achievement of the performance levels as proposed in FEMA 356 are reported. Copyright © 2009 John Wiley & Sons, Ltd.