L-lanthionine oxidation by snake venom L-amino acid oxidase

L-Lanthionine is oxidized by snake venom L-amino acid oxidase with the release of one mole of ammonia per mole of lanthionine. Spectrophotometric, chromatographic, and analytical properties are all consistent with the identification of the mono-keto derivative of lanthionine as the first enzymatic product of the reaction. This then cyclizes into a dihydrothiazine dicarboxylic acid which is further subject to spontaneous changes. Authentic samples of the thiazine derivative have been prepared by interacting L-cysteine with bromopyruvic acid. The properties of the synthetic product are described and compared with those exhibited by the enzymatic product.     

A meshless method for axi‐symmetric poroelastic simulations: numerical study

A meshless model, based on the meshless local Petrov–Galerkin (MLPG) approach, is developed and implemented for the solution of axi‐symmetric poroelastic problems. The solution accuracy and the code performance are investigated on a realistic application concerning the prediction of land subsidence above a deep compacting reservoir. The analysis addresses several numerical issues, including the parametric selection of the optimal size of the local sub‐domains for the weak form and the nodal supports, the appropriate integration rule, and the linear system solver. The results show that MLPG can be more accurate than the standard finite element (FE) method on coarse discretizations, with its superiority decreasing as the nodal resolution increases. This is due to both a slower convergence rate and a progressively higher computational cost compared to FE. These drawbacks can be partially mitigated by improving the efficiency of the numerical integration and the system solver with the aid of projection techniques based on Krylov subspace methods. The outcome of the present analysis supports the development of coupled methods where a limited number of MLPG nodes are used to locally improve a FE solution. Copyright © 2006 John Wiley & Sons, Ltd.     

Peak Response of a Nonlinear Beam

A model for estimating the peak dynamic response distribution of a nonlinear beam, based on a special class of non-Gaussian stochastic processes, is proposed in this paper. It is shown that the stochastic response of a cantilever beam with geometrically nonlinear behavior can be accurately calibrated with translation processes. Different models to describe the significant bimodal features in the marginal probability density functions of the response time histories are proposed. Finally, two of these models are used to estimate the response peak value distributions and the results are compared. This comparison demonstrates the effects of inaccurate models for the parent response processes on the peaks estimation.     

A transformed gamma process for bounded degradation phenomena

Most of the stochastic models adopted to describe the evolution over time of degradation phenomena of technological units assume that their degradation level can increase indeterminately. However, these degradation phenomena are typically subjected to obvious bounds, if only because technological units have finite size. In fact, very often, this inconsistency does not significantly affect the effectiveness of unbounded degradation models, since degrading units are usually assumed to fail when their degradation level exceeds a failure threshold that is much smaller than the obvious bounds. Nevertheless, in some cases, due to the very nature of the underlying degradation mechanism, less obvious bounds could exist, which are not necessarily far from the failure thresholds. The question that arises is whether the use of a bounded degradation model, in this latter type of experimental situations, could be beneficial. For this purpose, since a bounded degradation process should necessarily have dependent increments, in this paper we investigate the potential of a new bounded transformed gamma (TG) process to adequately describe bounded degradation phenomena and predict their future evolution. Differently from other existing gamma process based bounded degradation models, here the upper bound is treated as an unknown parameter that has to be estimated from the available degradation data. A numerical example is presented where the parameters of the proposed model are estimated from simulated data. Then the model is applied to a set of wear measures of cylinder liners that equip a diesel engine for marine propulsion, which have also stimulated this study. Model parameters are estimated by using the maximum likelihood (ML) method. The fitting ability of the proposed new bounded process is compared to that of an unbounded gamma process, which was previously adopted to analyze the same liner wear data. Obtained results are critically discussed in the paper.     

3D sound spatialization with game engines: the virtual acoustics performance of a game engine and a middleware for interactive audio design

Virtual Reality - This study analyses one of the most popular game engines and an audio middleware to reproduce sound according to sound propagation physics. The analysis focuses on the...     

Print base decorative paper with high-dimensional stability by chemical fiber modification: An experimental and analytical approach

The main structural component of wood fibers is cellulose, which, being highly hydrophilic, interacts with water. Cellulose-based paper has, therefore, the same affinity with water. However, for most products such as decorative paper, this is more of a disadvantage, where water uptake both as liquid and from humid air not only weakens the paper by breaking hydrogen bonds but also alters its dimension and stability over time. The dimensional stability (ability of the paper to retain the size as its moisture content changes) is a critical parameter when the paper is submitted to printing, copying, and converting operations. Humidity can cause sheet wrinkling or warping, thus compromising the processability and the results achievable. The modification of fibers with chemical additives can be a way to improve the performance of paper against water and water vapor uptake. For this reason, several tests of horizontal diffusion of solvents were carried out to evaluate the change in uptake of as-is paper and of papers modified by several different chemical treatments. Solvent uptake tests were performed to assess the interaction of chemically treated and untreated papers with water, dichloromethane, and ethanol. Diffusion mechanisms of the solvents flow within the fiber networks and their movement through the porous solids were analyzed. The chemical treatments of the fiber with silane, siloxane, and polyelectrolyte multilayer were found to considerably influence both solvent contact angles and absorption times of the papers, thus affecting the rate of solvent (more interestingly, of the water) diffusion into the fiber wall. By comparing all the treated and untreated samples, the contact angles with the solvents decreased by performing siloxane, oligo-siloxane, and silane treatments. More specifically, the diffusivity rates of water decreased because of the disappearance of a fraction of the hydrophilic sites and the onset of higher crystallinity regions on the paper sheets.     

Gene Transfer Potential of Outer Membrane Vesicles of Gram-Negative Bacteria

The increasing spread of multidrug-resistant pathogenic bacteria is one of the major threats to public health worldwide. Bacteria can acquire antibiotic resistance and virulence genes through horizontal gene transfer (HGT). A novel horizontal gene transfer mechanism mediated by outer membrane vesicles (OMVs) has been recently identified. OMVs are rounded nanostructures released during their growth by Gram-negative bacteria. Biologically active toxins and virulence factors are often entrapped within these vesicles that behave as molecular carriers. Recently, OMVs have been reported to contain DNA molecules, but little is known about the vesicle packaging, release, and transfer mechanisms. The present review highlights the role of OMVs in HGT processes in Gram-negative bacteria.     

Integrated Genomics Identifies miR-181/TFAM Pathway as a Critical Driver of Drug Resistance in Melanoma

MicroRNAs (miRNAs) are attractive therapeutic targets and promising candidates as molecular biomarkers for various therapy-resistant tumors. However, the association between miRNAs and drug resistance in melanoma remains to be elucidated. We used an integrative genomic analysis to comprehensively study the miRNA expression profiles of drug-resistant melanoma patients and cell lines. MicroRNA-181a and -181b (miR181a/b) were identified as the most significantly down-regulated miRNAs in resistant melanoma patients and cell lines. Re-establishment of miR-181a/b expression reverses the resistance of melanoma cells to the BRAF inhibitor dabrafenib. Introduction of miR-181 mimics markedly decreases the expression of TFAM in A375 melanoma cells resistant to BRAF inhibitors. Furthermore, melanoma growth was inhibited in A375 and M14 resistant melanoma cells transfected with miR-181a/b mimics, while miR-181a/b depletion enhanced resistance in sensitive cell lines. Collectively, our study demonstrated that miR-181a/b could reverse the resistance to BRAF inhibitors in dabrafenib resistant melanoma cell lines. In addition, miR-181a and -181b are strongly down-regulated in tumor samples from patients before and after the development of resistance to targeted therapies. Finally, melanoma tissues with high miR-181a and -181b expression presented favorable outcomes in terms of Progression Free Survival, suggesting that miR-181 is a clinically relevant candidate for therapeutic development or biomarker-based therapy selection.     

Novel Emerging Molecular Targets in Non-Small Cell Lung Cancer

In the scenario of systemic treatment for advanced non-small cell lung cancer (NSCLC) patients, one of the most relevant breakthroughs is represented by targeted therapies. Throughout the last years, inhibitors of the epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), c-Ros oncogene 1 (ROS1), and V-raf murine sarcoma viral oncogene homolog B (BRAF) have been approved and are currently used in clinical practice. However, other promising molecular drivers are rapidly emerging as therapeutic targets. This review aims to cover the molecular alterations with a potential clinical impact in NSCLC, including amplifications or mutations of the mesenchymal–epithelial transition factor (MET), fusions of rearranged during transfection (RET), rearrangements of the neurotrophic tyrosine kinase (NTRK) genes, mutations of the Kirsten rat sarcoma viral oncogene (KRAS) and phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA), as well as amplifications or mutations of human epidermal growth factor receptor 2 (HER2). Additionally, we summarized the current status of targeted agents under investigation for such alterations. This revision of the current literature on emerging molecular targets is needed as the evolving knowledge on novel actionable oncogenic drivers and targeted agents is expected to increase the proportion of patients who will benefit from tailored therapeutic approaches.     

Calving difficulty influences rumination time and inflammatory profile in Holstein dairy cows

Difficult calving may adversely affect dairy cow health and performance. Maternal:fetal disproportion is a major cause of dystocia. Therefore, the main objective of this study was to assess the effects of dam:calf body weight ratio (D:C) on calving difficulty, rumination time, lying time, and inflammatory profile in 25 Holstein dairy cows. Using automatic monitoring systems, we monitored behavior and production in 9 primiparous and 16 pluriparous cows between dry-off and 30 d in milk. During the same period, we collected blood samples to monitor metabolism and inflammatory profile of these cows. Calvings were video recorded to assess calving difficulty and observe the duration of the expulsive stage. After parturition, the cows were separated into 3 classes according to their D:C: easy (E; D:C >17), medium (M; 14 < D:C <17), and difficult (D; D:C <14). The cows in class D showed relatively longer labor durations (108 min vs. 54 and 51 min for classes D, M, and E, respectively) and higher calving assistance rates (50% vs. 0 and 11% of calvings for classes D, M, and E, respectively) than those in the other 2 classes. Compared with the cows in classes M and E, those in class D exhibited shorter rumination times on the day of calving (176 min/d vs. 288 and 354 min/d for classes D, M, and E, respectively) and during the first week of lactation (312 min/d vs. 339 and 434 min/d for classes D, M, and E, respectively) and maintained lower rumination values until 30 DIM (399 min/d vs. 451 and 499 min/d for classes D, M, and E, respectively). Primiparous class D cows had shorter resting times during the first week after calving compared with those in class M (8 vs. 11 h/d for classes D and M, respectively). Interclass differences were found in terms of the levels of inflammation markers such as acute-phase proteins (ceruloplasmin, albumin, retinol, and paraoxonase). Moreover, cows in class D had lower plasma levels of fructosamine and creatinine after calving. Low D:C reduced postcalving rumination time and increased inflammation grade, suggesting a lower welfare of these animals at the onset of lactation. The D:C might serve as a useful index for the identification of cows at relatively higher risk of metabolic and inflammatory disease, thus helping farmers and veterinarians improve the welfare and health of these cows.