MHD oblique stagnation-point flow of a Newtonian fluid

The steady two-dimensional oblique stagnation-point flow of an electrically conducting Newtonian fluid in the presence of a uniform external electromagnetic field (E ₀, H ₀) is analysed, and some physical situations are examined. In particular, if E ₀ vanishes, H ₀ lies in the plane of the flow, with a direction not parallel to the boundary, and the induced magnetic field is neglected, it is proved that the oblique stagnation-point flow exists if and only if the external magnetic field is parallel to the dividing streamline. In all cases it is shown that the governing nonlinear partial differential equations admit similarity solutions, and the resulting ordinary differential problems are solved numerically. Finally, the behaviour of the flow near the boundary is analysed; this depends on the Hartmann number if H ₀ is parallel to the dividing streamline.     

On the active site of mononuclear B1 metallo β-lactamases: a computational study

Metallo-β-lactamases (MβLs) are Zn(II)-based bacterial enzymes that hydrolyze β-lactam antibiotics, hampering their beneficial effects. In the most relevant subclass (B1), X-ray crystallography studies on the enzyme from Bacillus Cereus point to either two zinc ions in two metal sites (the so-called ‘3H’ and ‘DCH’ sites) or a single Zn(II) ion in the 3H site, where the ion is coordinated by Asp120, Cys221 and His263 residues. However, spectroscopic studies on the B1 enzyme from B. Cereus in the mono-zinc form suggested the presence of the Zn(II) ion also in the DCH site, where it is bound to an aspartate, a cysteine, a histidine and a water molecule. A structural model of this enzyme in its DCH mononuclear form, so far lacking, is therefore required for inhibitor design and mechanistic studies. By using force field based and mixed quantum–classical (QM/MM) molecular dynamics (MD) simulations of the protein in aqueous solution we constructed such structural model. The geometry and the H-bond network at the catalytic site of this model, in the free form and in complex with two common β-lactam drugs, is compared with experimental and theoretical findings of CphA and the recently solved crystal structure of new B2 MβL from Serratia fonticola (Sfh-I). These are MβLs from the B2 subclass, which features an experimentally well established mono-zinc form, in which the Zn(II) is located in the DCH site. From our simulations the εεδ and δεδ protomers emerge as possible DCH mono-zinc reactive species, giving a novel contribution to the discussion on the MβL reactivity and to the drug design process.     

On Oxygen‐Containing Groups in Chemically Modified Graphenes

Reduced graphenes (belonging to the class of chemically modified graphenes, CMG) are one of the most investigated and utilized materials in current research. Oxygen functionalities on the CMG surfaces have dramatic influences on material properties. Interestingly, these functionalities are rarely comprehensively characterized. Herein, the four most commonly used CMGs, mainly electrochemically reduced graphene oxide (ER‐GO), thermally reduced graphene oxide (TR‐GO), and the corresponding starting materials, that is, graphene oxide and graphite oxide, were comprehensively characterized by a wide variety of methods, such as high‐resolution X‐ray photoelectron spectroscopy, electrochemical impedance spectroscopy, UV/Vis spectroscopy, transmission electron microscopy (TEM), and voltammetry, to establish connections between the structures of these materials that carry different oxygen functionalities and their electrochemical behaviors. This was followed by the quantification of the negatively charged oxygen‐containing groups (OCGs) by UV/Vis spectroscopy and of the electrochemically reducible OCGs by voltammetry. Lastly, a biofunctionalization with gold nanoparticle (AuNP)‐modified DNA sequences was performed by the formation of covalent bonds with the carboxylic groups (? COOH) on the CMG surfaces. There was an evident predominance of functionalizable ? COOH groups on the ER‐GO surface, as confirmed by a higher amount of Au detected both with differential‐pulse voltammetry and impedance spectroscopy, coupled with visualization by TEM. We exploited the DNA–Au bioconjugates as highly specific stains to localize and visualize the positions of carboxylic groups. Our findings are very important to clearly identify the presence, nature, and distribution of oxygen functionalities on different chemically modified graphenes.     

Engineering of Streptoalloteichus tenebrarius 2444 for Sustainable Production of Tobramycin

Tobramycin is a broad-spectrum aminoglycoside antibiotic agent. The compound is obtained from the base-catalyzed hydrolysis of carbamoyltobramycin (CTB), which is naturally produced by the actinomycete Streptoalloteichus tenebrarius. However, the strain uses the same precursors to synthesize several structurally related aminoglycosides. Consequently, the production yields of tobramycin are low, and the compound’s purification is very challenging, costly, and time-consuming. In this study, the production of the main undesired product, apramycin, in the industrial isolate Streptoalloteichus tenebrarius 2444 was decreased by applying the fermentation media M10 and M11, which contained high concentrations of starch and dextrin. Furthermore, the strain was genetically engineered by the inactivation of the aprK gene (∆aprK), resulting in the abolishment of apramycin biosynthesis. In the next step of strain development, an additional copy of the tobramycin biosynthetic gene cluster (BGC) was introduced into the ∆aprK mutant. Fermentation by the engineered strain (∆aprK_1-17L) in M11 medium resulted in a 3- to 4-fold higher production than fermentation by the precursor strain (∆aprK). The phenotypic stability of the mutant without selection pressure was validated. The use of the engineered S. tenebrarius 2444 facilitates a step-saving, efficient, and, thus, more sustainable production of the valuable compound tobramycin on an industrial scale.     

Elliptic Fibrations and Symplectic Automorphisms on K3 Surfaces

Nikulin has classified all finite abelian groups acting symplectically on a K3 surface and he has shown that the induced action on the K3 lattice U ³ ⊕ E ₈(?1)² depends only on the group but not on the K3 surface. For all the groups in the list of Nikulin we compute the invariant sublattice and its orthogonal complement by using some special elliptic K3 surfaces.     

Conformational evolution of TFSI− in protic and aprotic ionic liquids

We here report on the conformational evolution of the bis(trifluoromethanesulfonyl)imide anion (TFSI⁻) in protic and aprotic TFSI⁻‐based ionic liquids as a function of temperature. The investigation is performed by Raman spectroscopy in the spectral ranges 240‐380 cm⁻¹ and 715‐765 cm⁻¹, where the interference from bands due to the cations is negligible. The contribution from each TFSI⁻ conformation, i.e. the cisoid (C₁) and the transoid (C₂), is quantified in order to estimate the enthalpy of conformational change, ΔH, which is found to be in the range 3.4–7.3 kJ/mol in the liquid state. Conformational information is for the first time determined from the 740 cm⁻¹ band, which previously mainly has been used as an indicator of ion‐ion interactions. The similarity in ΔH values obtained from the two spectral ranges demonstrates the validity of using also the 740 cm⁻¹ band for the quantification of the TFSI conformational evolution. Copyright © 2010 John Wiley & Sons, Ltd.     

A semiparametric Bayesian generalized linear mixed model for the reliability of Kevlar fibers

We analyze the reliability of NASA composite pressure vessels by using a new Bayesian semiparametric model. The data set consists of lifetimes of pressure vessels, wrapped with a Kevlar fiber, grouped by spool, subject to different stress levels; 10% of the data are right censored. The model that we consider is a regression on the log‐scale for the lifetimes, with fixed (stress) and random (spool) effects. The prior of the spool parameters is nonparametric, namely they are a sample from a normalized generalized gamma process, which encompasses the well‐known Dirichlet process. The nonparametric prior is assumed to robustify inferences to misspecification of the parametric prior. Here, this choice of likelihood and prior yields a new Bayesian model in reliability analysis. Via a Bayesian hierarchical approach, it is easy to analyze the reliability of the Kevlar fiber by predicting quantiles of the failure time when a new spool is selected at random from the population of spools. Moreover, for comparative purposes, we review the most interesting frequentist and Bayesian models analyzing this data set. Our credibility intervals of the quantiles of interest for a new random spool are narrower than those derived by previous Bayesian parametric literature, although the predictive goodness‐of‐fit performances are similar. Finally, as an original feature of our model, by means of the discreteness of the random‐effects distribution, we are able to cluster the spools into three different groups. Copyright © 2012 John Wiley & Sons, Ltd.     

Flavonoid-Inspired Vascular Disrupting Agents: Exploring Flavone-8-Acetic Acid and Derivatives in the New Century

Naturally occurring flavonoids are found as secondary metabolites in a wide number of plants exploited for both medicine and food and have long been known to be endowed with multiple biological activities, making them useful tools for the treatment of different pathologies. Due to the versatility of the scaffolds and the vast possibilities of appropriate decoration, they have also been regarded as fruitful sources of lead compounds and excellent chemical platforms for the development of bioactive synthetic compounds. Flavone-8-acetic acid (FAA) and 5,6-dimethylxanthone acetic acid (DMXAA) emerged for their antitumour potential due to the induction of cytokines and consequent rapid haemorrhagic necrosis of murine tumour vasculature, and different series of derivatives have been designed thereafter. Although the promising DMXAA failed in phase III clinical trials because of strict species-specificity, a boost in research came from the recent identification of the stimulator of interferon genes (STING), responsible for supporting tumoural innate immune responses, as a possible biological target. Consequently, in the last decade a renewal of interest for these flavonoid-based structures was noticed, and novel derivatives have been synthesised and evaluated for a deeper understanding of the molecular features needed for affecting human cells. Undoubtedly, these natural-derived molecules deserve further investigation and still appear attractive in an anticancer perspective.