Flexural-torsional bifurcations of a cantilever beam under potential and circulatory forces II. Post-critical analysis

The post-critical behavior of a cantilever beam with rectangular cross-section, under simultaneous action of conservative and non-conservative loads, is analyzed. An internally constrained Cosserat rod model is adopted to describe the dynamics of the beam in finite displacement regime. The bifurcation equations for simple buckling (divergence), simple flutter (Hopf) and double-zero (Takens-Bogdanova-Arnold) bifurcations are derived by means of the multiple time scales method. Due to the nilpotent eigenvalue at the double-zero critical point, the evaluation of the generalized Keldysh's eigenfunctions is required. Finally, some numerical results are shown and the bifurcation scenario of the beam is discussed.     

The Terminal-Oriented Ship Stowage Planning Problem

The Ship Stowage Planning Problem is the problem of determining the optimal position of containers to be stowed in a containership. In this paper we address the problem considering the objectives of the terminal management that are mainly related to the yard and transport operations. We propose a Binary Integer Program and a two-step heuristic algorithm. An extensive computational experience shows the efficiency and effectiveness of our approach. A classification scheme for stowage planning problems is also provided.     

Valence-band electronic structure of iron phthalocyanine: an experimental and theoretical photoelectron spectroscopy study

The electronic structure of iron phthalocyanine (FePc) in the valence region was examined within a joint theoretical-experimental collaboration. Particular emphasis was placed on the determination of the energy position of the Fe 3d levels in proximity of the highest occupied molecular orbital (HOMO). Photoelectron spectroscopy (PES) measurements were performed on FePc in gas phase at several photon energies in the interval between 21 and 150 eV. Significant variations of the relative intensities were observed, indicating a different elemental and atomic orbital composition of the highest lying spectral features. The electronic structure of a single FePc molecule was first computed by quantum chemical calculations by means of density functional theory (DFT). The hybrid Becke 3-parameter, Lee, Yang and Parr (B3LYP) functional and the semilocal 1996 functional of Perdew, Burke and Ernzerhof (PBE) of the generalized gradient approximation (GGA-)type, exchange-correlation functionals were used. The DFT/B3LYP calculations find that the HOMO is a doubly occupied π-type orbital formed by the carbon 2p electrons, and the HOMO-1 is a mixing of carbon 2p and iron 3d electrons. In contrast, the DFT/PBE calculations find an iron 3d contribution in the HOMO. The experimental photoelectron spectra of the valence band taken at different energies were simulated by means of the Gelius model, taking into account the atomic subshell photoionization cross sections. Moreover, calculations of the electronic structure of FePc using the GGA+U method were performed, where the strong correlations of the Fe 3d electronic states were incorporated through the Hubbard model. Through a comparison with our quantum chemical calculations we find that the best agreement with the experimental results is obtained for a U(eff) value of 5 eV.     

Synthesis of 2′‐Deoxy‐1′‐homo‐N‐nucleosides with Anti‐Influenza Activity by Catalytic Methyltrioxorhenium (MTO)/H2O2 Oxyfunctionalization

This paper describes a new route for the synthesis of 1′‐homo‐N‐nucleoside derivatives by means of either methyltrioxorhenium (MTO) or supported MTO catalysts, with H₂O₂ as the primary oxidant. Under these selective conditions, the oxyfunctionalization of the heterocyclic ring and the N heteroatom oxidation were operative processes, regardless of the type of substrate used, that is, purine or pyrimidine derivatives. In addition, the oxidation of 1′‐homo‐N‐thionucleosides, showed the occurrence of site‐specific oxidative nucleophilic substitutions of the heterocyclic ring. The MTO/H₂O₂ system showed, in general, high reactivity under both homogeneous and heterogeneous conditions, affording the final products with high conversion values of substrates and from medium to high yields. Many of the novel 1′‐homo‐N‐nucleoside analogues were active against the influenza A virus, without any cytotoxic effects, retaining their activity in both protected and unprotected forms.     

Compatibility of sildenafil citrate and pharmaceutical excipients by thermal analysis and LC–UV

The evaluation of sildenafil citrate (SC), the best-selling drug for treatment of impotence, for compatibility with various excipients was investigated using thermal and isothermal stress testing. Differential scanning calorimetry (DSC), hot-stage microscopy (HSM) and liquid chromatography (LC) with ultraviolet detection were successfully employed to investigate the compatibility between SC and various excipients commonly used in solid form in the pharmaceutical industry. The studies were performed using 1:1 (m/m) drug/excipient physical mixtures and samples were stored under accelerated stability conditions (40 °C at 75% relative humidity). All excipients tested (such as colloidal silicon dioxide, croscarmellose sodium, lactose, mannitol and sucrose) showed potential incompatibilities by DSC and LC analysis after accelerated stability testing. However, some incompatibilities were not detected by the DSC method and were observed only when LC analysis was performed. HSM was able to differentiate active pharmaceutical ingredient degradation from solubilisation, supporting the interpretation of DSC in excipients where thermal events either overlapped or disappeared. The combination of both the analytical techniques (DSC and LC) and use of a stability chamber is extremely helpful in detecting incompatibilities and providing more robust and accurate approaches for pre-formulation studies.     

Dual-color bioluminescent bioreporter for forensic analysis: evidence of androgenic and anti-androgenic activity of illicit drugs

Bioassays represent promising complementary techniques to conventional analytical approaches used in doping analysis to detect illicit drugs like anabolic-androgenic steroids (AAS). The fact that all AAS share a common mechanism of action via the human androgen receptor (hAR) enables the use of bioassays, relying on the activation of hAR as antidoping screening tools. Previously, we developed a dual-color bioreporter based on yeast cells engineered to express hAR and androgen response elements driving the expression of the bioluminescent (BL) reporter protein Photinus pyralis luciferase. A second reporter protein, the red-emitting luciferase PpyRE8, was introduced in the bioreporter as internal viability control. Here, we report the first forensic application of a straightforward, accurate, and cost-effective bioassay, relying on spectral resolution of the two BL signals, in 96-microwell format. The bioreporter responds to dihydrotestosterone as reference androgen in a concentration-dependent manner from 0.08 to 1,000 nM with intra- and inter-assay variation coefficients of 11.4 % and 13.1 %, respectively. We also demonstrated the suitability of this dual-color bioreporter to assess (anti)-androgenic activity of pure AAS, mixtures of AAS, and other illicit drugs provided by the Scientific Police. Significant anti-androgenic activity was observed in samples labeled as marijuana and hashish, containing Δ⁹-tetrahydrocannabinol as major constituent.

Development of a Biosensor for Copper Detection in Aqueous Solutions Using an Anemonia sulcata Recombinant GFP

Fluorescent proteins from marine organisms represent potential candidates for biosensor development. In this paper, we described the isolation of a native green fluorescent protein from Anemonia sulcata and the cloning and purification of its equivalent as a recombinant protein in Escherichia coli. Furthermore, the spectroscopic behaviours of the native and recombinant GFPs were investigated as a function of Cu²⁺, Cd²⁺, Pb²⁺ and Ni²⁺ concentration. Our results suggest the high selectivity of both proteins at copper than the other metals and, for the recombinant protein, a great sensitivity at a very low concentration (0.1–1 μM). Moreover, starting from these data, using the combination of molecular biology techniques and optical setup, we developed a device for the detection of Cu²⁺ in water solutions. The quenching effect detected with the device showed that the relative attenuation of the signal (0.46?±?0.02 AU) was slightly larger than the data measured by fluorescence spectra (0.65?±?0.03 AU). The good sensitivity in the span of two orders of the magnitude of Cu²⁺ concentration, the fact that the instrument is made up of low-cost and sturdy parts and the selective quenching of rAsGFP to copper ions make this setup suited as a low cost, on-the-field, copper ion-specific biosensor.     

Amygdalar glutamatergic neuronal systems play a key role on the hibernating state of hamsters

Background  

Excitatory transmitting mechanisms are proving to play a critical role on neuronal homeostasis conditions of facultative hibernators such as the Syrian golden hamster. Indeed works have shown that the glutamatergic system of the main olfactory brain station (amygdala) is capable of controlling thermoregulatory responses, which are considered vital for the different hibernating states. In the present study the role of amygdalar glutamatergic circuits on non-hibernating (NHIB) and hibernating (HIB) hamsters were assessed on drinking stimuli and subsequently compared to expression variations of some glutamatergic subtype mRNA levels in limbic areas. For this study the two major glutamatergic antagonists and namely that of N-methyl-D-aspartate receptor (NMDAR), 3-(+)-2-carboxypiperazin-4-yl-propyl-1-phosphonate (CPP) plus that of the acid α-amine-3-hydroxy-5-metil-4-isoxazol-propionic receptor (AMPAR) site, cyano-7-nitro-quinoxaline-2,3-dione (CNQX) were infused into the basolateral amygdala nucleus. Attempts were made to establish the type of effects evoked by amygdalar glutamatergic cross-talking processes during drinking stimuli, a response that may corroborate their major role at least during some stages of this physiological activity in hibernators.     

Synthesis and Biological Evaluation of Halogenated E-Stilbenols as Promising Antiaging Agents

The increased risk of illness and disability is related to the age inevitable biological changes. Oxidative stress is a proposed mechanism for many age-related diseases. The crucial importance of polyphenol pharmacophore for aging process is largely described thanks to its effects on concentrations of reactive oxygen species. Resveratrol (3,5,4′-trihydroxy-trans-stilbene, RSV) plays a critical role in slowing the aging process but has a poor bioavailabity after oral intake. In this present work, a series of RSV derivatives was designed, synthesized, and evaluated as potential antioxidant agents. These derivatives contain substituents with different electronic and steric properties in different positions of aromatic rings. This kind of substituents affects the activity and the bioavailability of these compounds compared with RSV used as reference compound. Studies of Log P values demonstrated that the introduction of halogens gives the optimum lipophilicity to be considered promising active agents. Among them, compound 6 showed the higher antioxidant activity than RSV. The presence of trifluoromethyl group together with a chlorine atom increased the antioxidant activity compared to RSV.     

Asymptotic profile of solutions for strongly damped Klein‐Gordon equations

We consider the Cauchy problem in R ⁿ for strongly damped Klein‐Gordon equations. We derive asymptotic profiles of solutions with weighted L^1,1( R ⁿ) initial data by a simple method introduced by the second author. Furthermore, from the obtained asymptotic profile, we get the optimal decay order of the L²‐norm of solutions. The obtained results show that the wave effect will be relatively weak because of the mass term, especially in the low‐dimensional case (n = 1,2) as compared with the strongly damped wave equations without mass term (m = 0), so the most interesting topic in this paper is the n = 1,2 cases to compare the difference.