Silicon analogues of the retinoid agonists TTNPB and 3-methyl-TTNPB, disila-TTNPB and disila-3-methyl-TTNPB: chemistry and biology

Twofold sila-substitution (C/Si exchange) in the saturated ring of the tetrahydronaphthalene skeleton of the retinoid agonists TTNPB (1 a) and 3-methyl-TTNPB (2 a) leads to disila-TTNPB (1 b) and disila-3-methyl-TTNPB (2 b), respectively. The silicon compounds 1 b and 2 b were synthesized in multiple steps, and their identities were established by elemental analyses, multinuclear NMR experiments, and single-crystal X-ray diffraction studies. Like TTNPB (1 a) and 3-methyl-TTNPB (2 a), the analogous silicon-based arotinoids 1 b and 2 b are strong pan-RAR agonists and display the same strong differentiation and apoptosis-inducing activity in NB4 promyelocytic leukemia cells as the parent carbon compounds. These results are in keeping with the nearly isomorphous structures of 1 a and 1 b bound to the complex of the RARbeta ligand-binding domain with the nuclear receptor (NR) box 2 peptide of the SRC-1 coactivator. The contacts within the ligand-binding pocket are identical except for helix H11, for which two turns are shifted in the disila-TTNPB (1 b) complex. This study represents the first comprehensive structure-function analysis of a carbon/silicon switch in a signaling molecule and demonstrates that silicon analogues can have the same biological functionalities and conserved structures as their parent carbon compounds, and it illustrates at the same time that silicon analogues of biologically active compounds have the potential to induce alternative allosteric effects, as in the case of helix H11, which might allow for novel options in drug design.     

On the prebiotic synthesis of ribonucleotides: photoanomerisation of cytosine nucleosides and nucleotides revisited

Recent work has emphasised the importance of D-ribose aminooxazoline 1 in the synthesis of cytidine ribonucleosides under potentially prebiotic conditions. Upon treatment with cyanoacetylene, 1 is transformed into alpha-D-cytidine (alpha-2), and if an efficient means of anomerising this nucleoside or a derivative thereof were to be found, then the synthesis of one of the key beta-D-nucleosides required to make RNA would be realised. Photoanomerisation of alpha-2 has previously been described, but the yield was extremely low. Therefore, the present study was initiated to determine whether this low yield was the result of a low conversion or competing reaction pathways.     

Simultaneous dynamic T1 and T2* measurement for AIF assessment combined with DCE MRI in a mouse tumor model

A double-delay SR-MGE-SNAP sequence allowing simultaneous T1 and T2* measurement was developed for integrating arterial input function (AIF) measurement into DCE MRI. Implemented on a 4.7-T animal MR system, this technique was applied to mice with colorectal tumor xenografts. AIF, measured in the mouse heart, was modeled by a bi-exponential function, whereas tumor K(trans) and v(e) parameter maps were obtained from analysis with a two- compartment model using an individually measured AIF. AIF analysis of T2*-corrected data yielded A1 = 9.2 +/- 4.3 kg/l, A(2) = 4.2 +/- 0.8 kg/l, m1 = 2.3 +/- 1.1 min(-1), and m2 = 0.05 +/- 0.02 min(-1). The mean initial plasma concentration C ( p )(t = 0) = 8.0 +/- 2.7 mM was compatible with estimated 8.6 mM. Without T2*-correction distribution phase parameters A1, m1, and C(p)(t = 0) were underestimated. In tumors, neglect of T2* effects yielded mean K(trans) values which were reduced by 14% (P < 0.05), whereas v(e) showed only a slight non-significant reduction. Simultaneous measurement of DeltaR1 and DeltaR2* studied in highly and poorly vascularized and (pre-)necrotic tumor regions revealed complementary behavior of both parameters with respect to vascular properties. In conclusion, the presented measurement technique is a promising tool for dynamic MRI applications studied in animal models at high field strengths and/or with CA of high relaxivities, as it combines classical DCE MRI integrating AIF assessment with dynamic T2* measurement.     

The evolution of the Canadian Code of Ethics over the years (1986–2011).

In this article, the evolution of the Canadian Code of Ethics for Psychologists (the Code) from its first adoption in 1986 to its third edition in 2000 is traced, and possible changes to the next edition of the Code are explored. Several characteristics maintained over all three editions of the Code are identified as its core. Clarifications that have been made to some of these core characteristics are outlined, including articulation of the concept of a “contract with society,” clarification of the legitimate use of personal conscience, additional steps in the ethical decision making process, and more detailed explanations in the Values Statements. Reasons for changes to standards are identified as primarily related to changes in society that have resulted in changes to the expectations and work of psychologists, as well as to the ongoing dialogue within the psychology and broader communities regarding ethical issues and challenges. Five tables outline the substantive changes made to the Code over the years. The author also presents some initial results from the current process of review of the 2000 Code. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Evaluation of digital PCR for absolute DNA quantification

The emerging technique of microfluidic digital PCR (dPCR) offers a unique approach to real-time quantitative PCR for measuring nucleic acids that may be particularly suited for low-level detection. In this study, we evaluated the quantitative capabilities of dPCR when measuring small amounts (<200 copies) of DNA and investigated parameters influencing technical performance. We used various DNA templates, matrixes, and assays to evaluate the precision, sensitivity and reproducibility of dPCR, and demonstrate that this technique can be highly reproducible when performed at different times and when different primer sets are targeting the same molecule. dPCR exhibited good analytical sensitivity and was reproducible outside the range recommended by the instrument manufacturer; detecting 16 estimated targets with high precision. The inclusion of carrier had no effect on this estimated quantity, but did improve measurement precision. We report disagreement when using dPCR to measure different template types and when comparing the estimated quantities by dPCR and UV spectrophotometry. Finally, we also demonstrate that preamplification can impose a significant measurement bias. These findings provide an independent assessment of low copy molecular measurement using dPCR and underline important factors for consideration in dPCR experimental design.     

Optical component interface scatter characterization by selective polarization extinction

A procedure for the selective extinction of the scattered light based on "null ellipsometry" [R. M. A. Azzam and N. M. Bashara, Ellipsometry and Polarized Light (North-Holland, 1977)] is presented. The technique allows scattering measurement from individual layers of a multilayer component by extinguishing the scattered light from the other layer interfaces. The technique is easily applicable to multilayer components with nearly identical surface profiles at every interface and little significant bulk scattering. Analysis is provided to determine the conditions required to extinguish the light from the excluded interfaces isolating the scattered light from the desired interface. An analysis of sensitivity of the extinction conditions to experimental parameters and to layer optical thickness is also provided. Experimental data collected using the technique are compared with measurements made using a white-light optical surface profilometry.     

Organoleptic characterization and PAH content of salmon (Salmo salar) fillets smoked according to four industrial smoking techniques

Four industrial processes for smoking food were studied through their effects on the organoleptic properties of smoked salmon and on the occurrence of 20 polycyclic aromatic hydrocarbons (PAHs) known as being contaminants of smoking processes. The contamination by PAHs of the food might be measured by their corresponding toxic equivalent quantity (TEQ) expressed in µg kg^?1. The results show a significant correlation between the smoking process parameters, the odour of the smoked fish and the presence of PAHs. Smouldering, thermostated plates and friction smoking processes allow smoked fish with very close odorant characteristics to be obtained. However, differences of pyrolysis temperature (between 380 and 500 °C) causes significant differences of PAHs concentration even if the contents are under the legal threshold concerning benzo(a)pyrene (5 µg kg^?1). Smoked fish obtained by liquid smoke vaporisation presented the lowest level of PAHs but benzo(a)pyrene concentration is nevertheless important. The odours brought by the liquid smoke process are more ‘cold smoke’ and ‘vegetal/green’ than the other techniques, which are smokier and fishier. Copyright © 2007 Society of Chemical Industry     

Housing finance for lower income urban households in Zimbabwe

Housing finance systems in developing countries have been the subject of considerable international agency research and lending attention in recent years. The lack of availability of finance for public sector housing programmes and for the purchase of construction of housing by all income groups in urban areas is typically a major constraint on the ability of supply to meet demand. However, national efforts have often not dealt systematically with the housing finance system as a whole. The housing finance system in Zimbabwe is described and critically analysed in this paper, paying particular attention to the provision of funds for local authority housing programmes for low income residents, the place of housing finance institutions in the national finance system, the ability of the building societies to attract savings, and their lending programmes. The results of government measures to transfer responsibility for lending to low‐income households from local authorities to the building societies since the mid‐1980s are evaluated. It is concluded that Zimbabwe has an unusually well‐developed financial sector and housing finance system for a recently independent developing country. Although this evolved to meet the needs of the settler population, the extension of its activities into lending for low‐income aided self‐help housing was successful, within limits. However, events of the early 1990s demonstrate the vulnerability of such a system to the changes accompanying liberalisation. Suggestions are made for further possible reforms and the importance of monitoring the effects of economic liberalisation on the system and its beneficiaries stressed.     

High voltage nickel manganese spinel oxides for Li-ion batteries

High voltage spinel oxides with composition LiMn_2 − xM_xO₄ (M, a transition metal element) have remarkable properties such as high potential, high energy density and high rate capability. We believe that these positive electrode materials could replace the widespread commercial layered nickel cobalt oxides in some applications. The present assessment highlights electrochemical performance of optimized LiNi_0.5Mn_1.5O₄ and substituted counterparts, all having a spinel structure (cubic close-packed oxygen array) similar to the relative LiMn₂O₄. To fully emphasize the benefit from high potential spinel oxides, tests have been performed versus lithium metal, Li₄Ti₅O₁₂ and graphite, using various electrode loadings (0.3-4.5 mAh cm⁻²) and cycling rates (from C/20 to 60C rate). Steady capacity retention (130-140 mAh g⁻¹ for nearly 500 cycles) and flat voltage (4.7 V vs. Li⁺/Li) have been obtained at C/5 rate at room temperature. Effect of cycling at high temperature has been shown to be less critical than for LiMn₂O₄. High voltage spinel oxides still sustain 100 mAh g⁻¹ and over after 400 cycles at 55 °C at 1C rate. Rate capability is also excellent, with only 4% loss of capacity when comparing C/8 and 8C rates (thin electrodes).