Lewis acid–base interactions enhance explosives sensing in silacycle polymers

The high sensitivity of silole- and silafluorene-containing polymers for detecting organic nitro, nitrate, and nitramine explosives cannot be solely attributed to favorable analyte–polymer hydrophobic interactions and amplified fluorescence quenching due to delocalization along the polymer chain. The Lewis acidity of silicon in conjugated poly(silafluorene-vinylene)s is shown to be important. This was established by examining the 29Si NMR chemical shifts (Δ) for the model trimer fragment of the polymer CH3–silafluorene–(trans-C2H2)–silafluorene–(trans-C2H2)–silafluorene–CH3. The peripheral and central silicon resonances are up-field from a TMS reference at −9.50 and −18.9 ppm, respectively. Both resonances shift down-field in the presence of donor analytes and the observed shifts (0 to 1 ppm) correlate with the basicity of a variety of added Lewis bases, including TNT. The most basic analyte studied was acetonitrile and an association constant (Ka) of 0.12 M−1 was calculated its binding to the peripheral silicon centers using the Scatchard method. Spin-lattice relaxation times (T1) of 5.86(3) and 4.83(4) s were measured for the methyl protons of acetonitrile in benzene-d6 at 20 °C in the absence and presence of the silafluorene trimer, respectively. The significant change in T1 values further supports a binding event between acetonitrile and the silafluorene trimer. These studies as well as significant changes and shifts observed in the characteristic UV–Vis absorption of the silafluorene group support an important role for the Lewis acid character of Si in polymer sensors that incorporate strained silacycles. The nitro groups of high explosives may act as weak Lewis-base donors to silacycles. This provides a donor–acceptor interaction that may be crucial for orienting the explosive analyte in the polymer film to provide an efficient pathway for inner-sphere electron transfer during the electron-transfer quenching process

Are prices of new dwellings different? A spectral analysis of UK property vintages

The work makes two contributions to Hui’s (2011) dynamic house price classification. First, a house price ripple in cycles from Modern to Older dwellings is revealed and, second, as New housing is shown to have lower volatility than the other two. Using spectral analysis, it is argued that there is a 7½-year repeat buyer-second-hand cycle and a five year, first time buyer-New housing cycle, common to three house price vintages. These cycles reinforce each other every fifteen years, which corresponds with a Minsky super-cycle in housing finance. The equity of the owner-occupier is fortified by higher house prices whereas new builds extract embedded equity from the market. Government should support builders and facilitate access to market to first time buyers and through programmes like Help-to-Buy 1. However, to address the greater price instability that should follow, Government should impose a capital gains tax on the house seller

The Quenching of Isopropyl Group Rotation in Van Der Waals Molecular Solids

X-ray diffraction experiments are employed to determine the molecular and crystal structure of 3-isopropylchrysene. Based on this structure, electronic structure calculations are employed to calculate methyl group and isopropyl group rotational barriers in a central molecule of a ten-molecule cluster. The two slightly inequivalent methyl group barriers are found to be 12 and 15 kJ mol(-1) and the isopropyl group barrier is found to be about 240 kJ mol(-1), meaning that isopropyl group rotation is completely quenched in the solid state. For comparison, electronic structure calculations are also performed in the isolated molecule, determining both the structure and the rotational barriers, which are determined to be 15 kJ mol(-1) for both the isopropyl group and the two equivalent methyl groups. These calculations are compared with, and are consistent with, previously published NMR (1)H spin-lattice relaxation experiments where it was found that the barrier for methyl group rotation was 11 +/- 1 kJ mol(-1) and that the barrier for isopropyl group rotation was infinite on the solid state NMR time scale

Transverse lipid organization dictates bending fluctuations in model plasma membranes

© 2020 The Royal Society of Chemistry. Membrane undulations play a vital role in many biological processes, including the regulation of membrane protein activity. The asymmetric lipid composition of most biological membranes complicates theoretical description of these bending fluctuations, yet experimental data that would inform any such a theory is scarce. Here, we used neutron spin-echo (NSE) spectroscopy to measure the bending fluctuations of large unilamellar vesicles (LUV) having an asymmetric transbilayer distribution of high- and low-melting lipids. The asymmetric vesicles were prepared using cyclodextrin-mediated lipid exchange, and were composed of an outer leaflet enriched in egg sphingomyelin (ESM) and an inner leaflet enriched in 1-palmitoyl-2-oleoyl-phosphoethanolamine (POPE), which have main transition temperatures of 37 °C and 25 °C, respectively. The overall membrane bending rigidity was measured at three temperatures: 15 °C, where both lipids are in a gel state; 45 °C, where both lipids are in a fluid state; and 30 °C, where there is gel-fluid co-existence. Remarkably, the dynamics for the fluid asymmetric LUVs (aLUVs) at 30 °C and 45 °C do not follow trends predicted by their symmetric counterparts. At 30 °C, compositional asymmetry suppressed the bending fluctuations, with the asymmetric bilayer exhibiting a larger bending modulus than that of symmetric bilayers corresponding to either the outer or inner leaflet. We conclude that the compositional asymmetry and leaflet coupling influence the internal dissipation within the bilayer and result in membrane properties that cannot be directly predicted from corresponding symmetric bilayers

Influence of ceramide on lipid domain stability studied with small-angle neutron scattering: The role of acyl chain length and unsaturation

Ceramides and diacylglycerols are groups of lipids capable of nucleating and stabilizing ordered lipid domains, structures that have been implicated in a range of biological processes. Previous studies have used fluorescence reporter molecules to explore the influence of ceramide acyl chain structure on sphingolipid-rich ordered phases. Here, we use small-angle neutron scattering (SANS) to examine the ability of ceramides and diacylglycerols to promote lipid domain formation in the well-characterized domain- forming mixture DPPC/DOPC/cholesterol. SANS is a powerful, probe-free technique for interrogating membrane heterogeneity, as it is differentially sensitive to hydrogen\u27s stable isotopes protium and deuterium. Specifcally, neutron contrast is generated through selective deuteration of lipid species, thus enabling the detection of nanoscopic domains enriched in deuterated saturated lipids dispersed in a matrix of protiated un- saturated lipids. Using large unilamellar vesicles, we found that upon replacing 10 mol % DPPC with either C16:0 or C18:0 ceramide, or 16:0 diacylglycerol (dag), lipid domains persisted to higher temperatures. However, when DPPC was replaced with short chain (C6:0 or C12:0) or very long chain (C24:0) ceramides, or ceramides with unsaturated acyl chains of any length (C6:1(3), C6:1(5), C18:1, and C24:1), as well as C18:1-dag, lipid domains were destabilized, melting at lower temperatures than those in the DPPC/DOPC/cholesterol system. These results show how ceramide acyl chain length and unsaturation influence lipid domains, and have implications for how cell membranes might modify their function through the generation of different ceramide species

Mismatch-repair protein expression in high-grade gliomas: A large retrospective multicenter study

Background: DNA mismatch repair (MMR) is a system for repairing errors in DNA replication. Cancer cells with MMR deficiency can have immunohistochemical loss of MMR protein expression leading to a hypermutable phenotype that may correlate with anti-PD1 efficacy. Scant data exist about immunohistochemical loss of MMR protein expression in high-grade gliomas (HGG). Materials and Methods: We performed a large multicenter retrospective study to investigate the frequency and the prognostic role of immunohistochemical loss of MMR protein expression in HGG patients; we nevertheless evaluated the association between this status and clinical or molecular characteristics. Immunohistochemical loss of MMR protein expression was recorded as partial or complete loss of at least 1 MMR protein. Results: We analyzed the expression of MMR proteins in tumor tissue of 355 consecutive patients. Partial and complete immunohistochemical loss of MMR proteins was found in 43/355 samples (12.1%) and among these, 15 cases (4.2%) showed a complete loss of at the least one MMR protein. Alteration of MSH2 expression was found in 55.8%, MSH6 in 46.5%, PMS2 in 34.9%, and MLH1 in 30.2%. Alteration of MMR protein expression was statistically more frequent in anaplastic gliomas, in recurrent disease, in patients treated with temozolomide, and in IDH-mut gliomas. Immunohistochemical loss of MMR proteins was not associated with survival, adjusting for clinically relevant confounders. Conclusions: MMR protein expression status did not affect survival in HGG patients. We identified clinical and molecular characteristics correlating with immunohistochemical loss of MMR proteins expression. A large study should be performed to analyze its predictive role of immune checkpoint inhibitor efficacy in these subgroups of patients

The antioxidant vitamin E as a membrane raft modulator: Tocopherols do not abolish lipid domains

© 2020 Elsevier B.V. The antioxidant vitamin E is a commonly used vitamin supplement. Although the multi-billion dollar vitamin and nutritional supplement industry encourages the use of vitamin E, there is very little evidence supporting its actual health benefits. Moreover, vitamin E is now marketed as a lipid raft destabilizing anti-cancer agent, in addition to its antioxidant behaviour. Here, we studied the influence of vitamin E and some of its vitamers on membrane raft stability using phase separating unilamellar lipid vesicles in conjunction with small-angle scattering techniques and fluorescence microscopy. We find that lipid phase behaviour remains unperturbed well beyond physiological concentrations of vitamin E (up to a mole fraction of 0.10). Our results are consistent with a proposed line active role of vitamin E at the domain boundary. We discuss the implications of these findings as they pertain to lipid raft modification in native membranes, and propose a new hypothesis for the antioxidant mechanism of vitamin E

Explaining spatial variation in housing construction activity in Turkey

In Turkey, there has been a strong policy narrative that has emphasized the importance of construction activity as a driver of economic growth. This has given shape to a central state-led policy regime that has sought to ensure that planners and other urban policy makers develop plans and strategies that support construction activity. Against this backdrop, and a recent history of uneven spatial development, this paper seeks to understand what this policy imperative might mean for housing construction activity in different provinces. It seeks to reflect on both the relationship between the state and the market, and the interaction between state policies, economic drivers and levels of construction activity. The evidence presented in the paper suggests that uneven spatial development might be explained in different ways in different provinces. Although, in many cases, patterns of construction activity are consistent with economic fundamentals, there are important exceptions in some regions where arguably activity levels are at odds with prior expectations

Prominent and regressive brain developmental disorders associated with nance-horan syndrome

Nance-Horan syndrome (NHS) is a rare X-linked developmental disorder caused mainly by loss of function variants in the NHS gene. NHS is characterized by congenital cataracts, dental anomalies, and distinctive facial features, and a proportion of the affected individuals also present intellectual disability and congenital cardiopathies. Despite identification of at least 40 distinct hemizygous variants leading to NHS, genotype-phenotype correlations remain largely elusive. In this study, we describe a Sicilian family affected with congenital cataracts and dental anomalies and diagnosed with NHS by whole-exome sequencing (WES). The affected boy from this family presented a late regression of cognitive, motor, language, and adaptive skills, as well as broad behavioral anomalies. Furthermore, brain imaging showed corpus callosum anomalies and periven-tricular leukoencephalopathy. We expand the phenotypic and mutational NHS spectrum and review potential disease mechanisms underlying the central neurological anomalies and the potential neu-rodevelopmental features associated with NHS