Two-step electrochemical annulation for the assembly of polycyclic systems

[reaction: see text] A two-step electrochemical annulation has been developed for the preparation of fused furans. The process involves an initial conjugate addition of a furyethyl cuprate and trapping of the enolate as the corresponding silyl enolether. The second step of the annulation involves the anodic coupling of the furan and the silyl enol ether to form a six-membered ring.     

The Aminotriazole Antagonist Cmpd‐1 Stabilises a Distinct Inactive State of the Adenosine 2A Receptor

The widely expressed G‐protein coupled receptors (GPCRs) are versatile signal transducer proteins that are attractive drug targets but structurally challenging to study. GPCRs undergo a number of conformational rearrangements when transitioning from the inactive to the active state but have so far been believed to adopt a fairly conserved inactive conformation. Using ¹⁹F NMR spectroscopy and advanced molecular dynamics simulations we describe a novel inactive state of the adenosine 2A receptor which is stabilised by the aminotriazole antagonist Cmpd‐1. We demonstrate that the ligand stabilises a unique conformation of helix V and present data on the putative binding mode of the compound involving contacts to the transmembrane bundle as well as the extracellular loop 2.     

Entanglement Generation Between Two Mechanical Resonators in Two Optomechanical Cavities

A standard model is suggested to explore correlation features of two spatially separated optomechanical cavities. The cavities are coupled through the photon-hopping process. In particular, we investigate the generation of entanglement between mechanical resonators in the strong coupling regime and the two cavities are assumed to be driven by a coherent laser field. In order to quantify entanglement we use the logarithmic negativity. The analytical solutions are presented for the system in a parameter regime very close to the current experimental results. We show that in the presence of the photon hopping process between the cavities, the two mechanical resonators and the field modes can be entangled. This shows clearly that the entanglement can be transfer via radiation pressure of a photon hopping coupling from the intracavity photon-phonon entanglements to an inter-cavity photon-photon or phonon-phonon entanglement.     

Functional neural network analysis in frontotemporal dementia and Alzheimer's disease using EEG and graph theory

Background  

Although a large body of knowledge about both brain structure and function has been gathered over the last decades, we still have a poor understanding of their exact relationship. Graph theory provides a method to study the relation between network structure and function, and its application to neuroscientific data is an emerging research field. We investigated topological changes in large-scale functional brain networks in patients with Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD) by means of graph theoretical analysis of resting-state EEG recordings. EEGs of 20 patients with mild to moderate AD, 15 FTLD patients, and 23 non-demented individuals were recorded in an eyes-closed resting-state. The synchronization likelihood (SL), a measure of functional connectivity, was calculated for each sensor pair in 0.5–4 Hz, 4–8 Hz, 8–10 Hz, 10–13 Hz, 13–30 Hz and 30–45 Hz frequency bands. The resulting connectivity matrices were converted to unweighted graphs, whose structure was characterized with several measures: mean clustering coefficient (local connectivity), characteristic path length (global connectivity) and degree correlation (network 'assortativity'). All results were normalized for network size and compared with random control networks.     

Delineating sources of groundwater recharge and carbon in Holocene aquifers of the central Gangetic basin using stable isotopic signatures

Stable isotopes of water (δ²H, δ¹⁸O) and δ¹³C_TIC were used as a tool to trace the recharge processes, natural carbon (organic and inorganic) source and dynamics in the aquifers of the central Gangetic basin, India. Stable isotope (δ²H, δ¹⁸O) record of groundwater (n?=?105) revealed that the groundwater of Piedmont was recharged by meteoric origin before evaporation, while aquifers of the older and younger alluvium were recharged by water that had undergone evaporation loss. River Ganges and its tributaries passing through this area have very little contribution in recharging while ponds play no role in the recharging of adjacent aquifers. The connectivity of shallow aquifers of aquitard formation (comprised of clay/sandy clay with thin patches of fine grey sand), i.e. 25–60?m below ground level (bgl) with the main upper aquifer (at a depth of >120?m?bgl) was found to be higher in older and younger alluvium. Negative values of δ¹³C_TIC (median ?9.6 ‰; range ?13.2 to ?5.4 ‰) and high TIC (median 35?mM; range 31–46?mM) coupled with low TOC (median 1.35?mg/L; range 0.99–1.77?mg/L) indicated acceleration in microbial activity in the younger alluvium, especially in the active floodplain of river Ganges and its proximity.     

Mycobacterial immune reconstitution inflammatory syndrome in HIV-1 infection after antiretroviral therapy is associated with deregulated specific T-cell responses: Beneficial effect of IL-2 and GM-CSF immunotherapy

Background  

With the advent of antiretroviral therapy (ART) cases of immune reconstitution inflammatory syndrome (IRIS) have increasingly been reported. IRIS usually occurs in individuals with a rapidly rising CD4 T-cell count or percentage upon initiation of ART, who develop a deregulated immune response to infection with or without reactivation of opportunistic organisms. Here, we evaluated rises in absolute CD4 T-cells, and specific CD4 T-cell responses in 4 HIV-1⁺ individuals presenting with mycobacterial associated IRIS who received in conjunction with ART, IL-2 plus GM-CSF immunotherapy.     

Studies on inducers of nerve growth factor: synthesis of the cyathin core

[formula: see text] Compounds that induce the synthesis of nerve growth factor (NGF) are of interest as alternatives to the administration of the native peptide. We have initiated a program to study the NGF synthesis stimulating activity of the erinacine and scabronine diterpenes. Herein, we report an approach to the core cyathin system by sequential application of an oxidative coupling and [4 + 3] cycloaddition.