Spontaneous Octahedral Tilting in the Cubic Inorganic Caesium Halide Perovskites CsSnX3_3 and CsPbX3_3 (X = F, Cl, Br, I)

The local crystal structures of many perovskite-structured materials deviate from the average space group symmetry. We demonstrate, from lattice-dynamics calculations based on quantum chemical force constants, that all the caesium-lead and caesium-tin halide perovskites exhibit vibrational instabilities associated with octahedral titling in their high-temperature cubic phase. Anharmonic double-well potentials are found for zone-boundary phonon modes in all compounds with barriers ranging from 108 to 512 meV. The well depth is correlated with the tolerance factor and the chemistry of the composition, but is not proportional to the imaginary harmonic phonon frequency. We provide quantitative insights into the thermodynamic driving forces and distinguish between dynamic and static disorder based on the potential-energy landscape. A positive band gap deformation (spectral blueshift) accompanies the structural distortion, with implications for understanding the performance of these materials in applications areas including solar cells and light-emitting diodes

In vitro characterisation of cell-level neurophysiological diversity in the rostral nucleus reuniens of adult mice

PublishedThis is the author accepted manuscript. The final version is available from Wiley via the DOI in this record.The nucleus reuniens (Re) is the largest of the midline thalamic nuclei. We have performed a detailed neurophysiological characterization of neurons in the rostral Re of brain slices prepared from adult male mice. At resting potential (−63.7 ± 0.6 mV), circa 90% of Re neurons fired action potentials, typically continuously at ∼8 Hz. Although Re neurons experience a significant spontaneous barrage of fast, amino-acid-mediate synaptic transmission, this was not predominantly responsible for spontaneous spiking as firing persisted in the presence of glutamate and GABA receptor antagonists. With resting potential preset to −80 mV −20 pA current injections revealed a mean input resistance of 615 MΩ and mean time constant of 38 ms. Following cessation of this stimulus a significant rebound potential was seen that was sometimes large enough to trigger a short burst of very high frequency (100–300 Hz) firing. In most cells short (2 ms), strong (2 nA) current injections elicited a single spike followed by a large afterdepolarizing potential (ADP) which, when suprathreshold, generated high frequency spiking. Similarly, in the majority of cells preset at −80 mV, 500 ms depolarizing current injections to cells led to a brief initial burst of very high frequency firing, although this was lost when cells were preset at −72 mV. Biophysical and pharmacological experiments indicate a prominent role for T-type Ca2+ channels in the high-frequency bursting of Re neurons. Finally, we describe a novel form of activity-dependent intrinsic plasticity that persistently eliminates the burst firing potential of Re neurons

Atomistic origins of the phase transition mechanism in Ge2Sb2Te5

Combined static and molecular dynamics first-principles calculations are used to identify a direct structural link between the metastable crystalline and amorphous phases of Ge2Sb2Te5. We find that the phase transition is driven by the displacement of Ge atoms along the rocksalt [111] direction from the stable-octahedron to high-energy-unstable tetrahedron sites close to the intrinsic vacancy regions, which give rise to the formation of local 4-fold coordinated motifs. Our analyses suggest that the high figures of merit of Ge2Sb2Te5 are achieved from the optimal combination of intrinsic vacancies provided by Sb2Te3 and the instability of the tetrahedron sites provided by GeTe

Eotaxin: a potent eosinophil chemoattractant cytokine detected in a guinea pig model of allergic airways inflammation.

Eosinophil accumulation is a prominent feature of allergic inflammatory reactions, such as those occurring in the lung of the allergic asthmatic, but the endogenous chemoattractants involved have not been identified. We have investigated this in an established model of allergic inflammation, using in vivo systems both to generate and assay relevant activity. Bronchoalveolar lavage (BAL) fluid was taken from sensitized guinea pigs at intervals after aerosol challenge with ovalbumin. BAL fluid was injected intradermally in unsensitized assay guinea pigs and the accumulation of intravenously injected 111In-eosinophils was measured. Activity was detected at 30 min after allergen challenge, peaking from 3 to 6 h and declining to low levels by 24 h. 3-h BAL fluid was purified using high performance liquid chromatography techniques in conjunction with the skin assay. Microsequencing revealed a novel protein from the C-C branch of the platelet factor 4 superfamily of chemotactic cytokines. The protein, eotaxin, exhibits homology of 53% with human MCP-1, 44% with guinea pig MCP-1, 31% with human MIP-1α, and 26% with human RANTES. Laser desorption time of flight mass analysis gave four different signals (8.15, 8.38, 8.81, and 9.03 kD), probably reflecting differential O-glycosylation. Eotaxin was highly potent, inducing substantial 111In-eosinophil accumulation at a 1-2-pmol dose in the skin, but did not induce significant 111In-neutrophil accumulation. Eotaxin was a potent stimulator of both guinea pig and human eosinophils in vitro. Human recombinant RANTES, MIP-1α, and MCP-1 were all inactive in inducing 111In-eosinophil accumulation in guinea pig skin; however, evidence was obtained that eotaxin shares a binding site with RANTES on guinea pig eosinophils. This is the first description of a potent eosinophil chemoattractant cytokine generated in vivo and suggests the possibility that similar molecules may be important in the human asthmatic lung

Remission vs low disease activity: function, quality of life and structural outcomes in the Early Rheumatoid Arthritis Study and Network

Objectives To examine associations between function, quality of life and structural outcomes in patients achieving remission vs low disease activity in early RA. Methods Demographic, clinical and radiographic variables were collected at baseline and then annually from the Early Rheumatoid Arthritis Study (ERAS) and Early Rheumatoid Arthritis Network (ERAN) inception cohorts in routine care from 1986 to 2012. Disease activity was categorized: mean DAS28 score between years 1 and 5: remission [mean remission DAS (mRDAS) <2.6] or low [mean low DAS (mLDAS) 2.6–3.2]; sustained low/remission DAS28 (sLDAS/sRDAS) at years 1 and 2; and sustained Boolean remission (sBR) at years 1 and 2. Changes in HAQ and Short Form 36 Health Survey Questionnaire [SF-36; physical (PCS) and mental (MCS) component score]) and total Sharp van der Heijde (SvdH) scores for each disease activity category were modelled using multi-level models. Covariates included year of onset, age, gender and DMARD use at first visit. Results Of 2701 patients, 562 (21%) were categorized mRDAS, 330 (12%) mLDAS, 279 (10%) sRDAS, 203 (7.5%) sLDAS and 93 (3%) sBR. Patients categorized as mRDAS had increasingly divergent improved HAQ, SF-36 PCS, MCS and total SvdH scores compared with mLDAS (P-values 0.001 to <0.0001, all time points). Patients categorized as sRDAS had better HAQ, SF-36 PCS and MCS scores (P-values 0.05 to <0.0001, all time points) and SvdH scores (P = 0.05, years 3–5) over sLDAS. sBR was associated with better HAQ, and SF-36 PCS and MCS scores over sLDAS (P-values 0.002 to <0.0001, all time points). Conclusion These findings from routine care support ACR/EULAR guidelines that remission is a preferable goal over low disease activity in early RA.Peer reviewedFinal Published versio

An update on emerging drugs for asthma

Peer reviewedPreprin

On the well-posedness of the stochastic Allen-Cahn equation in two dimensions

White noise-driven nonlinear stochastic partial differential equations (SPDEs) of parabolic type are frequently used to model physical and biological systems in space dimensions d = 1,2,3. Whereas existence and uniqueness of weak solutions to these equations are well established in one dimension, the situation is different for d \geq 2. Despite their popularity in the applied sciences, higher dimensional versions of these SPDE models are generally assumed to be ill-posed by the mathematics community. We study this discrepancy on the specific example of the two dimensional Allen-Cahn equation driven by additive white noise. Since it is unclear how to define the notion of a weak solution to this equation, we regularize the noise and introduce a family of approximations. Based on heuristic arguments and numerical experiments, we conjecture that these approximations exhibit divergent behavior in the continuum limit. The results strongly suggest that a series of published numerical studies are problematic: shrinking the mesh size in these simulations does not lead to the recovery of a physically meaningful limit.Comment: 21 pages, 4 figures; accepted by Journal of Computational Physics (Dec 2011