Direct evidence to support the restriction of intramolecular rotation hypothesis for the mechanism of aggregation-induced emission: Temperature resolved terahertz spectra of tetraphenylethene

In contrast to the traditional fluorescent dyes that exhibit a decrease in fluorescence upon aggregation, Aggregation-Induced Emission (AIE) molecules are a family of fluorophors which exhibit increased fluorescence upon aggregation. Consequently, AIE molecules represent an interesting new material with potential applications in fluorescent chemo/biosensors, light emitting devices and medical diagnostics. Numerous mechanisms have been proposed to explain this phenomenon, including isomerisation, and restriction of intramolecular rotations (RIR). However, there has not been any direct experimental evidence to support either one of these hypotheses. Here we use terahertz time-domain-spectroscopy (THz-TDS) and solid-state computational simulations of an AIE molecule to link the increase in intensity of intramolecular rotation and rocking modes to the measured fluorescence and reveal direct evidence supporting the RIR hypothesis. This is the first time that terahertz spectroscopy has been used to directly probe such molecular motions in AIE materials and in doing so we have found conclusive evidence to fully explain the AIE mechanism.This is the accepted version of an article first published in Materials Horizons. The version of record is available from the Royal Society of Chemistry at http://xlink.rsc.org/?DOI=c3mh00078

On Polynomial Stability of Coupled Partial Differential Equations in 1D

We study the well-posedness and asymptotic behaviour of selected PDE-PDE and PDE-ODE systems on one-dimensional spatial domains, namely a boundary coupled wave-heat system and a wave equation with a dynamic boundary condition. We prove well-posedness of the models and derive rational decay rates for the energy using an approach where the coupled systems are formulated as feedback interconnections of impedance passive regular linear systems.Comment: 12 pages, 1 figure, accepted for publication in the Proceedings of "Semigroups of Operators: Theory and Applications", Kazimierz Dolny, Poland, October 201

Denosumab in men receiving androgen-deprivation therapy for prostate cancer.

Androgen-deprivation therapy is well-established for treating prostate cancer but is associated with bone loss and an increased risk of fracture. We investigated the effects of denosumab, a fully human monoclonal antibody against receptor activator of nuclear factor-kappaB ligand, on bone mineral density and fractures in men receiving androgen-deprivation therapy for nonmetastatic prostate cancer. In this double-blind, multicenter study, we randomly assigned patients to receive denosumab at a dose of 60 mg subcutaneously every 6 months or placebo (734 patients in each group). The primary end point was percent change in bone mineral density at the lumbar spine at 24 months. Key secondary end points included percent change in bone mineral densities at the femoral neck and total hip at 24 months and at all three sites at 36 months, as well as incidence of new vertebral fractures. At 24 months, bone mineral density of the lumbar spine had increased by 5.6% in the denosumab group as compared with a loss of 1.0% in the placebo group (P<0.001); significant differences between the two groups were seen at as early as 1 month and sustained through 36 months. Denosumab therapy was also associated with significant increases in bone mineral density at the total hip, femoral neck, and distal third of the radius at all time points. Patients who received denosumab had a decreased incidence of new vertebral fractures at 36 months (1.5%, vs. 3.9% with placebo) (relative risk, 0.38; 95% confidence interval, 0.19 to 0.78; P=0.006). Rates of adverse events were similar between the two groups. Denosumab was associated with increased bone mineral density at all sites and a reduction in the incidence of new vertebral fractures among men receiving androgen-deprivation therapy for nonmetastatic prostate cancer. (ClinicalTrials.gov number, NCT00089674.

A Non-Invasive method of quantifying pancreatic volume in mice using micro-MRI

In experimental models of pancreatic growth and recovery, changes in pancreatic size are assessed by euthanizing a large cohort of animals at varying time points and measuring organ mass. However, to ascertain this information in clinical practice, patients with pancreatic disorders routinely undergo non-invasive cross-sectional imaging of the pancreas using magnetic resonance imaging (MRI) or computed tomography (CT). The aim of the current study was to develop a thinsliced, optimized sequence protocol using a high field MRI to accurately calculate pancreatic volumes in the most common experimental animal, the mouse. Using a 7 Telsa Bruker micro-MRI system, we performed abdominal imaging in whole-fixed mice in three standard planes: axial, sagittal, and coronal. The contour of the pancreas was traced using Vitrea software and then transformed into a 3-dimensional (3D) reconstruction, from which volumetric measurements were calculated. Images were optimized using heart perfusion-fixation, T1 sequence analysis, and 0.2 to 0.4 mm thick slices. As proof of principle, increases in pancreatic volume among mice of different ages correlated tightly with increasing body weight. In summary, this is the first study to measure pancreatic volumes in mice, using a high field 7 Tesla micro-MRI and a thin-sliced, optimized sequence protocol. We anticipate that micro-MRI will improve the ability to non-invasively quantify changes in pancreatic size and will dramatically reduce the number of animals required to serially assess pancreatic growth and recovery.© 2014 Paredes et al

Multivoxel Pattern Analysis Reveals Auditory Motion Information in MT+ of Both Congenitally Blind and Sighted Individuals

Cross-modal plasticity refers to the recruitment of cortical regions involved in the processing of one modality (e.g. vision) for processing other modalities (e.g. audition). The principles determining how and where cross-modal plasticity occurs remain poorly understood. Here, we investigate these principles by testing responses to auditory motion in visual motion area MT+ of congenitally blind and sighted individuals. Replicating previous reports, we find that MT+ as a whole shows a strong and selective responses to auditory motion in congenitally blind but not sighted individuals, suggesting that the emergence of this univariate response depends on experience. Importantly, however, multivoxel pattern analyses showed that MT+ contained information about different auditory motion conditions in both blind and sighted individuals. These results were specific to MT+ and not found in early visual cortex. Basic sensitivity to auditory motion in MT+ is thus experience-independent, which may be a basis for the region's strong cross-modal recruitment in congenital blindness

A Minimal Threshold of c-di-GMP Is Essential for Fruiting Body Formation and Sporulation in Myxococcus xanthus

Generally, the second messenger bis-(3’-5’)-cyclic dimeric GMP (c-di-GMP) regulates the switch between motile and sessile lifestyles in bacteria. Here, we show that c-di-GMP is an essential regulator of multicellular development in the social bacterium Myxococcus xanthus. In response to starvation, M. xanthus initiates a developmental program that culminates in formation of spore-filled fruiting bodies. We show that c-di-GMP accumulates at elevated levels during development and that this increase is essential for completion of development whereas excess c-di-GMP does not interfere with development. MXAN3735 (renamed DmxB) is identified as a diguanylate cyclase that only functions during development and is responsible for this increased c-di-GMP accumulation. DmxB synthesis is induced in response to starvation, thereby restricting DmxB activity to development. DmxB is essential for development and functions downstream of the Dif chemosensory system to stimulate exopolysaccharide accumulation by inducing transcription of a subset of the genes encoding proteins involved in exopolysaccharide synthesis. The developmental defects in the dmxB mutant are non-cell autonomous and rescued by co-development with a strain proficient in exopolysaccharide synthesis, suggesting reduced exopolysaccharide accumulation as the causative defect in this mutant. The NtrC-like transcriptional regulator EpsI/Nla24, which is required for exopolysaccharide accumulation, is identified as a c-diGMP receptor, and thus a putative target for DmxB generated c-di-GMP. Because DmxB can be—at least partially—functionally replaced by a heterologous diguanylate cyclase, these results altogether suggest a model in which a minimum threshold level of c-di-GMP is essential for the successful completion of multicellular development in M. xanthus

Disposition of Federally Owned Surpluses

PDZ domains are scaffolding modules in protein-protein interactions that mediate numerous physiological functions by interacting canonically with the C-terminus or non-canonically with an internal motif of protein ligands. A conserved carboxylate-binding site in the PDZ domain facilitates binding via backbone hydrogen bonds; however, little is known about the role of these hydrogen bonds due to experimental challenges with backbone mutations. Here we address this interaction by generating semisynthetic PDZ domains containing backbone amide-to-ester mutations and evaluating the importance of individual hydrogen bonds for ligand binding. We observe substantial and differential effects upon amide-to-ester mutation in PDZ2 of postsynaptic density protein 95 and other PDZ domains, suggesting that hydrogen bonding at the carboxylate-binding site contributes to both affinity and selectivity. In particular, the hydrogen-bonding pattern is surprisingly different between the non-canonical and canonical interaction. Our data provide a detailed understanding of the role of hydrogen bonds in protein-protein interactions

The ESR1 (6q25) locus is associated with calcaneal ultrasound parameters and radial volumetric bone mineral density in European men

<p><b>Purpose:</b> Genome-wide association studies (GWAS) have identified 6q25, which incorporates the oestrogen receptor alpha gene (ESR1), as a quantitative trait locus for areal bone mineral density (BMD(a)) of the hip and lumbar spine. The aim of this study was to determine the influence of this locus on other bone health outcomes; calcaneal ultrasound (QUS) parameters, radial peripheral quantitative computed tomography (pQCT) parameters and markers of bone turnover in a population sample of European men.</p> <p><b>Methods:</b> Eight single nucleotide polymorphisms (SNP) in the 6q25 locus were genotyped in men aged 40-79 years from 7 European countries, participating in the European Male Ageing Study (EMAS). The associations between SNPs and measured bone parameters were tested under an additive genetic model adjusting for centre using linear regression.</p> <p><b>Results:</b> 2468 men, mean (SD) aged 59.9 (11.1) years had QUS measurements performed and bone turnover marker levels measured. A subset of 628 men had DXA and pQCT measurements. Multiple independent SNPs showed significant associations with BMD using all three measurement techniques. Most notably, rs1999805 was associated with a 0.10 SD (95%CI 0.05, 0.16; p = 0.0001) lower estimated BMD at the calcaneus, a 0.14 SD (95%CI 0.05, 0.24; p = 0.004) lower total hip BMD(a), a 0.12 SD (95%CI 0.02, 0.23; p = 0.026) lower lumbar spine BMD(a) and a 0.18 SD (95%CI 0.06, 0.29; p = 0.003) lower trabecular BMD at the distal radius for each copy of the minor allele. There was no association with serum levels of bone turnover markers and a single SNP which was associated with cortical density was also associated with cortical BMC and thickness.</p> <p><b>Conclusions:</b> Our data replicate previous associations found between SNPs in the 6q25 locus and BMD(a) at the hip and extend these data to include associations with calcaneal ultrasound parameters and radial volumetric BMD.</p&gt