Polaronic effect in the x-ray absorption spectra of La1-x Ca x MnO3 manganites.

X-ray absorption spectroscopy (XAS) is performed to study changes in the electronic structures of colossal magnetoresistance (CMR) and charged ordered (CO) La1-x Ca x MnO3 manganites with respect to temperature. The pre-edge features in O and Mn K-edge XAS spectra, which are highly sensitive to the local distortion of MnO6 octahedral, exhibit contrasting temperature dependence between CMR and CO samples. The seemingly counter-intuitive XAS temperature dependence can be reconciled in the context of polarons. These results help identify the most relevant orbital states associated with polarons and highlight the crucial role played by polarons in understanding the electronic structures of manganites

Biomineralization mediated by anaerobic methane-consuming cell consortia

published_or_final_versio

A microchip optomechanical accelerometer

The monitoring of accelerations is essential for a variety of applications ranging from inertial navigation to consumer electronics. The basic operation principle of an accelerometer is to measure the displacement of a flexibly mounted test mass; sensitive displacement measurement can be realized using capacitive, piezo-electric, tunnel-current, or optical methods. While optical readout provides superior displacement resolution and resilience to electromagnetic interference, current optical accelerometers either do not allow for chip-scale integration or require bulky test masses. Here we demonstrate an optomechanical accelerometer that employs ultra-sensitive all-optical displacement read-out using a planar photonic crystal cavity monolithically integrated with a nano-tethered test mass of high mechanical Q-factor. This device architecture allows for full on-chip integration and achieves a broadband acceleration resolution of 10 \mu g/rt-Hz, a bandwidth greater than 20 kHz, and a dynamic range of 50 dB with sub-milliwatt optical power requirements. Moreover, the nano-gram test masses used here allow for optomechanical back-action in the form of cooling or the optical spring effect, setting the stage for a new class of motional sensors.Comment: 16 pages, 9 figure

Integrated multiple mediation analysis: A robustness–specificity trade-off in causal structure

Recent methodological developments in causal mediation analysis have addressed several issues regarding multiple mediators. However, these developed methods differ in their definitions of causal parameters, assumptions for identification, and interpretations of causal effects, making it unclear which method ought to be selected when investigating a given causal effect. Thus, in this study, we construct an integrated framework, which unifies all existing methodologies, as a standard for mediation analysis with multiple mediators. To clarify the relationship between existing methods, we propose four strategies for effect decomposition: two-way, partially forward, partially backward, and complete decompositions. This study reveals how the direct and indirect effects of each strategy are explicitly and correctly interpreted as path-specific effects under different causal mediation structures. In the integrated framework, we further verify the utility of the interventional analogues of direct and indirect effects, especially when natural direct and indirect effects cannot be identified or when cross-world exchangeability is invalid. Consequently, this study yields a robustness–specificity trade-off in the choice of strategies. Inverse probability weighting is considered for estimation. The four strategies are further applied to a simulation study for performance evaluation and for analyzing the Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer data set from Taiwan to investigate the causal effect of hepatitis C virus infection on mortality

Mouse models of atherosclerosis: a historical perspective and recent advances.

Atherosclerosis represents a significant cause of morbidity and mortality in both the developed and developing countries. Animal models of atherosclerosis have served as valuable tools for providing insights on its aetiology, pathophysiology and complications. They can be used for invasive interrogation of physiological function and provide a platform for testing the efficacy and safety of different pharmacological therapies. Compared to studies using human subjects, animal models have the advantages of being easier to manage, with controllable diet and environmental risk factors. Moreover, pathophysiological changes can be induced either genetically or pharmacologically to study the harmful effects of these interventions. There is no single ideal animal model, as different systems are suitable for different research objectives. A good understanding of the similarities and differences to humans enables effective extrapolation of data for translational application. In this article, we will examine the different mouse models for the study and elucidation of the pathophysiological mechanisms underlying atherosclerosis. We also review recent advances in the field, such as the role of oxidative stress in promoting endoplasmic reticulum stress, mitochondrial dysfunction and mitochondrial DNA damage, which can result in vascular inflammation and atherosclerosis. Finally, novel therapeutic approaches to reduce vascular damage caused by chronic inflammation using microRNA and nano-medicine technology, are discussed.YC is supported by a project grant from the ESRC for her doctoral studies at the University of Cambridge. GT was supported by the BBSRC Doctoral Training Award and Assistant Professorships from The Croucher Foundation of Hong Kong

Effective computational methods for hybrid stochastic gene networks

At the scale of the individual cell, protein production is a stochastic process with multiple time scales, combining quick and slow random steps with discontinuous and smooth variation. Hybrid stochastic processes, in particular piecewise-deterministic Markov processes (PDMP), are well adapted for describing such situations. PDMPs approximate the jump Markov processes traditionally used as models for stochastic chemical reaction networks. Although hybrid modelling is now well established in biology, these models remain computationally challenging. We propose several improved methods for computing time dependent multivariate probability distributions (MPD) of PDMP models of gene networks. In these models, the promoter dynamics is described by a finite state, continuous time Markov process, whereas the mRNA and protein levels follow ordinary differential equations (ODEs). The Monte-Carlo method combines direct simulation of the PDMP with analytic solutions of the ODEs. The push-forward method numerically computes the probability measure advected by the deterministic ODE flow, through the use of analytic expressions of the corresponding semigroup. Compared to earlier versions of this method, the probability of the promoter states sequence is computed beyond the naive mean field theory and adapted for non-linear regulation functions

A time for heroes? Conceptualization, development and validation of the brand hero scale

Purpose: Prior work underscores the important role of customer advocacy for brands. The purpose of this study is to explore the critical role customers can play as brand heroes. The authors developed and validated a measurement scale composed of properties that are derived from distinct brand hero motivational mechanisms. Design/methodology/approach: The authors conducted one exploratory pilot, using semi-structured interviews, with industry and academic experts, and employed three main studies across varying brands and market settings. Findings: This study explores and empirically demonstrates how the brand hero scale (BHS) is related to, yet distinct from, existing scales of opinion leaders, market mavens, attachment and customer advocacy. The six-item BHS demonstrates convergent, discriminant, nomological and predictive validity across several different brand contexts. Research limitations/implications: This research extends the extant body of work by identifying and defining brand heroes, developing and validating a parsimonious BHS, and demonstrating how its predictive validity extends both to a range of key advocacy and loyalty customer behaviors. Practical implications: The study provides provocative insights for marketing researchers and brand managers and ascertains the important role heroes may play for brands in terms of strong customer advocacy and loyalty behaviors. Originality/value: Building on the theory of meaning, this study shows that identifying and working with brand heroes is of great managerial importance and offers critical avenues for future research

Proteomics: in pursuit of effective traumatic brain injury therapeutics

Effective traumatic brain injury (TBI) therapeutics remain stubbornly elusive. Efforts in the field have been challenged by the heterogeneity of clinical TBI, with greater complexity among underlying molecular phenotypes than initially conceived. Future research must confront the multitude of factors comprising this heterogeneity, representing a big data challenge befitting the coming informatics age. Proteomics is poised to serve a central role in prescriptive therapeutic development, as it offers an efficient endpoint within which to assess post-TBI biochemistry. We examine rationale for multifactor TBI proteomic studies and the particular importance of temporal profiling in defining biochemical sequences and guiding therapeutic development. Lastly, we offer perspective on repurposing biofluid proteomics to develop theragnostic assays with which to prescribe, monitor and assess pharmaceutics for improved translation and outcome for TBI patients

Controlling Cherenkov angles with resonance transition radiation

Cherenkov radiation provides a valuable way to identify high energy particles in a wide momentum range, through the relation between the particle velocity and the Cherenkov angle. However, since the Cherenkov angle depends only on material's permittivity, the material unavoidably sets a fundamental limit to the momentum coverage and sensitivity of Cherenkov detectors. For example, Ring Imaging Cherenkov detectors must employ materials transparent to the frequency of interest as well as possessing permittivities close to unity to identify particles in the multi GeV range, and thus are often limited to large gas chambers. It would be extremely important albeit challenging to lift this fundamental limit and control Cherenkov angles as preferred. Here we propose a new mechanism that uses constructive interference of resonance transition radiation from photonic crystals to generate both forward and backward Cherenkov radiation. This mechanism can control Cherenkov angles in a flexible way with high sensitivity to any desired range of velocities. Photonic crystals thus overcome the severe material limit for Cherenkov detectors, enabling the use of transparent materials with arbitrary values of permittivity, and provide a promising option suited for identification of particles at high energy with enhanced sensitivity.Comment: There are 16 pages and 4 figures for the manuscript. Supplementary information with 18 pages and 5 figures, appended at the end of the file with the manuscript. Source files in Word format converted to PDF. Submitted to Nature Physic

Klebsiella pneumoniae is able to trigger epithelial-mesenchymal transition process in cultured airway epithelial cells

The ability of some bacterial pathogens to activate Epithelial-Mesenchymal Transition normally is a consequence of the persistence of a local chronic inflammatory response or depends on a direct interaction of the pathogens with the host epithelial cells. In this study we monitored the abilities of the K. pneumoniae to activate the expression of genes related to EMT-like processes and the occurrence of phenotypic changes in airway epithelial cells during the early steps of cell infection. We describe changes in the production of intracellular reactive oxygen species and increased HIF-1α mRNA expression in cells exposed to K. pneumoniae infection. We also describe the upregulation of a set of transcription factors implicated in the EMT processes, such as Twist, Snail and ZEB, indicating that the morphological changes of epithelial cells already appreciable after few hours from the K. pneumoniae infection are tightly regulated by the activation of transcriptional pathways, driving epithelial cells to EMT. These effects appear to be effectively counteracted by resveratrol, an antioxidant that is able to exert a sustained scavenging of the intracellular ROS. This is the first report indicating that strains of K. pneumoniae may promote EMT-like programs through direct interaction with epithelial cells without the involvement of inflammatory cells