GOLLUM: a next-generation simulation tool for electron, thermal and spin transport

We have developed an efficient simulation tool 'GOLLUM' for the computation of electrical, spin and thermal transport characteristics of complex nanostructures. The new multi-scale, multi-terminal tool addresses a number of new challenges and functionalities that have emerged in nanoscale-scale transport over the past few years. To illustrate the flexibility and functionality of GOLLUM, we present a range of demonstrator calculations encompassing charge, spin and thermal transport, corrections to density functional theory such as LDA+U and spectral adjustments, transport in the presence of non-collinear magnetism, the quantum-Hall effect, Kondo and Coulomb blockade effects, finite-voltage transport, multi-terminal transport, quantum pumps, superconducting nanostructures, environmental effects and pulling curves and conductance histograms for mechanically-controlled-break-junction experiments.Comment: 66 journal pages, 57 figure

Sleep disturbance in movement disorders:insights, treatments and challenges

Sleep and circadian rhythm disturbances are central features of many movement disorders, exacerbating motor and non-motor symptoms and impairing quality of life. Understanding these disturbances to sleep is clinically important and may further our understanding of the underlying movement disorder. This review evaluates the current anatomical and neurochemical understanding of normal sleep and the recognised primary sleep disorders. In addition, we undertook a systematic review of the evidence for disruption to sleep across multiple movement disorders. Rapid eye movement sleep behaviour disorder has emerged as the most reliable prodromal biomarker for the alpha synucleinopathies, including Parkinson’s disease and multiple system atrophy, often preceding motor symptom onset by several years. Abnormal sleep has also been described for many other movement disorders, but further evidence is needed to determine whether this is a primary or secondary phenotypic component of the underlying condition. Medication used in the treatment of motor symptoms also affects sleep and can aggravate or cause certain sleep disorders. Within the context of movement disorders, there is also some suggestion of a shared underlying mechanism for motor and sleep pathophysiology, with evidence implicating thalamic and brainstem structures and monoaminergic neurotransmission. This review highlights the need for an understanding of normal and abnormal sleep within the movement disorder clinic, an ability to screen for specific causes of poor sleep and to treat sleep disturbance to improve quality of life. Key sleep disorders also act as important biomarkers and have implications in diagnosis, prognosis and the development of future therapies

Identification of serum biomarkers for necrotizing enterocolitis using aptamer-based proteomics

Introduction Necrotizing enterocolitis (NEC) is a potentially fatal intestinal disease primarily affecting preterm infants. Early diagnosis of neonates with NEC is crucial to improving outcomes; however, traditional diagnostic tools remain inadequate. Biomarkers represent an opportunity to improve the speed and accuracy of diagnosis, but they are not routinely used in clinical practice. Methods In this study, we utilized an aptamer-based proteomic discovery assay to identify new serum biomarkers of NEC. We compared levels of serum proteins in neonates with and without NEC and identified ten differentially expressed serum proteins between these groups. Results We detected two proteins, C-C motif chemokine ligand 16 (CCL16) and immunoglobulin heavy constant alpha 1 and 2 heterodimer (IGHA1 IGHA2), that were significantly increased during NEC and eight that were significantly decreased. Generation of receiver operating characteristic (ROC) curves revealed that alpha-fetoprotein (AUC = 0.926), glucagon (AUC = 0.860), and IGHA1 IGHA2 (AUC = 0.826) were the proteins that best differentiated patients with and without NEC. Discussion These findings indicate that further investigation into these serum proteins as a biomarker for NEC is warranted. In the future, laboratory tests incorporating these differentially expressed proteins may improve the ability of clinicians to diagnose infants with NEC rapidly and accurately

Identification of serum biomarkers for necrotizing enterocolitis using aptamer-based proteomics

IntroductionNecrotizing enterocolitis (NEC) is a potentially fatal intestinal disease primarily affecting preterm infants. Early diagnosis of neonates with NEC is crucial to improving outcomes; however, traditional diagnostic tools remain inadequate. Biomarkers represent an opportunity to improve the speed and accuracy of diagnosis, but they are not routinely used in clinical practice.MethodsIn this study, we utilized an aptamer-based proteomic discovery assay to identify new serum biomarkers of NEC. We compared levels of serum proteins in neonates with and without NEC and identified ten differentially expressed serum proteins between these groups.ResultsWe detected two proteins, C-C motif chemokine ligand 16 (CCL16) and immunoglobulin heavy constant alpha 1 and 2 heterodimer (IGHA1 IGHA2), that were significantly increased during NEC and eight that were significantly decreased. Generation of receiver operating characteristic (ROC) curves revealed that alpha-fetoprotein (AUC = 0.926), glucagon (AUC = 0.860), and IGHA1 IGHA2 (AUC = 0.826) were the proteins that best differentiated patients with and without NEC.DiscussionThese findings indicate that further investigation into these serum proteins as a biomarker for NEC is warranted. In the future, laboratory tests incorporating these differentially expressed proteins may improve the ability of clinicians to diagnose infants with NEC rapidly and accurately

Mechanisms explaining transitions between tonic and phasic firing in neuronal populations as predicted by a low dimensional firing rate model

Several firing patterns experimentally observed in neural populations have been successfully correlated to animal behavior. Population bursting, hereby regarded as a period of high firing rate followed by a period of quiescence, is typically observed in groups of neurons during behavior. Biophysical membrane-potential models of single cell bursting involve at least three equations. Extending such models to study the collective behavior of neural populations involves thousands of equations and can be very expensive computationally. For this reason, low dimensional population models that capture biophysical aspects of networks are needed. \noindent The present paper uses a firing-rate model to study mechanisms that trigger and stop transitions between tonic and phasic population firing. These mechanisms are captured through a two-dimensional system, which can potentially be extended to include interactions between different areas of the nervous system with a small number of equations. The typical behavior of midbrain dopaminergic neurons in the rodent is used as an example to illustrate and interpret our results. \noindent The model presented here can be used as a building block to study interactions between networks of neurons. This theoretical approach may help contextualize and understand the factors involved in regulating burst firing in populations and how it may modulate distinct aspects of behavior.Comment: 25 pages (including references and appendices); 12 figures uploaded as separate file

The prevalence and experience of Australian naturopaths and Western herbalists working within community pharmacies

<p>Abstract</p> <p>Background</p> <p>Naturopaths and Western herbal medicine (WHM) practitioners were surveyed to identify their extent, experience and roles within the community pharmacy setting and to explore their attitudes to integration of complementary medicine (CM) practitioners within the pharmacy setting.</p> <p>Method</p> <p>Practising naturopaths and WHM practitioners were invited to participate in an anonymous, self-administered, on-line survey. Participants were recruited using the mailing lists and websites of CM manufacturers and professional associations.</p> <p>Results</p> <p>479 practitioners participated. 24% of respondents (n = 111) reported they had worked in community pharmacy, three-quarters for less than 5 years. Whilst in this role 74% conducted specialist CMs sales, 62% short customer consultations, 52% long consultations in a private room and 51% staff education. This was generally described as a positive learning experience and many appreciated the opportunity to utilise their specialist knowledge in the service of both customers and pharmacy staff. 14% (n = 15) did not enjoy the experience of working in pharmacy at all and suggested pharmacist attitude largely influenced whether the experience was positive or not. Few practitioners were satisfied with the remuneration received. 44% of the total sample provided comment on the issue of integration into pharmacy, with the main concern being the perceived incommensurate paradigms of practice between pharmacy and naturopathy. Of the total sample, 38% reported that they would consider working as a practitioner in retail pharmacy in future.</p> <p>Conclusions</p> <p>The level of integration of CM into pharmacy is extending beyond the mere stocking of supplements. Naturopaths and Western Herbalists are becoming utilised in pharmacies</p

Phonotactic response of female crickets on the Kramer treadmill: methodology, sensory and behavioural implications

Since population-level variation in female mating preferences can shape intraspecific communication systems within the context of sexual selection it is essential to quantify these preferences and their sources of variation. We calculated individual female response functions for four male calling song traits in the field cricket Gryllus bimaculatus, by performing untethered phonotaxis measurements on a spherical locomotor compensator (Kramer treadmill). Firstly, we quantify the population-level sources of phonotactic variation and correct for factors that adversely affect this measurement. Secondly, we develop methodology for the characterisation of individual female phonotactic response functions suitable for population-level analyses and demonstrate the applicability of our method with respect to recent literature on Orthopteran acoustic communication. Phonotaxis towards a preferred stimulus on different occasions is highly repeatable, with lower repeatabilities away from the most preferred signal traits. For certain male signal traits, female preference and selectivity are highly repeatable. Although phonotactic response magnitude deteriorated with age, preference functions of females remained the same during their lifetimes. Finally, the limitations of measuring phonotaxis using a spherical locomotor compensator are described and discussed with respect to the estimation of the selectivity of female response

LSST Science Book, Version 2.0

A survey that can cover the sky in optical bands over wide fields to faint magnitudes with a fast cadence will enable many of the exciting science opportunities of the next decade. The Large Synoptic Survey Telescope (LSST) will have an effective aperture of 6.7 meters and an imaging camera with field of view of 9.6 deg^2, and will be devoted to a ten-year imaging survey over 20,000 deg^2 south of +15 deg. Each pointing will be imaged 2000 times with fifteen second exposures in six broad bands from 0.35 to 1.1 microns, to a total point-source depth of r~27.5. The LSST Science Book describes the basic parameters of the LSST hardware, software, and observing plans. The book discusses educational and outreach opportunities, then goes on to describe a broad range of science that LSST will revolutionize: mapping the inner and outer Solar System, stellar populations in the Milky Way and nearby galaxies, the structure of the Milky Way disk and halo and other objects in the Local Volume, transient and variable objects both at low and high redshift, and the properties of normal and active galaxies at low and high redshift. It then turns to far-field cosmological topics, exploring properties of supernovae to z~1, strong and weak lensing, the large-scale distribution of galaxies and baryon oscillations, and how these different probes may be combined to constrain cosmological models and the physics of dark energy.Comment: 596 pages. Also available at full resolution at http://www.lsst.org/lsst/sciboo

Genome-wide identification of Ago2 binding sites from mouse embryonic stem cells with and without mature microRNAs

MicroRNAs (miRNAs) are 19–22-nucleotide noncoding RNAs that post-transcriptionally regulate mRNA targets. We have identified endogenous miRNA binding sites in mouse embryonic stem cells (mESCs), by performing photo-cross-linking immunoprecipitation using antibodies to Argonaute (Ago2) followed by deep sequencing of RNAs (CLIP-seq). We also performed CLIP-seq in Dicer[superscript −/−] mESCs that lack mature miRNAs, allowing us to define whether the association of Ago2 with the identified sites was miRNA dependent. A significantly enriched motif, GCACUU, was identified only in wild-type mESCs in 3′ untranslated and coding regions. This motif matches the seed of a miRNA family that constitutes ~68% of the mESC miRNA population. Unexpectedly, a G-rich motif was enriched in sequences cross-linked to Ago2 in both the presence and absence of miRNAs. Expression analysis and reporter assays confirmed that the seed-related motif confers miRNA-directed regulation on host mRNAs and that the G-rich motif can modulate this regulation.Leukemia & Lymphoma Society of AmericaUnited States. Public Health Service (Grant R01-GM34277)United States. Public Health Service (Grant R01-CA133404)National Cancer Institute (U.S.) (Grant P01-CA42063)National Cancer Institute (U.S.) Cancer Center Support (Grant P30-CA14051