Confronting a cardiovascular system model with heart rate and blood pressure data

The cardiovascular system may be investigated by observing fluctuations in the heart rate, blood pressure and rate of respiration. Its time evolution is governed by the baroreflex control mechanism, where the sympathetic and vagal nerves compete to increase and decrease the heart rate respectively. A nonlinear delay-differential equation model is constructed to describe this control mechanism and to explore the interactions between the heart rate and blood pressure. In this model, a time delay gives rise to the oscillations in the blood pressure known as Mayer waves. The model maintains an intrinsically stable heart rate in the absence of nervous control, and features baroreflex influence on both heart rate and peripheral resistance. The effect of respiratory sinus arrhythmia (RSA) is introduced using a sinusoidal driving component. Clinical recordings obtained by carefully controlling the rate and depth of respiration are used to test the suitability of the model for representing the complicated physiology of the cardiovascular system. The model is shown to be able to reproduce many of the empirical characteristics observed in these biomedical signals, including RSA, Mayer waves and synchronization. Key physiological parameters in the model, including the time delay and levels of sympathetic and vagal activity, could provide useful diagnostic information about the state of the cardiovascular system. 1

Enabling three-dimensional densitometric measurements using laboratory source X-ray micro-computed tomography

We present new software allowing significantly improved quantitative mapping of the three-dimensional density distribution of objects using laboratory source polychromatic X-rays via a beam characterisation approach (c.f. filtering or comparison to phantoms). One key advantage is that a precise representation of the specimen material is not required. The method exploits well-established, widely available, non-destructive and increasingly accessible laboratory-source X-ray tomography. Beam characterisation is performed in two stages: (1) projection data are collected through a range of known materials utilising a novel hardware design integrated into the rotation stage; and (2) a Python code optimises a spectral response model of the system. We provide hardware designs for use with a rotation stage able to be tilted, yet the concept is easily adaptable to virtually any laboratory system and sample, and implicitly corrects the image artefact known as beam hardening

SN 2005hj: Evidence for Two Classes of Normal-Bright SNe Ia and Implications for Cosmology

HET Optical spectra covering the evolution from about 6 days before to about 5 weeks after maximum light and the ROTSE-IIIb unfiltered light curve of the "Branch-normal" Type Ia Supernova SN 2005hj are presented. The host galaxy shows HII region lines at redshift of z=0.0574, which puts the peak unfiltered absolute magnitude at a somewhat over-luminous -19.6. The spectra show weak and narrow SiII lines, and for a period of at least 10 days beginning around maximum light these profiles do not change in width or depth and they indicate a constant expansion velocity of ~10,600 km/s. We analyzed the observations based on detailed radiation dynamical models in the literature. Whereas delayed detonation and deflagration models have been used to explain the majority of SNe Ia, they do not predict a long velocity plateau in the SiII minimum with an unvarying line profile. Pulsating delayed detonations and merger scenarios form shell-like density structures with properties mostly related to the mass of the shell, M_shell, and we discuss how these models may explain the observed SiII line evolution; however, these models are based on spherical calculations and other possibilities may exist. SN 2005hj is consistent with respect to the onset, duration, and velocity of the plateau, the peak luminosity and, within the uncertainties, with the intrinsic colors for models with M_shell=0.2 M_sun. Our analysis suggests a distinct class of events hidden within the Branch-normal SNe Ia. If the predicted relations between observables are confirmed, they may provide a way to separate these two groups. We discuss the implications of two distinct progenitor classes on cosmological studies employing SNe Ia, including possible differences in the peak luminosity to light curve width relation.Comment: ApJ accepted, 31 page

Prediction of peptide and protein propensity for amyloid formation

Understanding which peptides and proteins have the potential to undergo amyloid formation and what driving forces are responsible for amyloid-like fiber formation and stabilization remains limited. This is mainly because proteins that can undergo structural changes, which lead to amyloid formation, are quite diverse and share no obvious sequence or structural homology, despite the structural similarity found in the fibrils. To address these issues, a novel approach based on recursive feature selection and feed-forward neural networks was undertaken to identify key features highly correlated with the self-assembly problem. This approach allowed the identification of seven physicochemical and biochemical properties of the amino acids highly associated with the self-assembly of peptides and proteins into amyloid-like fibrils (normalized frequency of β-sheet, normalized frequency of β-sheet from LG, weights for β-sheet at the window position of 1, isoelectric point, atom-based hydrophobic moment, helix termination parameter at position j+1 and ΔGº values for peptides extrapolated in 0 M urea). Moreover, these features enabled the development of a new predictor (available at http://cran.r-project.org/web/packages/appnn/index.html) capable of accurately and reliably predicting the amyloidogenic propensity from the polypeptide sequence alone with a prediction accuracy of 84.9 % against an external validation dataset of sequences with experimental in vitro, evidence of amyloid formation

How consistent are the transcriptome changes associated with cold acclimation in two species of the Drosophila virilis group?

This work was financially support by a Marie Curie Initial Training Network grant, “Understanding the evolutionary origin of biological diversity” (ITN-2008–213780 SPECIATION), grants from the Academy of Finland to A.H. (project 132619) and M.K. (projects 268214 and 272927), a grant from NERC, UK to M.G.R. (grant NE/J020818/1), and NERC, UK PhD studentship to D.J.P. (NE/I528634/1).For many organisms the ability to cold acclimate with the onset of seasonal cold has major implications for their fitness. In insects, where this ability is widespread, the physiological changes associated with increased cold tolerance have been well studied. Despite this, little work has been done to trace changes in gene expression during cold acclimation that lead to an increase in cold tolerance. We used an RNA-Seq approach to investigate this in two species of the Drosophila virilis group. We found that the majority of genes that are differentially expressed during cold acclimation differ between the two species. Despite this, the biological processes associated with the differentially expressed genes were broadly similar in the two species. These included: metabolism, cell membrane composition, and circadian rhythms, which are largely consistent with previous work on cold acclimation/cold tolerance. In addition, we also found evidence of the involvement of the rhodopsin pathway in cold acclimation, a pathway that has been recently linked to thermotaxis. Interestingly, we found no evidence of differential expression of stress genes implying that long-term cold acclimation and short-term stress response may have a different physiological basis.PostprintPeer reviewe

The reporting radiographer's role: a contemporary insight

The aims of this study were to determine how the skills of reporting radiographers are being utilised and how reporting radiographers fulfil their mandatory Continuing Professional Development (CPD) commitment. Data were collected via an anonymous postal questionnaire from qualified diagnostic radiographers who were working in the NHS and who had successfully completed a post-registration qualification in radiographic reporting. There was a total return of 81 questionnaires. The majority of reporting radiographers report for at least half a day per week with a small number undertaking this role for the entire week. For most respondents qualifying as a reporting radiographer had a positive effect on their grade however a substantial proportion stated that their grade had not changed. Most of the respondents were audited on a regular basis with peer review being more prevalent than review by radiologist. Reporting radiographers were actively engaged in reporting related CPD with study days and activities in journals being more popular and e-learning the least preferred. The ability of reporting radiographers to undertake both reporting and image acquisition roles means they are a versatile workforce that has a positive impact on service delivery. Reporting radiographers are highly motivated to maintain their skills, develop their knowledge base and extend their role

CMB Telescopes and Optical Systems

The cosmic microwave background radiation (CMB) is now firmly established as a fundamental and essential probe of the geometry, constituents, and birth of the Universe. The CMB is a potent observable because it can be measured with precision and accuracy. Just as importantly, theoretical models of the Universe can predict the characteristics of the CMB to high accuracy, and those predictions can be directly compared to observations. There are multiple aspects associated with making a precise measurement. In this review, we focus on optical components for the instrumentation used to measure the CMB polarization and temperature anisotropy. We begin with an overview of general considerations for CMB observations and discuss common concepts used in the community. We next consider a variety of alternatives available for a designer of a CMB telescope. Our discussion is guided by the ground and balloon-based instruments that have been implemented over the years. In the same vein, we compare the arc-minute resolution Atacama Cosmology Telescope (ACT) and the South Pole Telescope (SPT). CMB interferometers are presented briefly. We conclude with a comparison of the four CMB satellites, Relikt, COBE, WMAP, and Planck, to demonstrate a remarkable evolution in design, sensitivity, resolution, and complexity over the past thirty years.Comment: To appear in: Planets, Stars and Stellar Systems (PSSS), Volume 1: Telescopes and Instrumentatio

Genome sequence of an Australian kangaroo, Macropus eugenii, provides insight into the evolution of mammalian reproduction and development.

BACKGROUND: We present the genome sequence of the tammar wallaby, Macropus eugenii, which is a member of the kangaroo family and the first representative of the iconic hopping mammals that symbolize Australia to be sequenced. The tammar has many unusual biological characteristics, including the longest period of embryonic diapause of any mammal, extremely synchronized seasonal breeding and prolonged and sophisticated lactation within a well-defined pouch. Like other marsupials, it gives birth to highly altricial young, and has a small number of very large chromosomes, making it a valuable model for genomics, reproduction and development. RESULTS: The genome has been sequenced to 2 × coverage using Sanger sequencing, enhanced with additional next generation sequencing and the integration of extensive physical and linkage maps to build the genome assembly. We also sequenced the tammar transcriptome across many tissues and developmental time points. Our analyses of these data shed light on mammalian reproduction, development and genome evolution: there is innovation in reproductive and lactational genes, rapid evolution of germ cell genes, and incomplete, locus-specific X inactivation. We also observe novel retrotransposons and a highly rearranged major histocompatibility complex, with many class I genes located outside the complex. Novel microRNAs in the tammar HOX clusters uncover new potential mammalian HOX regulatory elements. CONCLUSIONS: Analyses of these resources enhance our understanding of marsupial gene evolution, identify marsupial-specific conserved non-coding elements and critical genes across a range of biological systems, including reproduction, development and immunity, and provide new insight into marsupial and mammalian biology and genome evolution

Cooperation and Contagion in Web-Based, Networked Public Goods Experiments

A longstanding idea in the literature on human cooperation is that cooperation should be reinforced when conditional cooperators are more likely to interact. In the context of social networks, this idea implies that cooperation should fare better in highly clustered networks such as cliques than in networks with low clustering such as random networks. To test this hypothesis, we conducted a series of web-based experiments, in which 24 individuals played a local public goods game arranged on one of five network topologies that varied between disconnected cliques and a random regular graph. In contrast with previous theoretical work, we found that network topology had no significant effect on average contributions. This result implies either that individuals are not conditional cooperators, or else that cooperation does not benefit from positive reinforcement between connected neighbors. We then tested both of these possibilities in two subsequent series of experiments in which artificial seed players were introduced, making either full or zero contributions. First, we found that although players did generally behave like conditional cooperators, they were as likely to decrease their contributions in response to low contributing neighbors as they were to increase their contributions in response to high contributing neighbors. Second, we found that positive effects of cooperation were contagious only to direct neighbors in the network. In total we report on 113 human subjects experiments, highlighting the speed, flexibility, and cost-effectiveness of web-based experiments over those conducted in physical labs

Evaluation of the current knowledge limitations in breast cancer research: a gap analysis

BACKGROUND A gap analysis was conducted to determine which areas of breast cancer research, if targeted by researchers and funding bodies, could produce the greatest impact on patients. METHODS Fifty-six Breast Cancer Campaign grant holders and prominent UK breast cancer researchers participated in a gap analysis of current breast cancer research. Before, during and following the meeting, groups in seven key research areas participated in cycles of presentation, literature review and discussion. Summary papers were prepared by each group and collated into this position paper highlighting the research gaps, with recommendations for action. RESULTS Gaps were identified in all seven themes. General barriers to progress were lack of financial and practical resources, and poor collaboration between disciplines. Critical gaps in each theme included: (1) genetics (knowledge of genetic changes, their effects and interactions); (2) initiation of breast cancer (how developmental signalling pathways cause ductal elongation and branching at the cellular level and influence stem cell dynamics, and how their disruption initiates tumour formation); (3) progression of breast cancer (deciphering the intracellular and extracellular regulators of early progression, tumour growth, angiogenesis and metastasis); (4) therapies and targets (understanding who develops advanced disease); (5) disease markers (incorporating intelligent trial design into all studies to ensure new treatments are tested in patient groups stratified using biomarkers); (6) prevention (strategies to prevent oestrogen-receptor negative tumours and the long-term effects of chemoprevention for oestrogen-receptor positive tumours); (7) psychosocial aspects of cancer (the use of appropriate psychosocial interventions, and the personal impact of all stages of the disease among patients from a range of ethnic and demographic backgrounds). CONCLUSION Through recommendations to address these gaps with future research, the long-term benefits to patients will include: better estimation of risk in families with breast cancer and strategies to reduce risk; better prediction of drug response and patient prognosis; improved tailoring of treatments to patient subgroups and development of new therapeutic approaches; earlier initiation of treatment; more effective use of resources for screening populations; and an enhanced experience for people with or at risk of breast cancer and their families. The challenge to funding bodies and researchers in all disciplines is to focus on these gaps and to drive advances in knowledge into improvements in patient care