Bayesian inference of biochemical kinetic parameters using the linear noise approximation

Background Fluorescent and luminescent gene reporters allow us to dynamically quantify changes in molecular species concentration over time on the single cell level. The mathematical modeling of their interaction through multivariate dynamical models requires the deveopment of effective statistical methods to calibrate such models against available data. Given the prevalence of stochasticity and noise in biochemical systems inference for stochastic models is of special interest. In this paper we present a simple and computationally efficient algorithm for the estimation of biochemical kinetic parameters from gene reporter data. Results We use the linear noise approximation to model biochemical reactions through a stochastic dynamic model which essentially approximates a diffusion model by an ordinary differential equation model with an appropriately defined noise process. An explicit formula for the likelihood function can be derived allowing for computationally efficient parameter estimation. The proposed algorithm is embedded in a Bayesian framework and inference is performed using Markov chain Monte Carlo. Conclusion The major advantage of the method is that in contrast to the more established diffusion approximation based methods the computationally costly methods of data augmentation are not necessary. Our approach also allows for unobserved variables and measurement error. The application of the method to both simulated and experimental data shows that the proposed methodology provides a useful alternative to diffusion approximation based methods

Renal artery stenosis-when to screen, what to stent?

Renal artery stensosis (RAS) continues to be a problem for clinicians, with no clear consensus on how to investigate and assess the clinical significance of stenotic lesions and manage the findings. RAS caused by fibromuscular dysplasia is probably commoner than previously appreciated, should be actively looked for in younger hypertensive patients and can be managed successfully with angioplasty. Atheromatous RAS is associated with increased incidence of cardiovascular events and increased cardiovascular mortality, and is likely to be seen with increasing frequency. Evidence from large clinical trials has led clinicians away from recommending interventional revascularisation towards aggressive medical management. There is now interest in looking more closely at patient selection for intervention, with focus on intervening only in patients with the highest-risk presentations such as flash pulmonary oedema, rapidly declining renal function and severe resistant hypertension. The potential benefits in terms of improving hard cardiovascular outcomes may outweigh the risks of intervention in this group, and further research is needed

Australian Aboriginal Birth Cohort study: follow-up processes at 20 years

Background: In 1987, a prospective study of an Australian Aboriginal Birth Cohort was established focusing on the relationships of fetal and childhood growth with the risk of chronic adult disease. However as the study is being conducted in a highly marginalized population it is also an important resource for cross-sectional descriptive and analytical studies. The aim of this paper is to describe the processes of the third follow up which was conducted 20 years after recruitment at birth. Methods: Progressive steps in a multiphase protocol were used for tracing, with modifications for the expected rural or urban location of the participants. Results: Of the original 686 cohort participants recruited 68 were untraced and 27 were known to have died. Of the 591 available for examination 122 were not examined; 11 of these were refusals and the remainder were not seen for logistical reasons relating to inclement weather, mobility of participants and single participants living in very remote locations. Conclusion: The high retention rate of this follow-up 20 years after birth recruitment is a testament to the development of successful multiphase protocols aimed at overcoming the challenges of tracing a cohort over a widespread remote area and also to the perseverance of the study personnel. We also interpret the high retention rate as a reflection of the good will of the wider Aboriginal community towards this study and that researchers interactions with the community were positive. The continued follow-up of this life course study now seems feasible and there are plans to trace and reexamine the cohort at age 25 years.Susan Sayers, Gurmeet Singh, Dorothy Mackerras, Megan Lawrance,Wendy Gunthorpe, Lisa Jamieson, Belinda Davison, Kobi Schutz and Joseph Fit

Multi-wave coherent control of a solid-state single emitter

The authors acknowledge support by the European Research Council Starting Grant 'PICSEN' contract no. 306387.Coherent control of individual two-level systems (TLSs) is at the basis of any implementation of quantum information. An impressive level of control is now achieved using nuclear, vacancies and charge spins. Manipulation of bright exciton transitions in semiconductor quantum dots (QDs) is less advanced, principally due to the sub-nanosecond dephasing. Conversely, owing to their robust coupling to light, one can apply tools of nonlinear spectroscopy to achieve all-optical command. Here, we report on the coherent manipulation of an exciton via multi-wave mixing. Specifically, we employ three resonant pulses driving a single InAs QD. The first two induce a four-wave mixing (FWM) transient, which is projected onto a six-wave mixing (SWM) depending on the delay and area of the third pulse, in agreement with analytical predictions. Such a switch enables to demonstrate the generation of SWM on a single emitter and to engineer the spectro-temporal shape of the coherent response originating from a TLS. These results pave the way toward multi-pulse manipulations of solid state qubits via implementing the NMR-like control schemes in the optical domain.PostprintPeer reviewe

Tooth brushing, tongue cleaning and snacking behaviour of dental technology and therapist students

Objective: To determine the tooth brushing, tongue cleaning and snacking behaviour of dental technology and therapist students. Methods: A descriptive cross-sectional study of students of Federal School of Dental Therapy and Technology Enugu, Nigeria. Self-administered questionnaire was used to obtain information on demography, frequency, duration and technique of tooth brushing and tongue cleaning as well as information on consumption of snacks. Results: A total of 242 students responded. Dental technology students made up 52.5% of the respondents and dental therapist in training made up 47.5%. Majority (63.2%) of the respondents considered the strength of tooth brush when purchasing a tooth brush and 78.9% use tooth brushes with medium strength. Seven-tenth (71.9%) of the respondents brush their teeth twice daily and 52.1% brush for 3–5 minutes. About one-third (30.2%) brush their teeth in front of a mirror. Chewing stick was used by 51.7% of respondents in addition to the use of tooth brush. Tongue cleaning was done by 94.2% with only 9.5% using a tongue cleaner. Only 20.2% reported regular snacks consumption. Nine-tenth (90.4%) of respondents were previously involved in educating others, apart from their colleagues, on tooth brushing. Conclusion: This survey revealed that most of the dental therapy and technology students had satisfactory tooth-brushing behaviour. The zeal to educate others about proper tooth brushing revealed in this study suggests that the students may be helpful in oral health promotion

The Brecon Beacons

The Brecon Beacons of central and southern Wales offer the opportunity to explore a range of geomorphological processes, particularly those relating to the rapid climate changes associated with the period subsequent to the Last Glacial Maximum. The mountains present some of the best preserved evidence in the British Isles of the interplay between glacial, periglacial and paraglacial processes, associated with conditions of marginal glaciation, and provide the most southerly evidence of Younger Dryas/Loch Lomond Stadial glaciation of Britain. The absence of evidence for landscape evolution in the region prior to the Last Glacial Maximum has recently begun to be addressed through insights derived from the subterranean geomorphology of limestone found in the south of the region. As one of the key sites of the early Industrial Revolution, the Brecon Beacons also preserve a unique landscape of anthropogenic (or even anthropocenic) geomorphology associated with large scale coal and iron extraction

Analyses of carnivore microsatellites and their intimate association with tRNA-derived SINEs

BACKGROUND: The popularity of microsatellites has greatly increased in the last decade on account of their many applications. However, little is currently understood about the factors that influence their genesis and distribution among and within species genomes. In this work, we analyzed carnivore microsatellite clones from GenBank to study their association with interspersed repeats and elucidate the role of the latter in microsatellite genesis and distribution. RESULTS: We constructed a comprehensive carnivore microsatellite database comprising 1236 clones from GenBank. Thirty-three species of 11 out of 12 carnivore families were represented, although two distantly related species, the domestic dog and cat, were clearly overrepresented. Of these clones, 330 contained tRNA(Lys)-derived SINEs and 357 contained other interspersed repeats. Our rough estimates of tRNA SINE copies per haploid genome were much higher than published ones. Our results also revealed a distinct juxtaposition of AG and A-rich repeats and tRNA(Lys)-derived SINEs suggesting their coevolution. Both microsatellites arose repeatedly in two regions of the insterspersed repeat. Moreover, microsatellites associated with tRNA(Lys)-derived SINEs showed the highest complexity and less potential instability. CONCLUSION: Our results suggest that tRNA(Lys)-derived SINEs are a significant source for microsatellite generation in carnivores, especially for AG and A-rich repeat motifs. These observations indicate two modes of microsatellite generation: the expansion and variation of pre-existing tandem repeats and the conversion of sequences with high cryptic simplicity into a repeat array; mechanisms which are not specific to tRNA(Lys)-derived SINEs. Microsatellite and interspersed repeat coevolution could also explain different distribution of repeat types among and within species genomes. Finally, due to their higher complexity and lower potential informative content of microsatellites associated with tRNA(Lys)-derived SINEs, we recommend avoiding their use as genetic markers

Effect of tissue-harvesting site on yield of stem cells derived from adipose tissue: implications for cell-based therapies

The stromal vascular fraction (SVF) of adipose tissue contains an abundant population of multipotent adipose-tissue-derived stem cells (ASCs) that possess the capacity to differentiate into cells of the mesodermal lineage in vitro. For cell-based therapies, an advantageous approach would be to harvest these SVF cells and give them back to the patient within a single surgical procedure, thereby avoiding lengthy and costly in vitro culturing steps. However, this requires SVF-isolates to contain sufficient ASCs capable of differentiating into the desired cell lineage. We have investigated whether the yield and function of ASCs are affected by the anatomical sites most frequently used for harvesting adipose tissue: the abdomen and hip/thigh region. The frequency of ASCs in the SVF of adipose tissue from the abdomen and hip/thigh region was determined in limiting dilution and colony-forming unit (CFU) assays. The capacity of these ASCs to differentiate into the chondrogenic and osteogenic pathways was investigated by quantitative real-time polymerase chain reaction and (immuno)histochemistry. A significant difference (P = 0.0009) was seen in ASC frequency but not in the absolute number of nucleated cells between adipose tissue harvested from the abdomen (5.1 ± 1.1%, mean ± SEM) and hip/thigh region (1.2 ± 0.7%). However, within the CFUs derived from both tissues, the frequency of CFUs having osteogenic differentiation potential was the same. When cultured, homogeneous cell populations were obtained with similar growth kinetics and phenotype. No differences were detected in differentiation capacity between ASCs from both tissue-harvesting sites. We conclude that the yield of ASCs, but not the total amount of nucleated cells per volume or the ASC proliferation and differentiation capacities, are dependent on the tissue-harvesting site. The abdomen seems to be preferable to the hip/thigh region for harvesting adipose tissue, in particular when considering SVF cells for stem-cell-based therapies in one-step surgical procedures for skeletal tissue engineering

Microsatellites for the genus Cucurbita and an SSR-based genetic linkage map of Cucurbita pepo L.

Until recently, only a few microsatellites have been available for Cucurbita, thus their development is highly desirable. The Austrian oil-pumpkin variety Gleisdorfer Ölkürbis (C. pepo subsp. pepo) and the C. moschata cultivar Soler (Puerto Rico) were used for SSR development. SSR-enriched partial genomic libraries were established and 2,400 clones were sequenced. Of these 1,058 (44%) contained an SSR at least four repeats long. Primers were designed for 532 SSRs; 500 primer pairs produced fragments of expected size. Of these, 405 (81%) amplified polymorphic fragments in a set of 12 genotypes: three C. moschata, one C. ecuadorensis, and eight C. pepo representing all eight cultivar groups. On an average, C. pepo and C. moschata produced 3.3 alleles per primer pair, showing high inter-species transferability. There were 187 SSR markers detecting polymorphism between the USA oil-pumpkin variety “Lady Godiva” (O5) and the Italian crookneck variety “Bianco Friulano” (CN), which are the parents of our previous F2 mapping population. It has been used to construct the first published C. pepo map, containing mainly RAPD and AFLP markers. Now the updated map comprises 178 SSRs, 244 AFLPs, 230 RAPDs, five SCARs, and two morphological traits (h and B). It contains 20 linkage groups with a map density of 2.9 cM. The observed genome coverage (Co) is 86.8%