Shape-induced force fields in optical trapping

Advances in optical tweezers, coupled with the proliferation of two-photon polymerization systems, mean that it is now becoming routine to fabricate and trap non-spherical particles. The shaping of both light beams and particles allows fine control over the flow of momentum from the optical to mechanical regimes. However, understanding and predicting the behaviour of such systems is highly complex in comparison with the traditional optically trapped microsphere. In this Article, we present a conceptually new and simple approach based on the nature of the optical force density. We illustrate the method through the design and fabrication of a shaped particle capable of acting as a passive force clamp, and we demonstrate its use as an optically trapped probe for imaging surface topography. Further applications of the design rules highlighted here may lead to new sensors for probing biomolecule mechanics, as well as to the development of optically actuated micromachines

What work has to be done to implement collaborative care for depression? Process evaluation of a trial utilizing the Normalization Process Model

<p>Abstract</p> <p>Background</p> <p>There is a considerable evidence base for 'collaborative care' as a method to improve quality of care for depression, but an acknowledged gap between efficacy and implementation. This study utilises the Normalisation Process Model (NPM) to inform the process of implementation of collaborative care in both a future full-scale trial, and the wider health economy.</p> <p>Methods</p> <p>Application of the NPM to qualitative data collected in both focus groups and one-to-one interviews before and after an exploratory randomised controlled trial of a collaborative model of care for depression.</p> <p>Results</p> <p>Findings are presented as they relate to the four factors of the NPM (interactional workability, relational integration, skill-set workability, and contextual integration) and a number of necessary tasks are identified. Using the model, it was possible to observe that predictions about necessary work to implement collaborative care that could be made from analysis of the pre-trial data relating to the four different factors of the NPM were indeed borne out in the post-trial data. However, additional insights were gained from the post-trial interview participants who, unlike those interviewed before the trial, had direct experience of a novel intervention. The professional freedom enjoyed by more senior mental health workers may work both for and against normalisation of collaborative care as those who wish to adopt new ways of working have the freedom to change their practice but are not obliged to do so.</p> <p>Conclusions</p> <p>The NPM provides a useful structure for both guiding and analysing the process by which an intervention is optimized for testing in a larger scale trial or for subsequent full-scale implementation.</p

Syncopation and the Score

The first and second authors were supported by an EPSRC DTA (www.epsrc.ac.uk) studentship

Efficient counting of k-mers in DNA sequences using a bloom filter

<p>Abstract</p> <p>Background</p> <p>Counting <it>k</it>-mers (substrings of length <it>k </it>in DNA sequence data) is an essential component of many methods in bioinformatics, including for genome and transcriptome assembly, for metagenomic sequencing, and for error correction of sequence reads. Although simple in principle, counting <it>k</it>-mers in large modern sequence data sets can easily overwhelm the memory capacity of standard computers. In current data sets, a large fraction-often more than 50%-of the storage capacity may be spent on storing <it>k</it>-mers that contain sequencing errors and which are typically observed only a single time in the data. These singleton <it>k</it>-mers are uninformative for many algorithms without some kind of error correction.</p> <p>Results</p> <p>We present a new method that identifies all the <it>k</it>-mers that occur more than once in a DNA sequence data set. Our method does this using a Bloom filter, a probabilistic data structure that stores all the observed <it>k</it>-mers implicitly in memory with greatly reduced memory requirements. We then make a second sweep through the data to provide exact counts of all nonunique <it>k</it>-mers. For example data sets, we report up to 50% savings in memory usage compared to current software, with modest costs in computational speed. This approach may reduce memory requirements for any algorithm that starts by counting <it>k</it>-mers in sequence data with errors.</p> <p>Conclusions</p> <p>A reference implementation for this methodology, BFCounter, is written in C++ and is GPL licensed. It is available for free download at <url>http://pritch.bsd.uchicago.edu/bfcounter.html</url></p

Morphological evidence for an invasion-independent metastasis pathway exists in multiple human cancers

BACKGROUND: We have previously described an alternative invasion-independent pathway of cancer metastasis in a murine mammary tumor model. This pathway is initiated by intravasation of tumor nests enveloped by endothelial cells of sinusoidal vasculature within the tumor. In this study, we examined whether evidence for the invasion-independent pathway of metastasis is present in human cancers. METHODS: Archival specimens of 10 common types of human cancers were examined for the presence of sinusoidal vasculature enveloping tumor nests and subsequently generated endothelial-covered tumor emboli in efferent veins. RESULTS: A percentage of tumor emboli in all cancers was found to be enveloped by endothelial cells, but these structures were particularly prevalent in renal cell carcinomas, hepatocellular carcinomas and follicular thyroid carcinomas. A common feature of the vasculature in these tumors was the presence of dilated sinusoid-like structures surrounding tumor nests. A high mean vascular area within tumors, an indication of sinusoidal vascular development, was significantly related to the presence of endothelial-covered tumor emboli. CONCLUSIONS: These results suggest that an invasion-independent metastatic pathway is possible in a wide variety of human cancers. Further investigation of this phenomenon may present new therapeutic strategies for the amelioration of cancer metastasis

A study on spline quasi-interpolation based quadrature rules for the isogeometric Galerkin BEM

Two recently introduced quadrature schemes for weakly singular integrals [Calabr\`o et al. J. Comput. Appl. Math. 2018] are investigated in the context of boundary integral equations arising in the isogeometric formulation of Galerkin Boundary Element Method (BEM). In the first scheme, the regular part of the integrand is approximated by a suitable quasi--interpolation spline. In the second scheme the regular part is approximated by a product of two spline functions. The two schemes are tested and compared against other standard and novel methods available in literature to evaluate different types of integrals arising in the Galerkin formulation. Numerical tests reveal that under reasonable assumptions the second scheme convergences with the optimal order in the Galerkin method, when performing $h$-refinement, even with a small amount of quadrature nodes. The quadrature schemes are validated also in numerical examples to solve 2D Laplace problems with Dirichlet boundary conditions

Strategies for recruiting Hispanic women into a prospective cohort study of modifiable risk factors for gestational diabetes mellitus

BACKGROUND: The purpose of this article was to describe effective strategies for recruitment of Hispanic women into a prospective cohort study of modifiable risk factors for gestational diabetes mellitus (GDM). Although Hispanic women have two to four times the risk of developing GDM compared with non-Hispanic white women, few GDM prevention studies have included Hispanic women. METHODS: The study was conducted in the ambulatory obstetrical practices of Baystate Medical Center located in a socioeconomically and ethnically diverse city in Massachusetts. The study employed a range of strategies to recruit Hispanic women based on a review of the literature as well as prior experience with the study population. RESULTS: Over a period of 32 months, a total of 851 Hispanic prenatal care patients were recruited. Among eligible women, 52.4% agreed to participate. Participants were young (70% <25 years), with low levels of education, and on public health insurance (81.5%); 88% were unmarried. Study design features such as use of bilingual recruiters, a flexible recruitment process, training recruiters to be culturally sensitive, use of culturally tailored materials, prescreening participants, participant compensation, seeking the cooperation of clinic staff, and continuous monitoring of recruitment goals emerged as important issues influencing recruitment. CONCLUSIONS: Findings suggest that investigators can successfully recruit pregnant women from ethnic minority groups of low socioeconomic status into observational studies. The study provides culturally appropriate recruitment strategies useful for practice-based settings recruiting Hispanic research participation

DecGPU: distributed error correction on massively parallel graphics processing units using CUDA and MPI

<p>Abstract</p> <p>Background</p> <p>Next-generation sequencing technologies have led to the high-throughput production of sequence data (reads) at low cost. However, these reads are significantly shorter and more error-prone than conventional Sanger shotgun reads. This poses a challenge for the <it>de novo </it>assembly in terms of assembly quality and scalability for large-scale short read datasets.</p> <p>Results</p> <p>We present DecGPU, the first parallel and distributed error correction algorithm for high-throughput short reads (HTSRs) using a hybrid combination of CUDA and MPI parallel programming models. DecGPU provides CPU-based and GPU-based versions, where the CPU-based version employs coarse-grained and fine-grained parallelism using the MPI and OpenMP parallel programming models, and the GPU-based version takes advantage of the CUDA and MPI parallel programming models and employs a hybrid CPU+GPU computing model to maximize the performance by overlapping the CPU and GPU computation. The distributed feature of our algorithm makes it feasible and flexible for the error correction of large-scale HTSR datasets. Using simulated and real datasets, our algorithm demonstrates superior performance, in terms of error correction quality and execution speed, to the existing error correction algorithms. Furthermore, when combined with Velvet and ABySS, the resulting DecGPU-Velvet and DecGPU-ABySS assemblers demonstrate the potential of our algorithm to improve <it>de novo </it>assembly quality for <it>de</it>-<it>Bruijn</it>-graph-based assemblers.</p> <p>Conclusions</p> <p>DecGPU is publicly available open-source software, written in CUDA C++ and MPI. The experimental results suggest that DecGPU is an effective and feasible error correction algorithm to tackle the flood of short reads produced by next-generation sequencing technologies.</p

Functional alpha-1B adrenergic receptors on human epicardial coronary artery endothelial cells

Alpha-1-adrenergic receptors (α1-ARs) regulate coronary arterial blood flow by binding catecholamines, norepinephrine (NE), and epinephrine (EPI), causing vasoconstriction when the endothelium is disrupted. Among the three α1-AR subtypes (α1A, α1B, and α1D), the α1D subtype predominates in human epicardial coronary arteries and is functional in human coronary smooth muscle cells (SMCs). However, the presence or function of α1-ARs on human coronary endothelial cells (ECs) is unknown. Here we tested the hypothesis that human epicardial coronary ECs express functional α1-ARs. Cultured human epicardial coronary artery ECs were studied using quantitative real-time reverse transcription polymerase chain reaction, radioligand binding, immunoblot, and 3H-thymidine incorporation. The α1B-subtype messenger ribonucleic acid (mRNA) was predominant in cultured human epicardial coronary ECs (90–95% of total α1-AR mRNA), and total α1-AR binding density in ECs was twice that in coronary SMCs. Functionally, NE and EPI through the α1B subtype activated extracellular signal-regulated kinase (ERK) in ECs, stimulated phosphorylation of EC endothelial nitric oxide synthase (eNOS), and increased deoxyribonucleic acid (DNA) synthesis. These results are the first to demonstrate α1-ARs on human coronary ECs and indicate that the α1B subtype is predominant. Our findings provide another potential mechanism for adverse cardiac effects of drug antagonists that nonselectively inhibit all three α1-AR subtypes

Age Affects the Expression of Maternal Care and Subsequent Behavioural Development of Offspring in a Precocial Bird

Variations of breeding success with age have been studied largely in iteroparous species and particularly in birds: survival of offspring increases with parental age until senescence. Nevertheless, these results are from observations of free-living individuals and therefore, it remains impossible to determine whether these variations result from parental investment or efficiency or both, and whether these variations occur during the prenatal or the postnatal stage or during both. Our study aimed first, to determine whether age had an impact on the expression of maternal breeding care by comparing inexperienced female birds of two different ages, and second, to define how these potential differences impact chicks’ growth and behavioural development. We made 22 2-month-old and 22 8-month-old female Japanese quail foster 1-day-old chicks. We observed their maternal behaviour until the chicks were 11 days old and then tested these chicks after separation from their mothers. Several behavioural tests estimated their fearfulness and their sociality. We observed first that a longer induction was required for young females to express maternal behaviour. Subsequently as many young females as elder females expressed maternal behaviour, but young females warmed chicks less, expressed less covering postures and rejected their chicks more. Chicks brooded by elder females presented higher growth rates and more fearfulness and sociality. Our results reveal that maternal investment increased with age independently of maternal experience, suggesting modification of hormone levels implied in maternal behaviour. Isolated effects of maternal experience should now be assessed in females of the same age. In addition, our results show, for first time in birds, that variations in maternal care directly induce important differences in the behavioural development of chicks. Finally, our results confirm that Japanese quail remains a great laboratory model of avian maternal behaviour and that the way we sample maternal behaviour is highly productive