Towards conformationally-locked difluorosugar analogues : an unexpected sense of dihydroxylation

Difluorinated cyclooctenones, synthesised using RCM, can be used as templates for stereoselective oxidative transformations to products that undergo transannular reactions to afford conformationally-locked analogues of 2-deoxy-2,2-difluorosugars with different stereochemical relationships between the C-2 and C-3 hydroxyl groups

Using single-cell genomics to understand developmental processes and cell fate decisions.

High-throughput -omics techniques have revolutionised biology, allowing for thorough and unbiased characterisation of the molecular states of biological systems. However, cellular decision-making is inherently a unicellular process to which "bulk" -omics techniques are poorly suited, as they capture ensemble averages of cell states. Recently developed single-cell methods bridge this gap, allowing high-throughput molecular surveys of individual cells. In this review, we cover core concepts of analysis of single-cell gene expression data and highlight areas of developmental biology where single-cell techniques have made important contributions. These include understanding of cell-to-cell heterogeneity, the tracing of differentiation pathways, quantification of gene expression from specific alleles, and the future directions of cell lineage tracing and spatial gene expression analysis.J.A.G. was supported by Wellcome Trust Grant “Systematic Identification of Lineage Specification in Murine Gastrulation” (109081/Z/15/A). A.S. was supported by Wellcome Trust Grant “Tracing early mammalian lineage decisions by single cell genomics” (105031/B/14/Z). J.C.M. was supported by core funding from Cancer Research UK (award no. A17197) and EMBL

Mosaic autosomal aneuploidies are detectable from single-cell RNAseq data.

BACKGROUND: Aneuploidies are copy number variants that affect entire chromosomes. They are seen commonly in cancer, embryonic stem cells, human embryos, and in various trisomic diseases. Aneuploidies frequently affect only a subset of cells in a sample; this is known as "mosaic" aneuploidy. A cell that harbours an aneuploidy exhibits disrupted gene expression patterns which can alter its behaviour. However, detection of aneuploidies using conventional single-cell DNA-sequencing protocols is slow and expensive. METHODS: We have developed a method that uses chromosome-wide expression imbalances to identify aneuploidies from single-cell RNA-seq data. The method provides quantitative aneuploidy calls, and is integrated into an R software package available on GitHub and as an Additional file of this manuscript. RESULTS: We validate our approach using data with known copy number, identifying the vast majority of aneuploidies with a low rate of false discovery. We show further support for the method's efficacy by exploiting allele-specific gene expression levels, and differential expression analyses. CONCLUSIONS: The method is quick and easy to apply, straightforward to interpret, and represents a substantial cost saving compared to single-cell genome sequencing techniques. However, the method is less well suited to data where gene expression is highly variable. The results obtained from the method can be used to investigate the consequences of aneuploidy itself, or to exclude aneuploidy-affected expression values from conventional scRNA-seq data analysis

High velocity clouds in the Galactic All Sky Survey I. Catalogue

We present a catalogue of high-velocity clouds (HVCs) from the Galactic All Sky Survey (GASS) of southern-sky neutral hydrogen, which has 57 mK sensitivity and 1 km/s velocity resolution and was obtained with the Parkes Telescope. Our catalogue has been derived from the stray-radiation corrected second release of GASS. We describe the data and our method of identifying HVCs and analyse the overall properties of the GASS population. We catalogue a total of 1693 HVCs at declinations < 0 deg, including 1111 positive velocity HVCs and 582 negative velocity HVCs. Our catalogue also includes 295 anomalous velocity clouds (AVCs). The cloud line-widths of our HVC population have a median FWHM of ~19 km/s, which is lower than found in previous surveys. The completeness of our catalogue is above 95% based on comparison with the HIPASS catalogue of HVCs, upon which we improve with an order of magnitude in spectral resolution. We find 758 new HVCs and AVCs with no HIPASS counterpart. The GASS catalogue will shed an unprecedented light on the distribution and kinematic structure of southern-sky HVCs, as well as delve further into the cloud populations that make up the anomalous velocity gas of the Milky Way.Comment: 21 pages, 14 figures, accepted for publication in ApJ

Statistical analysis of hypersonic glide vehicle radar cross section

The capability to design, manufacture and test Hypersonic Glide Vehicles (HGVs) has been demonstrated by a number of nations, and they are increasingly forming part of military inventories, potentially offering capabilities highly unique to this technology. This article reports the simulated Monostatic Radar Cross Section of a generic HGV in five frequency ranges, HF, VHF, UHF, L, and S-bands associated with different radar types. Full spherical datasets of complex co- and cross-polar data are synthesised so that backscatter resulting from illumination by r.f./microwave energy of linear or circular polarisation can subsequently be computed from the raw dataset. Circular polarisation is commonly employed by ground-based Ballistic Missile Early Warning Systems and Space Object Surveillance and Identification radars to avoid polarisation mis-match losses resulting from ionospheric Faraday rotation effects. The data was generated using Ansys' Finite Element Solver at 10, 150 and 430 MHz, with the Geometric Optics/Physical Optics based SBR+ solver employed for 1.3 and 3 GHz data. All data was produced at below the Nyquist sampling interval relevant to the target's electrical size. These datasets were then imported into a Matlab routine which extracted data over limited angular ranges associated with the likely radar line-of-sight in particular scenarios, typically having a standard deviation of ±10° about the direction of flight, applying either a Gaussian or Uniform sampling distribution as part of a Monte Carlo analysis. These extracted data were then used to form histograms giving the probability of sampling particular RCS values. Probability density functions and cumulative distribution functions were then fitted, to aid in the representation of statistical target fluctuations for each band and angular sampling range. The HGV exists in either the ‘Rayleigh’, ‘resonance’ or ‘optical’ scattering regimes, depending on its relative electrical size. The results suggest that for this target shape at HF and VHF cases a simple Swerling 0 (fluctuation invariant) approximation is adequate in most instances, whilst a Gamma distribution may be applied for UHF band cases. At L and S-band a Beta distribution was found to provide a good fit to the available data

Social networks : the future for health care delivery

With the rapid growth of online social networking for health, health care systems are experiencing an inescapable increase in complexity. This is not necessarily a drawback; self-organising, adaptive networks could become central to future health care delivery. This paper considers whether social networks composed of patients and their social circles can compete with, or complement, professional networks in assembling health-related information of value for improving health and health care. Using the framework of analysis of a two-sided network – patients and providers – with multiple platforms for interaction, we argue that the structure and dynamics of such a network has implications for future health care. Patients are using social networking to access and contribute health information. Among those living with chronic illness and disability and engaging with social networks, there is considerable expertise in assessing, combining and exploiting information. Social networking is providing a new landscape for patients to assemble health information, relatively free from the constraints of traditional health care. However, health information from social networks currently complements traditional sources rather than substituting for them. Networking among health care provider organisations is enabling greater exploitation of health information for health care planning. The platforms of interaction are also changing. Patient-doctor encounters are now more permeable to influence from social networks and professional networks. Diffuse and temporary platforms of interaction enable discourse between patients and professionals, and include platforms controlled by patients. We argue that social networking has the potential to change patterns of health inequalities and access to health care, alter the stability of health care provision and lead to a reformulation of the role of health professionals. Further research is needed to understand how network structure combined with its dynamics will affect the flow of information and potentially the allocation of health care resources

Detection and removal of barcode swapping in single-cell RNA-seq data.

Barcode swapping results in the mislabelling of sequencing reads between multiplexed samples on patterned flow-cell Illumina sequencing machines. This may compromise the validity of numerous genomic assays; however, the severity and consequences of barcode swapping remain poorly understood. We have used two statistical approaches to robustly quantify the fraction of swapped reads in two plate-based single-cell RNA-sequencing datasets. We found that approximately 2.5% of reads were mislabelled between samples on the HiSeq 4000, which is lower than previous reports. We observed no correlation between the swapped fraction of reads and the concentration of free barcode across plates. Furthermore, we have demonstrated that barcode swapping may generate complex but artefactual cell libraries in droplet-based single-cell RNA-sequencing studies. To eliminate these artefacts, we have developed an algorithm to exclude individual molecules that have swapped between samples in 10x Genomics experiments, allowing the continued use of cutting-edge sequencing machines for these assays

Spontaneously generated online patient experience of Modafinil : a qualitative and NLP analysis

Objective: To compare the findings from a qualitative and a natural language processing (NLP) based analysis of online patient experience posts on patient experience of the effectiveness and impact of the drug Modafinil. Methods: Posts (n = 260) from 5 online social media platforms where posts were publicly available formed the dataset/corpus. Three platforms asked posters to give a numerical rating of Modafinil. Thematic analysis: data was coded and themes generated. Data were categorized into PreModafinil, Acquisition, Dosage, and PostModafinil and compared to identify each poster's own view of whether taking Modafinil was linked to an identifiable outcome. We classified this as positive, mixed, negative, or neutral and compared this with numerical ratings. NLP: Corpus text was speech tagged and keywords and key terms extracted. We identified the following entities: drug names, condition names, symptoms, actions, and side-effects. We searched for simple relationships, collocations, and co-occurrences of entities. To identify causal text, we split the corpus into PreModafinil and PostModafinil and used n-gram analysis. To evaluate sentiment, we calculated the polarity of each post between −1 (negative) and +1 (positive). NLP results were mapped to qualitative results. Results: Posters had used Modafinil for 33 different primary conditions. Eight themes were identified: the reason for taking (condition or symptom), impact of symptoms, acquisition, dosage, side effects, other interventions tried or compared to, effectiveness of Modafinil, and quality of life outcomes. Posters reported perceived effectiveness as follows: 68 positive, 12 mixed, 18 negative. Our classification was consistent with poster ratings. Of the most frequent 100 keywords/keyterms identified by term extraction 88/100 keywords and 84/100 keyterms mapped directly to the eight themes. Seven keyterms indicated negation and temporal states. Sentiment was as follows 72 positive sentiment 4 neutral 24 negative. Matching of sentiment between the qualitative and NLP methods was accurate in 64.2 of posts. If we allow for one category difference matching was accurate in 85 of posts. Conclusions: User generated patient experience is a rich resource for evaluating real world effectiveness, understanding patient perspectives, and identifying research gaps. Both methods successfully identified the entities and topics contained in the posts. In contrast to current evidence, posters with a wide range of other conditions found Modafinil effective. Perceived causality and effectiveness were identified by both methods demonstrating the potential to augment existing knowledge