Ship-based contributions to global ocean, weather, and climate observing systems

The role ships play in atmospheric, oceanic, and biogeochemical observations is described with a focus on measurements made within 100 m of the ocean surface. Ships include merchant and research vessels, cruise liners and ferries, fishing vessels, coast guard, military, and other government-operated ships, yachts, and a growing fleet of automated surface vessels. The present capabilities of ships to measure essential climate/ocean variables and the requirements from a broad community to address operational, commercial, and scientific needs are described. Following the guidance from the OceanObs'19 organizing committee, the authors provide a vision to expand observations needed from ships to understand and forecast the exchanges across the ocean-atmosphere interface. The vision addresses (1) recruiting vessels to improve both spatial and temporal sampling, (2) conducting multi-variate sampling on ships, (3) raising technology readiness levels of automated shipboard sensors and ship-to-shore data communications, (4) advancing quality evaluation of observations, and (5) developing a unified data management approach for observations and metadata that meets the needs of a diverse user community. Recommendations are made focusing on integrating private and autonomous vessels into the observing system, investing in sensor and communications technology development, developing an integrated data management structure that includes all types of ships, and moving towards a quality evaluation process that will result in a subset of ships being defined as mobile reference ships that will support climate studies. We envision a future where commercial, research, and privately-owned vessels are making multivariate observations using a combination of automated and human-observed measurements. All data and metadata will be documented, tracked, evaluated, distributed, and archived to benefit users of marine data. This vision looks at ships as a holistic network, not a set of disparate commercial, research, and/or third-party activities working in isolation, to bring these communities together for the mutual benefit of all

Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels

Vitamin D is a steroid hormone precursor that is associated with a range of human traits and diseases. Previous GWAS of serum 25-hydroxyvitamin D concentrations have identified four genome-wide significant loci (GC, NADSYN1/DHCR7, CYP2R1, CYP24A1). In this study, we expand the previous SUNLIGHT Consortium GWAS discovery sample size from 16,125 to 79,366 (all European descent). This larger GWAS yields two additional loci harboring genome-wide significant variants (P = 4.7x10(-9) at rs8018720 in SEC23A, and P = 1.9x10(-14) at rs10745742 in AMDHD1). The overall estimate of heritability of 25-hydroxyvitamin D serum concentrations attributable to GWAS common SNPs is 7.5%, with statistically significant loci explaining 38% of this total. Further investigation identifies signal enrichment in immune and hematopoietic tissues, and clustering with autoimmune diseases in cell-type-specific analysis. Larger studies are required to identify additional common SNPs, and to explore the role of rare or structural variants and gene-gene interactions in the heritability of circulating 25-hydroxyvitamin D levels.Peer reviewe

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

‘Everything seems to be pushed onto the businesses’: stakeholder perceptions of the policing of business crime in Staffordshire, United Kingdom

This article concerns the perceptions and policing of business crime in the Staffordshire Police area in England in 2019–2020. Based on collaborative mixed methods’ work analysis of business crime in Staffordshire, it considers the framing of official discourse, and how it is applied and understood in police practice. Using 74 qualitative interviews with small business owners and access to police data, the research team considered how business crime was framed by officials and stakeholders. Noting there is something of a disconnect between officials and stakeholders the paper suggests that this reveals the conceptual and practical limitations of policing business crime as a form of commercial victimisation. This is due, the paper argues, to the conceptual ambiguity of the contemporary official police discourse of business crime which, in praxis is ill-defined and largely restricted to a more obvious form of retail crime. It suggests that greater consideration and conceptual refinement of the varied nature of business and enterprise is necessary if authorities truly wish to recognise the varied ways in which commercial activity and victimisation intersect. Recognising these intersections should enable police and the CJS to provide more effective responses to stakeholders and the wide range of businesses that face varied and multifaceted victimisation

Label-free pathology by spectrally sliced femtosecond stimulated Raman scattering (SRS) microscopy

<div><p>Optical “virtual biopsy” is an attractive way to improve disease diagnosis and surgical guidance. Many optical microscopy techniques have been developed to provide diagnostic information without the need for tissue sectioning or staining. Among these techniques, label-free chemical imaging is the most desirable. Recently, it has been shown that narrowband, picosecond stimulated Raman scattering (SRS) can achieve comparable morphological contrast to hematoxylin and eosin staining (H&E staining), the ‘gold standard’ of pathology. However, to translate the technique from the bench to the bedside, optimal laser sources and parameters have yet to be identified. Here we describe an improvement to the narrowband SRS microscopy techniques for label-free tissue imaging. Through spectral slicing of broadband, femtosecond pulses, we are able to maintain the same protein/lipid contrast as narrowband SRS while achieving a higher signal-to-noise ratio (SNR). Our method draws upon the benefits of femtosecond pulses (e.g. higher peak power) while preserving those of picosecond pulses (e.g. adequate spectral resolution). We demonstrate this achievement through protein/lipid signal and contrast quantification of mouse brain tissue as a function of bandwidth, and comparison with numerical simulations. Further method validation is provided through imaging of additional mouse tissues: liver, kidney, and skin.</p></div

Signal and contrast dependence on bandwidth.

<p>(a) SRS imaging of mouse brain tissue 30 cm^-1 pulses. Total signal for the (b) lipid and protein channels as a function of bandwidth are also shown to illustrate the increase in signal as bandwidth increases. The dashed and dotted gray lines are theoretical curves at 75 and 50 cm^-1, respectively. (c) Contrast at four areas was averaged and plotted as a function of bandwidth. The image shown represents the four areas used and is the overlay at 30 cm^-1 from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0178750#pone.0178750.g003" target="_blank">Fig 3</a> for reference. Scale bar: 200 μm.</p

Broadband, femtosecond SRS imaging of mouse tissue using 40 cm^-1 pulses.

<p>The tissues shown are (a, b) kidney, (c, d) liver, and (e, f) skin. For each tissue, the above image is a larger field of view (FOV) and the below image is a smaller FOV indicated by the red outline. After unmixing, the images are color coded and merged; the proteins are colored blue and the lipids, green. Scale bars: 100 μm.</p

Label-Free Chemical Imaging of Latent Fingerprints with Stimulated Raman Scattering Microscopy

Fingerprints have long been the gold standard for personal identification in forensic investigations. Methods for cultivating and enhancing the visualization of latent fingerprints (LFPs) are continuously evolving. One important challenge is to identify suspicious chemicals present in fingerprint residues, which requires chemical imaging capability. Recently, vibrational spectroscopy has shown that LFP analysis through tape-lift, Raman mapping, and multivariate data analysis presents a useful tool for forensic investigation. However, there are still major difficulties in terms of acquisition speed, poor spatial resolution, and lack of sensitivity. This paper demonstrates the feasibility of stimulated Raman scattering microscopy to quickly and easily extract LFP patterns from different substrates. Contrary to what has been reported, no obvious fingerprint degradation or lipid diffusion is observed with either glass or stainless steel substrate. Importantly, we demonstrate that trace exogenous chemicals can be detected in fingerprints. We further demonstrate an improvement in directly acquiring a LFP pattern lifted from tape by spectrally removing signals from tape

SRS imaging of mouse brain tissue.

<p>Imaging at (a) 2935 cm^-1 (proteins) with bandwidths of 10 cm^-1, 20 cm^-1, 30 cm^-1, and 40 cm^-1 from left to right and (b) 2855 cm^-1 (lipids) with bandwidths of 10 cm^-1, 20 cm^-1, 30 cm^-1, and 40 cm^-1 from left to right. As expected, the mean intensity increases as the bandwidth broadens. After unmixing (subtracting the lipids out of the protein channel) the images are color coded and merged; the proteins are colored blue and the lipids, green. Composite tissue images (c) show only slight differences between 10, 20, 30, and 40 cm^-1 from left to right. Scale bar: 100 μm.</p

Simultaneous two-channel SRS imaging of mouse brain tissue using 30 cm^-1 pulses.

<p>The mouse brain image shown was collected using dual-phase lock-in detection [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0178750#pone.0178750.ref032" target="_blank">32</a>]. (a) Shows the proteins as blue and the lipids, green, while (b) provides a pseudo-H&E color scheme. Scale bars: 100 μm.</p