A collaborative hackathon to investigate climate change and extreme weather impacts in justice and insurance settings

By bringing together a large group of participants with diverse skillsets, hackathons aim to make good headway into a particular research topic over a short period of time. This collaborative approach supports relationship building, cross team working and the development of technical skills across different areas

An Eclipsing 47 minute Double White Dwarf Binary at 400 pc

We present the discovery of the eclipsing double white dwarf (WD) binary WDJ 022558.21-692025.38 that has an orbital period of 47.19 min. Following identification with the Transiting Exoplanet Survey Satellite, we obtained time-series ground based spectroscopy and high-speed multi-band ULTRACAM photometry which indicate a primary DA WD of mass 0.40 +- 0.04 Msol and a 0.28 +- 0.02 Msol mass secondary WD, which is likely of type DA as well. The system becomes the third-closest eclipsing double WD binary discovered with a distance of approximately 400 pc and will be a detectable source for upcoming gravitational wave detectors in the mHz frequency range. Its orbital decay will be measurable photometrically within 10 yrs to a precision of better than 1%. The fate of the binary is to merge in approximately 41 Myr, likely forming a single, more massive WD.Comment: Accepted for publication in MNRAS, 8 pages + 2 appendix pages, 6 figure

An eclipsing 47 minute double white dwarf binary at 400 pc

We present the discovery of the eclipsing double white dwarf (WD) binary WDJ 022558.21-692025.38 that has an orbital period of 47.19 min. Following identification with the Transiting Exoplanet Survey Satellite, we obtained time-series ground based spectroscopy and high-speed multi-band ULTRACAM photometry which indicate a primary DA WD of mass 0.40 +- 0.04 Msol and a 0.28 +- 0.02 Msol mass secondary WD, which is likely of type DA as well. The system becomes the third-closest eclipsing double WD binary discovered with a distance of approximately 400 pc and will be a detectable source for upcoming gravitational wave detectors in the mHz frequency range. Its orbital decay will be measurable photometrically within 10 yrs to a precision of better than 1%. The fate of the binary is to merge in approximately 41 Myr, likely forming a single, more massive WD

AMP-Activated Kinase Restricts Rift Valley Fever Virus Infection by Inhibiting Fatty Acid Synthesis

The cell intrinsic innate immune responses provide a first line of defense against viral infection, and often function by targeting cellular pathways usurped by the virus during infection. In particular, many viruses manipulate cellular lipids to form complex structures required for viral replication, many of which are dependent on de novo fatty acid synthesis. We found that the energy regulator AMPK, which potently inhibits fatty acid synthesis, restricts infection of the Bunyavirus, Rift Valley Fever Virus (RVFV), an important re-emerging arthropod-borne human pathogen for which there are no effective vaccines or therapeutics. We show restriction of RVFV both by AMPK and its upstream activator LKB1, indicating an antiviral role for this signaling pathway. Furthermore, we found that AMPK is activated during RVFV infection, leading to the phosphorylation and inhibition of acetyl-CoA carboxylase, the first rate-limiting enzyme in fatty acid synthesis. Activating AMPK pharmacologically both restricted infection and reduced lipid levels. This restriction could be bypassed by treatment with the fatty acid palmitate, demonstrating that AMPK restricts RVFV infection through its inhibition of fatty acid biosynthesis. Lastly, we found that this pathway plays a broad role in antiviral defense since additional viruses from disparate families were also restricted by AMPK and LKB1. Therefore, AMPK is an important component of the cell intrinsic immune response that restricts infection through a novel mechanism involving the inhibition of fatty acid metabolism

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

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

Vinyldimethylphenylsilanes as latent partners in cross-coupling reactions

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Parental and early life stage environments drive establishment of bacterial and dinoflagellate communities in a common coral

The establishment of coral microbial communities in early developmental stages is fundamental to coral fitness, but its drivers are largely unknown, particularly for bacteria. Using an in situ reciprocal transplant experiment, we examined the influence of parental, planulation and early recruit environments on the microbiome of brooded offspring in the coral Pocillopora damicornis. 16S rRNA and ITS2 rDNA gene metabarcoding showed that bacterial and microalgal endosymbiont communities varied according to parental and planulation environments, but not with early recruit environment. Only a small number of bacterial strains were shared between offspring and their respective parents, revealing bacterial establishment as largely environmentally driven in very early life stages. Conversely, microalgal communities of recruits were highly similar to those of their respective parents, but also contained additional low abundance strains, suggesting both vertical transmission and novel ('horizontal') acquisition. Altogether, recruits harboured more variable microbiomes compared to their parents, indicating winnowing occurs as corals mature

Management of hypothermia in the perioperative environment

Heidke, PV ORCiD: 0000-0002-8991-6570This standard provides guidance for the prevention and management of inadvertent perioperative hypothermia