Towards an analytical framework for tailoring supercontinuum generation

A fully analytical toolbox for supercontinuum generation relying on scenarios without pulse splitting is presented. Furthermore, starting from the new insights provided by this formalism about the physical nature of direct and cascaded dispersive wave emission, a unified description of this radiation in both normal and anomalous dispersion regimes is derived. Previously unidentified physics of broadband spectra reported in earlier works is successfully explained on this basis. Finally, a foundry-compatible few-millimeters-long silicon waveguide allowing octave-spanning supercontinuum generation pumped at telecom wavelengths in the normal dispersion regime is designed, hence showcasing the potential of this new analytical approach

The one year fate of iron oxide coated gold nanoparticles in mice

Safe implementation of nanotechnology and nanomedicine requires an in-depth understanding of the life cycle of nanoparticles in the body. Here, we investigate the long-term fate of gold/iron oxide heterostructures after intravenous injection in mice. We show these heterostructures degrade in vivo and that the magnetic and optical properties change during the degradation process. These particles eventually eliminate from the body. The comparison of two different coating shells for heterostructures, amphiphilic polymer or polyethylene glycol, reveals the long lasting impact of initial surface properties on the nanocrystal degradability and on the kinetics of elimination of magnetic iron and gold from liver and spleen. Modulation of nanoparticles reactivity to the biological environment by the choice of materials and surface functionalization may provide new directions in the design of multifunctional nanomedicines with predictable fate

Quantitative and qualitative evaluations of impacts and benefits of nine INHERIT case studies

The INHERIT report Quantitative and Qualitative Evaluations of Impacts and Benefits of Nine INHERIT Case Studies documents the findings relevant to potential impacts and benefits of nine case studies for health, equity and a more sustainable environment. It uses a mixed method approach with quantitative methods augmented in some cases by written responses to survey questions, or by focus group discussions on impacts, as appropriate. Each case study evaluation was led by a different INHERIT partner. In each case, partners formulated the research design appropriate to their case studies and the associated research questions identified within the framework of INHERIT. The coordinating partner, University College London (UCL), developed an evaluation framework to suit the range of case studies examined for impacts and benefits, the case specific logic models developed, and the research questions identified. The nine chapters describe the impact evaluations and findings from the nine case studies using the following format: Background; Overall aims; Context; Research Questions; Methodology; Results; Discussion; Limitations; Learning points for future research; Learning points for potential scale up and transferability

Creating triple-wins for health, equity and environmental sustainability: elements of good practice based on learning from the INHERIT case studies

This report draws out dimensions of good practice for building this triple-win, based on learning from the INHERIT project’s 15 case studies. In the context of the project, good practice refers to ways that support changing contexts and create conditions to enable behaviour change to reach the triple-win. This report summarises key information for consideration by governmental and non-governmental policy-makers and practitioners planning to work across sectors to achieve the triple-win through behaviour change at every level. INHERIT researchers have focused their evaluations of the 15 INHERIT case studies on implementation, intersectoral cooperation, impacts and cost benefits. The researchers have taken dimensions of good practice from INHERIT research to be those elements that appear to be promising or necessary in the contexts in which the INHERIT cases studies are implemented. The extent to which these elements of good practice can be generalised to other contexts merits consideration in developing future initiatives towards creating synergies across sectors. INHERIT researchers have drawn out lessons learned from information gathered in evaluations about triggers for the initiatives, key elements for implementation, success factors in intersectoral cooperation, what could have been done better, what should be done in the future, and the most important learnings from the evaluation of outcomes, costs and benefits

The caecal microbiota promotes the acute inflammatory response and the loss of the intestinal barrier integrity during severe Eimeria tenella infection

IntroductionCoccidiosis, a disease caused by intestinal apicomplexan parasites Eimeria, is a threat to poultry production. Eimeria tenella is one of the most pathogenic species, frequently causing a high prevalence of opportunistic infections.ObjectiveThe objective of this study is to investigate the role of the microbiota in the pathogenesis of severe Eimeria tenella infection.MethodsWe have previously shown that microbiota can promote parasite development. To study the effect of the microbiota on the pathogenesis of this infection, we used an experimental condition (inoculum of 10 000 oocysts E. tenella INRAE) in which the parasite load is similar between germ-free and conventional broilers at 7 days post-infection (pi). Thirteen conventional and 24 germ-free chickens were infected. Among this latter group, 12 remained germ-free and 12 received a microbiota from conventional healthy chickens at 4 days pi. Caeca and spleens were collected at 7 days pi.ResultsOur results demonstrated caecal lesions and epithelium damage in conventional chickens at 7 days pi but not in germ-free infected chickens. Administration of conventional microbiota to germ-free chickens partially restored these deleterious effects. At day 7 pi, both infected conventional and germ-free chickens exhibited increased gene expression of inflammatory mediators, including IL15, IFNγ, TNFα and the anti-inflammatory mediator SOCS1, whereas the inflammatory mediators CXCLi2, CCL20, IL18, CSF1, NOS2, PTGS2, IL1β, IL6, the receptor CCR2, and the anti-inflammatory mediators TGFβ1 and IL10 were upregulated only in infected conventional chickens. Notably, the IL18, PTGS2 gene expression was significantly higher in the infected conventional group. Overall, the inflammatory response enhanced by the microbiota might be in part responsible for higher lesion scores. Epithelial tight junction protein gene expression analysis revealed a significant upregulation of CLDN1 with the infection and microbiota, indicating a potential loss of the intestinal barrier integrity.ConclusionThese observations imply that, during E. tenella infection, the caecal microbiota could trigger an acute inflammatory response, resulting in a loss of intestinal integrity. Increase in bacterial translocation can then lead to the likelihood of opportunistic infections. Hence, modulating the microbiota may offer a promising strategy for improving poultry gut health and limiting caecal coccidiosis

Targeting the tumor mutanome for personalized vaccination in a TMB low non-small cell lung cancer.

BackgroundCancer is characterized by an accumulation of somatic mutations, of which a significant subset can generate cancer-specific neoepitopes that are recognized by autologous T cells. Such neoepitopes are emerging as important targets for cancer immunotherapy, including personalized cancer vaccination strategies.MethodsWe used whole-exome and RNA sequencing analysis to identify potential neoantigens for a patient with non-small cell lung cancer. Thereafter, we assessed the autologous T-cell reactivity to the candidate neoantigens using a long peptide approach in a cultured interferon gamma ELISpot and tracked the neoantigen-specific T-cells in the tumor by T-cell receptor (TCR) sequencing. In parallel, identified gene variants were incorporated into a Modified Vaccinia Ankara-based vaccine, which was evaluated in the human leucocyte antigen A*0201 transgenic mouse model (HHD).ResultsSequencing revealed a tumor with a low mutational burden: 2219 sequence variants were identified from the primary tumor, of which 23 were expressed in the transcriptome, involving 18 gene products. We could demonstrate spontaneous T-cell responses to 5/18 (28%) mutated gene variants, and further analysis of the TCR repertoire of neoantigen-specific CD4+ and CD8+ T cells revealed TCR clonotypes that were expanded in both blood and tumor tissue. Following vaccination of HHD mice, de novo T-cell responses were generated to 4/18 (22%) mutated gene variants; T cells reactive against two variants were also evident in the autologous setting. Subsequently, we determined the major histocompatibility complex restriction of the T-cell responses and used in silico prediction tools to determine the likely neoepitopes.ConclusionsOur study demonstrates the feasibility of efficiently identifying tumor-specific neoantigens that can be targeted by vaccination in tumors with a low mutational burden, promising successful clinical exploitation, with trials currently underway

Measurement of the soliton number in guiding media through continuum generation

No general approach is available yet to directly measure the ratio between the chromatic dispersion and the nonlinear coefficient, and hence the soliton number for a given optical pulse, in an arbitrary guiding medium. Here we solve this problem using continuum generation. We experimentally demonstrate our method in polarization-maintaining and single-mode fibers with positive and negative chromatic dispersion. Our technique also offers new opportunities to determine the chromatic dispersion of guiding media over a broad spectral range while pumping at a fixed wavelength

Protein Aggregation and Protein Instability Govern Familial Amyotrophic Lateral Sclerosis Patient Survival

The nature of the “toxic gain of function” that results from amyotrophic lateral sclerosis (ALS)-, Parkinson-, and Alzheimer-related mutations is a matter of debate. As a result no adequate model of any neurodegenerative disease etiology exists. We demonstrate that two synergistic properties, namely, increased protein aggregation propensity (increased likelihood that an unfolded protein will aggregate) and decreased protein stability (increased likelihood that a protein will unfold), are central to ALS etiology. Taken together these properties account for 69% of the variability in mutant Cu/Zn-superoxide-dismutase-linked familial ALS patient survival times. Aggregation is a concentration-dependent process, and spinal cord motor neurons have higher concentrations of Cu/Zn-superoxide dismutase than the surrounding cells. Protein aggregation therefore is expected to contribute to the selective vulnerability of motor neurons in familial ALS

Creating triple-wins for health, equity and environmental sustainability: elements of good practice based on learning from the INHERIT case studies

This report draws out dimensions of good practice for building this triple-win, based on learning from the INHERIT project’s 15 case studies. In the context of the project, good practice refers to ways that support changing contexts and create conditions to enable behaviour change to reach the triple-win. This report summarises key information for consideration by governmental and non-governmental policy-makers and practitioners planning to work across sectors to achieve the triple-win through behaviour change at every level. INHERIT researchers have focused their evaluations of the 15 INHERIT case studies on implementation, intersectoral cooperation, impacts and cost benefits. The researchers have taken dimensions of good practice from INHERIT research to be those elements that appear to be promising or necessary in the contexts in which the INHERIT cases studies are implemented. The extent to which these elements of good practice can be generalised to other contexts merits consideration in developing future initiatives towards creating synergies across sectors. INHERIT researchers have drawn out lessons learned from information gathered in evaluations about triggers for the initiatives, key elements for implementation, success factors in intersectoral cooperation, what could have been done better, what should be done in the future, and the most important learnings from the evaluation of outcomes, costs and benefits

Quantitative and qualitative evaluations of impacts and benefits of nine INHERIT case studies

The INHERIT report Quantitative and Qualitative Evaluations of Impacts and Benefits of Nine INHERIT Case Studies documents the findings relevant to potential impacts and benefits of nine case studies for health, equity and a more sustainable environment. It uses a mixed method approach with quantitative methods augmented in some cases by written responses to survey questions, or by focus group discussions on impacts, as appropriate. Each case study evaluation was led by a different INHERIT partner. In each case, partners formulated the research design appropriate to their case studies and the associated research questions identified within the framework of INHERIT. The coordinating partner, University College London (UCL), developed an evaluation framework to suit the range of case studies examined for impacts and benefits, the case specific logic models developed, and the research questions identified. The nine chapters describe the impact evaluations and findings from the nine case studies using the following format: Background; Overall aims; Context; Research Questions; Methodology; Results; Discussion; Limitations; Learning points for future research; Learning points for potential scale up and transferability