180 research outputs found

    Geometrical Aberration Suppression for Large Aperture Sub-THz Lenses

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    Advanced THz setups require high performance optical elements with large numerical apertures and small focal lengths. This is due to the high absorption of humid air and relatively low efficiency of commercially available detectors. Here, we propose a new type of double-sided sub-THz diffractive optical element with suppressed geometrical aberration for narrowband applications (0.3 THz). One side of the element is designed as thin structure in non-paraxial approach which is the exact method, but only for ideally flat elements. The second side will compensate phase distribution differences between ideal thin structure and real volume one. The computer-aided optimization algorithm is performed to design an additional phase distribution of correcting layer assuming volume designing of the first side of the element. The experimental evaluation of the proposed diffractive component created by 3D printing technique shows almost two times larger performance in comparison with uncorrected basic diffractive lens

    In situ formed reactive oxygen species-responsive scaffold with gemcitabine and checkpoint inhibitor for combination therapy

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    Patients with low-immunogenic tumors respond poorly to immune checkpoint blockade (ICB) targeting the programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway. Conversely, patients responding to ICB can experience various side effects. We have thus engineered a therapeutic scaffold that, when formed in situ, allows the local release of gemcitabine (GEM) and an anti-PD-L1 blocking antibody (aPDL1) with distinct release kinetics. The scaffold consists of reactive oxygen species (ROS)-degradable hydrogel that releases therapeutics in a programmed manner within the tumor microenvironment (TME), which contains abundant ROS. We found that the aPDL1-GEM scaffold elicits an immunogenic tumor phenotype and promotes an immune-mediated tumor regression in the tumor-bearing mice, with prevention of tumor recurrence after primary resection

    Genome assembly and transcriptome resource for river buffalo, Bubalus bubalis (2n = 50)

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    Water buffalo is a globally important species for agriculture and local economies. A de novo assembled, well annotated, reference sequence for the water buffalo is an important prerequisite for studying the biology of this species, and necessary to manage genetic diversity and to use modern breeding and genomic selection techniques. However, no such genome assembly has been previously reported. There are two species of domestic water buffalo, the river (2n = 50) and the swamp (2n = 48) buffalo. Here we describe a draft quality reference sequence for the river buffalo created from Illumina GA and Roche 454 short read sequences using the MaSuRCA assembler. The assembled sequence is 2.83 Gb, consisting of 366,983 scaffolds with a scaffold N50 of 1.41 Mb and contig N50 of 21,398 bp. Annotation of the genome was supported by transcriptome data from 30 tissues, and identified 21,711 predicted protein coding genes. Searches for complete mammalian BUSCO gene groups found 98.6% of curated single copy orthologs present among predicted genes, which suggests a high level of completeness of the genome. The annotated sequence is available from NCBI at accession GCA_000471725.1.John L. Williams, Daniela Iamartino, Kim D. Pruitt, Tad Sonstegard, Timothy P.L. Smith, Wai Yee Low, Tommaso Biagini, Lorenzo Bomba, Stefano Capomaccio, Bianca Castiglioni, Angelo Coletta, Federica Corrado, Fabrizio FerrĂ©, Leopoldo Iannuzzi, Cynthia Lawley, NicolĂČ Macciotta, Matthew McClure, Giordano Mancini, Donato Matassino, Raffaele Mazza, Marco Milanesi, Bianca Moioli, Nicola Morandi, Luigi Ramunno, Vincenzo Peretti, Fabio Pilla, Paola Ramelli, Steven Schroeder, Francesco Strozzi, Francoise Thibaud-Nissen, Luigi Zicarelli, Paolo Ajmone-Marsan, Alessio Valentini, Giovanni Chillemi, and Aleksey Zimi

    Genetic Drivers of Epigenetic and Transcriptional Variation in Human Immune Cells

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    Characterizing the multifaceted contribution of genetic and epigenetic factors to disease phenotypes is a major challenge in human genetics and medicine. We carried out high-resolution genetic, epigenetic, and transcriptomic profiling in three major human immune cell types (CD14+^{+} monocytes, CD16+^{+} neutrophils, and naive CD4+^{+} T cells) from up to 197 individuals. We assess, quantitatively, the relative contribution of cis\textit{cis}-genetic and epigenetic factors to transcription and evaluate their impact as potential sources of confounding in epigenome-wide association studies. Further, we characterize highly coordinated genetic effects on gene expression, methylation, and histone variation through quantitative trait locus (QTL) mapping and allele-specific (AS) analyses. Finally, we demonstrate colocalization of molecular trait QTLs at 345 unique immune disease loci. This expansive, high-resolution atlas of multi-omics changes yields insights into cell-type-specific correlation between diverse genomic inputs, more generalizable correlations between these inputs, and defines molecular events that may underpin complex disease risk.This work was predominantly funded by the EU FP7 High Impact Project BLUEPRINT (HEALTH-F5-2011-282510) and the Canadian Institutes of Health Research (CIHR EP1-120608). The research leading to these results has received funding from the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement no 282510 (BLUEPRINT), the European Molecular Biology Laboratory, the Max Planck society, the Spanish Ministry of Economy and Competitiveness, ‘Centro de Excelencia Severo Ochoa 2013-2017’, SEV-2012-0208 and Spanish National Bioinformatics Institute (INB-ISCIII) PT13/0001/0021 co-funded by FEDER "“Una Manera de hacer Europa”. D.G. is supported by a “la Caixa”-Severo Ochoa pre-doctoral fellowship, M.F. was supported by the BHF Cambridge Centre of Excellence [RE/13/6/30180], K.D. is funded as a HSST trainee by NHS Health Education England, S.E. is supported by a fellowship from La Caixa, V.P. is supported by a FEBS long-term fellowship and N.S.'s research is supported by the Wellcome Trust (Grant Codes WT098051 and WT091310), the EU FP7 (EPIGENESYS Grant Code 257082 and BLUEPRINT Grant Code HEALTH-F5-2011-282510) and the NIHR BRC. The Blood and Transplant Unit (BTRU) in Donor Health and Genomics is part of and funded by the National Institute for Health Research (NIHR) and is a partnership between the University of Cambridge and NHS Blood and Transplant (NHSBT) in collaboration with the University of Oxford and the Wellcome Trust Sanger Institute. The T-cell data was produced by the McGill Epigenomics Mapping Centre (EMC McGill). It is funded under the Canadian Epigenetics, Environment, and Health Research Consortium (CEEHRC) by the Canadian Institutes of Health Research and by Genome Quebec (CIHR EP1-120608), with additional support from Genome Canada and FRSQ. T.P. holds a Canada Research Chair

    Comparison of user groups' perspectives of barriers and facilitators to implementing electronic health records: a systematic review

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    <p>Abstract</p> <p>Background</p> <p>Electronic health record (EHR) implementation is currently underway in Canada, as in many other countries. These ambitious projects involve many stakeholders with unique perceptions of the implementation process. EHR users have an important role to play as they must integrate the EHR system into their work environments and use it in their everyday activities. Users hold valuable, first-hand knowledge of what can limit or contribute to the success of EHR implementation projects. A comprehensive synthesis of EHR users' perceptions is key to successful future implementation. This systematic literature review was aimed to synthesize current knowledge of the barriers and facilitators influencing shared EHR implementation among its various users.</p> <p>Methods</p> <p>Covering a period from 1999 to 2009, a literature search was conducted on nine electronic databases. Studies were included if they reported on users' perceived barriers and facilitators to shared EHR implementation, in healthcare settings comparable to Canada. Studies in all languages with an empirical study design were included. Quality and relevance of the studies were assessed. Four EHR user groups were targeted: physicians, other health care professionals, managers, and patients/public. Content analysis was performed independently by two authors using a validated extraction grid with pre-established categorization of barriers and facilitators for each group of EHR users.</p> <p>Results</p> <p>Of a total of 5,695 potentially relevant publications identified, 117 full text publications were obtained after screening titles and abstracts. After review of the full articles, 60 publications, corresponding to 52 studies, met the inclusion criteria. The most frequent adoption factors common to all user groups were design and technical concerns, ease of use, interoperability, privacy and security, costs, productivity, familiarity and ability with EHR, motivation to use EHR, patient and health professional interaction, and lack of time and workload. Each user group also identified factors specific to their professional and individual priorities.</p> <p>Conclusions</p> <p>This systematic review presents innovative research on the barriers and facilitators to EHR implementation. While important similarities between user groups are highlighted, differences between them demonstrate that each user group also has a unique perspective of the implementation process that should be taken into account.</p
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