320 research outputs found
From the deposit to the exhibit floor: an exploration on giving museum objects personality and social life
Museum objects have fascinating stories but are often presented in a detached, objective way that tends to keep visitors at a distance. In a collaborative research we have explored a different way to present museum objects: fifteen exhibits from the museum deposit compete for one of the four display cases on the exhibit floor. Objects are given a personal voice and a character and they talk directly to the visitor: those that capture visitors' interest as physical presence or Twitter conversation stay on display; the lower scorer is replaced. We report the co-design and preliminary evaluation carried out in the museum with both museum professionals and casual visitors
Methodology for the comparative assessment of the Satellite Power System (SPS) and alternative technologies
The energy systems concerned are the satellite power system, several coal technologies, geothermal energy, fission, fusion, terrestrial solar systems, and ocean thermal energy conversion. Guidelines are suggested for the characterization of these systems, side-by-side analysis, alternative futures analysis, and integration and aggregation of data. A description of the methods for assessing the technical, economic, environmental, societal, and institutional issues surrounding the development of the selected energy technologies is presented
Feasibility and usability of a regional hub model for colorectal cancer services during the COVID-19 pandemic
The outbreak of the COVID-19 pandemic produced unprecedented challenges, at a global level, in the provision of cancer care. With the ongoing need in the delivery of life-saving cancer treatment, the surgical management of patients with colorectal cancer required prompt significant transformation. The aim of this retrospective study is to report the outcome of a bespoke regional Cancer Hub model in the delivery of elective and essential colorectal cancer surgery, at the height of the first wave of the COVID-19 pandemic. 168 patients underwent colorectal cancer surgery from April 1st to June 30th of 2020. Approximately 75% of patients operated upon underwent colonic resection, of which 47% were left-sided, 34% right-sided and 12% beyond total mesorectal excision surgeries. Around 79% of all resectional surgeries were performed via laparotomy, and the remainder 21%, robotically or laparoscopically. Thirty-day complication rate, for Clavien-Dindo IIIA and above, was 4.2%, and 30-day mortality rate was 0.6%. Re-admission rate, within 30 days post-discharge, was 1.8%, however, no patient developed COVID-19 specific complications post-operatively and up to 28 days post-discharge. The established Cancer Hub offered elective surgical care for patients with colorectal cancer in a centralised, timely and efficient manner, with acceptable post-operative outcomes and no increased risk of contracting COVID-19 during their inpatient stay. We offer a practical model of care that can be used when elective surgery "hubs" for streamlined delivery of elective care needs to be established in an expeditious fashion, either due to the COVID-19 pandemic or any other future pandemics
Atypical chemokine receptor 1 on nucleated erythroid cells regulates hematopoiesis
Healthy individuals of African ancestry have neutropenia that has been linked with the variant rs2814778(G) of the gene encoding atypical chemokine receptor 1 (ACKR1). This polymorphism selectively abolishes the expression of ACKR1 in erythroid cells, causing a Duffy-negative phenotype. Here we describe an unexpected fundamental role for ACKR1 in hematopoiesis and provide the mechanism that links its absence with neutropenia. Nucleated erythroid cells had high expression of ACKR1, which facilitated their direct contact with hematopoietic stem cells. The absence of erythroid ACKR1 altered mouse hematopoiesis including stem and progenitor cells, which ultimately gave rise to phenotypically distinct neutrophils that readily left the circulation, causing neutropenia. Individuals with a Duffy-negative phenotype developed a distinct profile of neutrophil effector molecules that closely reflected the one observed in the ACKR1-deficient mice. Thus, alternative physiological patterns of hematopoiesis and bone marrow cell outputs depend on the expression of ACKR1 in the erythroid lineage, findings with major implications for the selection advantages that have resulted in the paramount fixation of the ACKR1 rs2814778(G) polymorphism in Africa
Statement on bioinformatics and capturing the benefits of genome sequencing for society
The HUGO Committee on Ethics, Law and Society (CELS) undertook a Working Group exploration of the key ethical issues arising from genome sequencing in 2013. The Imagined Futures paper the group subsequently published proposed points to consider when applying genomic bioinformatics to data repositories used in genomic medicine and research ( http://www.hugo-international.org/Resources/Documents/CELS_Article-ImaginedFutures_2014.pdf ). Given the ever-increasing power to sequence the human genome rapidly and inexpensively-as well as trends toward "Big Data" and "Open Science"-we take this opportunity to update and refine the key findings of that paper
Specialized dynamical properties of promiscuous residues revealed by simulated conformational ensembles
The ability to interact with different partners is one of the most important features in proteins. Proteins that bind a large number of partners (hubs) have been often associated with intrinsic disorder. However, many examples exist of hubs with an ordered structure, and evidence of a general mechanism promoting promiscuity in ordered proteins is still elusive. An intriguing hypothesis is that promiscuous binding sites have specific dynamical properties, distinct from the rest of the interface and pre-existing in the protein isolated state. Here, we present the first comprehensive study of the intrinsic dynamics of promiscuous residues in a large protein data set. Different computational methods, from coarse-grained elastic models to geometry-based sampling methods and to full-atom Molecular Dynamics simulations, were used to generate conformational ensembles for the isolated proteins. The flexibility and dynamic correlations of interface residues with a different degree of binding promiscuity were calculated and compared considering side chain and backbone motions, the latter both on a local and on a global scale. The study revealed that (a) promiscuous residues tend to be more flexible than nonpromiscuous ones, (b) this additional flexibility has a higher degree of organization, and (c) evolutionary conservation and binding promiscuity have opposite effects on intrinsic dynamics. Findings on simulated ensembles were also validated on ensembles of experimental structures extracted from the Protein Data Bank (PDB). Additionally, the low occurrence of single nucleotide polymorphisms observed for promiscuous residues indicated a tendency to preserve binding diversity at these positions. A case study on two ubiquitin-like proteins exemplifies how binding promiscuity in evolutionary related proteins can be modulated by the fine-tuning of the interface dynamics. The interplay between promiscuity and flexibility highlighted here can inspire new directions in protein-protein interaction prediction and design methods. © 2013 American Chemical Society
Optimised resource construction for verifiable quantum computation
Recent developments make the possibility of achieving scalable quantum
networks and quantum devices closer. From the computational point of view these
emerging technologies become relevant when they are no longer classically
simulatable. Hence a pressing challenge is the construction of practical
methods to verify the correctness of the outcome produced by universal or
non-universal quantum devices. A promising approach that has been extensively
explored is the scheme of verification via encryption through blind quantum
computing initiated by Fitzsimons and Kashefi. We present here a new
construction that simplifies the required resources for any such verifiable
blind quantum computating protocol. We obtain an overhead that is linear in the
size of the input, while the security parameter remains independent of the size
of the computation and can be made exponentially small. Furthermore our
construction is generic and could be applied to any non-universal scheme with a
given underlying graph.Comment: 26 pages, 2 figure
Water channel pore size determines exclusion properties but not solute selectivity
Aquaporins (AQPs) are a ubiquitous family of transmembrane water channel proteins. A subgroup of AQP water channels also facilitates transmembrane diffusion of small, polar solutes. A constriction within the pore, the aromatic/arginine (ar/R) selectivity filter, is thought to control solute permeability: previous studies on single representative water channel proteins suggest narrow channels conduct water, whilst wider channels permit passage of solutes. To assess this model of selectivity, we used mutagenesis, permeability measurements and in silico comparisons of water-specific as well as glycerol-permeable human AQPs. Our studies show that single amino acid substitutions in the selectivity filters of AQP1, AQP4 and AQP3 differentially affect glycerol and urea permeability in an AQP-specific manner. Comparison between in silico-calculated channel cross-sectional areas and in vitro permeability measurements suggests that selectivity filter cross-sectional area predicts urea but not glycerol permeability. Our data show that substrate discrimination in water channels depends on a complex interplay between the solute, pore size, and polarity, and that using single water channel proteins as representative models has led to an underestimation of this complexity
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