Risk and reliability modelling for multi-vehicle marine domains

It is well-known that autonomous underwater vehicle (AUV) missions are a challenging, high-risk robotics application. With many parallels to Mars rovers, AUV missions involve operating a vehicle in an inherently uncertain environment of which our prior knowledge is often sparse or low-resolution. The lack of an accurate prior, coupled with poor situational awareness and potentially significant sensor noise, presents substantial engineering challenges in navigation, localisation, state estimation and control. When constructing missions and operating AUVs, it is important to consider the risks involved. Stakeholders need to be reassured that risks of vehicle loss or damage have been minimised where possible, and scientists need to be confident that the mission is likely to produce sufficient high-quality data to meet the aims of the deployment. In this paper, we consider the challenges associated with risk analysis methods and representations for multi-vehicle missions, reviewing the relevant literature and proposing a methodology

Risk and reliability modelling for multi-vehicle marine domains

It is well-known that autonomous underwater vehicle (AUV) missions are a challenging, high-risk robotics application. With many parallels to Mars rovers, AUV missions involve operating a vehicle in an inherently uncertain environment of which our prior knowledge is often sparse or low-resolution. The lack of an accurate prior, coupled with poor situational awareness and potentially significant sensor noise, presents substantial engineering challenges in navigation, localisation, state estimation and control. When constructing missions and operating AUVs, it is important to consider the risks involved. Stakeholders need to be reassured that risks of vehicle loss or damage have been minimised where possible, and scientists need to be confident that the mission is likely to produce sufficient high-quality data to meet the aims of the deployment. In this paper, we consider the challenges associated with risk analysis methods and representations for multi-vehicle missions, reviewing the relevant literature and proposing a methodology

How do road traffic noise and residential greenness correlate with noise annoyance and long-term stress? Protocol and pilot study for a large field survey with a cross-sectional design

Urban areas are continuously growing, and densification is a frequent strategy to limit urban expansion. This generally entails a loss of green spaces (GSs) and an increase in noise pollution, which has negative effects on health. Within the research project RESTORE (Restorative potential of green spaces in noise-polluted environments), an extended cross-sectional field study in the city of Zurich, Switzerland, is conducted. The aim is to assess the relationship between noise annoyance and stress (self-perceived and physiological) as well as their association with road traffic noise and GSs. A representative stratified sample of participants from more than 5000 inhabitants will be contacted to complete an online survey. In addition to the self-reported stress identified by the questionnaire, hair cortisol and cortisone probes from a subsample of participants will be obtained to determine physiological stress. Participants are selected according to their dwelling location using a spatial analysis to determine exposure to different road traffic noise levels and access to GSs. Further, characteristics of individuals as well as acoustical and non-acoustical attributes of GSs are accounted for. This paper presents the study protocol and reports the first results of a pilot study to test the feasibility of the protocol

Anti-SARS-CoV2 antibody responses in serum and cerebrospinal fluid of COVID-19 patients with neurological symptoms

Antibody responses to SARS-CoV-2 in serum and CSF from 16 COVID-19 patients with neurological symptoms were assessed using two independent methods. IgG specific for the virus spike protein was found in 81% of cases in serum and in 56% in CSF. SARS-CoV-2 IgG in CSF was observed in two cases with negative serology. Levels of IgG in both serum and CSF were associated with disease severity (p<0.05). All patients with elevated markers of CNS damage in CSF also had CSF antibodies (p=0.002), and CSF antibodies had the highest predictive value for neuronal damage markers of all tested clinical variables

β-(1,4)-Galactan remodelling in Arabidopsis cell walls affects the xyloglucan structure during elongation

Galactan turnover occurs during cell elongation and affects the cell wall xyloglucan structure which is involved in the interaction between cellulose and xyloglucan. β-(1,4)-Galactan is one of the main side chains of rhamnogalacturonan I. Although the specific function of this polymer has not been completely established, it has been related to different developmental processes. To study β-(1,4)-galactan function, we have generated transgenic Arabidopsis plants overproducing chickpea βI-Gal β-galactosidase under the 35S CaMV promoter (35S::βI-Gal) to reduce galactan side chains in muro. Likewise, an Arabidopsis double loss-of-function mutant for BGAL1 and BGAL3 Arabidopsis β-galactosidases (bgal1/bgal3) has been obtained to increase galactan levels. The characterization of these plants has confirmed the role of β-(1,4)-galactan in cell growth, and demonstrated that the turnover of this pectic side chain occurs during cell elongation, at least in Arabidopsis etiolated hypocotyls and floral stem internodes. The results indicate that BGAL1 and BGAL3 β-galactosidases act in a coordinate way during cell elongation. In addition, this work indicates that galactan plays a role in the maintenance of the cell wall architecture during this process. Our results point to an involvement of the β-(1,4)-galactan in the xyloglucan structure and the interaction between cellulose and xyloglucan

IL-21 production by CD4+ effector T cells and frequency of circulating follicular helper T cells are increased in type 1 diabetes patients.

AIMS/HYPOTHESIS: Type 1 diabetes results from the autoimmune destruction of insulin-secreting pancreatic beta cells by T cells. Despite the established role of T cells in the pathogenesis of the disease, to date, with the exception of the identification of islet-specific T effector (Teff) cells, studies have mostly failed to identify reproducible alterations in the frequency or function of T cell subsets in peripheral blood from patients with type 1 diabetes. METHODS: We assessed the production of the proinflammatory cytokines IL-21, IFN-γ and IL-17 in peripheral blood mononuclear cells from 69 patients with type 1 diabetes and 61 healthy donors. In an additional cohort of 30 patients with type 1 diabetes and 32 healthy donors, we assessed the frequency of circulating T follicular helper (Tfh) cells in whole blood. IL-21 and IL-17 production was also measured in peripheral blood mononuclear cells (PBMCs) from a subset of 46 of the 62 donors immunophenotyped for Tfh. RESULTS: We found a 21.9% (95% CI 5.8, 40.2; p = 3.9 × 10(-3)) higher frequency of IL-21(+) CD45RA(-) memory CD4(+) Teffs in patients with type 1 diabetes (geometric mean 5.92% [95% CI 5.44, 6.44]) compared with healthy donors (geometric mean 4.88% [95% CI 4.33, 5.50]). Consistent with this finding, we found a 14.9% increase in circulating Tfh cells in the patients (95% CI 2.9, 26.9; p = 0.016). CONCLUSIONS/INTERPRETATION: These results indicate that increased IL-21 production is likely to be an aetiological factor in the pathogenesis of type 1 diabetes that could be considered as a potential therapeutic target.This work was supported by the JDRF UK Centre for Diabetes - Genes, Autoimmunity and Prevention (D-GAP; 4-2007-1003) in collaboration with M. Peakman and T. Tree at King’s College London, the JDRF, the Wellcome Trust (WT; WT061858/091157 and 083650/Z/07/Z) and the National Institute for Health Research Cambridge Biomedical Research Centre (CBRC). The Cambridge Institute for Medical Research (CIMR) is in receipt of a Wellcome Trust Strategic Award (100140). RCF is funded by a JDRF post-doctoral fellowship (3-2011-374). CW is funded by the Wellcome Trust (088998). The funding organisations had no involvement with the design and conduct of the study; collection,management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.This is the final published version. It first appeared at http://link.springer.com/article/10.1007%2Fs00125-015-3509-8

Pectic galactan affects cell wall architecture during secondary cell wall deposition

Despite recent advances regarding the role of pectic β-(1,4)-galactan neutral side chains in primary cell wall remodelling during growth and cell elongation, little is known about the specific function of this polymer in other developmental processes. We have used transgenic Arabidopsis plants overproducing chickpea βI-Gal β-galactosidase under the 35S CaMV promoter (35S::βI-Gal) with reduced galactan levels in the basal non-elongating floral stem internodes to gain insight into the role of β-(1,4)-galactan in cell wall architecture during the cessation of elongation and the beginning of secondary growth. The loss of galactan mediated by βI-Gal in 35S::βI-Gal plants is accompanied by a reduction in the levels of KOH-extracted xyloglucan and an increase in the levels of xyloglucan released by a cellulose-specific endoglucanase. These variations in cellulose–xyloglucan interactions cause an altered xylan and mannan deposition in the cell wall that in turn results in a deficient lignin deposition. Considering these results, we can state that β-(1,4)-galactan plays a key structural role in the correct organization of the different domains of the cell wall during the cessation of growth and the early events of secondary cell wall development. These findings reinforce the notion that there is a mutual dependence between the different polysaccharides and lignin polymers to form an organized and functional cell wall

A class of quasi-sparse companion pencils

In this paper, we introduce a general class of quasi-sparse potential companion pencils for arbitrary square matrix polynomials over an arbitrary field, which extends the class introduced in [B. Eastman, I.-J. Kim, B. L. Shader, K.N. Vander Meulen, Companion matrix patterns. Linear Algebra Appl. 436 (2014) 255-272] for monic scalar polynomials. We provide a canonical form, up to permutation, for companion pencils in this class. We also relate these companion pencils with other relevant families of companion linearizations known so far. Finally, we determine the number of different sparse companion pencils in the class, up to permutation.This work has been partially supported by theMinisterio de Economía y Competitividad of Spain through grants MTM2015-68805-REDT and MTM2015-65798-P

Frequent use of IGHV3-30-3 in SARS-CoV-2 neutralizing antibody responses

The antibody response to SARS-CoV-2 shows biased immunoglobulin heavy chain variable (IGHV) gene usage, allowing definition of genetic signatures for some classes of neutralizing antibodies. We investigated IGHV gene usage frequencies by sorting spike-specific single memory B cells from individuals infected with SARS-CoV-2 early in the pandemic. From two study participants and 703 spike-specific B cells, the most used genes were IGHV1-69, IGHV3-30-3, and IGHV3-30. Here, we focused on the IGHV3-30 group of genes and an IGHV3-30-3-using ultrapotent neutralizing monoclonal antibody, CAB-F52, which displayed broad neutralizing activity also in its germline-reverted form. IGHV3-30-3 is encoded by a region of the IGH locus that is highly variable at both the allelic and structural levels. Using personalized IG genotyping, we found that 4 of 14 study participants lacked the IGHV3-30-3 gene on both chromosomes, raising the question if other, highly similar IGHV genes could substitute for IGHV3-30-3 in persons lacking this gene. In the context of CAB-F52, we found that none of the tested IGHV3-33 alleles, but several IGHV3-30 alleles could substitute for IGHV3-30-3, suggesting functional redundancy between the highly homologous IGHV3-30 and IGHV3-30-3 genes for this antibody

Environmental and genetic risk factors and gene-environment interactions in the pathogenesis of chronic obstructive lung disease.

Current understanding of the pathogenesis of chronic obstructive pulmonary disease (COPD), a source of substantial morbidity and mortality in the United States, suggests that chronic inflammation leads to the airways obstruction and parenchymal destruction that characterize this condition. Environmental factors, especially tobacco smoke exposure, are known to accelerate longitudinal decline of lung function, and there is substantial evidence that upregulation of inflammatory pathways plays a vital role in this process. Genetic regulation of both inflammatory responses and anti-inflammatory protective mechanisms likely underlies the heritability of COPD observed in family studies. In alpha-1 protease inhibitor deficiency, the only genetic disorder known to cause COPD, lack of inhibition of elastase activity, results in the parenchymal destruction of emphysema. Other genetic polymorphisms have been hypothesized to alter the risk of COPD but have not been established as causes of this condition. It is likely that multiple genetic factors interacting with each other and with a number of environmental agents will be found to result in the development of COPD