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Tandem mass spectrometry coupled with liquid chromatography (LC-MS/MS) has proven a versatile tool for the identification and quantification of proteins and their post-translational modifications (PTMs). Protein glycosylation is a critical PTM for the stability and biological function of many proteins, but full characterization of site-specific glycosylation of proteins remains analytically challenging. Collision-induced dissociation (CID) is the most common fragmentation method used in LC-MS/MS workflows, but the loss of labile modifications renders CID inappropriate for detailed characterization of site-specific glycosylation. Electron-based dissociation methods provide alternatives that retain intact glycopeptide fragments for unambiguous site localization, but these methods often underperform CID due to increased reaction times and reduced efficiency. Electron-activated dissociation (EAD) is another strategy for glycopeptide fragmentation. Here, we use a ZenoTOF 7600 SCIEX instrument to compare the performance of various fragmentation techniques for the analysis of a complex mixture of mammalian O- and N-glycopeptides. We found CID fragmentation identified the most glycopeptides and generally produced higher quality spectra, but EAD provided improved confidence in glycosylation site localization. Supplementing EAD with CID fragmentation (EAciD) further increased the number and quality of glycopeptide identifications, while retaining localization confidence. These methods will be useful for glycoproteomics workflows for either optimal glycopeptide identification or characterization.

In this paper, we propose a data-driven predictive control scheme based on measured frequency-domain data of the plant. This novel scheme complements the well-known data-driven predictive control (DeePC) approach based on time series data. To develop this new frequency-domain data-driven predictive control (FreePC) scheme, we introduce a novel version of Willems’ fundamental lemma based on frequency-domain data. By exploiting frequency-domain data, we allow recent direct data-driven (predictive) control methodologies to benefit from the available expertise and techniques for non-parametric frequency-domain identification in academia and industry. We prove that, under appropriate conditions, the new FreePC scheme is equivalent to the corresponding DeePC scheme. The strengths of FreePC are demonstrated in a numerical case study.

Model Predictive Control (MPC) is a successful control methodology, which is applied to increasingly complex systems. However, real-time feasibility of MPC can be challenging for complex systems, certainly when an (extremely) large number of constraints have to be adhered to. For such scenarios with a large number of state constraints, this paper proposes two novel MPC schemes for general nonlinear systems, which we call constraint-adaptive MPC. These novel schemes dynamically select at each time step a (varying) set of constraints that are included in the on-line optimization problem. Carefully selecting the included constraints can significantly reduce, as we will demonstrate, the computational complexity with often only a slight impact on the closed-loop performance. Although not all (state) constraints are imposed in the on-line optimization, the schemes still guarantee recursive feasibility and constraint satisfaction. A numerical case study illustrates the proposed MPC schemes and demonstrates the achieved computation time improvements exceeding two orders of magnitude without loss of performance.

Concerns about China’s ambitions to return to the global centre stage as a great power have recently begun to focus on the Digital Silk Road (DSR), an umbrella term for various activities – commercial and diplomatic – of interest to the Chinese government in the cyber realm. Part of (or a spin-off from) the 2013 Belt and Road Initiative, by 2020 the DSR had become a focal point of China’s foreign policy. But the DSR remains ill-defined and poorly understood.At the heart of such concerns is not that Chinese technology companies are becoming globally competitive, but rather that Beijing could use them to ‘rewire’ the global digital architecture, from physical cables to code. Dominance by Chinese technology could shift global norms from a free cyber commons to competing systems of cyber sovereignty or cyber freedom. This Adelphibook brings together eight experts to examine the development of the DSR; explore its impact on economics, security and governance in recipient countries; and assess its broader impact on patterns of economic and technological dependence, on the emerging rules and norms of tech globalisation, and on global geopolitics and great-power relations.Beijing has grasped the opportunity to leverage the entrepreneurial strengths of its private tech sector to gain prominence in the world’s digital ecosystem. But the more interventionist Beijing becomes, the more Chinese firms will be seen as instruments of the state, and the greater the pushback against Chinese technology and the DSR may be. To achieve great-power status and global centrality, Beijing might ultimately need to change tack. How it innovates in further rolling out Chinese tech across the world, and what the DSR will then look like, will have far-reaching impacts on global economics, politics and security.

Concerns about China’s ambitions to return to the global centre stage as a great power have recently begun to focus on the Digital Silk Road (DSR), an umbrella term for various activities – commercial and diplomatic – of interest to the Chinese government in the cyber realm. Part of (or a spin-off from) the 2013 Belt and Road Initiative, by 2020 the DSR had become a focal point of China’s foreign policy. But the DSR remains ill-defined and poorly understood.At the heart of such concerns is not that Chinese technology companies are becoming globally competitive, but rather that Beijing could use them to ‘rewire’ the global digital architecture, from physical cables to code. Dominance by Chinese technology could shift global norms from a free cyber commons to competing systems of cyber sovereignty or cyber freedom. This Adelphibook brings together eight experts to examine the development of the DSR; explore its impact on economics, security and governance in recipient countries; and assess its broader impact on patterns of economic and technological dependence, on the emerging rules and norms of tech globalisation, and on global geopolitics and great-power relations.Beijing has grasped the opportunity to leverage the entrepreneurial strengths of its private tech sector to gain prominence in the world’s digital ecosystem. But the more interventionist Beijing becomes, the more Chinese firms will be seen as instruments of the state, and the greater the pushback against Chinese technology and the DSR may be. To achieve great-power status and global centrality, Beijing might ultimately need to change tack. How it innovates in further rolling out Chinese tech across the world, and what the DSR will then look like, will have far-reaching impacts on global economics, politics and security.

Concerns about China’s ambitions to return to the global centre stage as a great power have recently begun to focus on the Digital Silk Road (DSR), an umbrella term for various activities – commercial and diplomatic – of interest to the Chinese government in the cyber realm. Part of (or a spin-off from) the 2013 Belt and Road Initiative, by 2020 the DSR had become a focal point of China’s foreign policy. But the DSR remains ill-defined and poorly understood.At the heart of such concerns is not that Chinese technology companies are becoming globally competitive, but rather that Beijing could use them to ‘rewire’ the global digital architecture, from physical cables to code. Dominance by Chinese technology could shift global norms from a free cyber commons to competing systems of cyber sovereignty or cyber freedom. This Adelphibook brings together eight experts to examine the development of the DSR; explore its impact on economics, security and governance in recipient countries; and assess its broader impact on patterns of economic and technological dependence, on the emerging rules and norms of tech globalisation, and on global geopolitics and great-power relations.Beijing has grasped the opportunity to leverage the entrepreneurial strengths of its private tech sector to gain prominence in the world’s digital ecosystem. But the more interventionist Beijing becomes, the more Chinese firms will be seen as instruments of the state, and the greater the pushback against Chinese technology and the DSR may be. To achieve great-power status and global centrality, Beijing might ultimately need to change tack. How it innovates in further rolling out Chinese tech across the world, and what the DSR will then look like, will have far-reaching impacts on global economics, politics and security.

Fatigue is a major concern for patients with severe asthma.

Free nitrous acid (FNA) exerts a broad range of antimicrobial effects on bacteria, although susceptibility varies considerably among microorganisms. Among nitrifiers found in activated sludge of wastewater treatment processes (WWTPs), nitrite-oxidizing bacteria (NOB) are more susceptible to FNA compared to ammonia-oxidizing bacteria (AOB). This selective inhibition of NOB over AOB in WWTPs bypasses nitrate production and improves the efficiency and costs of the nitrogen removal process in both the activated sludge and anaerobic ammonium oxidation (Anammox) system. However, the molecular mechanisms governing this atypical tolerance of AOB to FNA have yet to be understood. Herein we investigate the varying effects of the antimicrobial FNA on activated sludge containing AOB and NOB using an integrated metagenomics and label-free quantitative sequential windowed acquisition of all theoretical fragment ion mass spectra (SWATH-MS) metaproteomic approach. The Nitrosomonasgenus of AOB, on exposure to FNA, maintains internal homeostasis by upregulating a number of known oxidative stress enzymes, such as pteridine reductase and dihydrolipoyl dehydrogenase. Denitrifying enzymes were upregulated on exposure to FNA, suggesting the detoxification of nitrite to nitric oxide. Interestingly, proteins involved in stress response mechanisms, such as DNA and protein repair enzymes, phage prevention proteins, and iron transport proteins, were upregulated on exposure to FNA. In addition enzymes involved in energy generation were also upregulated on exposure to FNA. The total proteins specifically derived from the NOB genus Nitrobacterwas low and, as such, did not allow for the elucidation of the response mechanism to FNA exposure. These findings give us an understanding of the adaptive mechanisms of tolerance within the AOB Nitrosomonasto the biocidal agent FNA.

Modern beer production is a complex industrial process. However, some of its biochemical details remain unclear. Using mass spectrometry proteomics, we have performed a global untargeted analysis of the proteins present across time during nanoscale beer production. Samples included sweet wort produced by a high temperature infusion mash, hopped wort, and bright beer. This analysis identified over 200 unique proteins from barley and yeast, emphasizing the complexity of the process and product. We then used data independent SWATH-MS to quantitatively compare the relative abundance of these proteins throughout the process. This identified large and significant changes in the proteome at each process step. These changes described enrichment of proteins by their biophysical properties, and identified the appearance of dominant yeast proteins during fermentation. Altered levels of malt modification also quantitatively changed the proteomes throughout the process. Detailed inspection of the proteomic data revealed that many proteins were modified by protease digestion, glycation, or oxidation during the processing steps. This work demonstrates the opportunities offered by modern mass spectrometry proteomics in understanding the ancient process of beer production.

Introducing into operations new rolling stocks requires re-educating technicians and operators for being able to properly work on new and different assets. The training sessions are often performed under substantial time constraints and with a lack of resources. Re-training the technicians is a cost intensive process as it is for training new employees. The aim of the paper is to test and evaluate a virtual reality (VR) training solutions to decrease costs and to increase technicians' availability, safety during maintenance operations and education performance with the support of Netherlands Railways (Nederlandse Spoorwegen - NS). Firstly, the study explores the possible maintenance tasks analysing the benefits for VR implementations; secondly, it evaluates the attitude of technicians trained with the proposed VR approach. Finally, it discusses the results and provides general applicable suggestions for the use of VR in other training activities.

Introduction One third of patients with acute stroke have aphasia. The majority receive speech and language therapy. There is evidence for a beneficial effect of speech and language therapy on restoring communication, but it is unknown whether and how efficacy of speech and language therapy is influenced by timing of treatment. We studied whether speech and language therapy early after stroke by way of intensive cognitive-linguistic treatment is more effective than no speech and language therapy in the Rotterdam Aphasia Therapy Study-3, a multicentre randomised single-blind trial.Methods and patients Stroke patients with first-ever aphasia were randomised within 2 weeks of onset to either 4 weeks of early intensive cognitive-linguistic treatment (1 h/day) or no language treatment. Hereafter, both groups received regular speech and language therapy. Primary outcome was the score on the Amsterdam-Nijmegen Everyday Language Test, measuring everyday verbal communication, 4 weeks after randomisation. Secondary outcomes were Amsterdam-Nijmegen Everyday Language Test at 3 and 6 months. The study was powered to detect a clinically relevant difference of four points on the Amsterdam-Nijmegen Everyday Language Test.Results Of the 152 included patients, 80 patients were allocated to intervention. Median treatment intensity in the intervention-group was 24.5 h. The adjusted difference between groups in mean Amsterdam-Nijmegen Everyday Language Test-scores 4 weeks after randomisation was 0.39, 95% confidence interval: [−2.70 to 3.47], p= 0.805. No statistically significant differences were found at 3 and 6 months after randomisation either.Conclusion Four weeks of intensive cognitive-linguistic treatment initiated within 2 weeks of stroke is not more effective than no language treatment for the recovery of post-stroke aphasia. Our results exclude a clinically relevant effect of very early cognitive-linguistic treatment on everyday language.

The article evaluates several home furnishings and decoration products including Kennedy coffee table from Freedom, Terrazzo planter from Kmart and Monmouth Glass Studio dome lamp from Tessuti.

The article focuses on the makeover of the bedroom owned by Fred Martin, son of tax advisor Amanda Martin, which features neutral tone walls, geometric patterns furnishings, and patterned pillowcases and cushions.

The article offers suggestions for Christmas decorative products including pentagram wall handing by Bed Bath & Beyond, gold geo tealight holder by Kmart, and pom pom cushion from Shut The Front Door.

The article provides suggestions for setting and designing outdoor courtyards, which includes three looks tropical, urban, and botanical, focusing on the color combinations, furniture and accessories.

The article presents simple and effective tricks in designing and renovating a kitchen, and mentions topics including how to cost-effectively paint the kitchen walls to create the illusion of space, tips on replacing cabinet doors, and tips on replacing benchtops.

The article evaluates bathroom products including brass ceiling pendant from uniform store Freedom, Marble and brass table from home accessories company Perch Home, and Oasis navy face cloth from bedding accessories company Wallace Cotton.

The article offers suggestions homeowners going on family vacations and relaxation, on factors of selecting the place ambience, rearranging living room furniture and selection of summer themed colors such as blue and yellow.

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Chinese hamster ovary (CHO) cells are the preferred production host for therapeutic monoclonal antibodies (mAb) due to their ability to perform post-translational modifications and their successful approval history. The completion of the genome sequence for CHO cells has reignited interest in using quantitative proteomics to identify markers of good production lines. Here we applied two different proteomic techniques, iTRAQ and SWATH, for the identification of expression differences between a high- and low-antibody-producing CHO cell lines derived from the same transfection. More than 2000 proteins were quantified with 70 of them classified as differentially expressed in both techniques. Two biological processes were identified as differentially regulated by both methods: up-regulation of glutathione biosynthesis and down-regulation of DNA replication. Metabolomic analysis confirmed that the high producing cell line displayed higher intracellular levels of glutathione. SWATH further identified up-regulation of actin filament processes and intracellular transport and down regulation of several growth-related processes. These processes may be important for conferring high mAb production and as such are promising candidates for targeted engineering of high-expression cell lines.

We have generated a next-generation whole-exome sequencing data set of 2628 participants of the population-based Rotterdam Study cohort, comprising 669 737 single-nucleotide variants and 24 019 short insertions and deletions. Because of broad and deep longitudinal phenotyping of the Rotterdam Study, this data set permits extensive interpretation of genetic variants on a range of clinically relevant outcomes, and is accessible as a control data set. We show that next-generation sequencing data sets yield a large degree of population-specific variants, which are not captured by other available large sequencing efforts, being ExAC, ESP, 1000G, UK10K, GoNL and DECODE.

The article offers ideas to decorate the entrance of the house during Christmas like giving it a minimal look, a warm entrance that offers a modern romantic look, and the Scandi fan look and also evaluates Christmas decorative items like Paper Collective pine cone print from manufacturer Tea Pea.

The article offers tips from interior designer Vanessa Nouwens for home decoration including to use leather sofas with cushions from Adairs, paint the walls with the rustic texture of the bricks, and evaluates home furnishing products including frames, tables, and pot from leading retailer Adairs.

The article offers suggestions to parents to create bedroom for children. It adds that every child's bedroom should have a bed, a beside table, a chest of drawers, and a bookshelf. It further adds that the parents should go for classic designs and quality materials while choosing major articles as these act as investments that will see child through the years.

There is a pressing need for patient-derived cell models of brain diseases that are relevant and robust enough to produce the large quantities of cells required for molecular and functional analyses. We describe here a new cell model based on patient-derived cells from the human olfactory mucosa, the organ of smell, which regenerates throughout life from neural stem cells. Olfactory mucosa biopsies were obtained from healthy controls and patients with either schizophrenia, a neurodevelopmental psychiatric disorder, or Parkinson’s disease, a neurodegenerative disease. Biopsies were dissociated and grown as neurospheres in defined medium. Neurosphere-derived cell lines were grown in serum-containing medium as adherent monolayers and stored frozen. By comparing 42 patient and control cell lines we demonstrated significant disease-specific alterations in gene expression, protein expression and cell function, including dysregulated neurodevelopmental pathways in schizophrenia and dysregulated mitochondrial function, oxidative stress and xenobiotic metabolism in Parkinson’s disease. The study has identified new candidate genes and cell pathways for future investigation. Fibroblasts from schizophrenia patients did not show these differences. Olfactory neurosphere-derived cells have many advantages over embryonic stem cells and induced pluripotent stem cells as models for brain diseases. They do not require genetic reprogramming and they can be obtained from adults with complex genetic diseases. They will be useful for understanding disease aetiology, for diagnostics and for drug discovery.

The characteristics and diagnostics of wheezing during induced airway obstruction are well documented. The present study addressed (a) the characteristics of spontaneous wheezing with respect to a possible distinction between wheezes during in vivo versus induced airway obstruction, and (b) the relationship between in vivo wheezing and fluctuations in peak expiratory flow (PEF). Tracheal sounds were continuously recorded from 50 children and adolescents with asthma and 10 without asthma in the home environment. Wheezes underwent a qualitative analysis, including their concomittant sound frequencies. Presence of wheezing was scored by two examiners independently and was related to PEF. Spontaneous wheeze varied from solitary rhonchi to prolonged rhythms of loud stridor, and resembled the "induced" wheezes recorded previously. Power spectra showed that the spectral contents (frequency distribution) were comparable, although the in vivo patterns were more prolonged in duration.The diagnostic sensitivity and specificity of wheezing for a reduction in PEF of >20% were 88% and 92%, respectively. It was concluded that in vivo wheeze resembled induced wheeze and was a diagnostically reliable symptom with respect to asthma exacerbations.

This study tested the hypothesis that cough frequency during induced airway obstruction in children and adolescents with asthma relates significantly to other symptoms. The second hypothesis was that cough during remission may often be a conditioned or voluntary response. In experiment 1, tracheal sounds were recorded from 30 participants with asthma during a histamine challenge test. In experiment 2, tracheal sounds were recorded from 30 participants with and 30 without asthma during a standardized physical exercise task. Cough and respiratory wheeze were assessed from the sound records by two examiners independently. The results showed that cough during airway obstruction did not relate to other variables. Only the second hypothesis was supported. In both experiments the frequency of cough was independent of lung function (forced expiratory volume in 1 sec [FEV1]), wheezing, dyspnea, and severity of asthma. The percentage of participants with asthma who coughed in experiment 1 increased from 21% (baseline) to 71% after histamine inhalation. During experiment 2, the cough percentage increased from 52% to 69% in asthmatics, and from zero to 57% in controls. It was concluded that cough in asthma is not diagnostically useful for assessment of airway obstruction. Excessive baseline cough among asthmatics could be the result of acquired responses to anticipated exercise-induced symptoms.

Spontaneous cough is a symptom with diffuse diagnostic significance for childhood asthma. Information on the interrelations between presence/frequency of cough and other symptoms of asthma are not available to the physician. Tracheal sounds were continuously recorded in the homes of 60 children with and 30 without asthma, at 72 and 24 h, respectively. Presence and frequency of cough and presence of wheeze were scored by trained examiners. Wheeze was used to indicate airway obstruction during hours when peak expiratory flow (PEF) values were not available. PEF and self-reported dyspnea were assessed every 4 h. Results showed that asthmatics coughed significantly more often than control subjects during exacerbations, but not during remission. The highest diagnostic sensitivity percentages of cough were 72% for wheeze and 69% for a reduction in PEF >20%. However, the diagnostic specificity was poor, 41% for wheeze and 34% for a reduction in PEF >20%. Cough and dyspnea were independent. Three children did not cough during exacerbations. Persistent, isolated cough was observed in two children. It was concluded that spontaneous cough is modestly predictive of asthmatic exacerbations, but not of a diagnosis of asthma or severity of asthma.