•Estimation of instantaneous vehicle fuel consumption using smartphone measurements.•Deep Neural Network estimation assessment and comparison to other methods.•Deep Neural Network training evaluation ...and proposal of a novel hybrid training technique.•Performance loss investigation for less information-rich inputs.
The high level of air pollution in urban areas, caused in no small extent by road transport, requires the implementation of continuous and accurate monitoring techniques if emissions are to be minimized. The primary motivation for this paper is to enable fine spatiotemporal monitoring based on crowd sensing, whereby the instantaneous fuel consumption of a vehicle is estimated using smartphone measurements. To this end, a surrogate method based on indirect monitoring using Recurrent Neural Networks (RNNs) that process a smartphone's GPS position, speed, altitude, acceleration and number of visible satellites is proposed. Extensive field trials were conducted to gather smartphone and fuel consumption data at a wide range of driving conditions. Two different RNN types were explored, and a parametric analysis was performed to define a suitable architecture. Various training methods for tuning the RNN were evaluated based on performance and computational burden. The resulting estimator was compared with others found in the literature, and the results confirm its superior performance. The potential impact of the proposed method is noteworthy as it can facilitate accurate monitoring of in-use vehicle fuel consumption and emissions at large scales by exploiting available smartphone measurements.
•Truss optimization using fruit fly optimization algorithm.•Advanced modelling of fruit fly food search behaviour.•Efficiency in truss optimization with frequency constraints.•Intuitive, few tuning ...parameters.
A recent biological study shows that the extremely good efficiency of fruit flies in finding food, despite their small brain, emerges by two distinct stimuli: smell and visual contrast. “contrast-based fruit fly optimization”, presented in this paper, is for the first time mimicking this fruit fly behaviour and developing it as a means to efficiently address multi-parameter optimization problems. To assess its performance a study was carried out on ten mathematical and three truss optimization problems. The results are compared to those obtained using twelve state-of-the-art optimization algorithms and confirm its good and robust performance. A sensitivity analysis and an evaluation of its performance under parallel computing were conducted. The proposed algorithm has only a few tuning parameters, is intuitive, and multi-faceted, allowing application to complex n-dimensional design optimization problems.
Mucosal-associated invariant T (MAIT) cells are innate sensors of viruses and can augment early immune responses and contribute to protection. We hypothesized that MAIT cells may have inherent ...adjuvant activity in vaccine platforms that use replication-incompetent adenovirus vectors. In mice and humans, ChAdOx1 (chimpanzee adenovirus Ox1) immunization robustly activated MAIT cells. Activation required plasmacytoid dendritic cell (pDC)-derived interferon (IFN)-α and monocyte-derived interleukin-18. IFN-α-induced, monocyte-derived tumor necrosis factor was also identified as a key secondary signal. All three cytokines were required in vitro and in vivo. Activation of MAIT cells positively correlated with vaccine-induced T cell responses in human volunteers and MAIT cell-deficient mice displayed impaired CD8
T cell responses to multiple vaccine-encoded antigens. Thus, MAIT cells contribute to the immunogenicity of adenovirus vectors, with implications for vaccine design.
Selective-laser-melting (SLM) is a powder-bed fusion additive-manufacturing process that has the potential to deliver three-dimensional complex parts with mechanical properties comparable or superior ...to parts produced via traditional manufacturing using cast and wrought alloys. Concerns for metallic parts built via SLM are the process-induced residual stresses, and anisotropic mechanical properties. This paper investigates the effect of residual stresses on the fatigue crack growth rate of SLM Ti6Al4V in as-built and stress-relieved conditions. Neutron diffraction and the contour method are employed to measure residual stresses in compact-tension samples. Neutron diffraction results are in good agreement with the contour method. It was found that tensile stresses are present at the notch root and the free edge areas, and compressive stress is seen in the middle of the sample. The tensile stresses in the as-built condition resulted in a higher fatigue crack growth rate. After stress relieving by heat treatment, the tensile residual stress diminished by around 90%, resulting in decreased crack growth rate. The build direction was seen to affect the crack growth rate, although the trend was different between the as-built and stress-relieved conditions.
Interactions with commensal microbes shape host immunity on multiple levels and play a pivotal role in human health and disease. Tissue-dwelling, antigen-specific T cells are poised to respond to ...local insults, making their phenotype important in the relationship between host and microbes. Here we show that MHC-II restricted, commensal-reactive T cells in the colon of both humans and mice acquire transcriptional and functional characteristics associated with innate-like T cells. This cell population is abundant and conserved in the human and murine colon and endowed with polyfunctional effector properties spanning classic Th1- and Th17-cytokines, cytotoxic molecules, and regulators of epithelial homeostasis. T cells with this phenotype are increased in ulcerative colitis patients, and their presence aggravates pathology in dextran sodium sulphate-treated mice, pointing towards a pathogenic role in colitis. Our findings add to the expanding spectrum of innate-like immune cells positioned at the frontline of intestinal immune surveillance, capable of acting as sentinels of microbes and the local cytokine milieu.
Mucosal-associated invariant T (MAIT) cells are innate-like T cells that recognize microbial metabolites through a semi-invariant T cell receptor (TCR). Major questions remain regarding the extent of ...human MAIT cell functional and clonal diversity. To address these, we analyzed the single-cell transcriptome and TCR repertoire of blood and liver MAIT cells and developed functional RNA-sequencing, a method to integrate function and TCR clonotype at single-cell resolution. MAIT cell clonal diversity was comparable to conventional memory T cells, with private TCR repertoires shared across matched tissues. Baseline functional diversity was low and largely related to tissue site. MAIT cells showed stimulus-specific transcriptional responses in vitro, with cells positioned along gradients of activation. Clonal identity influenced resting and activated transcriptional profiles but intriguingly was not associated with the capacity to produce IL-17. Overall, MAIT cells show phenotypic and functional diversity according to tissue localization, stimulation environment and clonotype.
The pathogenesis of immune checkpoint inhibitor (ICI)–colitis remains incompletely understood. We sought to identify key cellular drivers of ICI-colitis and their similarities to idiopathic ...ulcerative colitis, and to determine potential novel therapeutic targets.
We used a cross-sectional approach to study patients with ICI-colitis, those receiving ICI without the development of colitis, idiopathic ulcerative colitis, and healthy controls. A subset of patients with ICI-colitis were studied longitudinally. We applied a range of methods, including multiparameter and spectral flow cytometry, spectral immunofluorescence microscopy, targeted gene panels, and bulk and single-cell RNA sequencing.
We demonstrate CD8+ tissue resident memory T (TRM) cells are the dominant activated T cell subset in ICI-colitis. The pattern of gastrointestinal immunopathology is distinct from ulcerative colitis at both the immune and epithelial-signaling levels. CD8+ TRM cell activation correlates with clinical and endoscopic ICI-colitis severity. Single-cell RNA sequencing analysis confirms activated CD8+ TRM cells express high levels of transcripts for checkpoint inhibitors and interferon-gamma in ICI-colitis. We demonstrate similar findings in both anti–CTLA-4/PD-1 combination therapy and in anti–PD-1 inhibitor-associated colitis. On the basis of our data, we successfully targeted this pathway in a patient with refractory ICI-colitis, using the JAK inhibitor tofacitinib.
Interferon gamma–producing CD8+ TRM cells are a pathological hallmark of ICI-colitis and a novel target for therapy.
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We present an analysis of the immunopathology in checkpoint-inhibitor colitis, a common adverse effect of cancer immunotherapy. We used our findings to successfully identify a novel therapy for a case of refractory colitis.
•Design of a transferable time series anomaly detection method.•Novel deep neural network structure facilitates learning short and long-term pattern interdependencies.•Detection of anomalies in the ...Seismic Electrical Signal for predicting earthquake activity.•Detection of road anomalies using smartphone data, facilitating crowdsourcing applications.
The quest for more efficient real-time detection of anomalies in time series data is critically important in numerous applications and systems ranging from intelligent transportation, structural health monitoring, heart disease, and earthquake prediction. Although the range of application is wide, anomaly detection algorithms are usually domain specific and build on experts’ knowledge. Here a new signal processing algorithm – inspired by the deep learning paradigm – is presented that combines wavelets, neural networks, and Hilbert transform. The algorithm performs robustly and is transferable. The proposed neural network structure facilitates learning short and long-term pattern interdependencies; a task usually hard to accomplish using standard neural network training algorithms. The paper provides guidelines for selecting the neural network's buffer size, training algorithm, and anomaly detection features. The algorithm learns the system's normal behavior and does not require the existence of anomalous data for assessing its statistical significance. This is an essential attribute in applications that require customization. Anomalies are detected by analysing hierarchically the instantaneous frequency and amplitude of the residual signal using probabilistic Receiver Operating Characteristics. The method is shown to be able to automatically detect anomalies in the Seismic Electrical Signal that could be used to predict earthquake activity. Furthermore, the method can be used in combination with crowdsourcing of smartphone data to locate road defects such as potholes and bumps for intervention and repair.
The role of the future physician in the NHS is of interest to current doctors, patients, policymakers and the wider public. Amid the COVID-19 pandemic, it has never been more clear that the ...healthcare needs of the population, and the technical and scientific advances with which to solve them, are rapidly evolving and the medical workforce must adapt to these changes to deliver personalised healthcare. This article considers the current challenges that need to be addressed to deliver a future physician-led healthcare service that works for its patients. Key themes are expanded upon, including the changing healthcare workforce, digital and technological innovation, service delivery, complex conditions and changing patient demographics. The impact and challenges of the ongoing COVID-19 pandemic on these factors are highlighted. Avenues for development are suggested, both in postgraduate medical training and the health service as a whole. These changes will be required to deliver the physicians of the future, imbued with the skills and attributes they will need to provide a high standard of care in the mid-21st century.
Tissue-resident memory T (TRM) cells provide key adaptive immune responses in infection, cancer, and autoimmunity. However, transcriptional heterogeneity of human intestinal TRM cells remains ...undefined. Here, we investigate transcriptional and functional heterogeneity of human TRM cells through study of donor-derived TRM cells from intestinal transplant recipients. Single-cell transcriptional profiling identifies two transcriptional states of CD8+ TRM cells, delineated by ITGAE and ITGB2 expression. We define a transcriptional signature discriminating these populations, including differential expression of cytotoxicity- and residency-associated genes. Flow cytometry of recipient-derived cells infiltrating the graft, and lymphocytes from healthy gut, confirm these CD8+ TRM phenotypes. CD8+ CD69+CD103+ TRM cells produce interleukin-2 (IL-2) and demonstrate greater polyfunctional cytokine production, whereas β2-integrin+CD69+CD103− TRM cells have higher granzyme expression. Analysis of intestinal CD4+ T cells identifies several parallels, including a β2-integrin+ population. Together, these results describe the transcriptional, phenotypic, and functional heterogeneity of human intestinal CD4+ and CD8+ TRM cells.
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•Human intestinal transplants were used to identify bona fide TRM cells•Single-cell RNA sequencing identifies two distinct CD8+ TRM subsets•CD103+CD69+ and CD103−CD69+ TRM cell subsets show distinct localization and function•β2-integrin is highly expressed on CD103− TRM cells
It has been historically difficult to accurately identify human tissue-resident memory T (TRM) cells. FitzPatrick et al. use a model of human intestinal transplantation to more definitively identify human TRM cells. Single-cell RNA sequencing reveals two transcriptionally distinct populations of intestinal CD8+ TRM cells, which show differences in localization and function.
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