Using Artificial Neural Networks for the Estimation of Subsurface Tidal Currents from High-Frequency Radar Surface Current Measurements

An extensive record of current velocities at all levels in the water column is an indispensable requirement for a tidal resource assessment and is fully necessary for accurate determination of available energy throughout the water column as well as estimating likely energy capture for any particular device. Traditional tidal prediction using the least squares method requires a large number of harmonic parameters calculated from lengthy acoustic Doppler current profiler (ADCP) measurements, while long-term in situ ADCPs have the advantage of measuring the real current but are logistically expensive. This study aims to show how these issues can be overcome with the use of a neural network to predict current velocities throughout the water column, using surface currents measured by a high-frequency radar. Various structured neural networks were trained with the aim of finding the network which could best simulate unseen subsurface current velocities, compared to ADCP data. This study shows that a recurrent neural network, trained by the Bayesian regularisation algorithm, produces current velocities highly correlated with measured values: r2 (0.98), mean absolute error (0.05 ms−1), and the Nash–Sutcliffe efficiency (0.98). The method demonstrates its high prediction ability using only 2 weeks of training data to predict subsurface currents up to 6 months in the future, whilst a constant surface current input is available. The resulting current predictions can be used to calculate flow power, with only a 0.4% mean error. The method is shown to be as accurate as harmonic analysis whilst requiring comparatively few input data and outperforms harmonics by identifying non-celestial influences; however, the model remains site specific.</jats:p

Tropomyosin 2.1 collaborates with fibronectin to promote TGF-β1-induced contraction of human lung fibroblasts

Many lung diseases are characterized by fibrosis, leading to impaired tissue patency and reduced lung function. Development of fibrotic tissue depends on two-way interaction between the cells and the extra-cellular matrix (ECM). Concentration-dependent increased stiffening of the ECM is sensed by the cells, which in turn increases intracellular contraction and pulling on the matrix causing matrix reorganization and further stiffening. It is generally accepted that the inflammatory cytokine growth factor β1 (TGF-β1) is a major driver of lung fibrosis through the stimulation of ECM production. However, TGF-β1 also regulates the expression of members of the tropomyosin (Tm) family of actin associating proteins that mediate ECM reorganization through intracellular-generated forces. Thus, TGF-β1 may mediate the bi-directional signaling between cells and the ECM that promotes tissue fibrosis. Using combinations of cytokine stimulation, mRNA, protein profiling and cellular contractility assays with human lung fibroblasts, we show that concomitant induction of key Tm isoforms and ECM by TGF-β1, significantly accelerates fibrotic phenotypes. Knocking down Tpm2.1 reduces fibroblast-mediated collagen gel contraction. Collectively, the data suggest combined ECM secretion and actin cytoskeleton contractility primes the tissue for enhanced fibrosis. Our study suggests that Tms are at the nexus of inflammation and tissue stiffening. Small molecules targeting specific Tm isoforms have recently been designed; thus targeting Tpm2.1 may represent a novel therapeutic target in lung fibrosis

Vocal Communications and the Maintenance of Population Specific Songs in a Contact Zone

Bird song has been hypothesized to play a role in several important aspects of the biology of songbirds, including the generation of taxonomic diversity by speciation; however, the role that song plays in speciation within this group may be dependent upon the ability of populations to maintain population specific songs or calls in the face of gene flow and external cultural influences. Here, in an exploratory study, we construct a spatially explicit model of population movement to examine the consequences of secondary contact of populations singing distinct songs. We concentrate on two broad questions: 1) will population specific songs be maintained in a contact zone or will they be replaced by shared song, and 2) what spatial patterns in the distribution of songs may result from contact? We examine the effects of multiple factors including song-based mating preferences and movement probabilities, oblique versus paternal learning of song, and both cultural and genetic mutations. We find a variety of conditions under which population specific songs can be maintained, particularly when females have preferences for their population specific songs, and we document many distinct patterns of song distribution within the contact zone, including clines, banding, and mosaics

Developing a digital intervention for cancer survivors: an evidence-, theory- and person-based approach

This paper illustrates a rigorous approach to developing digital interventions using an evidence-, theory- and person-based approach. Intervention planning included a rapid scoping review which identified cancer survivors’ needs, including barriers and facilitators to intervention success. Review evidence (N=49 papers) informed the intervention’s Guiding Principles, theory-based behavioural analysis and logic model. The intervention was optimised based on feedback on a prototype intervention through interviews (N=96) with cancer survivors and focus groups with NHS staff and cancer charity workers (N=31). Interviews with cancer survivors highlighted barriers to engagement, such as concerns about physical activity worsening fatigue. Focus groups highlighted concerns about support appointment length and how to support distressed participants. Feedback informed intervention modifications, to maximise acceptability, feasibility and likelihood of behaviour change. Our systematic method for understanding user views enabled us to anticipate and address important barriers to engagement. This methodology may be useful to others developing digital interventions

Read-across of 90-day rat oral repeated-dose toxicity: A case study for selected β-olefinic alcohols

There are no in vivo repeated-dose data for the vast majority of β-olefinic alcohols. However, there are robust and consistent ex vivo data suggesting many of these chemicals are metabolically transformed, especially in the liver, to reactive electrophilic toxicants which react in a mechanistically similar manner to acrolein, the reactive metabolite of 2-propen-1-ol. Hence, an evaluation was conducted to determine suitability of 2-propen-1-ol as a read-across analogue for other β-olefinic alcohols. The pivotal issue to applying read-across to the proposed category is the confirmation of the biotransformation to metabolites having the same mechanism of electrophilic reactivity, via the same metabolic pathway, with a rate of transformation sufficient to induce the same in vivo outcome. The applicability domain for this case study was limited to small (C3 to C6) primary and secondary -olefinic alcohols. Mechanistically, these -unsaturated alcohols are considered to be readily metabolised by alcohol dehydrogenase to polarised α, -unsaturated aldehydes and ketones. These metabolites are able to react via the Michael addition reaction mechanism with thiol groups in proteins resulting in cellular apoptosis and/or necrosis. The addition of the non-animal in chemico reactivity data (50% depletion of free glutathione) reduced the uncertainty so the read-across prediction for the straight-chain olefinic -unsaturated alcohols is deemed equivalent to a standard test. Specifically, the rat oral 90-day repeated-dose No Observed Adverse Effect Level (NOAEL) for 2-propen-1-ol of 6 mg/kg body weight bw/d in males based on increase in relative weight of liver and 25 mg/kg bw/d in females based on bile duct hyperplasia and periportal hepatocyte hypertrophy in the liver, is read across to fill data gaps for the straight-chained analogues

The All-Data-Based Evolutionary Hypothesis of Ciliated Protists with a Revised Classification of the Phylum Ciliophora (Eukaryota, Alveolata)

This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ The file attached is the published version of the article

Clinician-facilitated physical activity intervention versus pulmonary rehabilitation for improving physical activity in COPD: a feasibility study

Pulmonary rehabilitation (PR) may not suit all individuals with chronic obstructive pulmonary disease (COPD) and may not result in increased physical activity. Higher levels of physical activity are associated with reduced mortality and morbidity. The aim of this study was to assess the feasibility of conducting a trial to investigate the effectiveness of a clinician-facilitated physical activity intervention (PAI) versus PR in improving physical activity in patients with COPD referred to PR. In this randomised controlled mixed methods feasibility study, all patients referred to PR who were eligible and willing were assessed at baseline and then randomised to the PAI or to PR. The assessments were repeated post-intervention and at 3-month follow-up. The main outcome was step count measured by Actigraph. Semi-structured interviews were conducted post-intervention. The N = 50 patients; mean (SD) age, 64.1(8.6) years, 24M were recruited and randomised; N = 23 (PAI) and n = 26 (PR): one patient was excluded from the analysis as that person did not meet the GOLD diagnostic criteria. Key feasibility criteria were met; recruitment was 11%, dropouts in PAI were 26% (n = 6) and 50% (n = 13/26) PR. Participants in both groups experienced a range of health benefits from their respective programmes. The PAI appears to be effective in increasing step counts in people with COPD: mean change (standard deviation) [confidence interval] for the PAI group was 972.0(3230.3)[–1080.3 to 3024.4], n = 12 and 4.3(662.7)[-440.9 to 449.5], n = 11 for the PR group. The PAI met all domains of fidelity. This study provides key information to inform a future-randomised controlled trial in physical activity

Microparticle-mediated transfer of the viral receptors CAR and CD46, and the CFTR channel in a CHO cell model confers new functions to target cells

Cell microparticles (MPs) released in the extracellular milieu can embark plasma membrane and intracellular components which are specific of their cellular origin, and transfer them to target cells. The MP-mediated, cell-to-cell transfer of three human membrane glycoproteins of different degrees of complexity was investigated in the present study, using a CHO cell model system. We first tested the delivery of CAR and CD46, two monospanins which act as adenovirus receptors, to target CHO cells. CHO cells lack CAR and CD46, high affinity receptors for human adenovirus serotype 5 (HAdV5), and serotype 35 (HAdV35), respectively. We found that MPs derived from CHO cells (MP-donor cells) constitutively expressing CAR (MP-CAR) or CD46 (MP-CD46) were able to transfer CAR and CD46 to target CHO cells, and conferred selective permissiveness to HAdV5 and HAdV35. In addition, target CHO cells incubated with MP-CD46 acquired the CD46-associated function in complement regulation. We also explored the MP-mediated delivery of a dodecaspanin membrane glycoprotein, the CFTR to target CHO cells. CFTR functions as a chloride channel in human cells and is implicated in the genetic disease cystic fibrosis. Target CHO cells incubated with MPs produced by CHO cells constitutively expressing GFP-tagged CFTR (MP-GFP-CFTR) were found to gain a new cellular function, the chloride channel activity associated to CFTR. Time-course analysis of the appearance of GFP-CFTR in target cells suggested that MPs could achieve the delivery of CFTR to target cells via two mechanisms: the transfer of mature, membrane-inserted CFTR glycoprotein, and the transfer of CFTR-encoding mRNA. These results confirmed that cell-derived MPs represent a new class of promising therapeutic vehicles for the delivery of bioactive macromolecules, proteins or mRNAs, the latter exerting the desired therapeutic effect in target cells via de novo synthesis of their encoded proteins

The Epoxygenases CYP2J2 Activates the Nuclear Receptor PPARα In Vitro and In Vivo

Peroxisome proliferator-activated receptors (PPARs) are a family of three (PPARalpha, -beta/delta, and -gamma) nuclear receptors. In particular, PPARalpha is involved in regulation of fatty acid metabolism, cell growth and inflammation. PPARalpha mediates the cardiac fasting response, increasing fatty acid metabolism, decreasing glucose utilisation, and is the target for the fibrate lipid-lowering class of drugs. However, little is known regarding the endogenous generation of PPAR ligands. CYP2J2 is a lipid metabolising cytochrome P450, which produces anti-inflammatory mediators, and is considered the major epoxygenase in the human heart.Expression of CYP2J2 in vitro results in an activation of PPAR responses with a particular preference for PPARalpha. The CYP2J2 products 8,9- and 11-12-EET also activate PPARalpha. In vitro, PPARalpha activation by its selective ligand induces the PPARalpha target gene pyruvate dehydrogenase kinase (PDK)4 in cardiac tissue. In vivo, in cardiac-specific CYP2J2 transgenic mice, fasting selectively augments the expression of PDK4.Our results establish that CYP2J2 produces PPARalpha ligands in vitro and in vivo, and suggests that lipid metabolising CYPs are prime candidates for the integration of global lipid changes to transcriptional signalling events

Scoliotic posture as the initial symptom in adolescents with lumbar disc herniation: its curve pattern and natural history after lumbar discectomy

<p>Abstract</p> <p>Background</p> <p>There have been few studies focusing on the curve pattern of scoliosis caused by lumbar disc herniation (LDH) in adolescents and the natural history of scoliosis after discectomy. The current study was carried out to identify the curve pattern of scoliosis and investigate the effect of posterior discectomy on the curve improvement in adolescents with LDH.</p> <p>Methods</p> <p>This review focused on a group of 26 adolescents with LDH who initially presented to our clinic for evaluation of scoliosis, followed by posterior discectomy between 2000 and 2009. Radiographic measurements included curve pattern, specific curve features, trunk shift, and sagittal profile. The correlation between the side of disc herniation and the direction of lumbosacral curve and the trunk shift was evaluated.</p> <p>Results</p> <p>A typical curve pattern was initially identified in all of the patients as a short lumbosacral curve accompanied with a long thoracic or thoracolumbar curve toward the opposite side. 23 of 26 patients (88.5%) had a trunk shift more than 2.0 cm away from the midline, showing a poor coronal balance. A relatively straight sagittal profile was noted in all the patients. 84.6% (22/26) patients had a disc herniation at the convex side of lumbosacral curve. Similarly, 73.1% (19/26) patients showed a trunk shift toward the opposite side of disc herniation. All of the patients had an marked curve improvement immediately after discectomy. In the 17 patients with a more than 2-year follow-up, only two had a residual lumbosacral curve greater than or equal to 20 degrees. The mean ODI improved from 21.4% before surgery to 7.3% at the final follow-up.</p> <p>Conclusions</p> <p>A short lumbosacral curve accompanied with a long thoracic or thoracolumbar curve toward the opposite side, and a relatively straight sagittal profile have been noted in all the patients. The direction of lumbosacral curve and trunk shift was related to the side of disc herniation. A majority of patients have a small curve size while assosiated with a significant coronal imbalance. Earlier decompression can provide a greater opportunity for spontaneous correction of scoliosis.</p