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Detection of high impedance faults (HIF) is one of the biggest challenges in power distribution networks. HIF usually occurs when conductors in the distribution network are broken and accidently come into contact the ground or a tree branch. The current of this fault is close to the load current level and cannot be detected by overcurrent relays. Also, some regular system phenomena such as capacitor switching, load switching, and inrush current and saturation phenomena in current transformer (CT) represent some features which may overlap the components of HIF; making HIF detection schemes more complex. In this paper, a new method for HIF detection is presented which is able to distinguish any type of HIF from regular system phenomena. To achieve this, the scheme of morphological gradient edge detection (MGED) is used to process voltage signals. The MGED extracts two main features from the processed signals: first, the edges or changes in the signal are elicited and then, these features are extracted after two cycles from the onset of the fault. Then, based on these features, a high impedance fault detection index (HIFDI) is introduced for distinguishing and classifying HIF from other regular system phenomena. The simulation results for different types of HIF fault in a sample 20 kV distribution feeder and IEEE 34-bus distribution test system using EMTP confirm the fast and accurate performance of the proposed method.

Plants are essential components of urban microclimates, as they can help mitigate some of the adverse effects of urbanisation, enhance environmental quality, and thus contribute to overall species well-being and the sustainability of cities. Urban planners and policymakers often incorporate green infrastructure and urban greening into their strategies to create healthier and more livable urban environments. Plants are primary producers, serving as a baseline for the attraction and habitat of other species; they also provide vital ecosystem services, such as climate amelioration. Landscape designers and horticulturalists can influence plant selection through built environment interventions, increasing urban ecosystem services and benefits. Based on the evidence of native plant preferences by insects and people and their natural adaptation to regional climatic extremes, we tested, through an experimental study, the potential of native grassland plants to survive in assemblages in current urban environments. The study specifically monitored the tolerance of nine native grassland plant species to urban environments over six months in Gauteng, South Africa. A stratified random sampling was done by monitoring permanent quadrats in two purposefully engineered urban native gardens. Plant vitality was evaluated using chlorophyll a fluorescence. General climate data were obtained from a local weather station. Microclimatic temperature and humidity data were collected at each site and quadrat using Hygrochron High-Resolution Temperature and Humidity data loggers. The results indicated that all nine native plant species functioned with good photosynthetic health and can be recommended as resilient species that tolerate current urban conditions. Correlation studies indicated that two forb species, Haplocarpha lyrata and Scabiosa columbaria, showed great tolerance to current urban conditions. This vitality is likely contributed to their winter dormancy morphologically based on below-ground biomass, and their physiological adaptation to tolerate both wet and dry habitat conditions. This points to the potential of grassland forb species for urban use and the potential for climate adaptation in grassland areas.

Abstract A technique is presented for shifting the manufacturing quality control of complex biomechanical catheters away from destructive testing of finished parts. This technique uses a more efficient real-time in-process monitoring through the application of machine vision inspection of patient critical quality parameters. The approach acknowledges the challenge of this industry operating in a strict regulated environment. The higher standards of built-in quality are achieved by developing automated inspection solutions that are more accurate and repeatable. Machine vision system and associated inspection job tools are developed and used to detect defects at crucial stages of manufacturing. The vision system is then tested for its robustness using a statistical approach to ensure its measurement capability is within the allowable process range and tolerances. The integrated solution developed is proven to be robust and highly precise in maintaining the manufacturing process stable. It enabled the manufacturing process to move away from a destructive double sampling plan with a standard LTPD of 5% to an otherwise real-time 100% non-destructive verification of units. This technique provides an alternative to otherwise cost-inefficient quality control inspections utilized in regulated manufacturing environment. It gives confidence to these conservative industries to move towards adopting digital manufacturing and Industry 4.0 practices.

Abstract A model is presented for shifting the manual intensive manufacturing process of complex biomedical devices towards more lean and efficient production process via application of concepts of cyber physical systems in combination with big data and analytics in a closed loop manner. The concept model is capable of handling high product volumes and variety, has ability for self-adaptation and correction in various operating conditions, and offers real-time quality control. The approach acknowledges the challenge of these industries operating in a strict regulated environment and the higher standards of built-in quality required by developing a closed loop process, proposed to be built in accordance to the requirements of regulatory bodies and current Industry 4.0 practices. The proposed model illustrates that modern manufacturing methodologies and concepts can be integrated and adopted in such highly regulated manufacturing environments and that the model can be deployed to different production scenarios.

Consensus algorithms that function in permissionless blockchain systems must randomly select new block proposers in a decentralised environment. Our contribution is a new blockchain consensus algorithm called Proof-of-Publicly Verifiable Randomness (PoPVR). It may be used in blockchain design to make permissionless blockchain systems function as pseudo-random number generators and to use the results for decentralised consensus. The method employs verifiable random functions to embed pseudo-random number seeds in the blockchain that are confidential, tamper-resistant, unpredictable, collision-resistant, and publicly verifiable. PoPVR does not require large-scale computation, as is the case with Proof-of-Work and is not vulnerable to the exclusion of less wealthy stakeholders from the consensus process inherent in stake-based alternatives. It aims to promote fairness of participation in the consensus process by all participants and functions transparently using only open-source algorithms. PoPVR may also be useful in blockchain systems where asset values cannot be directly compared, for example, logistical systems, intellectual property records and the direct trading of commodities and services. PoPVR scales well with complexity linear in the number of transactions per block.

In Mimosa pudica plants, local and global responses to environmental stimuli are associated with different types of electrical activity. Non-damaging stimuli (e.g. cooling) generate action potentials (APs), whereas damaging stimuli (e.g. heating) are associated with variation potentials (VPs). Local cooling of Mimosa branches resulted in APs that propagated up to the branch-stem interface and caused drooping of the branch (local response). This electrical activation did not pass the interface. If the branch was triggered by heat, however, a VP was transferred to the stem and caused activation of the entire plant (global response). VPs caused by heat were always preceded by APs and summation of the two types of activation appeared to be necessary for the activation to pass the branch-stem interface. Mechanical cutting of leaves also resulted in VPs preceded by APs, but in those cases a time delay was present between the two activations, which prevented adequate summation and transmission of activation. Simultaneous cold-induced activation of a branch and the stem below the interface occasionally resulted in summation sufficient to activate the stem beyond the interface. To investigate the effect of activation delay on summation, a similar structure of excitable converging pathways, consisting of a star-shaped pattern of neonatal rat heart cells, was used. In this model, summation of activation was not hindered by a small degree of asynchrony. The observations indicate that summation occurs in excitable branching structures and suggest that summation of activation plays a role in the propagation of nocuous stimuli in Mimosa.

Many blockchain processes require pseudo-random numbers. This is especially true of blockchain consensus mechanisms that aim to fairly distribute the opportunity to propose new blocks between the participants in the system. The starting point for these processes is a source of randomness that participants cannot manipulate. This paper proposes two methods for embedding random number seeds in a blockchain data structure to serve as inputs to pseudo-random number generators. Because the output of a pseudo-random number generator depends deterministically on its seed, the properties of the seed are critical to the quality of the eventual pseudo-random number produced. Our protocol, B-Rand, embeds random number seeds that are confidential, tamper-resistant, unpredictable, collision-resistant, and publicly verifiable as part of every transaction. These seeds may then be used by transaction owners to participate in processes in the blockchain system that require pseudo-random numbers. Both the Single Secret and Double Secret B-Rand protocols are highly scalable with low space and computational cost, and the worst case is linear in the number of transactions per block.

Abstract Background Intervertebral disc (IVD) degeneration continues to be a major global health challenge, with strong links to lower back pain, while the pathogenesis of this disease is poorly understood. In cartilage, much more is known about mechanotransduction pathways involving the strain‐generated potential (SGP) and function of voltage‐gated ion channels (VGICs) in health and disease. This evidence implicates a similar important role for VGICs in IVD matrix turnover. However, the field of VGICs, and to a lesser extent the SGP, remains unexplored in the IVD. Methods A two‐step process was utilized to investigate the role of VGICs in the IVD. First, immunohistochemical staining was used to identify and localize several different VGICs in bovine and human IVDs. Second, a pilot study was conducted on the function of L‐type voltage gated calcium channels (VGCCs) by inhibiting these channels with nifedipine (Nf) and measuring calcium influx in monolayer or gene expression from 3D cell‐embedded alginate constructs subject to dynamic compression. Results Several VGICs were identified at the protein level, one of which, Cav2.2, appears to be upregulated with the onset of human IVD degeneration. Inhibiting L‐type VGCCs with Nf supplementation led to an altered cell calcium influx in response to osmotic loading as well as downregulation of col 1a, aggrecan and ADAMTS‐4 during dynamic compression. Conclusions This study demonstrates the presence of several VGICs in the IVD, with evidence supporting a role for L‐type VGCCs in mechanotransduction. These findings highlight the importance of future detailed studies in this area to fully elucidate IVD mechanotransduction pathways and better inform treatment strategies for IVD degeneration.

This paper presents a novel travelling wave-based placement strategy and fault detection scheme to locate faults on complex power grids. A fault occurring on a power grid results in travelling waves propagating from the fault location towards detectors. In this paper, the power grid is transformed to a simple, weighted, undirected graph and the shortest path information is leveraged using two well-known graph invariants to place detectors and detect and locate faults accurately. An offline algorithm is presented to determine the number and position of detectors, while an online algorithm is proposed for locating the fault. The proposed fault detection algorithm is benchmarked using the IEEE 30-bus distribution system.

Around 10 million people chew the fresh leaves and twigs of Catha edulis Forsk (khat), which synthesize cathinone, for its psychostimulatory effect. Several studies have reported that regular khat users show executive and cognitive dysfunction, such as impaired inhibitory control and poor performance on memory tests. In this study, the effect of fresh khat extract (100 and 250 mg/kg) on spatial working memory and short-term memory in mice was assessed using spontaneous and rewarded alternation T-maze tests. In the spontaneous alternation test, mice treated with fresh khat extract decreased their spontaneous alternation level to around chance level, and it remained at this level over the 7 days of khat administration and testing. On testing after a 7-day khat free period, the previously khat treated mice showed alternation level above chance but below their pre-khat alternation level. In the rewarded alternation test, acute treatment with khat caused the mice to alternate well below chance level, and then over the next 3 days of khat treatment, the alternation level increased. After a 2 and 9-day khat-free period, the previously khat treated mice alternated above chance level but below their pre-khat level. In both these tests, the mice did not show any position preference before khat treatment; however, during the khat treatment, the mice showed a right side tendency. The results show that khat treatment causes persistent changes in alternation behavior and promotes perseverative behavior, presumably due to its effect on the neural circuits activity and the neurotransmitters and promotion of position preference.

Abstract Drought is a major constraint on plant productivity globally. Sorghum [Sorghum bicolor (L.) Moench] landraces have evolved in drought‐prone regions, but the genetics of their adaptation is poorly understood. Here we sought to identify novel drought‐tolerance loci and test hypotheses on the role of known loci including those underlying stay‐green (Stg) postflowering drought tolerance. We phenotyped 590 diverse sorghum accessions from West Africa in 10 environments, under field‐based managed drought stress [preflowering water stress (WS1), postflowering water stress (WS2), and well‐watered (WW)] and rainfed (RF) conditions over 4 yr. Days to 50% flowering (DFLo), aboveground dry biomass (DBM), plant height (PH), and plant grain yield components (including grain weight [GrW], panicle weight [PW] and grain number [GrN] per plant, and 1000‐grain weight [TGrW]) were measured, and genome‐wide association studies (GWAS) was conducted. Broad‐sense heritability for biomass and plant grain yield was high (33–92%) across environments. There was a significant correlation between stress tolerance index (STI) for GrW per plant across WS1 and WS2. Genome‐wide association studies revealed that SbZfl1 and SbCN12, orthologs of maize (Zea mays L.) flowering genes, likely underlie flowering time variation under these conditions. Genome‐wide association studies further identified associations (n = 134; common between two GWAS models) for STI and drought effects on plant yield components including 16 putative pleiotropic associations. Thirty of the associations colocalized with Stg1, Stg2, Stg3, and Stg4 loci and had large effects. Seven lead associations, including some within Stg1, overlapped with positive selection outliers. Our findings reveal previously undescribed natural genetic variation for drought‐tolerance‐related traits and suggest a broad role of Stg loci in drought adaptation of sorghum.

This study aims at establishing specimens pooling approach for the detection of SARS-CoV-2 using the RT-PCR BGI and Sansure-Biotech kits used in Gabon. To validate this approach, 14 positive samples, stored at -20°C for three to five weeks were analyzed individually (as gold standard) and in pools of five, eight and ten in the same plate. We created 14 pools of 5, 8 and 10 samples using 40 μL from each of the selected positive samples mixed with 4, 7 and 9 confirmed negative counterparts in a total volume of 200 μL, 320 μL and 400 μL for the pools of 5, 8 and 10 respectively. Both individual and pooled samples testing was conducted according to the BGI and Sansure-Biotech RT-PCR protocols used at the Professor Daniel Gahouma Laboratory (PDGL). Furthermore, the pooling method was also tested by comparing results of 470 unselected samples tested in 94 pools and individually. Results of our experiment showed that using a BGI single positive sample with cycle threshold (Ct) value of 28.42, confirmed by individual testing, detection occurred in all the pools. On the contrary samples with Ct >31 were not detected in pools of 10 and for these samples (Ct value as high as 37.17) their detection was possible in pool of 8. Regarding the Sansure-Biotech kit, positive samples were detected in all the pool sizes tested, irrespective of their Ct values. The specificity of the pooling method was 100% for the BGI and Sansure-Biotech RT-PCR assays. The present study found an increase in the Ct values with pool size for the BGI and Sansure-Biotech assays. This trend was statistically significant (Pearson’s r = 0.978; p = 0,022) using the BGI method where the mean Ct values were 24.04±1.1, 26.74±1.3, 27.91±1.1 and 28.32±1.1 for the individual, pool of 5, 8 and 10 respectively. The testing of the 470 samples showed that one of the 94 pools had a positive test similar to the individual test using the BGI and Sansure-Biotech kits. The saving of time and economizing test reagents by using the pooling method were demonstrated in this study. Ultimately, the pooling method could be used for the diagnosis of SARS-CoV-2 without modifying the accuracy of results in Gabon. We recommend a maximum pool size of 8 for the BGI kit. For the Sansure-Biotech kit, a maximum pool size of 10 can be used without affecting its accuracy compared to the individual testing.

Abstract Local landrace and breeding germplasm is a useful source of genetic diversity for regional and global crop improvement initiatives. Sorghum (Sorghum bicolor L. Moench) in western Africa (WA) has diversified across a mosaic of cultures and end uses and along steep precipitation and photoperiod gradients. To facilitate germplasm utilization, a West African sorghum association panel (WASAP) of 756 accessions from national breeding programs of Niger, Mali, Senegal, and Togo was assembled and characterized. Genotyping‐by‐sequencing (GBS) was used to generate 159,101 high‐quality biallelic single nucleotide polymorphisms (SNPs), with 43% in intergenic regions and 13% in genic regions. High genetic diversity was observed within the WASAP (π = .00045), only slightly less than in a global diversity panel (GDP) (π = .00055). Linkage disequilibrium (LD) decayed to background level (r2 < .1) by ∼50 kb in the WASAP. Genome‐wide diversity was structured both by botanical type and by populations within botanical type with eight ancestral populations identified. Most populations were distributed across multiple countries, suggesting several potential common gene pools across the national programs. Genome‐wide association studies (GWAS) of days to flowering (DFLo) and plant height (PH) revealed eight and three significant quantitative trait loci (QTL), respectively, with major height QTL at canonical height loci Dw3 and SbHT7.1. Colocalization of two of eight major flowering time QTL with flowering genes previously described in U.S. germplasm (Ma6 and SbCN8) suggests that photoperiodic flowering in West African sorghum is conditioned by both known and novel genes. This genomic resource provides a foundation for genomics‐enabled breeding of climate‐resilient varieties in WA.

IntroductionTorsade de pointes arrhythmias (TdP) in the chronic atrioventricular block (CAVB) dog model result from proarrhythmic factors, which trigger TdP and/or reinforce the arrhythmic substrate. This study investigated electrophysiological and arrhythmogenic consequences of severe bradycardia for TdP.MethodsDofetilide (25 μg/kg per 5 min) was administered to eight anesthetized, idioventricular rhythm (IVR) remodeled CAVB dogs in two serial experiments: once under 60 beats per minute (bpm), right ventricular apex paced (RVA60) conditions, once under more bradycardic IVR conditions. Recordings included surface electrocardiogram and short-term variability (STV) of repolarization from endocardial unipolar electrograms. TdP inducibility (three or more episodes within 10 min after start of dofetilide) and arrhythmic activity scores (AS) were established. Mapping experiments in 10 additional dogs determined the effect of lowering rate on STV and spatial dispersion of repolarization (SDR) in baseline.ResultsIVR-tested animals had longer baseline RR-interval (1,403 ± 271 ms) and repolarization intervals than RVA60 animals. Dofetilide increased STV similarly under both rhythm strategies. Nevertheless, TdP inducibility and AS were higher under IVR conditions (6/8 and 37 ± 27 vs. 1/8 and 8 ± 12 in RVA60, respectively, both p < 0.05). Mapping: Pacing from high (128 ± 10 bpm) to middle (88 ± 10 bpm) to experimental rate (61 ± 3 bpm) increased all electrophysiological parameters, including interventricular dispersion, due to steeper left ventricular restitution curves, and intraventricular SDR: maximal cubic dispersion from 60 ± 14 (high) to 69 ± 17 (middle) to 84 ± 22 ms (p < 0.05 vs. high and middle rate).ConclusionIn CAVB dogs, severe bradycardia increases the probability and severity of arrhythmic events by heterogeneously causing electrophysiological instability, which is mainly reflected in an increased spatial, and to a lesser extent temporal, dispersion of repolarization.

Abstract Uncovering the genomic basis of climate adaptation in traditional crop varieties can provide insight into plant evolution and facilitate breeding for climate resilience. In the African cereal sorghum (Sorghum bicolor L. [Moench]), the genomic basis of adaptation to the semiarid Sahelian zone versus the subhumid Soudanian zone is largely unknown. To address this issue, we characterized a large panel of 421 georeferenced sorghum landrace accessions from Senegal and adjacent locations at 213,916 single‐nucleotide polymorphisms (SNPs) using genotyping‐by‐sequencing. Seven subpopulations distributed along the north‐south precipitation gradient were identified. Redundancy analysis found that climate variables explained up to 8% of SNP variation, with climate collinear with space explaining most of this variation (6%). Genome scans of nucleotide diversity suggest positive selection on chromosome 2, 4, 5, 7, and 10 in durra sorghums, with successive adaptation during diffusion along the Sahel. Putative selective sweeps were identified, several of which colocalize with stay‐green drought tolerance (Stg) loci, and a priori candidate genes for photoperiodic flowering and inflorescence morphology. Genome‐wide association studies of photoperiod sensitivity and panicle compactness identified 35 and 13 associations that colocalize with a priori candidate genes, respectively. Climate‐associated SNPs colocalize with Stg3a, Stg1, Stg2, and Ma6 and have allelic distribution consistent with adaptation across Sahelian and Soudanian zones. Taken together, the findings suggest an oligogenic basis of adaptation to Sahelian versus Soudanian climates, underpinned by variation in conserved floral regulatory pathways and other systems that are less understood in cereals.

The cardiac autonomic nervous system produces various neuropeptides, such as neurokinin substance-P (Sub-P), whose function remains largely unclear. Here, authors show that Sub-P causes a receptor-mediated prolongation of the atrial action potential through a reduced background potassium current, and prevents atrial fibrillation.

Mechanotransduction is the initiation of an electrochemical signal as a result of mechanical stimuli. It is found predominately in biological tissue and its mechanisms are well documented. In the gel like tissues of the body, such as articular cartilage and intervertebral discs, mechanotransduction regulates matrix building and degrading processes as well as keeping the tissues adequately hydrated, both with the aim of minimizing degradation. The electrochemical responses to mechanical loading at constant volume of an inanimate hydrogel could assist in the understanding of these processes.There is considerable evidence that the modulus of hydrated tissues and hydrogels depend explicitly on ionic concentration. By modeling the mechano-electrochemical relationship of a hydrogel, the coupling of the elastic and electrochemical energies can be quantified. In turn, the mechanisms that govern this phenomenon can be better understood. This study modifies the Flory-Rehner theory of gels, using material-specific experimental data as input. The results show up to a 11% difference in equilibrium swelling magnitude compared to the Flory-Rehner model. Furthermore, under isochoric deformation, an increase in electrical potential is shown with increasing shear strain, something which is not possible with conventional Flory-Rehner and Donnan theory. This aligns the continuum model presented here more closely with both experiment and microscopic theories. The mechanosensing capabilities as well as varying swelling responses in different solution concentrations highlight the models potential applications in both biological and technological settings.

Abstract Due to its fundamental role in shaping host selection behavior, we have analyzed the chemosensory repertoire of Chrysomela lapponica. This specialized leaf beetle evolved distinct populations which shifted from the ancestral host plant, willow (Salix sp., Salicaceae), to birch (Betula rotundifolia, Betulaceae). We identified 114 chemosensory candidate genes in adult C. lapponica: 41 olfactory receptors (ORs), eight gustatory receptors, 17 ionotropic receptors, four sensory neuron membrane proteins, 32 odorant binding proteins (OBPs), and 12 chemosensory proteins (CSP) by RNA‐seq. Differential expression analyses in the antennae revealed significant upregulation of one minus‐C OBP (ClapOBP27) and one CSP (ClapCSP12) in the willow feeders. In contrast, one OR (ClapOR17), four minus‐C OBPs (ClapOBP02, 07, 13, 20), and one plus‐C OBP (ClapOBP32) were significantly upregulated in birch feeders. The differential expression pattern in the legs was more complex. To narrow down putative ligands acting as cues for host discrimination, the relative abundance and diversity of volatiles of the two host plant species were analyzed. In addition to salicylaldehyde (willow‐specific), both plant species differed mainly in their emission rate of terpenoids such as (E,E)‐α‐farnesene (high in willow) or 4,8‐dimethylnona‐1,3,7‐triene (high in birch). Qualitatively, the volatiles were similar between willow and birch leaves constituting an “olfactory bridge” for the beetles. Subsequent structural modeling of the three most differentially expressed OBPs and docking studies using 22 host volatiles indicated that ligands bind with varying affinity. We suggest that the evolution of particularly minus‐C OBPs and ORs in C. lapponica facilitated its host plant shift via chemosensation of the phytochemicals from birch as novel host plant.

Canola plants were fumigated in open-top chambers with ozone (O3) (120 ppb) under well-watered (WW) and water-stressed (WS) conditions for 4 weeks. Non-fumigated plants were also studied to facilitate comparison between treatments for the same week and over time. Therefore, the treatments were: WW, WW-O3, WS and WS-O3. The fast chlorophyll a fluorescence transients OJIP for the four treatments emitted upon illumination of dark-adapted leaves were measured after week 1, 2, 3, 4 and analysed by the JlP-test to evaluate the resulting changes in photosynthetic performance. Ozone fumigation led to a decline of total performance index (Pltotal) in well-watered plants. The effect of O3 was minor under drought conditions, as revealed by a decrease of Pltotal by 3%. The Pltotal decreased as the treatment was prolonged, due to leaf ageing for all cases and the decline was more pronounced under WW-O3. Taking the average of all weeks, WW had the highest Pltotal and the lowest WW-O3 (decrease by 27%), while in WS and WS-O3, it was lower than WW (14 and 17%, respectively). We found that the absorption (ABS)/reaction centre (RC) increases, while the maximum quantum yield of primary photochemistry (ϕPo) undergoes slight changes, and trapping (TR0)/RC closely followed the increase in ABS/RC. This indicates that O3 and drought caused an increase in the functional antenna size. The maximum quantum yield of primary photochemistry showed slight differences for all treatments and over time, suggesting that this parameter is less sensitive to drought and O3 stress. Therefore, the more sensitive components of the photosynthetic electron transport chain appeared to be the probability that an electron from the intersystem electron carriers is transferred to reduce end electron acceptors at the PSl acceptor side (δRo) and the RC density on a chlorophyll basis (RC/ABS).

There is an increasing prevalence of chronic kidney disease (CKD), which associates with the development of interstitial fibrosis. Pericytes (perivascular fibroblasts) provide a major source of α-SMA-positive myofibroblasts that are responsible for the excessive deposition of extracellular matrix. In order to identify pericyte long non-coding RNAs (lncRNAs) that could serve as a target to decrease myofibroblast formation and counteract the progression of kidney fibrosis we employed two models of experimental kidney injury, one focused on kidney fibrosis (unilateral ureteral obstruction; UUO), and one focused on acute kidney injury that yields kidney fibrosis in the longer term (unilateral ischemia-reperfusion injury; IRI). This was performed in FoxD1-GC;tdTomato stromal cell reporter mice that allowed pericyte fate tracing. Tomato red-positive FoxD1-derivative cells of control and injured kidneys were FACS-sorted and used for lncRNA and mRNA profiling yielding a distinctive transcriptional signature of pericytes and myofibroblasts with 244 and 586 differentially expressed lncRNAs (>twofold, P < 0.05), in the UUO and IRI models, respectively. Next, we selected two differentially expressed and conserved lncRNAs, Rian (RNA imprinted and accumulated in nucleus) and Miat (Myocardial infarction associated transcript), and explored their potential regulatory role in myofibroblast formation through knockdown of their function with gapmers. While Miat was upregulated in myofibroblasts of UUO and IRI in mice, gapmer silencing of Miat attenuated myofibroblast formation as evidenced by decreased expression of α-SMA, col1α1, SMAD2, and SMAD3, as well as decreased α-SMA and pro-collagen-1α1 protein levels. In contrast, silencing Rian, which was found to be downregulated in kidney myofibroblast after IRI and UUO, resulted in increased myofibroblast formation. In addition, we found microRNAs that were previously linked to Miat (miR-150) and Rian (14q32 miRNA cluster), to be dysregulated in the FoxD1-derivative cells, suggesting a possible interaction between miRNAs and these lncRNAs in myofibroblast formation. Taken together, lncRNAs play a regulatory role in myofibroblast formation, possibly through interacting with miRNA regulation, implicating that understanding their biology and their modulation may have the potential to counteract the development of renal fibrosis.

Post-transcriptional control of RNA is important in health and disease. Here, the authors show that the RNA-binding protein Quaking guides pre-mRNA splicing and transcript abundance during monocyte to macrophage differentiation, and that Quaking depletion impairs pro-atherogenic foam cell formation.

The Flory−Rehner theoretical description of the free energy in a hydrogel swelling model can be broken into two swelling components: the mixing energy and the ionic energy. Conventionally for ionized gels, the ionic energy is characterized as the main contributor to swelling and, therefore, the mixing energy is assumed negligible. However, this assumption is made at the equilibrium state and ignores the dynamics of gel swelling. Here, the influence of the mixing energy on swelling ionized gels is quantified through numerical simulations on sodium polyacrylate using a Mixed Hybrid Finite Element Method. For univalent and divalent solutions, at initial porosities greater than 0.90, the contribution of the mixing energy is negligible. However, at initial porosities less than 0.90, the total swelling pressure is significantly influenced by the mixing energy. Therefore, both ionic and mixing energies are required for the modeling of sodium polyacrylate ionized gel swelling. The numerical model results are in good agreement with the analytical solution as well as experimental swelling tests.

In the pathophysiologic setting of acute and chronic kidney injury, the excessive activation and recruitment of blood-borne monocytes prompts their differentiation into inflammatory macrophages, a process that leads to progressive glomerulosclerosis and interstitial fibrosis. Importantly, this differentiation of monocytes into macrophages requires the meticulous coordination of gene expression at both the transcriptional and post-transcriptional level. The transcriptomes of these cells are ultimately determined by RNA-binding proteins such as QUAKING (QKI), that define their pre-mRNA splicing and mRNA transcript patterns. Using two mouse models, namely (1) quaking viable mice (qkv) and (2) the conditional deletion in the myeloid cell lineage using the lysozyme 2-Cre (QKIFL/FL;LysM-Cre mice), we demonstrate that the abrogation of QKI expression in the myeloid cell lineage reduces macrophage infiltration following kidney injury induced by unilateral urethral obstruction (UUO). The qkv and QKIFL/FL;LysM-Cre mice both showed significant diminished interstitial collagen deposition and fibrosis in the UUO-damaged kidney, as compared to wild-type littermates. We show that macrophages isolated from QKIFL/FL;LysM-Cre mice are associated with defects in pre-mRNA splicing. Our findings demonstrate that reduced expression of the alternative splice regulator QKI in the cells of myeloid lineage attenuates renal interstitial fibrosis, suggesting that inhibition of this splice regulator may be of therapeutic value for certain kidney diseases.

Fragmented QRS complexes (fQRS) are common in patients with arrhythmogenic cardiomyopathy (ACM). A new method of fQRS quantification may aid early disease detection in pathogenic variant carriers and assessment of prognosis in patients with early stage ACM. Patients with definite ACM (n = 221, 66%), carriers of a pathogenic ACM-associated variant without a definite ACM diagnosis (n = 57, 17%) and control subjects (n = 58, 17%) were included. Quantitative fQRS (Q-fQRS) was defined as the total amount of deflections in the QRS complex in all 12 electrocardiography (ECG) leads. Q-fQRS was scored by a single observer and reproducibility was determined by three independent observers. Q-fQRS count was feasible with acceptable intra- and inter-observer agreement. Q-fQRS count is significantly higher in patients with definite ACM (54 ± 15) and pathogenic variant carriers (55 ± 10) compared to controls (35 ± 5) (p < 0.001). In patients with ACM, Q-fQRS was not associated with sustained ventricular arrhythmia (p = 0.701) at baseline or during follow-up (p = 0.335). Both definite ACM patients and pathogenic variant carriers not fulfilling ACM diagnosis have a higher Q-fQRS than controls. This may indicate that increased Q-fQRS is an early sign of disease penetrance. In concealed and early stages of ACM the role of Q-fQRS for risk stratification is limited.

Background. Acute rejection (AR) of kidney transplants is associated with the loss of endothelial integrity, microvascular rarefaction and, ultimately, graft dysfunction. Circulating angiogenic microRNAs (miRNAs) may serve as markers for microvascular injury. Here, we investigated the short- and long-term effects of AR after kidney transplantation on systemic vascular injury and the associated circulating miRNA profile. Methods. Systemic vascular injury was determined by measuring capillary tortuosity and density within the oral mucosa as well as by assessing circulating levels of angiopoietin-2/angiopoietin-1 ratio, vascular endothelial growth factor and soluble thrombomodulin. After a pilot study, we selected 48 miRNAs to assess the AR- and microvascular injury associated circulating miRNAs. Results. In stable transplant recipients (n = 25) and patients with AR (n = 13), which were also studied longitudinally (1, 6, and 12 months post-AR), we found an AR-associated increase in markers of systemic vascular injury, of which vascular endothelial growth factor and soluble thrombomodulin normalized within 1 year after AR. Of the 48 selected miRNAs, 8 were either decreased (miR-135a, miR-199a-3p, and miR-15a) or increased (miR-17, miR-140-3p, miR-130b, miR-122 and miR-192) in AR. Of these, miR-130b, miR-199a, and miR-192 associated with markers of vascular injury, whereas miR-140-3p, miR-130b, miR-122, and miR-192 normalized within 1 year after AR. Conclusions. AR after kidney transplantation is characterized by systemic microvascular injury and associates with specific circulating miRNA levels.

BackgroundStem cell therapy to improve cardiac function after myocardial infarction is hampered by poor cell retention, while it may also increase the risk of arrhythmias by providing an arrhythmogenic substrate. We previously showed that porcine adipose tissue-derived-stromal cells (pASC) induce conduction slowing through paracrine actions, whereas rat ASC (rASC) and human ASC (hASC) induce conduction slowing by direct coupling. We postulate that biomaterial microspheres mitigate the conduction slowing influence of pASC by interacting with paracrine signaling.AimTo investigate the modulation of ASC-loaded recombinant human collagen-based microspheres, on the electrophysiological behavior of neonatal rat ventricular myocytes (NRVM).MethodUnipolar extracellular electrograms, derived from microelectrode arrays (8x8 electrodes) containing NRVM, co-cultured with ASC or ASC loaded microspheres, were used to determine conduction velocity (CV) and conduction heterogeneity. Conditioned medium (Cme) of (co)cultures was used to assess paracrine mechanisms.ResultsMicrospheres did not affect CV in control (NRVM) monolayers. In co-cultures of NRVM and rASC, hASC or pASC, CV was lower than in controls (14.4±1.0, 13.0±0.6 and 9.0± 1.0 vs. 19.5±0.5 cm/s respectively, pConclusionThe application of recombinant human collagen-based microspheres mitigates indirect paracrine conduction slowing through interference with a secondary autocrine myocardial factor.

ABSTRACT Bacterial mycetoma is a neglected disease mainly observed in tropical area countries and typically associated with rural conditions, making its presence in developed countries of temperate climate areas rare. However, we report the first case of an autochthonous mycetoma case in continental France that originated from a new Nocardia species. A Gram-positive filamentous bacterium (OFN 14.177T) was isolated from a pus sample from the mycetoma of a male French patient 92 years old suffering from chronic lymphocytic leukemia. The isolate was analyzed by a polyphasic taxonomic approach by coupling morphological, biochemical, physiological, and chemotaxonomic aspects to genomic and phylogenetic analyses. Multilocus sequence analysis (MLSA) using four housekeeping genes (16S rRNA gene, secA1, hsp65, and sod) combined with phylogenetic analysis revealed that the strain OFN 14.177T is phylogenetically closer not only to Nocardia altamirensis but also to all other species comprising the Nocardia brasiliensis clade (i.e., N. brasiliensis, N. altamirensis, N. vulneris, N. iowensis, and N. tenerifensis), some of which present cutaneous tropism. The G+C content of isolate OFN 14.177T was 68.2 mol%. DNA-DNA hybridization analyses demonstrated 38.25% relative reassociation with N. altamirensis. The strain OFN 14.177T is different from the closest species at genetic and phenotypical levels, and the data obtained indicate that it should be recognized as a new species, for which the name of Nocardia boironii sp. nov. is proposed. The type strain is OFN 14.177T (= EML 1451 = DSM 101696). IMPORTANCE Bacterial mycetoma is an endemic infection in areas with tropical and subtropical climates. Thus, its presence in temperate climate areas remains rare. We report here the first case of autochthonous actinomycetoma in continental France originating from a Nocardia species other than N. brasiliensis, namely, Nocardia boironii. Considering the history of the patient, the infection source of strain OFN 14.177T may be from frequent contact with the soil over many years because of his gardening activities. The discovery of a French autochthonous Nocardia species responsible for actinomycetoma reveals the importance of considering the possibility of having autochthonous infections of this type in nontropical countries, not only imported cases from tropical countries. However, further studies are needed to elucidate the real incidence of this new species.

A hydrogel is a polymeric three-dimensional network structure. The applications of this material type are diversified over a broad range of fields. Their soft nature and similarity to natural tissue allows for their use in tissue engineering, medical devices, agriculture, and industrial health products. However, as the demand for such materials increases, the need to understand the material mechanics is paramount across all fields. As a result, many attempts to numerically model the swelling and drying of chemically responsive hydrogels have been published. Material characterization of the mechanical properties of a gel bead under osmotic loading is difficult. As a result, much of the literature has implemented variants of swelling theories. Therefore, this article focuses on reviewing the current literature and outlining the numerical models of swelling hydrogels as a result of exposure to chemical stimuli. Furthermore, the experimental techniques attempting to quantify bulk gel mechanics are summarized. Finally, an overview on the mechanisms governing the formation of geometric surface instabilities during transient swelling of soft materials is provided.

The effects of elevated CO2 (700 ppm) and O3 (80 ppb) alone and in combination on the photosynthetic efficiency of canola and wheat plants were investigated in open-top chambers (OTCs). The plants were fumigated for four weeks under well-watered and water-stressed (water deficit) conditions. The fast chlorophyll a fluorescence transients were measured after 2 and 4 weeks of fumigation, as well as in control plants, and analyzed by the JIP-test, which is a non-destructive, non-invasive, informative, very fast and inexpensive technique used to evaluate the changes in photosynthetic efficiency. Biomass measurements were taken only after 4 weeks of fumigation. The performance index (PItotal), an overall parameter calculated from the JIP-test formulae, was reduced by elevated CO2 and O3 under well-watered conditions. In the absence of any other treatment, water stress caused a decrease of the PItotal, and it was partly eliminated by fumigation with elevated CO2 and CO2 + O3. This finding was also supported by the biomass results, which revealed a higher biomass under elevated CO2 and CO2 + O3. The decrease in biomass induced by elevated O3 was likely caused by the decline of photosynthetic efficiency. Our findings suggest that elevated CO2 reduces the drought effect both in the absence and presence of O3 in canola and wheat plants. The study also indicates that elevated O3 would pose a threat in future to agricultural crops.

In numerous industrial applications, the microstructure of materials is critical for performance. However, finite element models tend to average out the microstructure. Hence, finite element simulations are often unsuitable for optimisation of the microstructure. The present paper presents a modelling technique that addresses this limitation for superabsorbent polymers with a partially cross-linked surface layer. These are widely used in the industry for a variety of functions. Different designs of the cross-linked layer have different material properties, influencing the performance of the hydrogel. In this work, the effects of intrinsic properties on the fracture nucleation and propagation in cross-linked hydrogels are studied. The numerical implementation for crack propagation and nucleation is based on the framework of the extended finite element method and the enhanced local pressure model to capture the pressure difference and fluid flow between the crack and the hydrogel, and coupled with the cohesive method to achieve crack propagation without re-meshing. Two groups of numerical examples are given: (1) effects on crack propagation, and (2) effects on crack nucleation. Within each example, we studied the effects of the stiffness (shear modulus) and ultimate strength of the material separately. Simulations demonstrate that the crack behaviour is influenced by the intrinsic properties of the hydrogel, which gives numerical support for the structural design of the cross-linked hydrogel.

Sustained pacemaker function is a challenge in biological pacemaker engineering. Human cardiomyocyte progenitor cells (CMPCs) have exhibited extended survival in the heart after transplantation. We studied whether lentivirally transduced CMPCs that express the pacemaker current If (encoded by HCN4) can be used as functional gene delivery vehicle in biological pacing. Human CMPCs were isolated from fetal hearts using magnetic beads coated with Sca-1 antibody, cultured in nondifferentiating conditions, and transduced with a green fluorescent protein (GFP)- or HCN4-GFP-expressing lentivirus. A patch-clamp analysis showed a large hyperpolarization-activated, time-dependent inward current (−20 pA/pF at −140 mV, n = 14) with properties typical of If in HCN4-GFP-expressing CMPCs. Gap-junctional coupling between CMPCs and neonatal rat ventricular myocytes (NRVMs) was demonstrated by efficient dye transfer and changes in spontaneous beating activity. In organ explant cultures, the number of preparations showing spontaneous beating activity increased from 6.3% in CMPC/GFP-injected preparations to 68.2% in CMPC/HCN4-GFP-injected preparations (P < 0.05). Furthermore, in CMPC/HCN4-GFP-injected preparations, isoproterenol induced a significant reduction in cycle lengths from 648 ± 169 to 392 ± 71 ms (P < 0.05). In sum, CMPCs expressing HCN4-GFP functionally couple to NRVMs and induce physiologically controlled pacemaker activity and may therefore provide an attractive delivery platform for sustained pacemaker function.

Autonomous vehicles use sensors and artificial intelligence to drive themselves. Surveys indicate that people are fascinated by the idea of autonomous driving, but are hesitant to relinquish control of the vehicle. Lack of trust seems to be the core reason for these concerns. In order to address this, an intelligent agent approach was implemented, as it has been argued that human traits increase trust in interfaces. Where other approaches mainly use anthropomorphism to shape appearances, the current approach uses anthropomorphism to shape the interaction, applying Gricean maxims (i.e., guidelines for effective conversation). The contribution of this approach was tested in a simulator that employed both a graphical and a conversational user interface, which were rated on likability, perceived intelligence, trust, and anthropomorphism. Results show that the conversational interface was trusted, liked, and anthropomorphized more, and was perceived as more intelligent, than the graphical user interface. Additionally, an interface that was portrayed as more confident in making decisions scored higher on all four constructs than one that was portrayed as having low confidence. These results together indicate that equipping autonomous vehicles with interfaces that mimic human behavior may help increasing people’s trust in, and, consequently, their acceptance of them.

Predicting how a genetic change affects a given character is a major challenge in biology, and being able to tackle this problem relies on our ability to develop realistic models of gene networks. However, such models are rarely tractable mathematically. In this paper, we propose a mathematical analysis of the sigmoid variant of the Wagner gene-network model. By considering the simplest case, that is, one unique self-regulating gene, we show that numerical simulations are not the only tool available to study such models: theoretical studies can be done too, by mathematical analysis of discrete dynamical systems. It is first shown that the particular sigmoid function can be theoretically investigated. Secondly, we provide an illustration of how to apply such investigations in the case of the dynamical system representing the one self-regulating gene. In this context, we focused on the composite function f a ( m . x ) where f a is the parametric sigmoid function and m is a scalar not in { 0 , 1 } and we have proven that the number of fixed-point can be deduced theoretically, according to the values of a and m.