Conductivity Imaging from Internal Measurements with Mixed Least-Squares Deep Neural Networks

In this work we develop a novel approach using deep neural networks to reconstruct the conductivity distribution in elliptic problems from one internal measurement. The approach is based on a mixed reformulation of the governing equation and utilizes the standard least-squares objective to approximate the conductivity and flux simultaneously, with deep neural networks as ansatz functions. We provide a thorough analysis of the neural network approximations for both continuous and empirical losses, including rigorous error estimates that are explicit in terms of the noise level, various penalty parameters and neural network architectural parameters (depth, width and parameter bound). We also provide extensive numerical experiments in two- and multi-dimensions to illustrate distinct features of the approach, e.g., excellent stability with respect to data noise and capability of solving high-dimensional problems.Comment: 28 pages. 12 figure

Two‐Dimensional Design Strategy to Construct Smart Fluorescent Probes for the Precise Tracking of Senescence

The tracking of cellular senescence usually depends on the detection of senescence‐associated β‐galactosidase (SA‐β‐gal). Previous probes for SA‐β‐gal with this purpose only cover a single dimension: the accumulation of this enzyme in lysosomes. However, this is insufficient to determine the destiny of senescence because endogenous β‐gal enriched in lysosomes is not only related to senescence, but also to some other physiological processes. To address this issue, we introduce our fluorescent probes including a second dimension: lysosomal pH, since de‐acidification is a unique feature of the lysosomes in senescent cells. With this novel design, our probes achieved excellent discrimination of SA‐β‐gal from cancer‐associated β‐gal, which enables them to track cellular senescence as well as tissue aging more precisely. Our crystal structures of a model enzyme E. coli β‐gal mutant (E537Q) complexed with each probe further revealed the structural basis for probe recognition.<br/

Effects of electrostatic therapy on nighttime sleep and daytime symptoms in patients with chronic insomnia: Evidences from an open label study

IntroductionTranscranial electric stimulation (TES) is a neuromodulation approach that applies low-intensity electrical current to the brain and has been proposed as a treatment for insomnia. Electrostatic therapy is a kind of TES and people do not have a feeling of electrical stimuli when the voltage of static electricity is lower than 2,000 volts. However, no studies have examined the effects of electrostatic therapy on objective sleep and daytime symptoms in patients with insomnia.Materials and methodsThirty chronic insomnia patients were included. All patients received a 6 week electrostatic therapy and three comprehensive assessments including two consecutive polysomnography (PSG) and daytime symptoms assessments, at pre-treatment, 3 week and 6 week of treatment. Insomnia Severity Index (ISI) was used to assess the severity of insomnia. Multiple sleep latency test (MSLT), Epworth Sleepiness Scale (ESS), and Flinders Fatigue Scale (FFS) were used to assess objective and self-reported daytime sleepiness and fatigue, respectively. Attention network test (ANT) was used to assess attention levels.ResultsTotal ISI scores decreased significantly at 3 weeks (p &lt; 0.001) and 6 weeks (p &lt; 0.001) after initiation of treatment. Furthermore, objective total sleep time (TST, p = 0.020) and sleep efficiency (SE, p = 0.009) increased and wake time after sleep onset (p = 0.012) decreased significantly after 6 weeks electrostatic therapy. Regarding daytime symptoms, ESS and FFS scores decreased significantly at 3 weeks (ESS, p = 0.047; FFS, p = 0.017) and 6 weeks (ESS, p = 0.008; FFS, p = 0.003) after initiation of treatment. Moreover, executive control improved significantly from pre-treatment to 3 weeks (p = 0.006) and 6 weeks (p = 0.013) and altering network improved significantly at 6 weeks (p = 0.003) after initiation of treatment. Secondary analyses showed that TST and SE improved significantly after electrostatic therapy in insomnia patients who slept &lt; 390 min (all p-value &lt; 0.05). However, no significant changes regarding TST and SE were observed in insomnia patients who slept ≥ 390 min.ConclusionElectrostatic therapy improves both nighttime sleep and daytime symptoms in patients with chronic insomnia. The effect on objective sleep appears to be stronger in patient with objective short sleep duration. Electrostatic therapy might be a therapeutic choice for insomnia patients with difficulty maintaining sleep and not responding to behavioral treatments.Clinical trial registration[www.clinicaltrials.gov], identifier [ChiCTR2100051590]

Evaluation of Potential Reference Genes for Relative Quantification by RT-qPCR in Different Porcine Tissues Derived from Feeding Studies

Five potential reference genes for RT-qPCR application, namely histone H3, beta-actin, GAPDH, ubiquitin and 18S rRNA, were evaluated for normalization of gene expression in four selected tissues (liver, kidney, thyroid and abdominal fat). Tissues were derived from fattening pigs exposed to different amounts and type of dietary iodine. Two software applications (geNorm and NormFinder) were used to evaluate the stability of the potential reference genes. All studied genes displayed high expression stability but different stability patterns between the investigated tissues. The results suggest GAPDH and 18S rRNA as reference genes applicable in all tissues investigated. Beta-actin and histone H3 are suitable reference genes for all tissues investigated except fat. In contrast, ubiquitin should be excluded from use as a reference gene in the porcine tissues analyzed due to variations in expression levels, despite the good expression stability

Genome of Pythium myriotylum Uncovers an Extensive Arsenal of Virulence-Related Genes among the Broad-Host-Range Necrotrophic Pythium Plant Pathogens

The Pythium (Peronosporales, Oomycota) genus includes devastating plant pathogens that cause widespread diseases and severe crop losses. Here, we have uncovered a far greater arsenal of virulence factor-related genes in the necrotrophic Pythium myriotylum than in other Pythium plant pathogens. The genome of a plant-virulent P. myriotylum strain (~70 Mb and 19,878 genes) isolated from a diseased rhizome of ginger (Zingiber officinale) encodes the largest repertoire of putative effectors, proteases, and plant cell wall-degrading enzymes (PCWDEs) among the studied species. P. myriotylum has twice as many predicted secreted proteins than any other Pythium plant pathogen. Arrays of tandem duplications appear to be a key factor of the enrichment of the virulence factor-related genes in P. myriotylum. The transcriptomic analysis performed on two P. myriotylum isolates infecting ginger leaves showed that proteases were a major part of the upregulated genes along with PCWDEs, Nep1-like proteins (NLPs), and elicitin-like proteins. A subset of P. myriotylum NLPs were analyzed and found to have necrosis-inducing ability from agroinfiltration of tobacco (Nicotiana benthamiana) leaves. One of the heterologously produced infection-upregulated putative cutinases found in a tandem array showed esterase activity with preferences for longer-chain-length substrates and neutral to alkaline pH levels. Our results allow the development of science-based targets for the management of P. myriotylum-caused disease, as insights from the genome and transcriptome show that gene expansion of virulence factor-related genes play a bigger role in the plant parasitism of Pythium spp. than previously thought. IMPORTANCE Pythium species are oomycetes, an evolutionarily distinct group of filamentous fungus-like stramenopiles. The Pythium genus includes several pathogens of important crop species, e.g., the spice ginger. Analysis of our genome from the plant pathogen Pythium myriotylum uncovered a far larger arsenal of virulence factor-related genes than found in other Pythium plant pathogens, and these genes contribute to the infection of the plant host. The increase in the number of virulence factor-related genes appears to have occurred through the mechanism of tandem gene duplication events. Genes from particular virulence factor-related categories that were increased in number and switched on during infection of ginger leaves had their activities tested. These genes have toxic activities toward plant cells or activities to hydrolyze polymeric components of the plant. The research suggests targets to better manage diseases caused by P. myriotylum and prompts renewed attention to the genomics of Pythium plant pathogens

A sheep pangenome reveals the spectrum of structural variations and their effects on tail phenotypes

Structural variations (SVs) are a major contributor to genetic diversity and phenotypic variations, but their prevalence and functions in domestic animals are largely unexplored. Here we generated high-quality genome assemblies for 15 individuals from genetically diverse sheep breeds using Pacific Biosciences (PacBio) high-fidelity sequencing, discovering 130.3 Mb nonreference sequences, from which 588 genes were annotated. A total of 149,158 biallelic insertions/deletions, 6531 divergent alleles, and 14,707 multiallelic variations with precise breakpoints were discovered. The SV spectrum is characterized by an excess of derived insertions compared to deletions (94,422 vs. 33,571), suggesting recent active LINE expansions in sheep. Nearly half of the SVs display low to moderate linkage disequilibrium with surrounding single-nucleotide polymorphisms (SNPs) and most SVs cannot be tagged by SNP probes from the widely used ovine 50K SNP chip. We identified 865 population-stratified SVs including 122 SVs possibly derived in the domestication process among 690 individuals from sheep breeds worldwide. A novel 168-bp insertion in the 5' untranslated region (5' UTR) of HOXB13 is found at high frequency in long-tailed sheep. Further genome-wide association study and gene expression analyses suggest that this mutation is causative for the long-tail trait. In summary, we have developed a panel of high-quality de novo assemblies and present a catalog of structural variations in sheep. Our data capture abundant candidate functional variations that were previously unexplored and provide a fundamental resource for understanding trait biology in sheep

Nanobodies ciblant spécifiquement et modulant le récepteur nicotinique acétylcholine alpha 7 humain

Les récepteurs nicotiniques de l'acétylcholine alpha7 (nAChR alpha7) sont des pentamères homomériques exprimés abondamment dans le système nerveux central, en particulier dans l'hippocampe et le cortex frontal qui sont impliqués dans la mémoire et la cognition. Les dysfonctions de ces récepteurs sont impliquées dans de multiples maladies neurologiques et psychiatriques, en particulier l'addiction, la douleur, la maladie de Parkinson, ADHD et la maladie d'Alzheimer. Il a été bien établi que l'augmentation de l'activité de ces récepteurs par des modulateurs allostériques positifs (MAPs) était une stratégie prometteuse pour améliorer les déficits cognitifs. Dans ce travail, nous avons construit un procédé pour isoler efficacement des nanobodies ciblant les nAChRs, qui a permis d'isoler plusieurs nanobodies ciblant alpha7. L'un d'eux, nommés E3, a toutes les caractéristiques d'un MAP de type 1, produisant une potentialisation des effets de l'ACh à de concentrations dans la gamme des nanomolaires, augmentant fortement l'efficacité de l'ACh et faiblement sa puissance. Une construction bivalente où deux nanobodies sont fusionnés (E3-E3) montre une potentiation prolongée, même après un rinçage des cellules pendant une heure, indiquant une augmentation importante d'affinité. Un autre nanobodie (C4) de la librairie n'a pas d'effet sur l'activation par l'ACh, mais bloque l'effet de E3. Ces deux nanobodies sont spécifiques pour alpha? et ne reconnaissent pas l'autre nAChR majeur du cerveau, le nAChR alpha4beta2. L'ensemble des données sont prometteuses pour le développement de MAPs servant d'outils pharmacologiques avec un potentiel lointain en clinique.The α7 nicotinic acetylcholine receptors (α7 nAChR) are homomeric pentamers widely expressed in the central nervous system (CNS), especially in hippocampus and frontal cortex that are tightly connected to cognition and memory. The dysfunctions of α7 nAChRs are involved in multiple neurological and psychiatrie disorders, including addiction, pain, Parkinson's disease (PD), attention deficit hyperactivity disorder (ADHD) and Alzheimer's disease (AD). lt has been well-documented that enhancement of α7 nAChRs activity bypositive allosteric modulators CPAMs) is an attractive therapeutic strategy to ameliorate cognitive defects. In the present study, we have constructed an innovative pipeline to efficiently isolate nanobodies targeting pentameric ligand-gated ion channels(pLGICs), by which we managed to isolated α7 nAChR specifically targeted nanobodies. One of them (E3) exhibits prototypical features of type 1 PAM by showing a 5 times potentiation effect on ACh evoked current in nanomolar concentration range (n>SO), which has much more effect on potentiating ACh's efficacy to α7 nAChRs than apparent affinity. The bivalent construct (EE) based on this VHH shows long-standing potentiation affects that can retain the similar potentiation even after 1 hour of washing, demonstrating its superior affinity property against α7 nAChRs. Another VHH from the library has no modulation effect on ACh evoked current. lnstead, it could block the potentiation effect of E3 VHH by both coapplication manner or biparatopic construct (CE). Both of VHHs showed α7 nAChRs selectivity by direct staining with fluorophore-labeled VHH

MADFORWATER: WP2: Adaptation of wastewater treatment technologies for agricultural reuse: Task2.4: Industrial wastewater treatment: Treatment of different types of wastewater by means of innovative resins: Subset2

<p>This dataset contains the data underlying the following publication: Li Qimeng, Wang Cheng, Hua Ming, Shuang Chendong, Li Aimin, Gao Canzhu. (2017). High-efficient removal of phthalate esters from aqueous solution with an easily regenerative magnetic resin: Hydrolytic degradation and simultaneous adsorption. <em>Journal of Cleaner Production</em><em>. </em> <a href="https://doi.org/10.1016/j.jclepro.2017.11.121">https://doi.org/10.1016/j.jclepro.2017.11.121</a></p

MADFORWATER: WP2: Adaptation of wastewater treatment technologies for agricultural reuse: Task2.4: Industrial wastewater treatment: Treatment of different types of wastewater by means of innovative resins: Subset2

<p>This dataset contains the data underlying the following publication: Li Qimeng, Wang Cheng, Hua Ming, Shuang Chendong, Li Aimin, Gao Canzhu. (2017). High-efficient removal of phthalate esters from aqueous solution with an easily regenerative magnetic resin: Hydrolytic degradation and simultaneous adsorption. <em>Journal of Cleaner Production</em><em>. </em> <a href="https://doi.org/10.1016/j.jclepro.2017.11.121">https://doi.org/10.1016/j.jclepro.2017.11.121</a></p

MADFORWATER: WP2: Adaptation of wastewater treatment technologies for agricultural reuse: Task2.4: Industrial wastewater treatment: Treatment of different types of wastewater by means of innovative resins: Subset3

<p>This dataset contains the data underlying the following publication: Li Qimeng, Wu Ji, Hua Ming, Zhang Guang, Li Wentao, Shuang Chendong, Li Aimin. (2017). Preparation of Permanent Magnetic Resin Crosslinking by Diallyl Itaconate and Its Adsorptive and Anti-fouling Behaviors for Humic Acid Removal. <em>Scientific Report. </em> <a href="https://doi.org/10.1038/s41598-017-17360-8">https://doi.org/10.1038/s41598-017-17360-8</a></p