Absolute Activity Research Articles

Using a Network-Based Analysis Approach to Investigate the Involvement of S. aureus in the Pathogenesis of Granulomatosis with Polyangiitis.

Chronic nasal carriage of Staphylococcus aureus (SA) has been shown to be significantly higher in GPA patients when compared to healthy subjects, as well as being associated with increased endonasal activity and disease relapse. The aim of this study was to investigate SA involvement in GPA by applying a network-based analysis (NBA) approach to publicly available nasal transcriptomic data. Using these data, our NBA pipeline generated a proteinase 3 (PR3) positive ANCA associated vasculitis (AAV) disease network integrating differentially expressed genes, dysregulated transcription factors (TFs), disease-specific genes derived from GWAS studies, drug-target and protein-protein interactions. The PR3+ AAV disease network captured genes previously reported to be dysregulated in AAV associated. A subnetwork focussing on interactions between SA virulence factors and enriched biological processes revealed potential mechanisms for SA's involvement in PR3+ AAV. Immunosuppressant treatment reduced differential expression and absolute TF activities in this subnetwork for patients with inactive nasal disease but not active nasal disease symptoms at the time of sampling. The disease network generated identified the key molecular signatures and highlighted the associated biological processes in PR3+ AAV and revealed potential mechanisms for SA to affect these processes.

Monte Carlo-derived 99m Tc uptake quantification with commercial planar MBI: Absolute tumor activity.

Molecular breast imaging (MBI) of 99m Tc-sestamibi is an emerging adjunct qualitative tool in the detection and diagnosis of breast cancer. This work outlines the development and performance evaluation of a methodology to absolutely quantify tumor 99m Tc activity uptake using a commercially available dual-headed MBI system by implementing corrections for background, scatter, attenuation, and detector characteristics. A validated Monte Carlo application of a commercial MBI system was used to simulate over 7000 unique acquisitions of spherical and ellipsoidal tumors in breast tissue. Tumor absolute activity was calculated following background, scatter, and attenuation corrections of tumor region of interest counts. The methodology was first optimized using a set of high-uptake spherical tumors, and its accuracy and precision was then assessed in a set of spherical tumors with clinical uptake conditions. Finally, the performance of the activity methodology was evaluated under various bias and uncertainty conditions to better characterize the technique under expected clinical measurement conditions. In a test set of images with clinically relevant contrast and noise conditions, the mean ± standard deviation relative error in total tumor activity was 0.5% ± 6.5% (n = 2363) under ideal measurement conditions. Allowing for variability in tumor and background contours and in estimated tumor depths, the expected accuracy of the methodology in clinical practice was 0.5% ± 11.1% (n = 2363), with minimal loss of accuracy for ellipsoidal tumors. Planar MBI photopeak images acquired with standard-of-care protocols can be used to accurately quantify absolute tumor 99m Tc activity with an accuracy and precision of 0.5% ± 11.1%. The reported precision was based on a comprehensive evaluation of random errors and systematic biases.

Персонализированная дозиметрия внутреннего облучения опухолевых образований и органов риска пациентов: разработка и реализация методического базиса для дозиметрического обеспечения клинических исследований терапевтических радиофармпрепаратов

The cluster of calculational and instrumental methods for estimation of personalized internal radiation doses to foci and organs at risk among patients undergoing to therapy by radiopharmaceuticals has been developed. The developed set of methods was used for dosimetrical support of clinical trials of therapeutic radiopharmaceuticals: a) Lu-177-DOTA-PSMA (or "Lutaprost") targeted for radioligand therapy of metastatic castrate-resistant prostate cancer; b) Re-188 albumin microspheres 5-10 μm (or "Artroren") targeted for radiosynovectomy in the local treatment of chronic inflammatory diseases of the joints and c) 188Re albumin microspheres 20-40 μm (or "Gepatoren") targeted for intra-arterial radionuclide embolization in the treatment of inoperable liver cancer. The results of estimations absolute activities of radiopharmaceuticals and their dynamics during SPECT/CT scanning of radiopharmaceuticals in the body of patients were verified by measurements using physical phantoms of humans with different body weights and various standard activities of radionuclides distributed inside the phantoms. The developed cluster of programs (for calculating the absorbed fraction of energy in biostructures), relevant databases and instrumental methods were used as the basis for estimations personalized internal radiation doses in foci and organs at risk among patients included in clinical trials of the studied radiopharmaceuticals. Individual internal radiation doses in foci among 39 patients, included in the first phase of clinical trials of the three studied radiopharmaceuticals, were estimated. The analysis of the distribution of estimated doses shows that absorbed doses in foci are very differing not only in different patients, but also in different foci in the same patient. Irradiation doses in foci increase with an increasing in the administered activities of radiopharmaceuticals and, depending on the volume of foci, are within the following ranges: 1) in a case of “Lutaprost” – from 1.4 to 32 Gy (planned administered activity – 5 GBq), from 5.1 to 59 Gy (planned activity – 7.5 GBq), from 13 to 94 Gy (planned activity – 10 GBq); 2) in a case of "Arthroren" – from 17.5 to 74 Gy (planned administered activities – from 0.37 to 0.925 GBq); 3) in a case of “Gepatoren” – from 10.7 to 43 Gy (planned administered activities – from 1 to 3 GBq). Individual absorbed doses in organs at risk were estimated as well. Dose values in organs at risk also vary greatly between different patients and between different critical organs. These doses ranged from 0.01 to 7.4 Gy (39 patients), which is many times less than “commonly applied dose constraints” in radiotherapy.

Investigation of (_^111)Cd(y,y^')(_^111m)Cd Average Cross Section

A method for determining the photo excitation reaction cross section of at gamma energy is investigated. A HPCe detector is used to measure the absolute activity induced, producing a practical value for calculating the average cross section. Which is found to be (0.6683) ub matching the expected theoretical value.
 This work may be considered of the pioneer measurements of such reaction cross – section.
 Key words: Activity induced,Cross section, Gamma energy, H P Ge detector

Continuous process technology for bottom-up synthesis of soluble cello-oligosaccharides by immobilized cells co-expressing three saccharide phosphorylases

BackgroundContinuous processing with enzyme reuse is a well-known engineering strategy to enhance the efficiency of biocatalytic transformations for chemical synthesis. In one-pot multistep reactions, continuous processing offers the additional benefit of ensuring constant product quality via control of the product composition. Bottom-up production of cello-oligosaccharides (COS) involves multistep iterative β-1,4-glycosylation of glucose from sucrose catalyzed by sucrose phosphorylase from Bifidobacterium adeloscentis (BaScP), cellobiose phosphorylase from Cellulomonas uda (CuCbP) and cellodextrin phosphorylase from Clostridium cellulosi (CcCdP). Degree of polymerization (DP) control in the COS product is essential for soluble production and is implemented through balance of the oligosaccharide priming and elongation rates. A whole-cell E. coli catalyst co-expressing the phosphorylases in high yield and in the desired activity ratio, with CdP as the rate-limiting enzyme, was reported previously.ResultsFreeze-thaw permeabilized E. coli cells were immobilized in polyacrylamide (PAM) at 37–111 mg dry cells/g material. PAM particles (0.25–2.00 mm size) were characterized for COS production (~ 70 g/L) in mixed vessel with catalyst recycle and packed-bed reactor set-ups. The catalyst exhibited a dry mass-based overall activity (270 U/g; 37 mg cells/g material) lowered by ~ 40% compared to the corresponding free cells due to individual enzyme activity loss, CbP in particular, caused by the immobilization. Temperature studies revealed an operational optimum at 30 °C for stable continuous reaction (~ 1 month) in the packed bed (volume: 40 mL; height: 7.5 cm). The optimum reflects the limits of PAM catalyst structural and biological stability in combination with the requirement to control COS product solubility in order to prevent clogging of the packed bed. Using an axial flow rate of 0.75 cm− 1, the COS were produced at ~ 5.7 g/day and ≥ 95% substrate conversion (sucrose 300 mM). The product stream showed a stable composition of individual oligosaccharides up to cellohexaose, with cellobiose (48 mol%) and cellotriose (31 mol%) as the major components.ConclusionsContinuous process technology for bottom-up biocatalytic production of soluble COS is demonstrated based on PAM immobilized E. coli cells that co-express BaScP, CuCbP and CcCdP in suitable absolute and relative activities.

Roller Speed Skating Kinematics and Electromyographic Analysis: A Methodological Approach

Roller speed skating is a discipline similar to hockey and ice skating from a biomechanical point of view, but there are no specific functional protocols for rehabilitation and performance improvement for these athletes. The aim of the study is to create a dedicated functional, kinematic and electromyographic protocol to be used as a tool for future studies on the subject. The protocol was created, starting from a correct and repeatable movement as a case study, on a world speed skating champion, using an inertial sensor positioned at the level of the first sacral vertebra, eight electromyographic probes positioned on one or the other lower limb, and a high-definition camera at 50 Hz. The results show the electromyographic activity of the muscles investigated, the degree of absolute muscle activation and compared to their maximum voluntary isometric contraction (MVIC), the level of co-activation of the agonist/antagonist muscles, and the accelerations of the body on the three axes of space. The results will represent the basis for physiotherapy and specific training use. Future developments will include the analysis of a sample of elite athletes to be able to build a normal range on the parameters investigated, and the possibility of treating in the most appropriate way possible muscle injuries (which mostly occur in the groin in such athletes) once they have occurred, even with oriented MVIC or co-activation oriented exercises.

Less daytime sleepiness and slow wave activity during sleep predict better physical readiness in military personnel

BackgroundMilitary personnel must maintain physical performance despite exposure to operational stressors such as sleep loss, caloric restriction and high cognitive load. Habitual sleep and specific sleep features are positively associated with fitness and may contribute to physical performance in operational settings. Further, by affecting muscle recovery, sleep may contribute to the ability to maintain performance across multiple days of exposure to operational stressors. ObjectivesWe examined the role of individual differences in baseline sleep on baseline physical performance and on change in physical performance throughout exposure to simulated military operational stress (SMOS). MethodsMilitary personnel (36 male, 9 female, 26.3 ± 5.3 years) completed a 5-day SMOS protocol during which they completed a tactical mobility test daily. Sleep questionnaires were administered at intake and sleep was monitored each night with polysomnography. Lasso regressions were used to identify meaningful predictors of physical performance at baseline and of change in physical performance across SMOS. ResultsBetter aerobic fitness, lower daytime sleepiness (Epworth Sleepiness Scale), and lower absolute slow wave activity (0.5-4 Hz) predicted better physical performance at baseline (66.1% of variance explained), but did not relate to changes in performance. ConclusionsCollectively, higher daytime sleepiness and slow wave activity may reflect more chronic exposure to insufficient sleep and higher baseline sleep drive, which in turn led to compromised physical performance. The findings suggest that low self-report sleepiness and low objective slow wave activity may reflect two quantifiable markers of healthy sleep behaviors that have implications for operational performance.

Artificial macropores and water management effects on reduction of greenhouse gas emissions from rice paddy fields

Rice production is an important sector of global agriculture, sustaining more than half of the world's population. However, rice production contributes significantly to global warming through increased emission of greenhouse gasses (GHGs), primarily CH4, into the atmosphere. Therefore, this study examined countermeasures to reduce GHG emissions from paddy fields without affecting rice production. A column experiment was conducted to investigate the effects of soil macroporous structure and water management on GHG emissions from flooded alluvial clay soil (paddy soil). The soils were subjected to different management regimes: with and without artificial macropores, compost, and drainage treatment. Drainage was maintained at 6.5 mm d − 1 to ensure infiltration yet prevent excessive leakage from the paddy field. The measured parameters included GHG emissions, soil water content, redox potential, soil temperature, soil swelling, total carbon, total nitrogen, iron, and manganese. The results showed that the soil column with macropores and drainage had significantly lower CO2 and CH4 emissions than that without macropores and drainage. In addition, the soil level increment, and thus, the amount of gas (CH4) produced in the soil column with drainage were lower than that without drainage. The combination of drainage treatment and macropores might have effectively acted as a hydrodynamic gradient and a structure that promotes freshwater intrusion into deeper soil profiles, inhibiting absolute anaerobic methanogenic activity. The redox potential of the column with drainage and macropores was the highest. Moreover, CO2 and CH4 emissions were reduced at a relatively small drainage rate of 6.5 mm d − 1 by adding macropores to the soil. The findings confirmed that GHG emissions were effectively reduced by a porous soil structure at a low drainage rate. Macropore application also exhibited effectiveness at mitigating nutrient loss (TOC and TN) through the drainage. Therefore, low tillage before flooding would be preferable to conserve the macroporous structure. However, the results also highlight an adverse effect on mineral leaching (particularly Mn) through the column with macropores.

Genomic Pathways Differentiating IgM-MGUS from Waldenstrom Macroglobulinemia: The Integrated microRNA and Gene Expression Landscape

Introduction Waldenstrom Macroglobulinemia (WM) is a rare non-Hodgkin lymphoma that is preceded by an IgM monoclonal gammopathy of undetermined significance (IgM-MGUS), a premalignant, clinically asymptomatic disorder. The factors underlying this malignant transformation remain poorly understood, but the stepwise accumulation of genomic abnormalities has been identified as a potential mechanism. Non-coding aspects of the genome are increasingly recognized as drivers of disease pathogenesis but remain under-explored in this disease spectrum. Previously, we have shown that several oncogenes are in close genomic proximity to overexpressed long non-coding RNAs in WM compared to IgM-MGUS (Paludo et al. 2019). In this study, we aimed to identify the microRNAs (miR) and genomic pathways which may facilitate the IgM-MGUS to WM malignant progression. Methodology Sorted CD19+ and CD138+ B cells from prospectively collected bone marrow samples of patients with IgM-MGUS (n=7) and WM (n=25) underwent total RNA extraction and sequencing. Profiling of miRNAs was conducted, and selection of targets of interest was performed through identifying differentially expressed miRNA between IgM-MGUS and WM with a log2 fold change (FC)>0.5 or <-0.5 and false discovery rate (FDR) <0.05. Next, mRNA sequencing was conducted on the same patient samples, and differential expression was performed the same way as the miRNA data to identify mRNA candidates. Differentially expressed miRNA/mRNA pairs between WM and IgM-MGUS with correlated biological expression, i.e. either upregulated (up) miRNA experimentally predicted to regulate downregulated (down) mRNA or vice versa, were selected. The miRNA/mRNA pairs identified here were evaluated using Ingenuity Pathway Analysis (IPA) to discover dysregulated genomic pathways between IgM-MGUS and WM. Only pathways with an absolute activation Z-score of ≥2 were selected, and dysregulated miRNA and associated genes involved in altered pathways were identified. Results There were 34 miRNAs (16 up/18 down) found to be significantly differentially expressed between IgM-MGUS and WM (Figure). Among these, miR-4532, miR-192, miR-3195, miR-6761, miR-1295, and miR-3934 were found to have the highest FC between these two conditions. After correlation of miRNA/mRNA pairs, the most differentially regulated pathways with recognized oncological relations were identified, among which, the ID-1, IL-8 and STAT3 pathways were found to be downregulated in WM compared to IgM-MGUS, while the PTEN pathway was found to be upregulated. More broadly, the G protein-coupled receptor (GPCR), and the tumor microenvironment (TM) pathways were both found to be downregulated in WM compared to IgM-MGUS. Some of the main miRNAs driving multiple pathways with key associated genes included: miR-20 (GPCR, TM, IL8, ID1) through regulation of cyclin D1 (CCND1), matrix metalloproteinase-2 (MMP2), and leukemia inhibitory factor (LIF), miR-1260 (ID1, GPCR, STAT3, TM) through regulation of B-cell lymphoma 2 (BCL-2), chemokine receptor 6 (CCR6), and ETS proto-oncogene 1 (ETS1), and miR-1295 (IL8, TM, GPCR) through regulation of vascular cell adhesion molecule 1 (VCAM1), matrix metallopeptidase 19 (MMP19), and hydroxycarboxylic acid receptor 2 (HCAR2). Conclusion Our study is one of the first to identify the altered non-coded transcriptomics in WM and MGUS. We found several differentially expressed miRNAs with a known oncological role, such as miR-4532, miR-20 and miR-1260, highlighting the role of miRNAs as potentially important epigenetic regulators in these two diseases. The genomic pathways found to be potentially regulated by miRNA may underlie the transition between the premalignant to malignant disease of IgM-MGUS to WM. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

A study of the non-uniformity of the PMT photocathode response and its influence on the results obtained in different scintillation counting experiments

This work presents an investigation on the non-uniformity of the response of the photocathode of two photomultiplier tubes (PMTs) and its potential influence on the results of scintillation measurements. An experimental system was developed which allows studies of the non-uniformity of the photocathode response and its influence on the shape of alpha spectra obtained after pulse-shape discrimination. The system is presented together with tests of Hamamatsu R7600U-200 and H11934-203 PMTs. A degradation of the counting efficiency and a shift of the peak position towards smaller values were identified in the measurements near the edges of the photocathode where the energy resolution is significantly worse compared to the central region of the PMT. Such non-uniformity also affects absolute activity measurements based on the free parameter model, i.e., the Triple to Double Coincidence Ratio and the CIEMAT/NIST efficiency tracing methods. A significant non-uniformity of the response of a PMT would interfere with the assumption of the traditional free parameter model of a Poisson distribution of the number of emitted photons. Experimental results are presented in the paper, together with a discussion of their practical influence on scintillation and absolute activity measurements.

Control of parallelized bioreactors II: probabilistic quantification of carboxylic acid reductase activity for bioprocess optimization

Autonomously operated parallelized mL-scale bioreactors are considered the key to reduce bioprocess development cost and time. However, their application is often limited to products with very simple analytics. In this study, we investigated enhanced protein expression conditions of a carboxyl reductase from Nocardia otitidiscaviarum in E. coli. Cells were produced with exponential feeding in a L-scale bioreactor. After the desired cell density for protein expression was reached, the cells were automatically transferred to 48 mL-scale bioreactors operated by a liquid handling station where protein expression studies were conducted. During protein expression, the feed rate and the inducer concentration was varied. At the end of the protein expression phase, the enzymatic activity was estimated by performing automated whole-cell biotransformations in a deep-well-plate. The results were analyzed with hierarchical Bayesian modelling methods to account for the biomass growth during the biotransformation, biomass interference on the subsequent product assay, and to predict absolute and specific enzyme activities at optimal expression conditions. Lower feed rates seemed to be beneficial for high specific and absolute activities. At the optimal investigated expression conditions an activity of 1153 U mL^{-1} was estimated with a 90% credible interval of [992, 1321] U mL^{-1}. This is about 40-fold higher than the highest published data for the enzyme under investigation. With the proposed setup, 192 protein expression conditions were studied during four experimental runs with minimal manual workload, showing the reliability and potential of automated and digitalized bioreactor systems.

Evaluation of activity kinetics in breast milk and calculation of the resulting effective radiation dose after 99mTc-MIBI scintigraphy of a breastfeeding women.

In breastfeeding women, the indication for scintigraphic imaging is strongly restricted due to potential transition of the radiopharmaceutical to the child via breast milk. The potential activity uptake of the breastfed child depends on the chemical compound of the radio pharmaceutical as well as biokinetics and metabolism in the maternal body. In the presented case 99mTc-MIBI scintigraphy was performed in a breastfeeding woman with sonographically suspicious thyroid nodules. Breastfeeding was interrupted for 30 hours and the breast milk during this period was collected and analysed to determine the excreted activity and the potentially resulting dose to the breastfed child. Activity concentration in the first breast milk sample (1.83 hours after administration of 500 MBq 99mTc-MIBI) was 380 Bq/mL, resulting in an absolute activity of 50 kBq for a sample size of 132 mL. Subsequently activity concentration decreased to 6 Bq/mL (29.8 hours p.i.). The calculated effective half-life of the secretion of 99mTc-MIBI via breast milk was 4.7 hours. The potentially resulting effective dose for the breastfed child was 13.4 µSv (ICRP80: dose coefficient: 0.13 mSv/MBq for 99mTc). Time activity curve showed a rapid decrease of the 99mTc-MIBI activity secreted to the breast milk. More than 90 % of the total secreted activity is attributable to the first 12 hours after administration. Therefore, an interruption of breastfeeding of 24 hours seems to be adequate.

Lack of evidence for ribosomal frameshifting in ATP7B mRNA decoding

SummaryThe research article describing the discovery of ribosomal frameshifting in the bacterial CopA gene also reported the occurrence of frameshifting in the expression of the human ortholog ATP7B based on assays using dual luciferase reporters. An examination of the publicly available ribosome profiling data and the phylogenetic analysis of the proposed frameshifting site cast doubt on the validity of this claim and prompted us to reexamine the evidence. We observed similar apparent frameshifting efficiencies as the original authors using the same type of vector that synthesizes both luciferases as a single polyprotein. However, we noticed anomalously low absolute luciferase activities from the N-terminal reporter that suggests interference of reporter activity or levels by the ATP7B test cassette. When we tested the same proposed ATP7B frameshifting cassette in a more recently developed reporter system in which the reporters are released without being included in a polyprotein, no frameshifting was detected above background levels.

Criterion validity of the Saltin-Grimby Physical Activity Level Scale in adolescents. The Fit Futures Study.

The Saltin-Grimby Physical Activity Level Scale (SGPALS) is commonly used to measure physical activity (PA) in population studies, but its validity in adolescents is unknown. This study aimed to assess the criterion validity of the SGPALS against accelerometry in a large sample of adolescents. A secondary aim was to examine the validity across strata of sex, body mass index (BMI), parental educational level, study program and self-reported health. The study is based on data from 572 adolescents aged 15-17 years who participated in the Fit Futures Study 2010-11 in Northern Norway. The participants were invited to wear an accelerometer (GT3X) attached to their hip for seven consecutive days. We used Spearman's rho and linear regression models to assess the validity of the SGPALS against the following accelerometry estimates of PA; mean counts/minute (CPM), steps/day, and minutes/day of moderate-to-vigorous physical activity (MVPA). The SGPALS correlated with mean CPM (ρ = 0.40, p<0.01), steps/day (ρ = 0.35, p<0.01) and MVPA min/day (ρ = 0.35, p<0.01). We observed no differences between correlations within demographic strata (all p>0.001). Higher scores on SGPALS were associated with a higher CPM, higher number of steps per day and more minutes of MVPA per day, with the following mean differences in PA measurements between the SGPALS ranks: CPM increased by 53 counts (95% CI: 44 to 62), steps/day increased by 925 steps (95% CI: 731 to 1118), and MVPA by 8.4 min/day (95% CI: 6.7 to 10.0). Mean difference between the highest and lowest SGPALS category was 2947 steps/day (6509 vs. 9456 steps/day) and 26.4 min/day MVPA (35.2 minutes vs 61.6 minutes). We found satisfactory ranking validity of SGPALS measured against accelerometry in adolescents, which was fairly stable across strata of sex, BMI, and education. However, the validity of SGPALS in providing information on absolute physical activity levels seem limited.

Training and match demands differ between the regular season and finals in semi-professional basketball.

Basketball competitions often include a scheduled regular season followed by knock-out finals. Understanding training and match demands through the season can help optimize performance and reduce injury risk. This study investigated whether training and/or match demands differed between the regular season and finals, and whether these differences were dependent on player role. Average session intensity and volume and durations of relative exercise intensities (inactive, light, moderate-vigorous, maximal, supramaximal) were quantified during training sessions and matches using accelerometry in two semi-professional basketball teams (n = 23; 10 women, 13 men). Training and match demands were compared between the regular season (training: 445 observations; matches: 387 observations) and finals (training: 113 observations, matches: 75 observations) with consideration of player role (starters, in-rotation bench, out-rotation bench). During finals matches, starters received 4.4 min more playing time (p = 0.03), performed 14% more absolute maximal activity (p < 0.01) and had 8% less relative inactive time (p = 0.02) when compared to the regular season. Out-rotation bench players received 2.1 min less playing time (p < 0.01), performed 33% less absolute maximal activity (p = 0.01) and 57% less absolute supramaximal activity (p < 0.01) in finals when compared to the regular season. During finals training sessions, average training intensity was 5% higher (p = 0.02), absolute moderate-vigorous activity was 3% higher (p = 0.04), relative maximal activity was 12% higher (p < 0.01), and relative inactive time was 5% lower (p = 0.03) when compared to the regular season. These findings suggest starters need to be physically prepared for greater match demands during finals, while out-rotation bench players should supplement their training during finals with extra supramaximal activity to maintain their conditioning levels for matches.

Analytic Function Approximation by Path-Norm-Regularized Deep Neural Networks.

We show that neural networks with an absolute value activation function and with network path norm, network sizes and network weights having logarithmic dependence on can -approximate functions that are analytic on certain regions of .

Layer‐wise contribution‐filtered propagation for deep learning‐based fault isolation

AbstractDeep learning is gradually mainstreaming into data‐driven methods, relying on the advantages of extracting complicated nonlinear features. However, the black‐box property makes its decision rules non‐transparent, resulting in difficulty in attribution tasks, which aim to backtrack the contribution of network inputs to the outputs. Fault isolation and localization are techniques for diagnosing the root cause of system failures, which have a consistent objective with attribution for a deep learning‐based fault observer or classifier. Unfortunately, most fault isolation methods are based on shallow learning methods. Also, many attribution algorithms are linear without considering the influence of nonlinear activation functions. The related concerns motivate us to propose a new approach, namely layer‐wise contribution‐filtered propagation (LCP), for deep learning‐based fault isolation. In LCP, reasonable contributions are defined based on the influence of each layer input on maximizing the absolute output activation. A symbolic function is designed to identify neurons with negative contributions, which are then filtered and forbidden to backpropagate to the previous layer. By guiding correct attribution, LCP is available for any nonlinear activation functions and their combinations. It also provides a solution for fault isolation with stacked sample inputs, in which one single variable has several attributions associated with different times. Finally, two chemical simulations verify the effectiveness of the proposed method.

Abs-CAM: a gradient optimization interpretable approach for explanation of convolutional neural networks

The black-box nature of deep neural networks severely hinders its performance improvement and application in specific scenes. In recent years, class activation mapping-based method has been widely used to interpret the internal decisions of models in computer vision tasks. However, when this method uses backpropagation to obtain gradients, it will cause noise in the saliency map and even locate features that are irrelevant to decisions. In this paper, we propose an absolute value class activation mapping-based (Abs-CAM) method, which optimizes the gradients derived from the backpropagation and turns all of them into positive gradients to enhance the visual features of output neurons’ activation and improve the localization ability of the saliency map. The framework of Abs-CAM is divided into two phases: generating initial saliency map and generating final saliency map. The first phase improves the localization ability of the saliency map by optimizing the gradient, and the second phase linearly combines the initial saliency map with the original image to enhance the semantic information of the saliency map. We conduct qualitative and quantitative evaluation of the proposed method, including Deletion, Insertion, and Pointing Game. The experimental results show that the Abs-CAM can obviously eliminate the noise in the saliency map, and can better locate the features related to decisions, and is superior to the previous methods in recognition and localization tasks.

Cytotoxic CD4+ T cells driven by T-cell intrinsic IL-18R/MyD88 signaling predominantly infiltrate Trypanosoma cruzi-infected hearts

Increasing attention has been directed to cytotoxic CD4+ T cells (CD4CTLs) in different pathologies, both in humans and mice. The impact of CD4CTLs in immunity and the mechanisms controlling their generation, however, remain poorly understood. Here, we show that CD4CTLs abundantly differentiate during mouse infection with the intracellular parasite Trypanosoma cruzi. CD4CTLs display parallel kinetics to Th1 cells in the spleen, mediate specific cytotoxicity against cells presenting pathogen-derived antigens and express immunoregulatory and/or exhaustion markers. We demonstrate that CD4CTL absolute numbers and activity are severely reduced in both Myd88-/- and Il18ra-/- mice. Of note, the infection of mixed-bone marrow chimeras revealed that wild-type (WT) but not Myd88-/- cells transcribe the CD4CTL gene signature and that Il18ra-/- and Myd88-/- CD4+ T cells phenocopy each other. Moreover, adoptive transfer of WT CD4+GzB+ T cells to infected Il18ra-/- mice extended their survival. Importantly, cells expressing the CD4CTL phenotype predominate among CD4+ T cells infiltrating the infected mouse cardiac tissue and are increased in the blood of Chagas patients, in which the frequency of CD4CTLs correlates with the severity of cardiomyopathy. Our findings describe CD4CTLs as a major player in immunity to a relevant human pathogen and disclose T-cell intrinsic IL-18R/MyD88 signaling as a key pathway controlling the magnitude of the CD4CTL response.

Bactericidal effect of laser synthesized silver nanoparticle-impregnated cellulose paper against E. Coli

The search for affordable, safe, and effective water disinfection method is being pursued for several decades. In this study, we evaluated the efficacy of silver nanoparticles embedded filter paper for the removal of antibiotic-resistant bacteria from water. Pulsed laser ablation of a pure silver target in distilled liquid is used to synthesize bare AgNPs with a mean diameter of 25 nm. The concentration of 20 µg/ml of AgNPs gave a decent 18 mm zone of inhibition against ampicillin-resistant E. coli on Lysogeny Broth (LB) agar plates. When embedded onto filter paper, 26 µg of Ag NPs demonstrated an absolute bactericidal activity within 15 min of incubation with antibiotic-resistant E. coli containing water. Furthermore, the absence of bacteria from the filtrate suggests the removal of bacteria from the water. Reusing AgNP-embedded filter paper at least three times showed no substantial decline in its bactericidal activity and exhibited almost 100% reduction in bacterial growth.