A document by Jhonatan Andres A. Manco. Click on the document to view its contents.

Genotoxicity assessment is a critical component in the development and evaluation of chemicals. Traditional genotoxicity assays (i.e., mutagenicity, clastogenicity, aneugenicity) have been limited to dichotomous hazard classification, while other toxicity endpoints are assessed through quantitative determination of points-of-departure (PODs) for setting exposure limits. The more recent higher-throughput in vitro genotoxicity assays, many of which also provide mechanistic information, offer a powerful approach for determining high-precision PODs for potency ranking and risk assessment. In order to obtain relevant human dose context from the in vitro assays, in vitro to in vivo extrapolation (IVIVE) models are required to determine what dose would elicit a concentration in the body demonstrated to be genotoxic using in vitro assays. Previous work has demonstrated that application of IVIVE models to in vitro bioactivity data can provide PODs that are protective of human health, but there has been no evaluation of how these models perform with in vitro genotoxicity data. Thus, the Genetic Toxicology Technical Committee, under the Health and Environmental Sciences Institute, conducted a case study on 31 reference chemicals to evaluate the performance of IVIVE application to genotoxicity data. The results demonstrate that for most chemicals (20/31), the PODs derived from in vitro data and IVIVE are highly health protective relative to in vivo PODs from animal studies. PODs were also protective by individual assay type: mutations (8/13 chemicals), micronuclei (9/12) and aneugenicity markers (4/4). It is envisioned that this novel testing strategy could enhance prioritization, rapid screening, and risk assessment of genotoxic chemicals.

The enzyme β-mannanase is widely used in industrial applications. In this study, we heterologously expressed a mannanase (Anman) strain from Aspergillus niger CBS513.88 in Pichia pastoris and found that it had the highest activity at pH 3.0 and 72.5°C with a molecular weight of approximately 47 kDa. The wild-type mannanase Anman remains stable below 65°C but inactivates rapidly at 70°C. To further improve the thermostability of Anman, we screened multiple mutation sites using B-factor and Gibbs unfolding free energy change, and then combined with multiple sequence alignment and consensus mutation to generate five excellent single-point mutants, the thermostability of combined mutant mut5 (E15C/S65P/A84P/A195P/T298P) was 70% increased than wild type Amman at 70℃, and the melting temperature ( T m) and half-life ( t 1/2) values were increased by 2°C and 7.8 folds, respectively. Molecular dynamics simulation showed reduced flexibility and additional chemical bonds in the region near the mutation site. These results indicate that we obtained a mannanase mutant that is more suitable for industrial application, and also confirm that a combination of rational and semi-rational techniques is helpful for screening mutant sites.

The integration of a transgene expression construct into the host genome is the initial step for the generation of recombinant cell lines used for biopharmaceutical production. The stability and level of recombinant gene expression in Chinese hamster ovary (CHO) can be correlated to the copy number, its integration site as well as the epigenetic context of the transgene vector. Also, undesired integration events, such as concatemers, truncated and inverted vector repeats, are impacting the stability of recombinant cell lines. Thus, to characterize cell clones and to isolate the most promising candidates it is crucial to obtain information on the site of integration, the structure of integrated sequence and the epigenetic status. Current sequencing techniques allow to gather this information separately but do not offer a comprehensive and simultaneous resolution. In this study, we present a fast and robust nanopore Cas9-targeted sequencing (nCats) pipeline to identify integration sites, the composition of the integrated sequence as well as its DNA methylation status in CHO cells that can be obtained simultaneously from the same sequencing run. A Cas9-enrichment step during library preparation enables targeted and directional nanopore sequencing with up to 724x median on-target coverage and up to 153 Kb long reads. The data generated by nCats provides sensitive, detailed and correct information on the transgene integration sites and the expression vector structure, which could only be partly produced by traditional Targeted Locus Amplification-Seq data. Moreover, with nCats the DNA methylation status can be analyzed from the same raw data without prior DNA amplification.

Energy usage is exactly proportional to population growth in the current environment. As a result, demand for power rises in tandem with population growth. However, daily and seasonal variations in electricity demand exist. So, we’ll talk about energy storage systems for balancing generation and demand in this article. Because of growing concerns about rising energy prices, most renewable energy sources are being combined into the power grid as distributed energy resources (DER). This increase in DER penetration raises concerns about load stability and matching and reliability and power quality. The electric grid must be able to encounter customer demand. The energy storage system (ESS) can boost efficiency and reliability while also giving the PV system more power control options.

When tracking a single maneuvering target in clutter environment, when the number of effective measurements within the detection threshold is small, it usually has a greater and more obvious impact on target tracking results. If the observation data error is large at this time, the tracking position and speed error will be larger. To solve this problem, a target tracking algorithm based on improved probabilistic data association is proposed in this paper. By dynamically adjusting the detection threshold, the effective quantity within the detection threshold of each frame is basically stable. Simulation results show that the improved algorithm is more accurate in location and speed than the traditional probabilistic data association method, and the availability and effectiveness of the algorithm are verified.

Children’s programming is widely aroused people’s concern, is a hotspot of research on education, the children’s programming attention to promoting the development of children’s programming education has important significance. Using Baidu index, elastic coefficient, Gini index and geographic concentration coefficient, this paper analyzes the evolution of spatial and temporal distribution and influencing factors of children’s programming attention in China, and establishes the model through panel data model and carries out empirical analysis. The results show that: the public’s attention to children’s programming continues to rise, and is in a gentle stage of development at the present stage. Spatial difference of children’s programming attention is opposite bigger, the eastern region is the most popular children’s programming in the three regions, followed by the, the western region, the internal unbalance in east and west region, the central region in balance, and the central region difference is small, to strengthen the development of the western region to close the gap and balanced development. Regional economic development level and education level have a significant impact on children’s programming attention on the Internet, while educational funds and education level have a significant impact on children’s programming attention in eastern and central China. To improve the development space of children’s programming, we can start from two aspects: strengthening the creation of characteristic learning fields for primary school children’s programming, and improving the wide application of online learning.

Waiting times can be a huge concern for companies, as long waiting times can result in lost sales, unsatisfied customers, and a bad reputation for organizations. Staff requirement planning can help reduce the average time in queue. We propose a capacity planning model that considers the dollar value of customers’ waiting time to determine the optimal production (service) rate that maximizes the total profit of organizations. The model balances the trade-off between customers’ waiting costs and staff’s idle time costs. This model introduces a delay discount factor that quantifies customers’ time in dollar value. We used two “inferred” models from healthcare and compared the current settings with the optimal ones resulting from the proposed model. The optimal setting significantly reduced waiting times and increased profits. The proposed model can be extremely helpful in adequate staff planning for service organizations.

We report a case of leprosy presented with a nasal tip necrosis in a female in her 50s with no, apparently, risk factors of leprosy. We highlight the importance of taking a thorough clinical history and widen the differential diagnosis to avoid misdiagnosis and delay of treatment.

Aim: To assess the effect of commonly used drugs in the treatment of hospitalized COVID-19 patients on the development of post-COVID-19 syndrome. Methods: Data from patients hospitalized in Medisch Spectrum Twente with an COVID-19 infection was collected from two separate databases, the MST clinical database containing the in-hospital electronic health records of COVID-19 patients and the Post-COVID cohort database containing patient follow-up data of the same patients. The aforementioned databases were then merged to determine the association between patient treatment with corticosteroids, antibiotics or anticoagulants during the hospital stay and the development of post-COVID-19 syndrome 6 months after hospital discharge. Results: A total of 123 patients had clinical data and 6 months follow-up data available. Out of these patients, 33 patients (26.8%) had developed and were still affected by post-COVID-19 syndrome 6 months after hospital discharge. Multivariate analysis showed that patients treated with corticosteroids were associated with a significantly lower chance (OR 0.32, 95% CI 0.11 to 0.90) of developing post-COVID-19 syndrome while antibiotics (OR 1.26, 95% CI 0.47 to 3.39) and anticoagulants (OR 0.55, 95% CI 0.18 to 1.71) were not significantly associated. Conclusion: This study showed that corticosteroids have a significant protective effect on the development of post-COVID-19 syndrome in hospitalized patients. While anticoagulants also indicate a protective trend, this effect was not statistically significant. On the contrary, patients treated with antibiotics were shown to have increased chances of developing post-COVID-19 syndrome, although this effect was also not statistically significant

The COVID-19 pandemic has pushed health policy frontstage and exposed the stark differences in government capacities to respond to the crisis. This has created new demands for comparative heath policy to support knowledge creation on a large scale. However, comparative health policy has been ill prepared; studies have focused on health systems and used typologies together with descriptive, quantitative methods. This clouds the view for the multi-level nature of health policy, the diverse actors involved and the many societal facets of governance performance. We argue for health policy as a bottom-up process with diverse interests and suggest researching these processes comparatively to support policy learning. This calls for expanding the methodology of comparative health policy to include approaches that make greater use of explorative, qualitative research. We introduce possible developmental pathways to illustrate what this may look like. Firstly, the Pan-European Commission points to novel transnational and cross-sectoral collaborations, and a coordinated policy response to global challenges like the pandemic. Secondly, feminist networks show how to shift the focus towards social inequalities and the health needs of women and vulnerable populations. Thirdly, researchers demonstrate the value of new knowledge emerging from small-scale bottom-up comparisons based on structured assessment frameworks. Together, these developmental pathways demonstrate the potential to refocus comparative health policy towards greater responsiveness to the societal performance of governments, such as social inequalities created by the COVID-19 pandemic. This also opens opportunities for strengthening the global outlook of comparative health policy.

Unperceived lithium battery ingestion in infants might be associated with significant morbidity, especially when medical assistance is restricted.

This work is concerned with the global existence of large solutions to the three-dimensional dissipative fluid-dynamical model, which is a strongly coupled nonlinear nonlocal system characterized by the incompressible Navier–Stokes–Poisson–Nernst–Planck equations. Making full use of the algebraic structure of the system, we obtain the global existence of solutions without smallness assumptions imposed on the third component of the initial velocity field and the summation of initial densities of charged species. More precisely, we prove that there exist two positive constants c 0 , C 0 such that if the initial data satisfies ( ∥ u 0 h ∥ B _ p , 1 − 1 + 3 p + ∥ N 0 − P 0 ∥ B _ q , 1 − 2 + 3 q ) exp { C 0 ( ∥ u 0 3 ∥ B _ p , 1 − 1 + 3 p 2 + ( ∥ N 0 + P 0 ∥ B _ r , 1 − 2 + 3 r + 1 ) exp { C 0 ∥ u 0 3 ∥ B _ p , 1 − 1 + 3 p } + 1 ) } ≤ c 0 , then the incompressible Navier–Stokes–Poisson–Nernst–Planck equations admits a unique global solution.

By evaluating genetic variation across the entire genome, one can address existing questions in a novel way while new can be asked. Such questions include how different local environments influence both adaptive and neutral genomic variation within and among populations, providing insights not only into local adaptation of natural populations, but also into their responses to global change and the exploitation-induced evolution. Here, under a seascape genomic approach, ddRAD genomic data were used along with environmental information to uncover the underlying processes (migration, selection) shaping European sardines (Sardina pilchardus) of the Western Mediterranean and adjacent Atlantic waters. This information can be relevant to the (re)definition of fishery stocks, and their short-term adaptive potential. We found that studied sardine samples form two clusters, detected using both neutral and adaptive (outlier) loci suggesting that natural selection and local adaptation play a key role in driving genetic change among the Atlantic and the Mediterranean sardines. Temperature and especially the trend in the number of days with sea surface temperature (SST) above 19oC was crucial at all levels of population structuring with implications on species’ key biological processes, especially reproduction. Our findings provide evidence for a dynamic equilibrium where population structure is maintained by physical and biological factors under the opposing influences of migration and selection. Given its dynamic nature, such a system postulates a continuous monitoring under a seascape genomic approach that can benefit by incorporating a temporal as well as a more detailed spatial dimension.

A middle-aged female veteran artistic gymnast sustained an avulsion-injury of the latissimus dorsi and teres major. The case reveals unclarity in the current classification system and illustrates how a non-operative approach, in opposition to interpretation of recommended guidelines, was adequate for an excellent clinical outcome.

A Coronavirus Disease 2019 (COVID-19) epidemiological model incorporating a boosted infection-acquired immunity and heterogeneity in infection-acquired immunity among recovered individuals is designed. The model is used to investigate whether incorporating these two processes can induce new epidemiological insights. Analytical findings reveal co-existence of multiple endemic equilibria on either regions divided by the fundamental threshold (control reproduction number). Numerical findings conducted to validate analytical results show that heterogeneity in infection-acquired immunity among recovered individuals can induce various bifurcation structures such as reversed backward bifurcation, forward bifurcation, backward bifurcation and reversed hysteresis effect. Moreover, numerical results show that reversed backward bifurcation is annihilated or switches to the usual forward bifurcation if infection-acquired immunity among recovered individuals with strong immunity is assumed to be everlasting. However, this is only possible if primary infection is more likely than reinfection. In case reinfection is more likely to occur than primary infection, reversed backward bifurcation structure switches to a backward bifurcation phenomenon. Further, longer duration of infection-acquired immunity does lead to COVID-19 decline over time but does not lead to flattening of the COVID-19 peak.

Increased access to genome-wide data provides new opportunities for plant conservation. However, information on neutral genetic diversity in a small number of marker loci can still be valuable because genomic data are not available to most rare plant species. In the hope of bridging the gap between conservation science and practice, we outline how conservation practitioners can more efficiently employ population genetic information in plant conservation. We first review the current knowledge about the within-population genetic variation and among-population differentiation in neutral genetic variation (NGV) and adaptive genetic variation (AGV) in seed plants. We then introduce the estimates of among-population genetic differentiation in quantitative traits (QST) and neutral markers (FST) to plant biology and summarize conservation applications derived from QST–FST comparisons, particularly on how to capture most AGV and NGV on both in-situ and ex-situ programs. Based on a review of published studies, we found that, on average, two and four populations would be needed for woody perennials (n = 18) to capture 99% of neutral and adaptive genetic variation, respectively, whereas four populations would be needed in case of herbaceous perennials (n = 14). On average, QST is about 3.6, 1.5, and 1.1 times greater than FST in woody plants, annuals, and herbaceous perennials, respectively. We suggest using maximum QST rather than average QST among trait comparisons. Hence, conservation and management policies or suggestions based solely on inference on FST could be misleading, particularly in woody species. We recommend conservation managers and practitioners consider this when formulating further conservation and restoration plans for plant species, and for woody species in particular.

Conversion of the North American prairies to cropland remains a prominent threat to grassland bird populations. Yet, a few species nest in these vastly modified systems. The thick-billed longspur (Rhynchophanes mccownii) is an obligate grassland bird whose populations have declined 4% annually during the past 50 years. Thick-billed longspurs historically nested in recently disturbed or sparsely vegetated patches within native mixed-grass prairie, but observations of longspurs in crop fields during the breeding season suggest such fields also provide cues for habitat selection. Maladaptive selection for poor quality habitat may contribute to ongoing declines in longspur populations, but information on thick-billed longspur breeding ecology in crop fields is lacking. We hypothesized that crop fields may function as ecological traps; specifically, we expected that crop fields may provide cues for territory selection but frequent human disturbance and increased exposure to weather and predators would have negative consequences for reproduction. To address this hypothesis, we compared measures of habitat selection (settlement patterns and trends in abundance) and productivity (nest density, nest survival, and number of young fledged) between crop fields and native sites in northeastern Montana, USA. Settlement patterns were similar across site types and occupancy ranged from 0.52 ± 0.17SE to 0.99 ± 0.01 on April 7 and 30, respectively. Early season abundance differed by year and changes in abundance during the breeding season were associated with precipitation-driven vegetation conditions, rather than habitat type. Standardized nest density (0.19 ± 0.27SD nests/plot/hour), the number of young fledged per successful nest (2.9 ± 0.18SE), and nest survival (0.24 ± 0.03 SE; n=222 nests) were similar for crop and native sites. Collectively, the data did not support our hypothesis that crop fields are ecological traps: longspurs did not exhibit a clear preference for cropland and reproductive output was not significantly reduced. Our results indicate that crop fields provide alternative breeding habitat within a human-dominated landscape.

Wolf spiders are typically the most common group of arthropod predators on both lake and marine shorelines, because of the high prey availability in these habitats. However, shores are also harsh environments due to flooding and, in proximity to marine waters, to toxic salinity levels. Here, we describe the spider community, prey availabilities and spider diets between shoreline sites with different salinities, albeit with comparatively small differences (5 vs. 7‰). Despite the small environmental differences, spider communities between low and higher saline sites showed an almost complete species turnover. At the same time, differences in prey availability or spider gut contents did not match changes in spider species composition but rather changed with habitat characteristics within region, where spiders collected at sites with thick wrack beds had a different diet than sites with little wrack. These data suggest that shifts in spider communities are due to habitat characteristics rather than prey availabilities, and the most likely candidate restricting species in high salinity would be saline sensitivity. At the same time, species absences from low-saline habitats remain unresolved.

A document by Clément Tanvet. Click on the document to view its contents.

Because of their high efficiency, better starting torque, and minimal electrical noise, permanent magnet brushless DC (PMBLDC) motors are frequently used in a variety of industrial applications. The speed of PMBLDC motors is controlled by a variety of controllers. In this study, P, PI, and PID controllers are used to compare the speed control of a permanent magnet brushless dc motor drive powered by solar PV arrays. The Perturb & Observe (P&O) technique is used to find the MPPT. The drive system’s simulation results for various operation modes, such as constant and variable load circumstances, are examined and evaluated. When using a PID Controller instead of a P or PI controller, the drive performs better at controlling speed. The software MATLAB/Simulink was used to model, control, and simulate the permanent magnet brushless DC motor drive. The whole drive system is put into operation with the help of the dSPACE MicroLabBox 1202

Background and Purpose Recent evidence suggests that postmenopausal osteoporosis is associated with increased bone resorption function in osteoclasts, of which Cathepsin K is a key molecule. In this study, we aimed to screen small molecule compounds targeting Cathepsin K and evaluate whether they affect osteoclast bone resorption function. Experimental Approach We screened out the small-molecule compound NVP-BHG712 targeting CTSK by molecular docking, and studied its pharmacological effect on bone resorption function of osteoclasts. To this end, we evaluated bone mass changes in postmenopausal mice by μCT, ELISA, and H&E staining. In addition, we also investigated the effects of NVP-BHG712 on osteoclast differentiation, bone resorption function and expression of osteoclast differentiation related factors in vitro. Key Results Surprisingly, we found that oral NVP-BHG712 treatment significantly reduced bone loss in postmenopausal mice. In vitro osteoclast culture, it was found that this effect was achieved by inhibiting osteoclast differentiation and bone resorption. Meanwhile, NVP-BHG712 significantly decreased the expression of genes related to osteoclast differentiation, including CTSK, MMP9, CTR, IP3R1, IP3R3, and OC-STAMP. Conclusion and Implications The present findings suggest that NVP-BHG712 reduces bone resorption function by inhibiting osteoclast differentiation, and is a potential drug for preventing and treating postmenopausal osteoporosis and other diseases.

In this study, Urtica dioica L extract as a stabilizing and reducing agent was utilized to synthesize silver nanoparticles in the aqueous medium. Various techniques containing UV-Vis. spectroscopy, FT-IR spectroscopy, X-ray diffraction (XRD), scanning electron microscopy (SEM), and Transmission electron microscopy (TEM) were used to characterize the synthesized nanoparticles (AgNPs). On the other hand, the MTT assay was run to evaluate anti lung cancer activity of AgNPs. The uniform spherical morphology ranging from 26.22 to 65.18 nm was detected in the SEM images for the biosynthesized nanoparticles. The crystal size of AgNPs, according to the XRD analysis, was 48.11 nm. In the cellular and molecular part of the recent study, the treated cells with AgNPs@Urtica dioica L were assessed by MTT assay for 48 h about the cytotoxicity and anti-human lung adenocarcinoma properties on normal (HUVEC) and lung adenocarcinoma cell lines i.e. HLC-1, LC-2/ad, and PC-14. The viability of malignant lung cell line reduced dose-dependently in the presence of AgNPs@Urtica dioica L. The IC50 of AgNPs@Urtica dioica L were 201, 108 and 143 µg/mL against HLC-1, LC-2/ad, and PC-14 cell lines, respectively. In the antioxidant test, the IC50 of AgNPs@Urtica dioica L and BHT against DPPH free radicals were 125 and 60 µg/mL, respectively.

Background：Asthma control level is much lower in children. This study aimed to determine the role of small airway function in predicting asthma control in preschool children. Method: In this retrospective cohort study, we enrolled preschool children who initially diagnosed with asthma and followed up 2 to 3 months by pediatric pulmonary physicians. Clinical history and lung function results were collected. Multivariable regression model was applied to determine risk factors in predicting poor asthma control. Results: The cohort study was comprised of 219 preschool children. Sixty-nine of them (31.5%) had poor asthma control. Poor adherence (14.5% vs 6.0%, p=0.038) and severe airway hyperresponsiveness (AHR) (20.6% vs 1.6%, p＜0.05) were more common in poor controlled group. Baseline FEV 1% (94.5 vs 101.4, p=0.001), FEF50% (66.1 vs 86.0, p＜0.001), FEF75% (60.9 vs 75.3, p=0.001), FEF25-75% (70.9 vs 86.0, p＜0.001) were significantly lower in poor controlled patients than those of well controlled group. While, FVC% was similar between the two groups (92.4 vs 96.7, p=0.093). Multivariable regression models showed severe AHR (OR 9.500, 95%CI 1.404-64.000, p=0.020), lower baseline FEF50% (OR 0.972, 95%CI 0.950-0.994, p=0.012) were significantly associated with short-term poor asthma control (AUC, 0.740, 95%CI 0.661-0.818). Conclusion: Preschool asthma children with severe AHR and decreased FEF50 were at risk of poor asthma control in next 2 to 3 months.