The use of Search-Based software engineering to address Model-Driven Engineering activities (SBMDE) is becoming more popular. Many maintenance tasks can be reformulated as a search problem, and, when those tasks are applied to software models, the search strategy has to retrieve a model fragment. There are no studies on the influence of the search parameters when applied to software models. This paper evaluates the impact of different search parameter values on the performance of an evolutionary algorithm whose population is in the form of software models. Our study takes into account the nature of the model fragment location problems (MFLPs) in which the evolutionary algorithm is applied. The evaluation searches 1,895 MFLPs (characterized through five measures that define MFLPs) from two industrial case studies and uses 625 different combinations of search parameter values. The results show that the impact on the performance when varying the population size, the replacement percentage, or the crossover rate produces changes of around 30% in performance. With regard to the nature of the problems, the size of the search space has the largest impact. Search parameter values and the nature of the MFLPs influence the performance when applying an evolutionary algorithm to perform fragment location on models. Search parameter values have a greater effect on precision values, and the nature of the model fragment location problems has a greater effect on recall values. Our results should raise awareness of the relevance of the search parameters and the nature of the problems for the SBMDE community.

Today’s internet technology is so prevalent that it has improved the quality of people’s lives in a variety of ways, such as online social networking and banking. Security risks to systems and networks are continually evolving because of the development of Internet technologies. Phishing is one such major issue, in which attackers try to steal the user’s credentials by using bogus emails, websites, or both. The creation of solutions to counter phishing attacks is a top priority for both businesses and academics. Therefore, it is crucial for businesses to focus on end-user education while preventing phishing threats. Consequently, our paper’s goal is demonstrate the different approaches to clone the webpage. We will start by going into great depth into the background of phishing attacks and the motivation of the perpetrators. Then, we will give a taxonomy of the many sorts of phishing.

A document by Ken H Andersen. Click on the document to view its contents.

This research paper examines the adoption of digital services for the vaccination in the COVID-19 pandemic in Germany. Based on a survey in Germany's federal state with the highest vaccination rate, which used digital vaccination services, its platform configuration and adoption barriers are analyzed to understand existing and future levers for optimizing vaccination success. Though technological adoption and resistance models have been originally developed for consumer goods markets, this study gives empirical evidence for the applicability of an adjusted model explaining platform adoption for vaccination services in special and for digital health services in general. In this model, the configuration areas personalization, communication, and data management have a remarkable effect to lower adoption barriers, but only functional and psychological factors affect the adoption intention. Above all, the usability barrier stands out with the strongest effect while the often-cited value barrier is not significant at all. Personalization is found to be the most important factor for managing the usability barrier and thus for addressing the needs, preferences, situation, and ultimately the adoption of the citizens as users. Implications are given for policy makers and managers in such pandemic crisis to focus on the click flow and server-to-human interaction rather than emphasizing value messages or touching traditional factors.

Combined exposure to stressors, including pesticides and pathogens, is common in natural insect populations. Pesticide resistance readily evolves in these populations and often coopts the same stress, detoxification, and immune pathways involved in physiological responses against primary pathogen and pesticide exposure. As a result, resistance evolution can alter antagonism or facilitation among chemical pesticides and pathogens in directions that remain difficult to predict. To investigate the interactive effects of chemical pesticide resistance, exposure, and bacterial infection on insect phenotypes, we experimentally evolved resistance to two different classes of pesticides (organophosphates and pyrethroids) in the red flour beetle, Tribolium castaneum. We exposed pesticide susceptible and resistant lines to pesticides, the entomopathogen and biocontrol agent Bacillus thuringiensis (Bt), or both. Pesticide resistance and Bt exposure were individually associated with slower development, indicating sub-lethal fitness costs of resistance and infection, respectively. After organophosphate exposure, however, beetles developed more quickly and were more likely to survive if also exposed to Bt. We used RNAseq to examine the interactive effects of pesticide resistance, pesticide exposure, and Bt exposure on gene expression. Pyrethroid-resistant insects exhibited dampened immune responses to Bt infection relative to susceptible ones. In a similar vein, simultaneous exposure to organophosphates and Bt resulted in muted stress-associated transcriptional responses compared to exposure with only one factor. Our results suggest that direct and host-mediated indirect interactions among pathogens and pesticides may buffer the cost of exposure to host fitness-associated traits within generations but exacerbate trade-offs over evolutionary time.

The perplexing innate immune response induced by SARS-CoV-2 infection remains inadequate uncovered. Previous studies showed that coronavirus papain-like protease (PLP) could evade type I interferons mediated innate immune responses. In this study, we found the inflammasome genes (NLRP3, NLRP6, PYCARD, IL1B, IL18, TRIM31, FBXL2, MARCH7) were down-regulated in CD14+ monocytes from COVID-19 patients. Secondly, we found that SARS-CoV-2 PLP may act on the NLRP3 inflammasome pathway. PLP may interact with ASC and interrupt ASC oligomerization by reducing the K48-linked and K63-linked ubiquitination of ASC, so that the excessive activation of the NLRP3 inflammatory pathway might be inhibited and the release of IL-1β was blocked. Thirdly, SARS-CoV-2 PLP negatively regulated the pyroptosis of host cells, which was mediated by caspase-1, the key regulator of the NLRP3 inflammasome pathway. In general, SARS-CoV-2 PLP avoids the excessive immune defenses in the early stage of virus infection, which provides the maximum advantage for virus replication. These insights uncover the flex function of CoV encoding proteases. Furthermore, this research may provide a new vision of COVID-19 epidemic prevention and new possibilities for new therapies.

Aim: To our knowledge; this is the first study that compared the efficacy and safety of aripiprazole 1-month and paliperidone 1-month and paliperidone 3-month long-acting forms preparations as well as plasma drug levels during the maintenance treatment of schizophrenia in the real world. Method: In our study, subjects were evaluated every month for four months with relevant psychiatric measures and plasma drug levels. Follow-up days were determined as days 0, 30, 60, and 90. Plasma drug levels of the treatments were analyzed by using LC/MS-MS. Results: No superiority was observed between the groups regarding PANSS positive and general psychopathology (p>0.05). It was observed that PANSS negative and total scores were statistically lower in the aripiprazole once-monthly group than in the paliperidone 3-month preparations (p<0.05). We observed that Quality of Life Scale interpersonal relations scores, the aripiprazole 1-month group exhibited higher scores than both of the paliperidone groups. Aripiprazole 1-month group scored higher than the paliperidone 1-month group in the intrapsychic foundations subscale (p<0.05). No significant difference was observed between extrapyramidal adverse effect, akathisia, and insight levels among the three groups (p>0.05). Aripiprazole 1- month group scored significantly lower than both paliperidone groups in the Arizona Sexual Experiences Scale (p<0.001). Aripiprazole metabolite was negatively correlated with depressive symptoms in the Calgary Depression Assessment Scale in Schizophrenia (p<0.05) and the Barnes Akathisia Rating Scale (p<0.05). Conclusion: Aripiprazole once-monthly showed superiority in efficacy aspects to PP3M but not PP1M and similar safety with both paliperidone formulations.

VitaminB12 is a water soluble vitamin and plays a significant role during metabolism. It also acts as the cofactor of many enzymes during DNA synthesis. Moreover Vitamin B12 is involved in red blood cells production, healthy nerve tissues and brain functions. Certain archaeon and bacteria has the ability to synthesize the vitamin B12 and it is not been synthesized in plants. The synthesized vitamin B12 in microbes has the ability to be transferred and can be present in many of the plants, mushrooms by microbial interaction also in Animal tissues so ruminant’s meat and milk can act as source of vitamin B12. By increasing demand of vitamin B12 Scientists have used microbes for its production at industrial scale by giving them optimized culture conditions including Sinorhizobium meliloti, Propionibacterium shermanii, or Pseudomonas denitrificans. The different substrates especially agro-industrial waste because of their low price and high content of carbon can be used for microbial growth. Both modes of fermentation (solid and submerged fermentation) are used for Vitamin B12 production from microbes. Different strains grow at different culture conditions. This review is based upon the short introduction of vitamin B12, its different sources, different substrates for production; optimized culture conditions its purification and extraction.

Ventricular tachycardia is a major cause of sudden death. Several pharmacological and device-based therapies in recent years have delayed the progression of heart failure and have improved survival. A new study reveals a significant increase in age-adjusted mortality from ventricular tachycardia over the past 13 years, with higher mortality in men, black Americans and patients from the Southern United States. These findings reinforce the previous observations made on the influence of age, gender, ethnicity and geography on cardiovascular outcomes. The use of ICD 10 codes to ascertain cause of death limits differentiation between ventricular tachycardia as the true underlying mechanism leading to death and the presence of ventricular tachycardia in patients dying from other causes. While the insights gained from the report on contemporary ventricular tachycardia related mortality in the general population with cardiovascular disease is hypothesis generating, further studies are needed to delineate ventricular tachycardia as a proximate cause of death from an association.

Introduction Pathophysiologic pathways of sickle cell disease (SCD) and air pollution involve inflammation, oxidative stress, and endothelial damage. It is therefore plausible that children with SCD are especially prone to air pollution’s harmful effects. Methods Patient data were collected from a single center, urban/peri-urban cohort of children with confirmed SCD. Daily ambient concentrations of particulate matter (PM 2.5) were collected via satellite-derived remote-sensing technology, and carbon monoxide (CO), nitrogen dioxide (NO 2), and ozone from local monitoring stations. We used multivariable regression to quantify associations of pollutant levels and daily counts of emergency department (ED) visits, accounting for weather and time trends. For comparison, we quantified the associations of pollutant levels with daily all-patient (non-SCD) ED visits to our center. Results From 2010-2018, there were 17 731 ED visits by 1740 children with SCD (64.8% HbSS/HbSβ 0). Vaso-occlusive events (57.8%), respiratory illness (17.1%), and fever (16.1%) were the most common visit diagnoses. Three-day (lags 0-2) rolling mean PM 2.5 and CO levels were associated with daily ED visits among those with SCD (PM 2.5 incident rate ratio (IRR) 1.051 (95% CI 1.010-1.094) per 9.4 µg/m 3 increase; CO 1.088 (1.045-1.132) per 0.5 ppm). NO 2 showed positive associations in secondary analyses; ozone levels were not associated with ED visits. The comparison, all-patient ED visit analyses showed lower IRR for all pollutants. Conclusions Our results suggest short-term air pollution levels as triggers for SCD events and that children with SCD may be more vulnerable to air pollution than those without SCD. Targeted pollution-avoidance strategies could have significant clinical benefits in this population.

Diamond-Blackfan anemia (DBA) is a rare congenital erythroid hypoplasia. An association with very early onset inflammatory bowel disease (VEO-IBD) has only been reported a few times. We report a Caucasian boy with a transfusion-dependent DBA phenotype from birth and severe ulcerative pancolitis from 10 months of age. He underwent successful allogeneic hematopoietic stem cell transplantation (HSCT) at 2 years of age. On follow-up 8 years old, he had normal bone marrow function and no bowel symptoms. HSCT was curative for both DBA and VEO-IBD. The underlying course of DBA and pancolitis remains elusive.

(Sceloporus undulatus) is a female-larger, sexually-size dimorphic lizard species that is heavily parasitized by chigger mites (Eutrombicula alfreddugesi). In particular, the intensity of mite parasitism is higher in male than in female juveniles during the period of time when sex differences in growth rate lead to the development of sexual size dimorphism (SSD). Sex-biased differences in fitness costs of parasitism have been documented in other species. We tested whether a sex-biased growth cost of parasitism contributes to the development of SSD in S. undulatus. We measured growth and mite loads in two cohorts of unmanipulated, field-active yearlings by conducting descriptive mark-recapture studies during the activity seasons of 2016 and 2019. Yearling males had consistently higher mid-summer mite loads and consistently lower growth rates than females. However, we found that growth rate and body condition were independent of mite load in both sexes. Furthermore, growth rates and mite loads were higher in 2019 than in 2016. Our findings suggest that juveniles of S. undulatus are highly tolerant of chigger mites and that any costs imposed by mites must be at the expense of functions other than growth. We conclude that sex-biased mite ectoparasitism does not contribute to sex differences in growth rate and the development of SSD.

Sogatella furcifera is an agricultural pest of great concern in China and Southeast Asian countries. However, the lack of accurate and complete reference genome resources has hindered the understanding of immunity and evolution of S. furcifera. Here, we utilized Nanopore sequencing to generate a chromosome-level assembly and annotation of the S. furcifera genome (0.64 Gb), with a GC content of 34.25%. This genome comprised 15 chromosomes covering 95.04% of the estimated genome size, together with an additional 624 small scaffolds making up the remaining 4.96% of the genome of S. furcifera. A total of 24,669 protein-coding genes as well as 1211 long noncoding RNA and 7595 circular RNA transcripts were well annotated and predicted. Comparative genomic analysis revealed the rapidly evolved genes associated with multiple immune-related pathways in S. furcifera, which may be responsible for its rapid evolutionary adaptation. In addition, 14 immune genes in the classic immune pathways were selected for functional validation through RNA interference experiments, demonstrating the antiviral effects of Dorsal and Dif genes in S. furcifera. Genome resequencing of 44 individuals from 12 geographic populations revealed an absence of population structures and frequent gene flow among all populations. Sweep analysis indicated that 2926 genes were under natural selection and significantly enriched in several biological processes of morphogenesis and immunity. The first systematic identification of immune genes and noncoding RNAs from chromosome-level genome assembly plus the comparative and population genomic analysis will provide more insights into the understanding of the immunity and evolutionary adaptation of S. furcifera.

RATIONALE Obtaining nitrous oxide isotopocule measurements with isotope ratio mass spectrometry (IRMS) involves analyzing the ion current ratios of the nitrous oxide parent ion (N2O+) as well as those of the NO+ fragment ion. The data analysis requires correcting for “scrambling” in the ion source, whereby the NO+ fragment ion obtains the outer N atom from the N2O+ molecule. While descriptions exist for this correction, and interlaboratory intercalibration efforts have been made, there has yet to be published a package of code for implementing isotopomer calibrations. METHODS We developed a user-friendly Python package (pyisotopomer) to determine two coefficients (γ and κ) that describe scrambling in the IRMS ion source, and then to use this calibration to obtain intramolecular isotope deltas in N2O samples. RESULTS We show that, with two reference materials distinct enough in their site preference, γ and κ can be determined robustly and accurately for a given IRMS. An additional third reference material is needed to define the zero-point of the delta scale. We show that the scrambling behavior of an IRMS can vary with time, necessitating regular calibrations. Finally, we present an intercalibration between two IRMS laboratories, using pyisotopomer to calculate γ and κ and to obtain intramolecular N2O isotope deltas in lake water unknowns. CONCLUSIONS Given these considerations, we discuss how to use pyisotopomer to obtain high-quality N2O isotopocule data from IRMS systems, including the use of appropriate reference materials and frequency of calibration.

Fracture mechanics can be defined as a methodology that is used to predict and diagnose failure of a part with some kind of existing crack or flaw. These models can be used to aid in the examination of laboratory experiments and possibly give an explanation into its fatigue life. This study utilized AFGROW as the fracture mechanics software. All models were used on a previous study conducted on aluminum light poles containing hand-holes and reinforcement (when applicable). The ultimate goal of this study was an attempt to replicate the laboratory results from these previous studies and to gain a deeper understanding of the failure modality. In total, eight fracture mechanics models were created to achieve this goal. Of these models, three contained an initial break, two had a beta correction added, one contained an open hole, and two were modeled as a plate. From all of the fracture mechanics models, models containing plates yielded the best results when it came to replicating lab results. Some finite element analysis (FEA) in ABAQUS was used in conjunction with the fracture mechanics models.

The COVID-19 pandemic posed a significant impediment to experimental research, leading several researchers to adapt psychophysical data acquisition. With the development and proliferation of information technology, paper-based organizational processes have gradually begun to be replaced by computer-based equivalents. This study describes how we developed, analyzed data, and validated the temporal bisection task in a remote data acquisition scenario. We implemented the data acquisition using the open science software OpenSesame, in conjunction with the JATOS platform. We described in detail all the steps to use our codes, which we made available for reuse. We acquired data from 28 participants using the remote acquisition system and compared them with data obtained in person (from Penney et al., 2000). Our remote data showed compatible results with live experiments, suggesting that the modality of data acquisition (remote or live) does not influence the results.

Recent studies have reported that coronavirus disease-2019 (COVID-19) vaccination can exacerbate asthma. Status asthmaticus sometimes induces takotsubo cardiomyopathy. We present a case of takotsubo cardiomyopathy triggered by asthma exacerbation after the mRNA-based vaccination. Therapies for status asthmaticus resulted in prompt improvement of respiratory failure and cardiac-apex ballooning.

The structure of the critical zone is a product of feedbacks between hydrologic, climatic, biotic, and chemical processes. Ample research within snow-dominated systems has shown that aspect-dependent solar radiation inputs can produce striking differences in vegetation composition, topography, and soil depth between opposing hillslopes. However, more research is needed to understand the role of microclimates on critical zone development within rain-dominated systems, especially below the soil and into weathered bedrock. To address this need, we characterized the critical zone of a north-facing and south-facing slope within a first-order headwater catchment located in central coastal California. We combined terrain analysis of vegetation distribution and topography with field-based soil pit characterization, geophysical surveys and hydrologic measurements between slope-aspects. We observed thicker soil profiles, higher shallow soil moisture, and denser vegetation on north facing slopes, which matched previously documented observations in snow-dominated sites. However, average topographic gradient and saprolite thickness were uniform across our study hillslopes, which did not match common observations from the literature. These results suggest dominant processes for critical zone evolution are not necessarily transferable across regions. Thus, there is a continued need to expand critical zone research, especially in rain-dominated systems. Here, we present four non-exclusive, testable hypotheses of mechanisms that may explain these unexpected similarities in slope and saprolite thickness between hillslopes with opposing aspects. Specifically, we propose both past and present ecohydrologic processes must be taken into account to understand what shaped the present day critical zone.

The non-collisional subduction margin of South America is characterized by different geometries of the subduction zone and upper-plate tectono-magmatic provinces. The localization of deformation in the southern Central Andes (29°S–39°S) has been attributed to numerous factors that combine the properties of the subducting oceanic Nazca plate and the continental South American plate. In this study, the present-day configuration of the subducting oceanic plate and the continental upper plate were integrated in a data-driven geodynamic workflow to assess their role in determining strain localization within the upper plate of the flat slab and its southward transition to a steeper segment. The model predicts two fundamental processes that drive deformation in the Andean orogen and its foreland: eastward propagation of deformation in the flat-slab segment by a combined bulldozing mechanism and pure-shear shortening that affects the broken foreland and simple-shear shortening in the fold-and-thrust belt of the orogen above the steep slab segment. The transition between the steep and subhorizontal subduction segments is characterized by a 370-km-wide area of diffuse shear, where deformation transitions from pure to simple shear, resembling the transition from thick to thin-skinned foreland deformation in the southern Sierras Pampeanas. This pattern is controlled by the change in dip geometry of the Nazca plate and the presence of mechanically weak sedimentary basins and inherited faults.

The nicotinic symptom in Organo-Phosphate (OP) poisoning is an unusual presentation in an adult, as in our case of a 38-year-old man who also experienced decreased motor power of all limbs and diffuses fasciculation of the tongue and lower limbs.

BACKGROUND Severe Pediatric Allergic Asthma (SPAA) induces a huge economic burden in terms of direct, indirect and intangible costs. The use of omalizumab for the treatment of these patients has produced a significant improvement in several clinical outcomes, but at the same time, the cost for the management of the disease has also increased. The aim of this report was to evaluate whether the use of omalizumab is cost-effective. METHODS A sample of 426 children with SPAA from the ANCHORS study was used to calculate the Incremental Cost Effectiveness Ratio (ICER) for the avoidance of Moderate to Severe Exacerbations (MSE), and also for the improvement in childhood Asthma Control Test (c-ACT) or the Asthma Control Questionnaire (ACQ5). We retrospectively collected data of health encounters and drug consumption before and up to six years after the beginning of the treatment with omalizumab. RESULTS The ICER per avoided MSE was \euro2,107 after one year, and it consistently decreased to \euro656 in those followed up to six years. Similarly, the ICER for the Minimally Important Difference in control tests showed a decrease from \euro2,059 to \euro380 per each 0.5 points of improvement in ACQ5, and from \euro3,141 to \euro2,322 per each 3 points improvement in c-ACT, at years 1 and 6 respectively. CONCLUSION The use of OMZ is a cost-effective option for most children with uncontrolled SPAA, mainly those who have frequent exacerbations, showing progressively reduced costs in successive years of treatment.

In this study, an Cournot duopoly model describing conformable fractional order differential equations with piecewise constant arguments is discussed. We have obtained two dimensional discrete dynamical system as a result of the discretization process is applied to the model. By using the center manifold theorem and the bifurcation theory, it is shown that the discrete dynamical system undergoes flip bifurcation about the Nash equilibrium point. Phase portraits, bifurcation diagrams, Lyaponov exponents show the existence of many complex dynamical behavior in the model such as stable equilibrium point, period-2 orbit, period-4 orbit, period-8 orbit, period-16 orbit and chaos according to changing the speed of adjustment parameter v 1 . Discrete Cournot duopoly game model is also considered on a Scale free network with N=10 and N=100 nodes. It is observed that the complex dynamical network exhibits similar dynamical behavior such as stable equilibrium point, Flip bifurcation and chaos depending on the changing the coupling strength parameter c s . Moreover, flip bifurcation and transition chaos happen earlier in more heterogeneous networks. Calculating the Largest Lyapunov exponents guarantee the transition from nonchaotic to chaotic states in complex dynamical networks.

The importance of lightning has long been recognized from the point of view of climate-related phenomena. However, the detailed investigation of lightning on global scales is currently hindered by the incomplete and spatially uneven detection efficiency of ground-based global lightning detection networks and by the restricted spatio-temporal coverage of satellite observations. We are developing different methods for investigating global lightning activity based on Schumann resonance (SR) measurements. SRs are global electromagnetic resonances of the Earth-ionosphere cavity maintained by the vertical component of lightning. Since charge separation in thunderstorms is gravity-driven, charge is typically separated vertically in thunderclouds, so every lightning flash contributes to the measured SR field. This circumstance makes SR measurements very suitable for climate-related investigations. In this study, 19 days of global lightning activity in January 2019 are analyzed based on SR intensity records from 18 SR stations and the results are compared with independent lightning observations provided by ground-based (WWLLN, GLD360 and ENTLN) and satellite-based (GLM, LIS/OTD) global lightning detection. Daily average SR intensity records from different stations exhibit strong similarity in the investigated time interval. The inferred intensity of global lightning activity varies by a factor of 2-3 on the time scale of 3-5 days which we attribute to continental-scale temperature changes related to cold air outbreaks from polar regions. While our results demonstrate that the SR phenomenon is a powerful tool to investigate global lightning, it is also clear that currently available technology limits the detailed quantitative evaluation of lightning activity on continental scales.

Passive acoustic monitoring (PAM) is a cost-effective method for monitoring cetacean populations compared to techniques such as aerial and ship-based surveys. The C-POD (Cetacean POrpoise Detector) has become an integral tool in monitoring programmes globally for over a decade, providing standardised metrics of occurrence that can be compared across time and space. However, the phasing out of C-PODs following development of the new F-POD (Full waveform capture Pod) with increased sensitivity, improved train detection, and reduced false positive rates, represents an important methodological change in data collection, particularly when being introduced into existing monitoring programmes. Here, we compare the performance of the C-POD with that of its successor, the F-POD, co-deployed in a field setting for 15 months, to monitor harbour porpoise (Phocoena phocoena). While similar temporal trends in detections were found for both devices, the C-POD detected only 58% of the detection positive minutes (DPM), recorded by the F-POD. Differences in detection rates were not consistent through time making it difficult to apply a correction factor or directly compare results obtained from the two PODs. To test whether these differences in detection rates would have an effect on analyses of temporal patterns and environmental drivers of occurrence, generalised additive models (GAMs) were applied. No differences were found in seasonal patterns or the environmental correlates of porpoise occurrence (month, diel period, temperature, environmental noise, and tide). However, the C-POD failed to detect sufficient foraging buzzes to identify temporal patterns in foraging behaviour that were clearly shown by the F-POD. Our results suggest that the switch to F-PODs will have little effect on determining broad-scale seasonal patterns of occurrence, but may improve our understanding of fine-scale behaviours such as foraging. We highlight how care must be taken interpreting F-POD results as indicative of increased occurrence when used in time-series analysis.