bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of different kinetic models for the production of fructo‐oligosaccharides through enzymatic synthesis
Authors: Ureta Maria Micaela , Salvadori Viviana O. , Gómez‐Zavaglia Andrea , Goñi Sandro
Published: June 2024

Mathematical modeling is a great tool to understand the mechanism of fructo‐oligosaccharides (FOS) synthesis. The objective in this work is to adapt different models designed for FOS synthesis. Two approaches for the reaction mechanism, chain reaction and ping‐pong, were included in the analysis and genetic algorithm was implemented to find the best fit. Both approaches offered good results, chain reaction approach showed lower overall relative errors (below 8.5%) while ping‐pong mechanism best fit presented an overall error of 10.5%. No matter the approach used, the models with best fit involved the concept of glucose inhibition for the transfructosylation reaction. Different objective functions can be tested to reduce the relative errors when the model struggled to describe the behavior of one component. The sensitive analysis helps to evaluate all the variables such as reaction rate, time, productivity, and FOS yield, to find an optimal reaction condition.

Practical applications

This research aims to describe and help understand the reaction mechanism involved in the enzymatic synthesis of fructo‐oligosaccharides, through the study of the kinetics using different mathematical models found in the consulted bibliography. This way, the operational conditions (substrate type and concentration, enzyme source [bacteria or fungi], enzyme configuration [purified or whole cells, free or immobilized], enzyme/substrate ratio, reaction time, temperature, and pH, batch or continuous mode) can be adapted, ensuring the attainment of the desired final product.
Parents' perceptions of care quality at child health centres: A cross‐sectional study from Sweden
Authors: Jacobzon Anna , Engström Åsa , Gustafsson Silje Rysst , Andersson Maria
Published: June 2024

Aim

To examine parents' perceptions of care quality at child health centres. Specific objectives were to examine parents' perceptions of the care received and the subjective importance of such care. Furthermore, to examine the relationship between parents' sociodemographic characteristics and the perceptions of care quality.

Design

A cross‐sectional study.

Methods

A random sample of parents of children born in Sweden in 2021 participated. Data were collected by the QPP‐CHC questionnaire and analysed using descriptive and analytical statistics.

Results

The response rate was 19.4%. The targeted sample size of 210 participants was reached as 584 parents responded to the questionnaire. Parents' overall ratings of care quality at child health centres indicated optimal quality with mean values >3. However, various potential improvements areas were identified as needing additional information. These included dental care (m = 2.82), allergy prevention (m = 2.25), breastfeeding (m = 2.97), sleep (m = 2.83), the child's behaviour (m = 2.47) and the child's crying (m = 2.47). Also, parents rated suboptimal quality regarding that the care was based on healthcare routines rather than parental preferences and needs (m = 2.86). Parents born outside of the Nordic countries rated higher care quality than those born in the Nordic countries, as well as parents with a non‐academic education.

Conclusion

Parents want information based on their preferences and needs. Parent's perceptions of areas for improvement are new and important knowledge for registered nurses at child health centres.

Implications for the Profession and/or Patient Care

The findings indicate that parents feel that insufficient attention is given to areas of care that they perceive as important. Parents' perspectives on the care quality at child health centres is an important component of quality work and might lead to improvements in the care quality at child health centres.

Reporting Method

The Strengthening the Reporting of Observational Studies (STROBE) checklist for cross‐sectional studies was used to guide reporting.

Implications for policy and practice

The findings of this study suggests that parents feel that insufficient attention is given to areas of care that they perceive as important. Parents' perspectives on the care quality at child health centres provides important knowledge which can guide further development of care quality at child health centres. The findings indicate that a family‐centred approach that integrates relational and routine‐oriented nursing can be a way to ensure that the care is based on parents' preferences and needs.

No patient or public contribution.
Red‐deer dung increases species diversity but does not influence species composition of open grasslands
Authors: Lepková Barbora , Horčičková Eva , Herben Tomáš
Published: June 2024

Questions

Free‐ranging herbivores are often seen as important endozoochorous dispersal vectors for plant propagules. Dispersal by free‐ranging animals, in contrast to domestic animals, and its effects on vegetation have rarely been studied. We ask what are the effects of deposition of dung on open landscape vegetation, how does it influence vegetation development after disturbance by soil removal, and does it change species richness or composition?

Location

The Doupov Mountains, Czech Republic.

Methods

We established a six‐year experiment in 2015 to study the effects of dung deposition on vegetation of an open grassland landscape. The experiment comprised 300 plots distributed across five fenced site locations and treatments were implemented in partially crossed design, with soil removed (disturbance) and dung pellets deposited; treatments were applied once to five replicates, from June to October 2015. We recorded plant species cover at the beginning of the vegetation seasons of 2016, 2017 and 2021.

Results

Dung deposition increased species richness and Ellenberg Indicator Values for nutrients, and these effects were stronger in disturbed plots; however, these effects diminished with time. There were no effects of dung deposition on species composition. In contrast, disturbance affected species diversity, composition, Ellenberg Indicator Values for nutrients, proportion of dung‐dispersed species, but not species richness. Surprisingly, there were no effects of timing of dung deposition.

Conclusions

Our results indicate that endozoochorous seed dispersal by red deer impacts vegetation dynamics of this open grassland landscape, but effects are weak and diminish with time. Considering the large seed load in dung, it is possible that endozoochorous seeds from wild herbivores are incorporated into the soil seed bank, where they persist until appropriate ecological conditions for germination arise.
Integrative analysis reveals different feature of intrahepatic cholangiocarcinoma subtypes
Authors: Chen Zhuomiaoyu , Gao Jie , Li Zuyin , Ma Delin , Wang Yang , Cheng Qian , Zhu Jiye , Li Zhao
Published: June 2024

Background & Aims

Intrahepatic cholangiocarcinoma (iCCA) has two main histological subtypes: large and small duct‐type iCCA, which are characterized by different clinicopathological features. This study was conducted with the purpose of expanding our understanding of their differences in molecular features and immune microenvironment.

Methods

We selected 132 patients who underwent radical surgery at our department between 2015 and 2021 for clinical and survival analyses. Whole‐exome sequencing was performed to analyse mutational landscapes. Bulk RNA sequencing and single‐cell RNA sequencing data were used for pathway enrichment and immune infiltration analyses based on differentially expressed genes. The function of PPP1R1B was analysed both in vitro and in vivo and the gene mechanism was further investigated.

Results

We found that large duct‐type iCCA had worse overall survival and recurrence‐free survival rates than small duct‐type iCCA. Mutations in ARID1A, DOT1L and ELF3 usually occur in large duct‐type iCCA, whereas mutations in IDH1 and BAP1 occur in small duct‐type iCCA. Among the differentially expressed genes, we found that PPP1R1B was highly expressed in large duct‐type iCCA tumour tissues. Expression of PPP1R1B promoted cell proliferation, migration and invasion and indicated a worse prognosis. A combination of USF2 with the promoter of PPP1R1B can enhance gene expression in iCCA, which may further affect the expression of genes such as AHNAK, C4BPA and activating the PI3K/AKT pathway.

Conclusions

Our findings extend our understanding of large and small duct‐type iCCA. In addition, PPP1R1B may serve as a potential marker and therapeutic target for large duct‐type iCCA.
A novel xylanase from a myxobacterium triggers a plant immune response in Nicotiana benthamiana
Authors: Zhao Yuqiang , Yang Kun , Wang Yanxin , Li Xu , Xia Chengyao , Huang Yan , Li Zhoukun , Zhu Cancan , Cui Zhongli , Ye Xianfeng
Published: June 2024

Xylanases derived from fungi, including phytopathogenic and nonpathogenic fungi, are commonly known to trigger plant immune responses. However, there is limited research on the ability of bacterial‐derived xylanases to trigger plant immunity. Here, a novel xylanase named CcXyn was identified from the myxobacterium Cystobacter sp. 0969, which displays broad‐spectrum activity against both phytopathogenic fungi and bacteria. CcXyn belongs to the glycoside hydrolases (GH) 11 family and shares a sequence identity of approximately 32.0%–45.0% with fungal xylanases known to trigger plant immune responses. Treatment of Nicotiana benthamiana with purified CcXyn resulted in the induction of hypersensitive response (HR) and defence responses, such as the production of reactive oxygen species (ROS) and upregulation of defence gene expression, ultimately enhancing the resistance of N. benthamiana to Phytophthora nicotianae. These findings indicated that CcXyn functions as a microbe‐associated molecular pattern (MAMP) elicitor for plant immune responses, independent of its enzymatic activity. Similar to fungal xylanases, CcXyn was recognized by the NbRXEGL1 receptor on the cell membrane of N. benthamiana. Downstream signalling was shown to be independent of the BAK1 and SOBIR1 co‐receptors, indicating the involvement of other co‐receptors in signal transduction following CcXyn recognition in N. benthamiana. Moreover, xylanases from other myxobacteria also demonstrated the capacity to trigger plant immune responses in N. benthamiana, indicating that xylanases in myxobacteria are ubiquitous in triggering plant immune functions. This study expands the understanding of xylanases with plant immune response‐inducing properties and provides a theoretical basis for potential applications of myxobacteria in biocontrol strategies against phytopathogens.
Repeatability of retinal and choroidal optical coherence tomography angiography indices in healthy children and young adults
Authors: Lal Barsha , Alonso‐Caneiro David , Read Scott A. , Carkeet Andrew
Published: June 2024

Purpose

To evaluate the repeatability of retinal and choroidal optical coherence tomography angiography (OCT‐A) indices among healthy children and compare it to healthy young adults.

Methods

This prospective study captured 3 mm × 3 mm and 6 mm × 6 mm macular OCT‐A scans including superficial and deep retinal layers, choriocapillaris and deep choroid over two visits, 1 week apart at approximately the same time of day, for 22 healthy adults (18–30 years) and 21 children (6–15 years). Magnification and projection‐artefact corrected indices extracted using a custom image analysis program and individual biometry were compared between visits using Bland–Altman analysis and intraclass correlation (ICC). Retinal indices included foveal avascular zone metrics, perfusion and vessel density and choroidal indices included choriocapillaris flow deficit metrics and deep choroid perfusion density, in the foveal, parafoveal and perifoveal regions. Repeatability between adults and children was compared with F‐test.

Results

Bland–Altman analysis showed that the mean differences between repeated OCT‐A indices were not significantly different from zero for either of the zones, layers and scan sizes in the two age groups (p > 0.05) except for foveal vessel density and foveal avascular zone perimeter (p = 0.04 for both) of 6‐mm‐deep retinal layer scans. The ICC ranged between 0.67 and 0.99. Significantly higher variability between visits (p < 0.05) in the indices was noted among adults than children, especially for choroidal indices of larger scan size.

Conclusion

The retinal and choroidal OCT‐A indices in the foveal, parafoveal and perifoveal zones were repeatable in healthy children except for the foveal vessel density and foveal avascular zone perimeter of the 6‐mm‐deep retinal layer, which exhibited statistically borderline differences between visits. The adult group showed more variability between visits compared to children, especially in the larger scan size for choroidal OCT‐A indices.
Salvage of Iatrogenic Sciatic Nerve Injury Caused by Operatively Treated Acetabular Fractures: Two Cases and Literature Review
Authors: Zhang Peng , Tao Fulin , Song Wenhao , Wu Shuai , Wang Dawei , Zhou Dongsheng , Liu Fanxiao
Published: June 2024

Background

While sciatic nerve injury has been described as a complication of acetabular fractures, iatrogenic nerve injury remains sparsely reported. This study aims to assess iatrogenic sciatic nerve injuries occurring during acetabular fracture surgery, tracking their neurological recovery and clinical outcomes, and investigating any correlation between recovery and the severity of neurologic injury to facilitate physicians in providing prediction of prognosis.

Case Presentation

We present two cases of male patients, aged 56 and 22, who developed sciatic palsy due to iatrogenic nerve injury during acetabular fracture surgery. Iatrogenic sciatic nerve injury resulted from operatively treated acetabular fractures. Surgical exploration, involving internal fixation removal and nerve decompression, successfully alleviated symptoms in both cases postoperatively. At the latest follow‐up, one patient achieved full recovery with excellent function, while the other exhibited residual deficits at the L5/S1 root level along with minimal pain.

Conclusion

Sciatic nerve injury likely stemmed from reduction techniques and internal fixation procedures for the posterior column, particularly when performed with the hip flexed, thereby placing tension on the sciatic nerve. Our case reports underscore the significance of liberal utilization of electrophysiologic examinations and intraoperative monitoring for the prediction of prognosis. Surgical exploration, encompassing internal fixation removal and nerve decompression, represents an effective intervention for resolving sciatic palsy, encompassing both sensory neuropathy and motor symptoms.
Advancements and applications of loop‐mediated isothermal amplification (LAMP) technology in the detection of viral diseases in fruit crops
Authors: Luo Liting , Khan Mehran , Chen Songshu , Wang Fen , Xie Xin
Published: June 2024

Early diagnosis has a pivotal role in the effective control and prevention of disease in fruit crops. Loop‐mediated isothermal amplification (LAMP) has emerged as a prominent modality for disease diagnosis owing to its rapid detection, heightened sensitivity, exceptional specificity and easy operational procedures. The advent of LAMP‐coupled CRISPR‐Cas12, multiplex LAMP (mLAMP) and digital LAMP (dLAMP) has contributed to a paradigm shift in the field and increased the applicability of LAMP technology in viral disease detection. Such advancements have further extended the reach and efficacy of LAMP methodologies in diagnostic research. Here, we review LAMP detection technology application to identify viral diseases in fruits (e.g., apple, passion fruit, banana and citrus) and summarize current developments in LAMP technology and its future prospects, which could enhance its application in the detection of fruit viral diseases.
Task‐based default mode network connectivity predicts cognitive impairment and negative symptoms in first‐episode schizophrenia
Authors: Guha Anika , Popov Tzvetan , Bartholomew Morgan E. , Reed Alexandra C. , Diehl Caroline K. , Subotnik Kenneth L. , Ventura Joseph , Nuechterlein Keith H. , Miller Gregory A. , Yee Cindy M.
Published: June 2024

Individuals diagnosed with schizophrenia (SZ) demonstrate difficulty distinguishing between internally and externally generated stimuli. These aberrations in “source monitoring” have been theorized as contributing to symptoms of the disorder, including hallucinations and delusions. Altered connectivity within the default mode network (DMN) of the brain has been proposed as a mechanism through which discrimination between self‐generated and externally generated events is disrupted. Source monitoring abnormalities in SZ have additionally been linked to impairments in selective attention and inhibitory processing, which are reliably observed via the N100 component of the event‐related brain potential elicited during an auditory paired‐stimulus paradigm. Given overlapping constructs associated with DMN connectivity and N100 in SZ, the present investigation evaluated relationships between these measures of disorder‐related dysfunction and sought to clarify the nature of task‐based DMN function in SZ. DMN connectivity and N100 measures were assessed using EEG recorded from SZ during their first episode of illness (N = 52) and demographically matched healthy comparison participants (N = 25). SZ demonstrated less evoked theta‐band connectivity within DMN following presentation of pairs of identical auditory stimuli than HC. Greater DMN connectivity among SZ was associated with better performance on measures of sustained attention (p = .03) and working memory (p = .09), as well as lower severity of negative symptoms, though it was not predictive of N100 measures. Together, present findings provide EEG evidence of lower task‐based connectivity among first‐episode SZ, reflecting disruptions of DMN functions that support cognitive processes. Attentional processes captured by N100 appear to be supported by different neural mechanisms.
Overseas institutional uncertainty and corporate innovation – evidence from an emerging economy
Authors: Fu Xiaoqing (Maggie) , Liu Zhaoyan , Xie Hongjun , Zhang Yang
Published: June 2024

Using the 2016 US presidential election as a source of plausibly exogenous variation in uncertainty, we examine the R&D effect of institutional uncertainty in Chinese listed firms. Our results show that innovation activities are adversely affected in firms exposed to external election shocks and that the effect is more pronounced in SOEs, older firms, and financially constrained firms. Our study contributes to the literature on uncertainty and R&D management by broadening the conceptual boundaries of institutional uncertainty and enriching the understanding of how overseas institutional uncertainty affects domestic firms' R&D activities. The findings have important implications for innovation strategy at firms and policymaking at governments.
Climate change mitigation potential of restoration of boreal peatlands drained for forestry can be adjusted by site selection and restoration measures
Authors: Laine Anna M. , Ojanen Paavo , Lindroos Tomi , Koponen Kati , Maanavilja Liisa , Lampela Maija , Turunen Jukka , Minkkinen Kari , Tolvanen Anne
Published: June 2024

Peatland restoration is seen as a key nature‐based solution to tackle climate change and biodiversity loss. In Europe, nearly 50% of peatlands have been drained during the last decades, which have shifted their soils to carbon dioxide (CO2) sources. Soils of forestry‐drained peatlands are known to vary from CO2 sources to small sinks depending on their fertility and wetness. When peatlands are restored, it can be expected that rates of CO2 and methane exchange will vary depending on site fertility and wetness. We generated seven restoration pathways with different starting and end points and assessed the climate impacts of them. The GHG emission coefficients were compiled from literature, and radiative forcing was calculated for a 500‐year time period since restoration. All seven restoration pathways improved carbon sink capacity; however, the climate impact differed from cooling to warming. The highest cooling impact occurred in a pathway leading from nutrient‐rich drained peatlands toward tree‐covered spruce or pine mires. Warming impacts occurred in a pathway leading from nutrient‐poor drained peatlands toward open peatlands. The results of this study can be used to help identify peatland sites and restoration targets to maximize climate change mitigation from restoration. In practice, however, restoration has to fulfill other targets, such as biodiversity safeguarding, improvement of hydrological conditions, and socio‐economic aspects. Fulfilling all targets simultaneously requires compromises on all targets.
Deservingness and Welfare Attitudes Through Young Eyes: The Future of the Swiss Welfare State
Authors: Sowula Jakub
Published: June 2024

This article demonstrates the value of including youth in deservingness and welfare attitude research by investigating Swiss adolescents' deservingness opinions and welfare attitudes (N = 1601, mean age = 14.6). Through a survey experiment focusing on different unemployed groups and unemployment‐related policies, the study revisits prominent research results like the immigrant deservingness gap from a novel perspective, generating insights relevant within and beyond the Swiss context. First, deservingness is a vital predictor of attitudes towards social rights and obligations already in younger years. Moreover, while some patterns of adult‐centred studies are replicated (older unemployed are seen as more deserving than younger unemployed), there are also stark deviations: EU unemployed living in Switzerland are not seen as less deserving than Swiss unemployed. More research focusing on youth can enhance the social legitimacy of policies, clarify the relationship between deservingness and welfare attitudes, and potentially indicate what to expect from the future of the welfare state.
Identification of a new HLA‐C allele, HLA‐C*05:01:81
Authors: Gönen Sevim , Demir Cemre
Published: June 2024

At position 778 (C→T) in exon 3, the new allele C*05:01:81 is distinct from C*05:01:01.
The novel HLA‐A*11:01:127 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual
Authors: Lin Qiao‐Xian , Zhang Guan‐Bin , An Lin , Li Ye‐Mo , Yang Ting
Published: June 2024

HLA‐A*11:01:127 differs from HLA‐A*11:01:01:01 by one nucleotide in exon 3.
Teaching Specialty Courses Using Educational Applications: Five Teaching Scenarios from Technical Vocational Education
Authors: Koutsoukos Marios , Mavropoulou Eleni , Triantafyllou Serafeim
Published: June 2024

The main objectives of this study are to examine the teaching of specialty courses using educational applications and to assess technology-enhanced learning. More specifically, a unit of analysis of 25 teachers from five different subjects developed five teaching scenarios that utilize specific educational applications. Emphasis was placed on the targeted integration of these applications into the learning process and their framing with participatory and learner-centered educational techniques. According to the teachers participating in the research, the most important criteria for selecting an educational application are the relevance of the application to the teaching unit, the structure and content of the application, the ease of use, the possibility of assessing progress with quizzes and interactive tests, and the free access and use of the application by students. Concerning the benefits of using the apps, these focus on differentiating traditional teaching and providing new learning incentives, enhancing student interest, developing digital skills, enhancing collaborative learning, and lifting time and space constraints. The originality of this research lies in the use of specific educational applications for the development of teaching scenarios for specialty courses.
SSR-BASED ASSESSMENT OF GENETIC DIVERSITY IN TOMATO CULTIVARS AND LINES GROWN IN KAZAKHSTAN
Authors: Genievskaya Yu. , Jantasov S. , Nurbayeva E. , Turuspekov Ye.
Published: June 2024

Tomato (Solanum lycopersicum L.) is a versatile crop known for its nutritional value and health benefits, thriving in diverse climates worldwide. Nevertheless, regional variations persist in tomato yield, with Kazakhstan serving as an example of lower productivity in contrast to global averages. Closing this disparity requires comprehensive genetic studies and breeding efforts. This study is focused on the genetic diversity of 49 tomato cultivars and hybrids sourced from Kazakh Research Institute of Fruit and Vegetable Growing (Almaty), employing 10 SSR markers associated with important agronomic traits. SSR genotyping unveiled polymorphisms across 6 markers with variable allele numbers. Genetic diversity metrics highlighted significant genetic diversity within both outdoor and greenhouse tomato cultivars and lines. Bayesian clustering, Neighbor-joining (NJ) clustering, and principal coordinate analysis (PCoA) delineated genetic differentiation between outdoor and greenhouse tomatoes with small admixture, indicating distinct breeding directions for these two types. Highly polymorphic SSRs (PIC > 0.5) associated with essential fruit traits emerge as promising targets for marker-assisted selection (MAS) that can be used to enhance tomato breeding efficiency in Kazakhstan. According to 8 SSRs, 22 out of 30 outdoor accessions and 8 greenhouse tomato accessions were genetically uniform. This study offers comprehensive insights into the genetic diversity and population structure of tomato cultivars and lines in Kazakhstan, laying the foundation for informed breeding endeavors aimed at bolstering yield and resilience in tomato crops.
MONOCLONAL ANTIBODIES AGAINST THE BABESIA BOVIS RAP1 ANTIGEN: OBTAINING AND CHARACTERIZATION
Authors: Mukantayev K. , Tursunov K. , Adish Zh. , Kanayev D. , Tokhtarova L. , Abirbekov B.
Published: June 2024

Bovine babesiosis is a disease caused by parasites of the genus Babesia. One of the main Babesia genera causing disease in cattle, according to the International Office of Epizootics (OIE), is Babesia bovis. Recovered cattle become permanent latent carriers and can be a source of tick infestation and spread of infection. Despite susceptibility and specificity, diagnostic methods such as enzyme-linked immunosorbent assays (ELISA) and indirect fluorescent antibody assays (IFA) have some disadvantages. These methods require a long analysis time, the use of specialized equipment and trained specialists. At the same time, immunochromatographic tests (ICA) are widely used in veterinary practice today. ICA is characterized by a short analysis time, ease of performance and interpretation of results. The main components of the ICA test system are monoclonal antibodies. As a result of the studies, three mAbs against the recombinant Rap1 antigen of B. bovis were obtained. The resulting mAbs have high diagnostic characteristics. A conjugate of colloidal gold with mAbs is capable of detecting the Rap1 antigen of the causative agent of babesiosis in cattle.
Reducing Helium Consumption in Valve Manufacturing: Alternative Test Fluid for Fugitive Emissions Production Testing
Authors: Lechevallier Emiel , Kruijer Alfred
Published: June 2024

Helium gas is used for fugitive emissions testing of industrial components such as valves. Purpose of these tests is to prevent unintentional and undesirable releases of process gas, from industrial sites, into the environment. These fugitive emissions are direct negative contributors to greenhouse gas emissions and local air quality, and therefore linked to environmental and health and safety rules. The valve industry has standards in place to qualify valves for fugitive emissions performance. For instance, ISO 15848-1 (2015, “Industrial Valves – Measurement, Test and Qualification Procedures for Fugitive Emissions Part 1: Classification System and Qualification Procedures for Type Testing of Valves”) classifies valve designs based on emissions, temperature, endurance, and describe the methods for prototype testing. ISO 15848-2 (2015, “Industrial Valves – Measurement, Test and Qualification Procedures for Fugitive Emissions Part 2: Production Acceptance of Test Valves”) defines the criteria for production testing. Test methods in these standards are currently based on Helium gas or Methane gas as the test fluid. With the perspective that governments and the energy industry are setting distinct and increasingly challenging goals to reduce emissions and decarbonize, it is expected that the volume of tests performed will increase in the near future, which, based on a finite resource of helium, may not be sustainable in the future.
Sparse Identification of Nonlinear Dynamics-Based Feature Extraction for Data Driven Model Predictive Control of a Buck Boost Switch Mode Power Supply
Authors: Mallamo Declan P. , Azarian Michael H. , Pecht Michael G.
Published: June 2024

This paper presents two methods of creating model predictive control (MPC) strategies for efficient real-time control algorithms for power electronics. Two novel methods of performing nonlinear modeling are presented in this research, the first being novel Takagi-Sugeno model, which combines two linear state space models using a membership function to model the nonlinear transitions between operating points. The second method involves using sparse identification of nonlinear dynamics (SINDy), a nonlinear modeling technique that uses L1 regularization of least squares for time-series data to define a parsimonious polynomial function set. This set is used to define the input feature space to extended dynamic mode decomposition (DMD) with control. These models are then used for data-driven model predictive control of a buck switch mode power supply to find the optimal duty cycle that regulates the output voltage over a finite tuned proportional integral derivative (PID) controller. Numerical accuracy challenges are discussed, and strategies are offered for their mitigation.
Verification and Validation of Turbulence Modeling of Flow Through Triply Periodic Minimal Surfaces Porous Structures
Authors: Piatti Cecilia , Hicks Alex , Gajetti Eleonora , Ward Caleb , Pourghasemi Mahyar , Marocco Luca , Savoldi Laura , Fathi Nima
Published: June 2024

This work is devoted to verification and validation (V&V) activities of modeling and simulation of flow through porous media, with a particular focus on Triply Periodic Minimal Surfaces (TPMS) porous structures. TPMS is a class of porous materials that have attracted significant attention in recent years due to their unique properties, including high porosity, large surface area to volume ratio, and tunable pore structures. Within the context of energy sector decarbonization, several power generation technologies demand components with high heat removal capabilities, as is the case for solar or nuclear fusion machines. TPMS-based devices can be designed to equip heat sinks and heat exchangers introducing significant advantages with respect to traditional solutions. However, accurately predicting the complex flow behavior through TPMS porous media remains a challenge due to the intricate geometry and intricate flow patterns. Consequently, V&V activities play a crucial role in assessing the credibility of various models applied in modeling flow through these structures, establishing a foundation for reliable predictions. This work presents the results of V&V activities on the simulations of three-dimensional CFD using three turbulence models, namely Realizable k-ε two-layer, Lag-EB k-ε and SST (Menter) k-ω. Spatial resolution limitations in the application simulation were identified via solution verification. The experimental data obtained from our experimental setup were used for our validation assessment. All TPMS cases were fabricated using 3D printing technology. The discrepancy between simulation and experiments was evaluated and discussed.
Performance enhancement in spin transfer torque magnetic random access memory through in situ cap layer optimization
Authors: Ji Zhenghui , Peng Yongzhao , Qiu Guoxiu , Han Guchang , Guo Qijun
Published: June 2024

Magnetic tunnel junctions (MTJs), a key component of spin transfer torque magnetic random access memory, are typically fabricated using two main processes: plasma etching and in situ protective cap layer deposition. It has been found that while the etching process predominantly affects MTJ performance, the cap layer process can further enhance electrical and magnetic properties. In this study, we achieved performance improvements in MTJs by optimizing the cap layer deposition process through various experimental methods, such as modifying the gas mixtures used in the deposition process and incorporating a novel post-plasma treatment. During the deposition of the silicon nitride (SiNx) cap layer, N-rich dissociated compounds can induce passivation of the MTJ layer, leading to additional loss of tunneling magnetoresistance (TMR) and coercive field (Hc). To circumvent this challenge, we prioritized modifying the gas ratio in the SiNx deposition process. Additionally, hydrogen introduced during SiNx deposition can penetrate the MTJ pillars and degrade their properties. To mitigate this, we developed a novel post-nitrogen plasma treatment in a plasma-enhanced chemical vapor deposition chamber, which effectively desorbed the excess hydrogen from the MTJ film stack. As a result of these optimized processes, the TMR loss, compared to a blanket wafer, was reduced from 25% to 8%, and Hc increased by up to 33% for the same stack, achieving significant performance enhancements.
Prevalence and Correlates of Adherence to the Global Total Physical Activity Guideline Based on Step Counting Among 3- to 4-Year-Olds: Evidence From SUNRISE Pilot Studies From 17 Countries
Authors: Mwase-Vuma Tawonga W. , Janssen Xanne , Chong Kar Hau , Okely Anthony D. , Tremblay Mark S. , Draper Catherine E. , Webster E. Kipling , Florindo Alex Antonio , Staiano Amanda E. , Pham Bang Nguyen , Tanaka Chiaki , Koh Denise , Guan Hongyan , Tang Hong K. , Löf Marie , Hossain Mohammad Sorowar , Munambah Nyaradzai E. , Cross Penny , Chathurangana PW Prasad , Reilly John J.
Published: June 2024

Background: There is limited evidence from globally diverse samples on the prevalence and correlates of meeting the global guideline of 180 minutes per day of total physical activity (TPA) among 3- to 4-year-olds. Methods: Cross-sectional study involving 797 (49.2% girls) 3- to 4-year-olds from 17 middle- and high-income countries who participated in the pilot phases 1 and 2 of the SUNRISE International Study of Movement Behaviours in the Early Years. Daily step count was measured using thigh-worn activPAL accelerometers. Children wore the accelerometers for at least one 24-hour period. Children were categorized as meeting the TPA guideline based on achieving ≥11,500 steps per day. Descriptive analyses were conducted to describe the proportion of meeting the TPA guideline for the overall sample and each of the sociodemographic variables, and 95% CIs were calculated. Multivariable logistic regression was used to determine the sociodemographic correlates of meeting the TPA guideline. Results: Mean daily step count was 10,295 steps per day (SD = 4084). Approximately one-third of the sample (30.9%, 95% CI, 27.6–34.2) met the TPA guideline. The proportion meeting the guideline was significantly lower among girls (adjusted OR [aOR] = 0.70, 95% CI, 0.51–0.96) and 4-year-olds (aOR = 0.50, 95% CI, 0.34–0.75) and higher among rural residents (aOR = 1.78, 95% CI, 1.27–2.49) and those from lower middle-income countries (aOR = 1.35, 95% CI, 0.89–2.04). Conclusions: The findings suggest that a minority of children might meet the TPA guideline globally, and the risk of not meeting the guideline differed by sociodemographic indicators. These findings suggest the need for more surveillance of TPA in young children globally and, possibly, interventions to improve childhood health and development.
Brilacidin, a novel antifungal agent against
Cryptococcus neoformans
Authors: Diehl Camila , Pinzan Camila Figueiredo , de Castro Patrícia Alves , Delbaje Endrews , García Carnero Laura C. , Sánchez-León Eddy , Bhalla Kabir , Kronstad James W. , Kim Dong-gyu , Doering Tamara L. , Alkhazraji Sondus , Mishra Nagendra N. , Ibrahim Ashraf S. , Yoshimura Mami , Vega Isuhuaylas Luis Alberto , Pham Lien Thi Kim , Yashiroda Yoko , Boone Charles , dos Reis Thaila Fernanda , Goldman Gustavo H.
Published: June 2024

Cryptococcus neoformans
causes cryptococcosis, one of the most prevalent fungal diseases, generally characterized by meningitis. There is a limited and not very effective number of drugs available to combat this disease. In this manuscript, we show the host defense peptide mimetic brilacidin (BRI) as a promising antifungal drug against
C. neoformans
. BRI can affect the organization of the cell membrane, increasing the fungal cell permeability. We also investigated the effects of BRI against the model system
Saccharomyces cerevisiae
by analyzing libraries of mutants grown in the presence of BRI. In
S. cerevisiae
, BRI also affects the cell membrane organization, but in addition the cell wall integrity pathway and calcium metabolism.
In vivo
experiments show BRI significantly reduces
C. neoformans
survival inside macrophages and partially clears
C. neoformans
lung infection in an immunocompetent murine model of invasive pulmonary cryptococcosis. We also observed that BRI interacts with caspofungin (CAS) and amphotericin (AmB), potentiating their mechanism of action against
C. neoformans
. BRI + CAS affects endocytic movement, calcineurin, and mitogen-activated protein kinases. Our results indicate that BRI is a novel antifungal drug against cryptococcosis.

IMPORTANCE

Invasive fungal infections have a high mortality rate causing more deaths annually than tuberculosis or malaria. Cryptococcosis, one of the most prevalent fungal diseases, is generally characterized by meningitis and is mainly caused by two closely related species of basidiomycetous yeasts,
Cryptococcus neoformans
and
Cryptococcus gattii
. There are few therapeutic options for treating cryptococcosis, and searching for new antifungal agents against this disease is very important. Here, we present brilacidin (BRI) as a potential antifungal agent against
C. neoformans
. BRI is a small molecule host defense peptide mimetic that has previously exhibited broad-spectrum immunomodulatory/anti-inflammatory activity against bacteria and viruses. BRI alone was shown to inhibit the growth of
C. neoformans
, acting as a fungicidal drug, but surprisingly also potentiated the activity of caspofungin (CAS) against this species. We investigated the mechanism of action of BRI and BRI + CAS against
C. neoformans
. We propose BRI as a new antifungal agent against cryptococcosis.
Genome sequencing of correlated pathogenic
Escherichia coli
and
Enterococcus
associated with recurrent urinary tract infections
Authors: Hogins Jacob , Do Hung P. , Dashti Marjan Ganjali , Zimmern Philippe E. , Reitzer Larry
Published: June 2024

Reported here are the sequences for 11
Escherichia coli
and four
Enterococcus
strains isolated from post-menopausal women with a recurrent urinary tract infection. Each of the
Enterococcus
strains were isolated along with an
E. coli
strain. This provides a resource of high-quality complete genomes from polymicrobial infections.
Coding-complete genome sequence of a bovine viral diarrhea virus isolate NX2023 from a calf in China
Authors: Liu Wei , Shao Junjun , Huang Haiyan , Liu Yijia , Guo Huichen , Chang Huiyun , Wang Jiandong , Shandian Gao
Published: June 2024

The coding-complete genome sequence of bovine viral diarrhea virus (BVDV) isolate NX2023 that originated from a calf in China was determined. Phylogenetic analysis showed that the NX2023 strain belongs to the BVDV-1d subgenotype.
Genomic sequence of three hydrocarbonoclastic pseudomonadaceae strains isolated from marine sediments of the port of Rosarito, Baja California, Mexico
Authors: Millán-López Sofía , Zurita-Artaloitia Juan M. , Silva-Jiménez Hortencia , Pardo-López Liliana , Sanchez-Flores Alejandro
Published: June 2024

We report the draft genome sequence of three marine bacteria belonging to
Pseudomonas
and
Stutzerimonas
genera, with hydrocarbonoclastic metabolism for oil and monoaromatic hydrocarbon degradation. The genomic information of these organisms contributes to the knowledge of natural and polluted marine environments with ubiquitous presence of hydrocarbons as a selective pressure.
Repurposing Hsp90 inhibitors as antimicrobials targeting two-component systems identifies compounds leading to loss of bacterial membrane integrity
Authors: Fernandez-Ciruelos Blanca , Albanese Marco , Adhav Anmol , Solomin Vitalii , Ritchie-Martinez Arabela , Taverne Femke , Velikova Nadya , Jirgensons Aigars , Marina Alberto , Finn Paul W. , Wells Jerry M.
Published: June 2024

The discovery of antimicrobials with novel mechanisms of action is crucial to tackle the foreseen global health crisis due to antimicrobial resistance. Bacterial two-component signaling systems (TCSs) are attractive targets for the discovery of novel antibacterial agents. TCS-encoding genes are found in all bacterial genomes and typically consist of a sensor histidine kinase (HK) and a response regulator. Due to the conserved Bergerat fold in the ATP-binding domain of the TCS HK and the human chaperone Hsp90, there has been much interest in repurposing inhibitors of Hsp90 as antibacterial compounds. In this study, we explore the chemical space of the known Hsp90 inhibitor scaffold 3,4-diphenylpyrazole (DPP), building on previous literature to further understand their potential for HK inhibition. Six DPP analogs inhibited HK autophosphorylation
in vitro
and had good antimicrobial activity against Gram-positive bacteria. However, mechanistic studies showed that their antimicrobial activity was related to damage of bacterial membranes. In addition, DPP analogs were cytotoxic to human embryonic kidney cell lines and induced the cell arrest phenotype shown for other Hsp90 inhibitors. We conclude that these DPP structures can be further optimized as specific disruptors of bacterial membranes providing binding to Hsp90 and cytotoxicity are lowered. Moreover, the X-ray crystal structure of resorcinol, a substructure of the DPP derivatives, bound to the HK CheA represents a promising starting point for the fragment-based design of novel HK inhibitors.

IMPORTANCE

The discovery of novel antimicrobials is of paramount importance in tackling the imminent global health crisis of antimicrobial resistance. The discovery of novel antimicrobials with novel mechanisms of actions, e.g., targeting bacterial two-component signaling systems, is crucial to bypass existing resistance mechanisms and stimulate pharmaceutical innovations. Here, we explore the possible repurposing of compounds developed in cancer research as inhibitors of two-component systems and investigate their off-target effects such as bacterial membrane disruption and toxicity. These results highlight compounds that are promising for further development of novel bacterial membrane disruptors and two-component system inhibitors.
Host-directed therapy with amiodarone in preclinical models restricts mycobacterial infection and enhances autophagy
Authors: Kilinç Gül , Boland Ralf , Heemskerk Matthias T. , Spaink Herman P. , Haks Mariëlle C. , van der Vaart Michiel , Ottenhoff Tom H. M. , Meijer Annemarie H. , Saris Anno
Published: June 2024

Mycobacterium tuberculosis
(
Mtb
) as well as nontuberculous mycobacteria are intracellular pathogens whose treatment is extensive and increasingly impaired due to the rise of mycobacterial drug resistance. The loss of antibiotic efficacy has raised interest in the identification of host-directed therapeutics (HDT) to develop novel treatment strategies for mycobacterial infections. In this study, we identified amiodarone as a potential HDT candidate that inhibited both intracellular
Mtb
and
Mycobacterium avium
in primary human macrophages without directly impairing bacterial growth, thereby confirming that amiodarone acts in a host-mediated manner. Moreover, amiodarone induced the formation of (auto)phagosomes and enhanced autophagic targeting of mycobacteria in macrophages. The induction of autophagy by amiodarone is likely due to enhanced transcriptional regulation, as the nuclear intensity of the transcription factor EB, the master regulator of autophagy and lysosomal biogenesis, was strongly increased. Furthermore, blocking lysosomal degradation with bafilomycin impaired the host-beneficial effect of amiodarone. Finally, amiodarone induced autophagy and reduced bacterial burden in a zebrafish embryo model of tuberculosis, thereby confirming the HDT activity of amiodarone
in vivo
. In conclusion, we have identified amiodarone as an autophagy-inducing antimycobacterial HDT that improves host control of mycobacterial infections.

IMPORTANCE

Due to the global rise in antibiotic resistance, there is a strong need for alternative treatment strategies against intracellular bacterial infections, including
Mycobacterium tuberculosis
(
Mtb
) and non-tuberculous mycobacteria. Stimulating host defense mechanisms by host‐directed therapy (HDT) is a promising approach for treating mycobacterial infections. This study identified amiodarone, an antiarrhythmic agent, as a potential HDT candidate that inhibits the survival of
Mtb
and
Mycobacterium avium
in primary human macrophages. The antimycobacterial effect of amiodarone was confirmed in an
in vivo
tuberculosis model based on
Mycobacterium marinum
infection of zebrafish embryos. Furthermore, amiodarone induced autophagy and inhibition of the autophagic flux effectively impaired the host-protective effect of amiodarone, supporting that activation of the host (auto)phagolysosomal pathway is essential for the mechanism of action of amiodarone. In conclusion, we have identified amiodarone as an autophagy-inducing HDT that improves host control of a wide range of mycobacteria.