bluuebunny/crossref_metadata_2025 huggingface dataset:
Esperienze didattiche di modellizzazione emergente: uno sguardo ai processi di matematizzazione
Authors: Passarella Simone
Published: November 2021

In questo contributo si presentano due esperienze didattiche di modellizzazione emergente. Dopo aver chiarito i costrutti di modellizzazione emergente e matematizzazione, vengono proposte due esperienze didattiche. La prima, condotta in una classe seconda della scuola primaria, ha riguardato la proprietà distributiva della moltiplicazione rispetto all’addizione; la seconda, in una classe quarta di una scuola secondaria di secondo grado, ha riguardato il calcolo del volume di solidi non noti. La descrizione di queste esperienze segue tre direzioni principali: l’esplicitazione dell’obiettivo di apprendimento; la scelta del problema nel contesto; l’analisi dei processi di matematizzazione orizzontale e verticale presenti nelle strategie risolutive degli studenti. Le esperienze descritte rappresentano un esempio significativo dell’importanza di proporre agli studenti attività di modellizzazione emergente, supportando gli studenti in un processo di reinvenzione di concetti matematici a partire dalle loro informali strategie risolutive.
The role of intellectual property in security defense capacity of the state.
Authors: Zaikivskyi Oleksandr , Onistrat Oleksandr
Published: November 2021

Keywords: defense capability, intellectual property, regulatory support

The conceptual issues of the legislation of Ukraine,which determine the state policy in the field of national security and defence, regardingthe settlement of issues related to ensuring the state defence capabilities are considered.The scientific publications on actual questions in this sphere concerningproblems and prospects of increase of defence capability of Ukraine are analysed.The role of intellectual property in all components of Ukraine's defence system hasbeen studied, and it has been noted that unresolved problems in the field of intellectualproperty management pose an increasing threat to Ukraine's national security.The importance of ensuring the protection of intellectual property in the process ofimplementing measures to improve the defence capabilities of the state and the needto improve legislation in this area is defined.

Recommendations for improving the regulatory framework for national securityand defence in order to address the problematic issues of intellectual property in thisarea are submitted.State defence capability is the ability of state to defend itself in the event of armedaggression or armed conflict. It consists of material and immaterial elements and is aset of military, economic, social and moral and political potential in the field of defenceand appropriate conditions for its implementation.Resolving the issues of reforming not only the Armed Forces of Ukraine, but firstthe entire state, modernization and rearmament of the Ukrainian army has become avital necessity. Only the solution of this issue will allow to raise the defence capabilityof our state to the proper level for the preservation of independent Ukraine.Ensuring the military security of Ukraine largely depends on equipping the ArmedForces of Ukraine with modern types and models of weapons and military equipment,developed on the basis of intellectual property rights.It is the military-technical sphere where the objects of intellectual property rightsbelonging to the sphere of national security and defence are created, and the state isobliged to ensure their protection. This will increase the competitiveness of the domesticdefence industry and make claims impossible for anyone in the mass productionof weapons and military equipment for their own needs and for exports, which directlyaffects defence capabilities.And this requires proper protection of intellectual property rights both in theprocess of own production of weapons and military equipment, as well as in militarytechnicalcooperation.
TAKING INTO ACCOUNT THE INFLUENCE OF WIND ROSE DURING THE DIVISION OF LANDS, ADJACENT TO THE "KARAZHYRA" COAL DEPOSIT
Authors:   Siberian State University of Geosystems and Technologies, Issabekova Kamila S. , Kuderinov Serikbek M. ,   Siberian State University of Geosystems and Technologies, Kuderinova Nazira A. ,   The Semey State University named after Shakarim
Published: November 2021

The article considers the influence of the wind rose on the lands adjacent to the Karazhyra coal mine on the territory of the Semipalatinsk nuclear test site. It is assumed that the influence of the wind rose is an important environmental factor in the cadastral value of land contaminated with radionuclides. The purpose of the study is to assess the impact of secondary pollution by technogenic radionuclides on the territory adjacent to the nuclear test site and to determine the movable boundaries of such pollution. The impact assessment was carried out on the basis of an analysis of the factors contributing to the spread of pollution at the mine itself and along the road used to deliver contaminated coal to Semey. As a result, the types of work affecting the radiation situation in the study area were identified, the main directions of air flows in the field area were determined. The conclusion is made about the influence of the situation on the methodology for performing geodetic works. Requirements for the accuracy of determining the boundaries of contaminated land plots are proposed.
IMPROVING THE METHODOLOGY FOR METROLOGICAL CERTIFICATION OF TOTAL STATIONS AND LIGHT RANGE FINDERS
Authors:   Siberian State University of Geosystems and Technologies, Ustavich Georgij A. , Kosarev Nikolay S. ,   Siberian State University of Geosystems and Technologies, Barannikov Dmitriy A. ,   Siberian State University of Geosystems and Technologies, Mezentsev Ivan A. ,   Siberian State University of Geosystems and Technologies, Birukov Dmitriy V. ,   Siberian State University of Geosystems and Technologies
Published: November 2021

To ensure the uniformity of measurements, it is necessary to perform periodic verifications of ge-odetic instruments in accordance with the requirements of the relevant regulatory documents. In relation to total stations and light meters, ensuring the uniformity of measurements should be carried out by conducting annual periodic checks with the use of stationary reference bases of the 2nd or 3rd category, which were previously created in almost all regions of the country. However, to date, only two such bases have been preserved on the territory of the Russian Federation. The reason for this situa-tion was the lack of proper metrological support for the line lengths of the reference bases themselves, caused by the need for organizational measures, the lack of trained specialists, as well as significant financial expenses for field work. In this regard, there was a scientific and technical task of developing a local calibration scheme (LCS) to provide periodic verifications of total stations and light-emitting diodes over the entire range of measured distances, which does not require the creation of stationary reference bases. For this purpose, the LCS scheme is proposed, based on the use of the method of direct distance measurements. Its essence lies in the simultaneous measurement of the selected distances by reference and verified total stations. To do this, a reference total station and a verifiable one are installed on two tripods located next to each other, which measure the same distance. After that, the total stations are swapped and the measurements are repeated. At the end of the measurement, the measured distances are compared with the reference and verified total stations. Then, based on the difference between these distances, a conclusion is made about the accuracy of the de-vice being tested, as stated in the technical data sheet. The results of the implementation of the proposed LCS showed that its scheme provides the accuracy of measurements at the level of the 2nd category reference basis, and the methodology and accuracy of the length unit transmission meets the of regulatory requirements.
TECHNIQUE OF AUTOMATIC MOBILE LASER SCANNING DATA ADJUSTMENT
Authors:   Siberian State University of Geosystems and Technologies, Altyntsev Maxim A. , Saber Karkokli Hamid Majid ,   Siberian State University of Geosystems and Technologies
Published: November 2021

Adjustment is a main step in the preliminary processing of mobile laser scanning (MLS) data. As a result of this step, a point cloud is generated in a certain coordinate system. The modern software, provided with the corresponding surveying system, is capable of performing in automatic mode most stages of MLS data adjustment obtained for territories with different quantity of buildings. With a suf-ficient number of vertically arranged planar objects, such as building walls, the algorithms embedded in the software provide a high accuracy of relative adjustment, which consists in calculating and ap-plying corrections for trajectories obtained with re-scanning the same area. Absolute adjustment can also be carried out automatically, subject to the rules for placing control points in order to automatically detect them. This kind of adjustment involves transforming a point cloud with using control point coordinates measured with more accurate surveying methods. The accuracy of automatic relative adjustment can be significantly reduced with the almost complete absence of vertical flat objects. In this case, it is necessary to develop additional adjustment techniques capable of using not only flat objects of a large area, but also vertical objects, such as road signs and poles. Comprehensive technique of MLS data adjustment, which can use information on the position of road signs and poles for territories with an insufficient number of vertical flat objects is proposed. The accuracy estimation of both the relative and absolute MLS data adjustment according to the proposed technique was carried out. The choice of the required control point density for territories with different quantity of buildings is explained.
Proto-Language as a Structurer and Enhancer of Perception
Authors: Scott James , Bozic Mirjana , Foley Robert
Published: November 2021

The evolution of the capacity for language remains a contested and important subject. Newer approaches consider language evolution to be a protracted and mosaic process, with selection operating in different contexts through multiple drivers. This research examines two potential factors in language evolution: cognitive-structuring functions of language, and non-arbitrariness (iconicity). It is based on the hypothesis that language exerts powerful facilitative effects on cognition, which may provide an additional adaptive advantage to early proto-language. Iconicity meanwhile may offer a foothold for the emergence of semantics by providing an innate link between sound and meaning. This study investigated both aspects through an online game in which participants had to categorise novel species of aliens. Results provided evidence for both cognitive structuring due to language, and iconicity, adding credence to the suggestion that both may have played important roles in language evolution.
A Pulmonary Vascular Model From Endothelialized Whole Organ Scaffolds
Authors: Yuan Yifan , Leiby Katherine L. , Greaney Allison M. , Raredon Micha Sam Brickman , Qian Hong , Schupp Jonas C. , Engler Alexander J. , Baevova Pavlina , Adams Taylor S. , Kural Mehmet H. , Wang Juan , Obata Tomohiro , Yoder Mervin C. , Kaminski Naftali , Niklason Laura E.
Published: November 2021

The development of an in vitro system for the study of lung vascular disease is critical to understanding human pathologies. Conventional culture systems fail to fully recapitulate native microenvironmental conditions and are typically limited in their ability to represent human pathophysiology for the study of disease and drug mechanisms. Whole organ decellularization provides a means to developing a construct that recapitulates structural, mechanical, and biological features of a complete vascular structure. Here, we developed a culture protocol to improve endothelial cell coverage in whole lung scaffolds and used single-cell RNA-sequencing analysis to explore the impact of decellularized whole lung scaffolds on endothelial phenotypes and functions in a biomimetic bioreactor system. Intriguingly, we found that the phenotype and functional signals of primary pulmonary microvascular revert back—at least partially—toward native lung endothelium. Additionally, human induced pluripotent stem cell-derived endothelium cultured in decellularized lung systems start to gain various native human endothelial phenotypes. Vascular barrier function was partially restored, while small capillaries remained patent in endothelial cell-repopulated lungs. To evaluate the ability of the engineered endothelium to modulate permeability in response to exogenous stimuli, lipopolysaccharide (LPS) was introduced into repopulated lungs to simulate acute lung injury. After LPS treatment, proinflammatory signals were significantly increased and the vascular barrier was impaired. Taken together, these results demonstrate a novel platform that recapitulates some pulmonary microvascular functions and phenotypes at a whole organ level. This development may help pave the way for using the whole organ engineering approach to model vascular diseases.
Distribution of Biominerals and Mineral-Organic Composites in Plant Trichomes
Authors: Ensikat Hans-Jürgen , Weigend Maximilian
Published: November 2021

Biomineralization is a common phenomenon in plants and has been shown to be chemically, functionally and topologically diverse. Silica and calcium carbonate have long been known as structural plant biominerals and calcium phosphate (apatite)–long known from animals–has recently been reported. Strikingly, up to three different biominerals may occur in a single trichome in, e.g., Urticaceae and Loasaceae, and in combination with organic compounds, can form organic/inorganic composite materials. This article presents an extension of previous studies on the distribution of these biominerals in Loasaceae trichomes with a focus on their spatial (three-dimensional) distribution and co-localization with organic substances. Light microscopy and scanning electron microscopy with high-resolution EDX element analyses of sample surfaces and sections illustrate the differential distribution and composition of the different biomineral phases across cell surfaces and cell walls. Raman spectroscopy additionally permits the identification of organic and inorganic compounds side by side. All three biominerals may be found in a nearly pure inorganic phase, e.g., on the plant surfaces and in the barbs of the glochidiate trichomes, or in combination with a larger proportion of organic compounds (cellulose, pectin). The cell lumen may be additionally filled with amorphous mineral deposits. Water-solubility of the mineral fractions differs considerably. Plant trichomes provide an exciting model system for biomineralization and enable the in-vivo study of the formation of complex composite materials with different biomineral and organic compounds involved.
Improvements in Smartphone and Night Vision Imaging Technologies Enable Low Cost, On-Site Assays of Bioluminescent Cells
Authors: Wienhold Mark , Kirkpatrick Andrew , Xu Tingting , Ripp Steven , Sayler Gary , Close Dan
Published: November 2021

Technologies enabling on-site environmental detection or medical diagnostics in resource-limited settings have a strong disruptive potential compared to current analytical approaches that require trained personnel in laboratories with immobile, resource intensive instrumentation. Handheld devices, such as smartphones, are now routinely produced with CPUs, RAM, wireless data transfer capabilities, and high-resolution complementary metal oxide semiconductor (CMOS) cameras capable of supporting the capture and processing of bioluminescent signals. In theory, combining the capabilities of these devices with continuously bioluminescent human cell-based bioreporters would allow them to replicate the functionality of more expensive, more complex, and less flexible platforms while supporting human-relevant conclusions. In this work, we compare the performance of smartphone (CMOS) and night vision (image intensifier) devices with in vivo (CCD camera), and in vitro (photomultiplier tube) laboratory instrumentation for monitoring signal dynamics from continuously bioluminescent human cellular models under toxic, stable, and induced expression scenarios. All systems detected bioluminescence from cells at common plating densities. While the in vivo and in vitro systems were more sensitive and detected signal dynamics representing cellular health changes earlier, the night vision and smartphone systems also detected these changes with relatively similar coefficients of variation and linear detection capabilities. The smartphone system did not detect transcriptional induction. The night vision system did detect transcriptional activation, but was less sensitive than the in vivo or in vitro systems and required a stronger induction before the change could be resolved.
Chronic Stress: Impacts on Tumor Microenvironment and Implications for Anti-Cancer Treatments
Authors: Tian Wentao , Liu Yi , Cao Chenghui , Zeng Yue , Pan Yue , Liu Xiaohan , Peng Yurong , Wu Fang
Published: November 2021

Chronic stress is common among cancer patients due to the psychological, operative, or pharmaceutical stressors at the time of diagnosis or during the treatment of cancers. The continuous activations of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS), as results of chronic stress, have been demonstrated to take part in several cancer-promoting processes, such as tumorigenesis, progression, metastasis, and multi-drug resistance, by altering the tumor microenvironment (TME). Stressed TME is generally characterized by the increased proportion of cancer-promoting cells and cytokines, the reduction and malfunction of immune-supportive cells and cytokines, augmented angiogenesis, enhanced epithelial-mesenchymal transition, and damaged extracellular matrix. For the negative effects that these alterations can cause in terms of the efficacies of anti-cancer treatments and prognosis of patients, supplementary pharmacological or psychotherapeutic strategies targeting HPA, SNS, or psychological stress may be effective in improving the prognosis of cancer patients. Here, we review the characteristics and mechanisms of TME alterations under chronic stress, their influences on anti-cancer therapies, and accessory interventions and therapies for stressed cancer patients.
Effect of Cavity Cleanser With Long-Term Antibacterial and Anti-Proteolytic Activities on Resin–Dentin Bond Stability
Authors: Gou Yaping , Jin Wei , He Yanning , Luo Yu , Si Ruirui , He Yuan , Wang Zhongchi , Li Jing , Liu Bin
Published: November 2021

Objective

Secondary caries caused by oral microbiome dysbiosis and hybrid layer degradation are two important contributors to the poor resin–dentin bond durability. Cavity cleansers with long-term antimicrobial and anti-proteolytic activities are in demand for eliminating bacteria-induced secondary caries and preventing hybrid layers from degradation. The objectives of the present study were to examine the long-term antimicrobial effect and anti-proteolytic potential of poly(amidoamine) dendrimers with amino terminal groups (PAMAM-NH2) cavity cleanser.

Methods

Adsorption tests by attenuated total reflectance–infrared (ATR-IR) spectroscopy and confocal laser scanning microscopy (CLSM) were first performed to evaluate whether the PAMAM-NH2 cavity cleanser had binding capacity to dentin surface to fulfill its relatively long-term antimicrobial and anti-proteolytic effects. For antibacterial testing, Streptococcus mutans, Actinomyces naeslundii, and Enterococcus faecalis were grown on dentin surfaces, prior to the application of cavity cleanser. Colony-forming unit (CFU) counts and live/dead bacterial staining were performed to assess antibacterial effects. Gelatinolytic activity within the hybrid layers was directly detected by in situ zymography. Adhesive permeability of bonded interface and microtensile bond strength were employed to assess whether the PAMAM-NH2 cavity cleanser adversely affected resin–dentin bonding. Finally, the cytotoxicity of PAMAM-NH2 was evaluated by the Cell Counting Kit-8 (CCK-8) assay.

Results

Adsorption tests demonstrated that the binding capacity of PAMAM-NH2 on dentin surface was much stronger than that of 2% chlorhexidine (CHX) because its binding was strong enough to resist phosphate-buffered saline (PBS) washing. Antibacterial testing indicated that PAMAM-NH2 significantly inhibited bacteria grown on the dentin discs as compared with the control group (p < 0.05), which was comparable with the antibacterial activity of 2% CHX (p > 0.05). Hybrid layers conditioned with PAMAM-NH2 showed significant decrease in gelatin activity as compared with the control group. Furthermore, PAMAM-NH2 pretreatment did not adversely affect resin–dentin bonding because it did not decrease adhesive permeability and microtensile strength. CCK-8 assay showed that PAMAM-NH2 had low cytotoxicity on human dental pulp cells (HDPCs) and L929.

Conclusions

PAMAM-NH2 cavity cleanser developed in this study could provide simultaneous long-term antimicrobial and anti-proteolytic activities for eliminating secondary caries that result from a dysbiosis in the oral microbiome and for preventing hybrid layers from degradation due to its good binding capacity to dentin collagen matrix, which are crucial for the maintenance of resin–dentin bond durability.
Periplocymarin Alleviates Doxorubicin-Induced Heart Failure and Excessive Accumulation of Ceramides
Authors: Yun Weijing , Qian Lei , Yuan Ruqiang , Xu Hu
Published: November 2021

Doxorubicin-driven cardiotoxicity could result in dilated cardiomyopathy and heart failure (HF). Previously, we showed that periplocymarin exerted a cardiotonic role by promoting calcium influx and attenuating myocardial fibrosis induced by isoproterenol (ISO) by improving the metabolism of cardiomyocytes. However, the impact of periplocymarin on doxorubicin (DOX)-triggered cardiomyopathy has not been investigated. In the current study, C57BL/6 mice were randomly divided into three groups, namely, the control, DOX, and DOX+periplocymarin groups. The cardiac function and apoptosis were measured. Our results revealed that periplocymarin administration greatly improved the DOX-induced cardiac dysfunction manifested by the ejection fraction (EF%), fractional shortening (FS%), left ventricular posterior wall thickness (LVPW), left ventricular anterior wall thickness (LVAW), left ventricular (LV) mass, and attenuated DOX-induced cardiomyocyte apoptosis assessed by hematoxylin and eosin (H&E) staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and western blotting. Further study using H9c2 cells revealed that the pretreatment of periplocymarin suppressed DOX-induced apoptosis evidenced by annexin V staining. Moreover, liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis demonstrated that DOX lead to an accumulation in serum ceramide, and the pre-treatment of periplocymarin could reverse this phenomenon. Network pharmacology also demonstrated that ceramide metabolism was involved in the process. Consistently, real-time PCR showed that periplocymarin significantly abolished the induction of the genes involved in the de novo synthesis of ceramide, i.e., CerS2, CerS4, CerS5, and CerS6, and the induction was attributed to the treatment of DOX. Collectively, these results suggested that periplocymarin reduced cardiomyocyte apoptosis to protect hearts from DOX-induced cardiotoxicity and the de novo synthesis of ceramides was involved in this process.
Small-Scale Soft-Sediment Deformation Structures in the Cross-Bedded Coconino Sandstone (Permian; Arizona, United States); Possible Evidence for Seismic Influence
Authors: Brand Leonard , Maithel Sarah
Published: November 2021

The Permian Coconino Sandstone of northern Arizona contains numerous small-scale, soft-sediment deformation structures (SSDSs). These novel structures may be indicators of paleoenvironment or sedimentary processes. These SSD are generally shallow and occur on the surfaces of cross-beds, in contrast to convoluted bedding up to tens of meters thick commonly observed in some other eolian sandstones. These differences in structures imply differences in the processes that formed the Coconino Sandstone, or differences in the underlying depositional conditions. These SSDSs occur in outcrops at the Grand Canyon, and farther south in quarries near the towns of Seligman and Ash Fork. Size, orientation, structure, sedimentary context, clay content, and porosity of the structures are described. The SSDSs occur as small folds and ridges on the paleo lee side of otherwise undisturbed cross-beds. Some are associated with small rotated sandstone blocks within the cross-beds. The structures are exposed on bedding plane surfaces and in cross-section on vertical quarry walls. A few SSDSs up to a meter thick also occur in the Coconino Sandstone, but the others are only up to a few cm thick, 2–10 cm wide, and 20 cm to 10 m long. Evidence is presented that liquidization (as fluidization or liquefaction) may have been involved in producing these features, implying a high water content in scattered locations at time of deformation, but this process also requires some stressor to trigger the deformation. Seismic events may provide a triggering mechanism. The Coconino Sandstone SSDSs represent unusual or previously overlooked small-scale features related to individual foreset surfaces.
Experimental Investigation of a Medium Temperature Single-Phase Thermosyphon in an Evacuated Tube Receiver Coupled With Compound Parabolic Concentrator
Authors: Akhter Javed , Gilani S. I. , Al-Kayiem Hussain H. , Mehmood Mubbashar , Ali Muzaffar , Ullah Barkat , Alam Mohammad Azad , Masood Faisal
Published: November 2021

The integration of evacuated tube receivers with non-imaging compound parabolic concentrators (CPCs) operating in thermosyphon mode provides the opportunity to deliver solar thermal energy in the medium temperature range that is suitable for many industrial applications. However, the performance of single-phase thermosyphon in the medium temperature range has not been comprehensively investigated. This paper presents the design, development, and performance evaluation of a single-phase thermosyphon in an evacuated tube receiver integrated with a modified CPC solar collector. The thermohydraulic performance of the developed system is evaluated in the tropical climate using Therminol-55 oil as heat transfer fluid. The results demonstrate that the maximum outlet temperature reached over 120°C using thermal oil as heat transfer fluid while it remained at 100°C in case of water. The zero-loss thermal efficiency reached up to 70% on a clear sky day. Comparing the thermal performance of the developed CPC collector with an existing model of a non-concentrating collector showed much improvement at elevated temperatures. This indicates that this system can effectively operate in tropical weather conditions to provide sustainable solar thermal energy in the medium temperature range.
Monitoring and Identifying Wind Turbine Generator Bearing Faults Using Deep Belief Network and EWMA Control Charts
Authors: Li Huajin , Deng Jiahao , Yuan Shuang , Feng Peng , Arachchige Dimuthu D. K.
Published: November 2021

Wind turbines are widely installed as the new source of cleaner energy production. Dynamic and random stress imposed on the generator bearing of a wind turbine may lead to overheating and failure. In this paper, a data-driven approach for condition monitoring of generator bearings using temporal temperature data is presented. Four algorithms, the support vector regression machine, neural network, extreme learning machine, and the deep belief network are applied to model the bearing behavior. Comparative analysis of the models has demonstrated that the deep belief network is most accurate. It has been observed that the bearing failure is preceded by a change in the prediction error of bearing temperature. An exponentially-weighted moving average (EWMA) control chart is deployed to trend the error. Then a binary vector containing the abnormal errors and the normal residuals are generated for classifying failures. LS-SVM based classification models are developed to classify the fault bearings and the normal ones. The proposed approach has been validated with the data collected from 11 wind turbines.
A Novel CLN6 Variant Associated With Juvenile Neuronal Ceroid Lipofuscinosis in Patients With Absence of Visual Loss as a Presenting Feature
Authors: Nicolaou Paschalis , Tanteles George A. , Votsi Christina , Zamba-Papanicolaou Eleni , Papacostas Savvas S. , Christodoulou Kyproula , Christou Yiolanda-Panayiota
Published: November 2021

The neuronal ceroid lipofuscinoses (NCLs), also known as Batten disease, are a group of autosomal recessive lysosomal storage disorders that are characterized by neurodegeneration, progressive cognitive decline, motor impairment, ataxia, loss of vision, seizures, and premature death. To date, pathogenic variants in more than 13 genes have been associated with NCLs. CLN6 encodes an endoplasmic reticulum non-glycosylated transmembrane protein, which is involved in lysosomal acidification. Mutations in CLN6 cause late-infantile juvenile NCL (JNCL) adult-onset NCL, and Kufs disease. Members from two available families with JNCL were clinically evaluated, and samples were collected from consenting individuals. The molecular investigation was performed by whole-exome sequencing, Sanger sequencing, and family segregation analysis. Furthermore, in silico prediction analysis and structural modeling of the identified CLN6 variants were performed. We report clinical and genetic findings of three patients from two Greek-Cypriot families (families 915 and 926) with JNCL. All patients were males, and the first symptoms appeared at the age of 6 years. The proband of family 926 presented with loss of motor abilities, ataxia, spasticity, seizure, and epilepsy. The proband of family 915 had ataxia, spasticity, dysarthria, dystonia, and intellectual disability. Both probands did not show initial signs of vision and/or hearing loss. Molecular analysis of family 926 revealed two CLN6 biallelic variants: the novel, de novo p.Tyr295Cys and the known p.Arg136His variants. In family 915, both patients were homozygous for the p.Arg136His CLN6 variant. Prediction analysis of the two CLN6 variants characterized them as probably damaging and disease-causing. Structural modeling of the variants predicted that they probably cause protein structural differentiation. In conclusion, we describe two unrelated Cypriot families with JNCL. Both families had variants in the CLN6 gene; however, they presented with slightly different symptoms, and notably none of the patients has loss of vision. In silico prediction and structural analyses indicate that both variants are most likely pathogenic.
Artificial Intelligence in Functional Food Ingredient Discovery and Characterisation: A Focus on Bioactive Plant and Food Peptides
Authors: Doherty Aoife , Wall Audrey , Khaldi Nora , Kussmann Martin
Published: November 2021

Scientific research consistently demonstrates that diseases may be delayed, treated, or even prevented and, thereby, health may be maintained with health-promoting functional food ingredients (FFIs). Consumers are increasingly demanding sound information about food, nutrition, nutrients, and their associated health benefits. Consequently, a nutrition industry is being formed around natural foods and FFIs, the economic growth of which is increasingly driven by consumer decisions. Information technology, in particular artificial intelligence (AI), is primed to vastly expand the pool of characterised and annotated FFIs available to consumers, by systematically discovering and characterising natural, efficacious, and safe bioactive ingredients (bioactives) that address specific health needs. However, FFI-producing companies are lagging in adopting AI technology for their ingredient development pipelines for several reasons, resulting in a lack of efficient means for large-scale and high-throughput molecular and functional ingredient characterisation. The arrival of the AI-led technological revolution allows for the comprehensive characterisation and understanding of the universe of FFI molecules, enabling the mining of the food and natural product space in an unprecedented manner. In turn, this expansion of bioactives dramatically increases the repertoire of FFIs available to the consumer, ultimately resulting in bioactives being specifically developed to target unmet health needs.
Shifting Baselines to Thresholds: Reframing Exploitation in the Marine Environment
Authors: Atmore Lane M. , Aiken Magie , Furni Fabricio
Published: November 2021

Current research on anthropogenic impacts on marine ecosystems often relies on the concept of a “baseline,” which aims to describe ecosystems prior to human contact. Recent research is increasingly showing that humans have been involved in marine ecosystems for much longer than previously understood. We propose a theoretical framework oriented around a system of “thresholds” referring to system-wide changes in human culture, ecosystem dynamics, and molecular evolution. The concept of the threshold allows conceptual space to account for the fluid nature of ecosystems throughout time while providing a critical framework for understanding drivers of ecosystem change. We highlight practical research approaches for exploring thresholds in the past and provide key insights for future adaptation to a changing world. To ensure ecological and societal goals for the future are met, it is critical that research efforts are contextualized into a framework that incorporates human society as integral to ecology and evolution.
Basic Properties of fly Ash/Slag -Concrete Slurry Waste Geopolymer Activated by Sodium Carbonate and Different Silicon Sources
Authors: Gao Yingli , Duan Kairui , Xiang Shuncheng , Zeng Wei
Published: November 2021

As a kind of granular waste with complex composition and alkali corrosiveness, concrete slurry waste (CSW) has severe recycling limitations in the ordinary Portland cement (OPC). Considering this, a new type of geopolymer, prepared by granulated blast furnace slag/fly ash, concrete slurry waste, and powdered activators (sodium carbonate and different silicon sources including sodium metasilicate pentahydrate and silica fume), was adopted to conduct a comparative study with the OPC counterpart. In this study, the homogenized CSW was mixed in the OPC and geopolymer with a constant ratio of 50 wt%, respectively. Then the properties were studied in terms of the flowability, setting times, mechanical strengths, and microstructures. The results showed that better flowability (200 mm) could be achieved in the obtained geopolymer than in the OPC reference group (95 mm) by increasing the powdered activators. The setting time of the OPC was significantly shortened due to the addition of CSW. The strengths of geopolymer were supported by the produced C-A-S-H and carbonates, with less chemically bonded water than the hydration products in the reference group. The dominant size of pores in the hardened geopolymer was much smaller than that in the OPC group which was 80 nm. Silica fume could be the alternate of the sodium metasilicate pentahydrate and had an insignificant negative impact on the fresh and hardened properties and microstructures of the geopolymer when the incorporation rate was within 5%.
Ultrasound Features Associated With Shoulder Complaints: Calcifications Larger Than 6 mm in Young Patients and Positive Doppler Are Associated With Pain
Authors: Janeiro João , Barreira Sofia C. , Martins Patrícia , Ninitas Pedro , Campos Jorge , Fonseca João E.
Published: November 2021

Objectives: To identify ultrasound (US) features associated with the presence of shoulder complaints.

Methods: This observational, case-control study, compared US findings between participants with and without shoulder complaints, matched for age, sex, and dominancy. Data was collected from February 2018 to June 2020. Two-tailed Fisher's and Mann-Whitney U-tests were used, with p-values < 0.05 considered significant.

Results: A total of 202 participants were enrolled (median age 56 years, range 18–70, 155 women), comprising 140 cases and 62 controls. A calcification size ≥6 mm, when age < 56 (p = 0.02), and a distance to tendon insertion ≥6 mm, when age ≥56 (p = 0.009), were only found in symptomatic shoulders. Color Doppler in rotator cuff (RC) tendons predominated in the presence of symptoms (26/140 vs. 2/62, p = 0.003). An algorithm also combining the number of calcifications, tendon echotexture and insertional thickening, osseous irregularity, cuff tears, and subacromial effusion showed a 92% (57/62) specificity for shoulder pain on this study sample.

Conclusion: Calcification diameter of 6 mm or more is associated with shoulder pain in patients younger than 56 years. A distance from calcification to tendon insertion of 6 mm or more is related to pain in older patients. Doppler signal also is associated with shoulder pain. An algorithm based on a set of specific ultrasonographic criteria have a strong association with the presence of symptoms.
Novel Clinical Risk Scoring Model for Predicting Amputation in Patients With Necrotizing Fasciitis: The ANF Risk Scoring System
Authors: Chaomuang Natthaya , Khamnuan Patcharin , Chuayunan Nipaporn , Duangjai Acharaporn , Saokaew Surasak , Phisalprapa Pochamana
Published: November 2021

Background: Necrotizing fasciitis (NF) is a life-threatening infection of the skin and soft tissue that spreads quickly and requires immediate surgery and medical treatment. Amputation or radical debridement of necrotic tissue is generally always required. The risks and benefits of both the surgical options are weighed before deciding whether to amputate or debride. This study set forth to create an easy-to-use risk scoring system for predicting the risk scoring system for amputation in patients with NF (ANF).

Methods: This retrospective study included 1,506 patients diagnosed with surgically confirmed NF at three general hospitals in Thailand from January 2009 to December 2012. All diagnoses were made by surgeons who strictly observed the guidelines for skin and soft tissue infections produced by the Infectious Diseases Society of America. Patients were randomly allocated to either the derivation (n = 1,193) or validation (n = 313) cohort. Clinical risk factors assessed at the time of recruitment were used to create the risk score, which was then developed using logistic regression. The regression coefficients were converted into item scores, and the total score was calculated.

Results: The following four clinical predictors were used to create the model: female gender, diabetes mellitus, wound appearance stage 3 (skin necrosis and gangrene), and creatinine ≥1.6 mg/dL. Using the area under the receiver operating characteristic curve (AuROC), the ANF system showed moderate power (78.68%) to predict amputation in patients with NF with excellent calibration (Hosmer-Lemeshow χ2 = 2.59; p = 0.8586). The positive likelihood ratio of amputation in low-risk (score ≤ 4) and high-risk (score ≥ 7) patients was 2.17 (95%CI: 1.66–2.82) and 6.18 (95%CI: 4.08–9.36), respectively. The ANF system showed good performance (AuROC 76.82%) when applied in the validation cohort.

Conclusion: The developed ANF risk scoring system, which includes four easy to obtain predictors, provides physicians with prediction indices for amputation in patients with NF. This model will assist clinicians with surgical decision-making in this time-sensitive clinical setting.
Analysis of Corneal Spherical Aberrations in Chinese Bilateral Ectopia Lentis Patients
Authors: Chen Jiahui , Tang Yating , Jing Qinghe , Lu Yi , Jiang Yongxiang
Published: November 2021

Purpose: To analyze the anterior, posterior, and total corneal spherical aberrations (ASA, PSA, and TSA) in patients with Chinese bilateral ectopia lentis (EL).

Methods: A cross-sectional study was conducted to evaluate corneal spherical aberration (CSA) using a Pentacam system at the 6-mm optical zone. Axial length, keratometry, astigmatism, and corneal asphericity were also determined.

Results: This study included 247 patients (420 eyes) with a mean age of 18.1 years. The values of ASA, PSA, and TSA were 0.136 ± 0.100 μm, −0.118 ± 0.030 μm, and 0.095 ± 0.095 μm, respectively. In the EL patients with Marfan syndrome (MFS), ASA and TSA were significantly lower than in the non-MFS patients (0.126 ± 0.094 μm vs. 0.155 ± 0.107 μm, P = 0.004 for ASA; 0.085 ± 0.091 μm vs. 0.114 ± 0.099 μm, P = 0.003 for TSA), whereas PSA was not significantly different (P = 0.061). The values of ASA and TSA were significantly higher in the patients with EL aged ≥ 40 years old than in younger patients, whereas ASA and PSA were lower in patients aged <10 years old than in older patients (all P < 0.05). In the multiple linear regression analysis, age, keratometry, astigmatism, anterior asphericity, higher-order aberration (HOA), and lower-order aberration (LOA) were positively or negatively correlated with TSA in the patients with EL (r = 0.681, P < 0.001).

Conclusions: Corneal spherical aberration was low in the patients with EL especially for MFS and tended to increase with aging. Preoperatively, individual measurement of CSA was necessary for bilateral EL patients with MFS.
The Role of Electrical Impedance Tomography for Management of High-Risk Pulmonary Embolism in a Postoperative Patient
Authors: Wang Xinchen , Zhao Hua , Cui Na
Published: November 2021

Electrical impedance tomography (EIT) is a non-invasive, radiation-free and bedside imaging tool that is widely used for real-time monitoring of lung ventilation. Recently, it has been proposed for use in quantitative assessment of regional lung perfusion with hypertonic saline bolus injection and consequently for pulmonary embolism (PE) detection. Here, we present a case of high-risk PE in a postoperative patient, in which EIT monitoring provided us with useful information for diagnosis and decision-making, especially with the challenge of anticoagulation and risk of bleeding.
The EU Response to the Presence of Nitrosamine Impurities in Medicines
Authors: Ruepp Robin , Frötschl Roland , Bream Robert , Filancia Maria , Girard Thomas , Spinei Andrei , Weise Martina , Whomsley Rhys
Published: November 2021

The unexpected detection of nitrosamine impurities in human medicines has recently seen global regulators act to understand the risks of these contaminations to patients and to limit their presence. Over 300 nitrosamines are known, many of which are highly potent mutagenic carcinogens. Regulators first became aware of the presence of nitrosamines in EU medicines in 2018, with reports of detection of N-nitroso-dimethylamine (NDMA) in valsartan from one manufacturer. A subsequent EU review of all valsartan medicines was triggered by the European Medicines Agency (EMA) and was later extended to other angiotensin receptor blockers/sartans. A separate review was also started for ranitidine medicines. This was followed by an EU-wide examination of the risk of presence of nitrosamines in all human medicines. This article reflects on the investigation of the EU regulatory network into the presence of nitrosamines and the scientific knowledge informing recommendations for developers on how to limit nitrosamines in medicines.
Long-Read Sequencing Reveals Evolution and Acquisition of Antimicrobial Resistance and Virulence Genes in Salmonella enterica
Authors: Li Cong , Tyson Gregory H. , Hsu Chih-Hao , Harrison Lucas , Strain Errol , Tran Thu-Thuy , Tillman Glenn E. , Dessai Uday , McDermott Patrick F. , Zhao Shaohua
Published: November 2021

Salmonella entericais a significant and phylogenetically diverse zoonotic pathogen. To understand its genomic heterogeneity and antimicrobial resistance, we performed long-read sequencing onSalmonellaisolated from retail meats and food animals. A collection of 134 multidrug-resistant isolates belonging to 33 serotypes were subjected to PacBio sequencing. One major locus of diversity among these isolates was the presence and orientation ofSalmonellapathogenic islands (SPI), which varied across different serotypes but were largely conserved within individual serotypes. We also identified insertion of an IncQ resistance plasmid into the chromosome of fourteen strains of serotype I 4,[5],12:i:– and theSalmonellagenomic island 1 (SGI-1) in five serotypes. The presence of various SPIs, SGI-1 and integrated plasmids contributed significantly to the genomic variability and resulted in chromosomal resistance in 55.2% (74/134) of the study isolates. A total of 93.3% (125/134) of isolates carried at least one plasmid, with isolates carrying up to seven plasmids. We closed 233 plasmid sequences of thirteen replicon types, along with twelve hybrid plasmids. Some associations betweenSalmonellaisolate source, serotype, and plasmid type were seen. For instance, IncX plasmids were more common in serotype Kentucky from retail chicken. Plasmids IncC and IncHI had on average more than five antimicrobial resistance genes, whereas in IncX, it was less than one per plasmid. Overall, 60% of multidrug resistance (MDR) strains that carried >3 AMR genes also carried >3 heavy metal resistance genes, raising the possibility of co-selection of antimicrobial resistance in the presence of heavy metals. We also found nine isolates representing four serotypes that carried virulence plasmids with thespvoperon. Together, these data demonstrate the power of long-read sequencing to reveal genomic arrangements and integrated plasmids with a high level of resolution for tracking and comparing resistant strains from different sources. Additionally, the findings from this study will help expand the reference set of closedSalmonellagenomes that can be used to improve genome assembly from short-read data commonly used in One Health antimicrobial resistance surveillance.