bluuebunny/crossref_metadata_2025 huggingface dataset:
Critical Amino Acid Variants in HLA-DRB1 and -DQB1 Allotypes in the Development of Classical Type 1 Diabetes and Latent Autoimmune Diabetes in Adults in the Japanese Population
Authors: Katahira Masahito , Tsunekawa Taku , Mizoguchi Akira , Yamaguchi Mariko , Tsuru Kahori , Takashima Hiromi , Terada Ryoma
Published: May 2021

The effects of amino acid variants encoded by the human leukocyte antigen (HLA) class II on the development of classical type 1 diabetes (T1D) and latent autoimmune diabetes in adults (LADA) have not been fully elucidated. We retrospectively investigated the HLA-DRB1 and -DQB1 genes of 72 patients with classical T1D and 102 patients with LADA in the Japanese population and compared the frequencies of HLA-DRB1 and -DQB1 alleles between these patients and the Japanese populations previously reported by another institution. We also performed a blind association analysis with all amino acid positions in classical T1D and LADA, and compared the associations of HLA-DRB1 and -DQB1 amino acid positions in classical T1D and LADA. The frequency of DRß-Phe-13 was significantly higher and those of DRß-Arg-13 and DQß-Gly-70 were significantly lower in patients with classical T1D and LADA than in controls. The frequencies of DRß-His-13 and DQß-Glu-70 were significantly higher in classical T1D patients than in controls. The frequency of DRß-Ser-13 was significantly lower and that of DQß-Arg-70 was significantly higher in LADA patients than in controls. HLA-DRß1 position 13 and HLA-DQß1 position 70 could be critical amino acid positions in the development of classical T1D and LADA.
Personalised Prophylaxis in a Child with Haemophilia A and Type 1 Diabetes
Authors: Cruz Maria Sol , Santillan Josefina , Lesser Julieta , Ortiz Juan Pablo , Forzani Laura
Published: May 2021

Poor management of either type 1 diabetes or haemophilia A can lead to complications such as organ dysfunction and haemarthropathy. Here, we describe the case of an 8-year-old boy diagnosed with severe haemophilia A shortly after birth. At 2 years old, he was also diagnosed with type 1 diabetes. After six years, the haemophilia treatment was changed from a plasma-derived factor VIII (FVIII) concentrate (octanate®, Octapharma, Lachen, Switzerland) to Nuwiq® (simocotocog alfa, Octapharma, Lachen, Switzerland), a recombinant FVIII (rFVIII) product from a human cell line, which allowed for a personalised treatment schedule that supported good adherence. The dosing regimen could be reduced to two weekly rFVIII infusions. The patient has experienced no spontaneous bleeds since switching to rFVIII and shows no signs of joint damage after over seven years of FVIII prophylaxis. rFVIII was well tolerated, with no treatment-related adverse events observed. This case illustrates the importance of treatment personalisation for young patients and their families managing concomitant diseases.
Design of Narrow-Band Absorber Based on Symmetric Silicon Grating and Research on Its Sensing Performance
Authors: Pan Miao , Huang Huazhu , Chen Wenzhi , Li Shuai , Xie Qinglai , Xu Feng , Wei Dongwei , Fang Jun , Fan Baodian , Cai Lihan
Published: May 2021

In this paper, using the surface plasmon and Fabry–Pérot (FP) cavity, the design of a symmetric silicon grating absorber is proposed. The time-domain finite difference method is used for simulation calculations. The basic unit structure is a dielectric grating composed of silicon dioxide, metal and silicon. Through the adjustment of geometric parameters, we have achieved the best of the symmetric silicon grating absorber. A narrowband absorption peak with an absorption rate greater than 99% is generated in the 3000–5000 nm optical band, and the wavelength of the absorption peak is λ = 3750 nm. The physical absorption mechanism is that silicon light generates surface plasmon waves under the interaction with incident light, and the electromagnetic field coupling of surface plasmon waves and light causes surface plasmon resonance, thereby exciting strong light response modulation. We also explore the influence of geometric parameters and polarization angle on the performance of silicon grating absorbers. Finally, we systematically study the refractive index sensitivity of these structures. These structures can be widely used in optical filtering, spectral sensing, gas detection and other fields.
Impact of Water-Repellent Products on the Moisture Transport Properties and Mould Susceptibility of External Thermal Insulation Composite Systems
Authors: Roncon Renata , Borsoi Giovanni , Parracha João L. , Flores-Colen Inês , Veiga Rosário , Nunes Lina
Published: May 2021

External Thermal Insulation Composite Systems (ETICS) are constructive solutions widely used to increase the thermal insulation in new and retrofitted buildings. However, these systems can present several anomalies due to their constant exposure to weathering agents and anthropic factors. Water is generally the major cause of degradation. Thus, the application of water-repellent products can minimize the appearance of anomalies and increase the durability of the systems. In this paper, acrylic-based and siloxane-based hydrophobic products were applied to ETICS, with the aim of assessing the compatibility, effectiveness, and durability of these products. The moisture transport properties and mould susceptibility were assessed through laboratory tests on untreated and treated specimens. The durability of the hydrophobic treatments was also evaluated through artificial aging tests (heat-cold and freeze-thaw cycles). Results show that the protection products generally decreased water absorption, slightly decreased the drying rate, and presented adequate water vapor permeability. After aging, the products still had reasonable effectiveness and, with one exception, improved the water vapor diffusion of the systems. Additionally, ETICS underwent an alteration in the finishing coat (possible modification of the porosity) due to the aging cycles. No clear linear correlation was found between the contact angle values and water absorption results, evidencing the influence of other factors related to the composition of the water-repellent products.
Test-Rig Simulation on Hybrid Thermal Barrier Coating Assisted with Cooling Air System for Advanced Gas Turbine under Prolonged Exposures—A Review
Authors: Mohd Yunus Salmi , Mahalingam Savisha , Manap Abreeza , Mohd Afandi Nurfanizan , Satgunam Meenaloshini
Published: May 2021

Thermal barrier coating (TBC) and cooling air systems are among the technologies that have been introduced and applied in pursuing the extensive development of advanced gas turbine. TBC is used to protect the gas turbine components from the higher operating temperature of advanced gas turbine, whereas cooling air systems are applied to assist TBC in lowering the temperature exposure of protected surfaces. Generally, a gas turbine operates in three main operational modes, which are base load, peak load, and part peak load. TBC performance under these three operational modes has become essential to be studied, as it will provide the gas turbine owners not only with the behaviors and damage mechanism of TBC but also a TBC life prediction in a particular operating condition. For TBC under base load or so called steady-state condition, a number of studies have been reviewed and discussed. However, it has been found that most of the studies have been conducted without the assistance of a cooling air system, which does not simulate the TBC in advanced gas turbine completely. From this review, the studies on TBC-assisted cooling air system to simulate the advanced gas turbine operating conditions have also been summarized, which are limited to test rig simulations under thermal cyclic mode where thermal cyclic represents peak and part peak load conditions. The equipment used to simulate the gas turbine operating condition, test temperatures, and durations are parameters that have been taken into consideration under this review. Finally, a test rig that is capable of simulating both TBC and cooling air effects at a high operating temperature of advanced gas turbines for prolonged exposure under steady-state condition has been proposed to be developed.
Towards Inferring Influential Facebook Users
Authors: Alsaif Suleiman Ali , Hidri Adel , Hidri Minyar Sassi
Published: May 2021

Because of the complexity of the actors and the relationships between them, social networks are always represented by graphs. This structure makes it possible to analyze the effectiveness of the network for the social actors who are there. This work presents a social network analysis approach that focused on processing Facebook pages and users who react to posts to infer influential people. In our study, we are particularly interested in studying the relationships between the posts of the page, and the reactions of fans (users) towards these posts. The topics covered include data crawling, graph modeling, and exploratory analysis using statistical tools and machine learning algorithms. We seek to detect influential people in the sense that the influence of a Facebook user lies in their ability to transmit and disseminate information. Once determined, these users have an impact on business for a specific brand. The proposed exploratory analysis has shown that the network structure and its properties have important implications for the outcome of interest.
ZnO Nano-Rod Arrays Synthesized with Exposed {0001} Facets and the Investigation of Photocatalytic Activity
Authors: Yang Xinying , Tian Jin , Guo Yang , Teng Mengyuan , Liu Haixia , Li Tianduo , Lv Pingli , Wang Xuping
Published: May 2021

Zinc oxide (ZnO) possesses superior chemical and physical properties so that it can occupy an essential position in the application of nanostructures. In this paper, ZnO nano-rod arrays were synthesized by a simple one-step hydrothermal approach with the assistance of cetyl trimethyl ammonium bromide (CTAB). Exposure of the {0001} facets could be controlled by adjusting the amount of CTAB and the maximum exposure of the {0001} facets of ZnO nanorods is obtained at 1.2 g of CTAB. The photocurrent, EIS, and PL measurements support the facile charge transfer with minimum recombination of the photogenerated excitons of the ZnO nano-rod arrays obtained at 1.2 g of CTAB. Consequently, the obtained ZnO nano-rod arrays at the optimal CTAB of 1.2 g exhibit an excellent photocatalytic degradation rate of 99.7% for rhodamine B (RhB), while the degradation rate of RhB by the ZnO obtained without CTAB is only 35%.
Representation of the Universe as a Dendrogramic Hologram Endowed with Relational Interpretation
Authors: Shor Oded , Benninger Felix , Khrennikov Andrei
Published: May 2021

A proposal for a fundamental theory is described in which classical and quantum physics as a representation of the universe as a gigantic dendrogram are unified. The latter is the explicate order structure corresponding to the purely number-theoretical implicate order structure given by p-adic numbers. This number field was zero-dimensional, totally disconnected, and disordered. Physical systems (such as electrons, photons) are sub-dendrograms of the universal dendrogram. Measurement process is described as interactions among dendrograms; in particular, quantum measurement problems can be resolved using this process. The theory is realistic, but realism is expressed via the the Leibniz principle of the Identity of Indiscernibles. The classical-quantum interplay is based on the degree of indistinguishability between dendrograms (in which the ergodicity assumption is removed). Depending on this degree, some physical quantities behave more or less in a quantum manner (versus classic manner). Conceptually, our theory is very close to Smolin’s dynamics of difference and Rovelli’s relational quantum mechanics. The presence of classical behavior in nature implies a finiteness of the Universe-dendrogram. (Infinite Universe is considered to be purely quantum.) Reconstruction of events in a four-dimensional space type is based on the holographic principle. Our model reproduces Bell-type correlations in the dendrogramic framework. By adjusting dendrogram complexity, violation of the Bell inequality can be made larger or smaller.
Artificial Intelligence and Computational Methods in the Modeling of Complex Systems
Authors: Sosnowski Marcin , Krzywanski Jaroslaw , Ščurek Radomír
Published: May 2021

Based on the increased attention, the Special Issue aims to investigate the modeling of complex systems using artificial intelligence and computational methods [...]
Unveiling Operator Growth Using Spin Correlation Functions
Authors: Carrega Matteo , Kim Joonho , Rosa Dario
Published: May 2021

In this paper, we study non-equilibrium dynamics induced by a sudden quench of strongly correlated Hamiltonians with all-to-all interactions. By relying on a Sachdev-Ye-Kitaev (SYK)-based quench protocol, we show that the time evolution of simple spin-spin correlation functions is highly sensitive to the degree of k-locality of the corresponding operators, once an appropriate set of fundamental fields is identified. By tracking the time-evolution of specific spin-spin correlation functions and their decay, we argue that it is possible to distinguish between operator-hopping and operator growth dynamics; the latter being a hallmark of quantum chaos in many-body quantum systems. Such an observation, in turn, could constitute a promising tool to probe the emergence of chaotic behavior, rather accessible in state-of-the-art quench setups.
Measurement and Evaluation of the Defect Size in Soft Magnetic Composites Using Magnetic Field Inspections
Authors: Jakubas Adam , Jabłoński Paweł
Published: May 2021

This article presents a method for detecting defects and assessing their size in soft magnetic composites (SMCs) based on magnetograms obtained from a magnetic field camera and a numerical analysis of the magnetic field around them. For the purpose of the experiment, toroidal samples of a metal–polymer composite were made, in which holes and gaps simulating defects were prepared. The magnetic camera allowed for registering the magnetic flux density image near the surface of the samples. As a result, magnetograms with information about the location and geometry of defects were obtained. A numerical analysis was used to investigate the influence of various factors, such as defect depth, its size and material permeability. Theoretical changes in magnetic field over defects stay in good agreement with measurements, which is a strong indication that surface field magnetograms can be useful in a quality assessment of the considered composites. The effectiveness and usefulness of the method in detecting surface and shallow subsurface defects in SMC materials was confirmed. The influence of a possible tangent component of the exciting field was demonstrated and discussed.
Innovation of Pump as Turbine According to Calculation Model for Francis Turbine Design
Authors: Polák Martin
Published: May 2021

The effective utilization of micro hydropower sources is often realized through the use of pumps as turbines (PAT). The efficiency of PAT is about the same as that of the original pump. A further increase in efficiency and power output can be achieved by modifying the parts interacting with the flow, especially the impeller and the adjacent volute casing and draft tube. This paper presents a user-friendly calculation model of Francis turbine design and its application for PAT geometry modification. Two different modifications of a single-stage radial centrifugal pump were designed according to this model. The first modification (Turbine) consisted of a complete revision of the impeller geometry, volute casing and draft tube, which corresponded to a conventional Francis turbine. The second modification (Hybrid) was based on altered calculation model and consisted of a modification of only the impeller, which can be used in the original volute casing. Both modifications were tested on hydraulic test circuit at different heads. A comparison of the results of the Hybrid and the Turbine modification with the unmodified machine (Original) proved an increase in overall efficiency by 10%. Both modifications provided a higher flow rate and torque. This resulted in an overall power output increase—an increase of approximately 25% and 40% due to the Turbine and Hybrid modifications, respectively.
Growth and Economic Performance of the Norwegian Wind Power Industry and Some Aspects of the Nordic Electricity Market
Authors: Idsø Johannes
Published: May 2021

Electricity has been produced in Norway in hydropower plants since 1877. The first wind power plant was put into operation in 1986. The growth in wind power production was weak in the first years after the turn of the millennium, but after Norway joined the Swedish subsidy scheme Tradable Green Certificates in 2012, there was significant growth in the wind power industry. While most of the hydropower production in Norway is owned by the public sector, the majority of wind power production is owned by foreign investors. Since wind power has been very much discussed in Norway, a levelized cost of energy (LCOE) model that can be well suited for this type of discussion is presented. The point here is that one must include all the costs, including the externalities. The Norwegian electricity market is dominated by a single player: Nord Pool. Ninety-six percent of all the electricity produced in Norway is sold through the power exchange Nord Pool, and the prices set by Nord Pool affect the finances of all the electricity producers in Norway, as well as producers in Scandinavia and the Baltic countries. This paper is a survey of the growth, development of production and economic performance of the Norwegian wind power industry and some aspects of the electricity market in the Nordic countries.
Implementation of Climate/Energy Targets of the Europe 2020 Strategy by the EU Member States
Authors: Kryk Barbara , Guzowska Małgorzata Klaudia
Published: May 2021

The most important goals on the Europe 2020 Strategy contained were the climate/energy goals, which determine the achievement of other targets of the strategy. The aim of the article is to evaluate the implementation of the climate/energy targets of the Europe 2020 Strategy by the EU Member States in 2010 and 2019 and to compare the results achieved by them. To measure them, a basic set of indicators was used for this purpose, which the authors supplemented with additional indicators. The evaluation was done using the taxonomic and zero-unitarization method. They made it possible to integrate all indicators. Moreover, the added value in relation to other studies is: the use of individual indicators, instead of general ones obtaining additional information about the internal structure and nature of the implementation of multidimensional groups of targets and focusing solely on the achievement of climate/energy targets. The achieved results not only reflect the progress of the Member States in achieving the climate/energy targets and the differences in the level of achieving objectives between countries, but they are also discussion on future strategic objectives, their indicators and necessary directions for a further community climate/energy policy.
Integrating Concentrated Optics for Ambient Perovskite Solar Cells
Authors: Khalid Maria , Roy Anurag , Bhandari Shubhranshu , Sundaram Senthilarasu , Mallick Tapas K.
Published: May 2021

Metal halide perovskite solar cells (PSCs) are considered an effectual way to enhance photovoltaic (PV) properties, leading to low-cost and high efficiency. PSCs have experienced rapid improvement in the last ten years. The device’s energy production increases extensively in the presence of concentrated light. The use of concentrated optics in solar cells has spurred the PV industry towards tremendous research. Incorporating the concentrated optic into the PV system as a concentrated PV (CPV) means it can capture light effectively and operate at increased efficiencies under concentrated irradiance. This work addresses an initial assessment of the power conversion efficiency (PCE) enhancement of the ambient PSCs by externally integrating concentrated optics. Significantly, the concentrated optics exhibit ~90% of the PCE enhancement under the solar irradiance of 400 W/m2, whereas 16% of the PCE increase was observed when the solar irradiance changed to 1000 W/m2. During optics integration, a considerable elevation of short-circuit current predominately facilitated the overall efficiency enhancement of the PSC. A systematic PV parameters effect on the optic integration on PSCs was further scrutinized. Therefore, this work signifies a possible way to alleviate the PCE of carbon-based PSC using concentrated optics. This work focuses on integrating CPVs into PSCs, preventing PSC stability and scalability issues, with light conditioning techniques.
A Novel Surface Parameterization Method for Optimizing Radial Impeller Design in Fuel Cell System
Authors: Li Wei , Liu Jisheng , Fang Pengcheng , Cheng Jinxin
Published: May 2021

The aerodynamic performance improvement of radial impellers is of positive significance to improve the overall performance of hydrogen fuel cell systems (FCS). Our team proposes a multi-degree-of-freedom (MDOF) surface parameterization method for the global automatic optimization of radial impeller aerodynamics. The MDOF surface parameterization is characterized by fewer variables, construction ease, smoothness, good flexibility, and blade strength maintenance. In this paper, a radial impeller for a 100-kW fuel cell stack is optimized, showing the isentropic efficiency increase of 0.7%, the flow rate increase of 3.77%, and the total pressure ratio increase of 0.37%. The results revealed that the performance of the optimized radial impeller significantly improved, verifying the validity and reliability of the proposed novel design optimization method and providing technical support and methodological research of radial impeller aerodynamic optimization for hydrogen FCS.
Comparative Evaluation of Non-Intrusive Load Monitoring Methods Using Relevant Features and Transfer Learning
Authors: Houidi Sarra , Fourer Dominique , Auger François , Sethom Houda Ben Attia , Miègeville Laurence
Published: May 2021

Non-Intrusive Load Monitoring (NILM) refers to the analysis of the aggregated current and voltage measurements of Home Electrical Appliances (HEAs) recorded by the house electrical panel. Such methods aim to identify each HEA for a better control of the energy consumption and for future smart grid applications. Here, we are interested in an event-based NILM pipeline, and particularly in the HEAs’ recognition step. This paper focuses on the selection of relevant and understandable features for efficiently discriminating distinct HEAs. Our contributions are manifold. First, we introduce a new publicly available annotated dataset of individual HEAs described by a large set of electrical features computed from current and voltage measurements in steady-state conditions. Second, we investigate through a comparative evaluation a large number of new methods resulting from the combination of different feature selection techniques with several classification algorithms. To this end, we also investigate an original feature selection method based on a deep neural network architecture. Then, through a machine learning framework, we study the benefits of these methods for improving Home Electrical Appliance (HEA) identification in a supervised classification scenario. Finally, we introduce new transfer learning results, which confirm the relevance and the robustness of the selected features learned from our proposed dataset when they are transferred to a larger dataset. As a result, the best investigated methods outperform the previous state-of-the-art results and reach a maximum recognition accuracy above 99% on the PLAID evaluation dataset.
Resonant Periods of Seiches in Semi-Closed Basins with Complex Bottom Topography
Authors: Magdalena Ikha , Karima Nadhira , Rif’atin Hany Qoshirotur
Published: May 2021

Seiches and resonances are two closely related phenomena that can cause damage to coastal areas. Seiches that occur in a basin at a distinct period named the resonant period may generate resonance when a wave induced by external forces enters the basin and has the same period as the seiches. Studying this period has become essential if we want to understand the resonance better. Thus, in this paper, we derive the resonant period in various shapes of semi-closed basin using the shallow water equations. The equations are then solved analytically using the separation of variables method and numerically using the finite volume method on staggered grid to discover the resonant period for each basin. To validate the numerical scheme, we compare its results against the analytical resonant periods, resulting in a very small error for each basin, suggesting that the numerical model is quite reliable in the estimation of the analytical resonant period. Further, resonant wave profiles are also observed. It is revealed that, in the coupled rectangular basin, the maximum wave elevation is disproportionate to the ratio of the length of the basin, while, in the trapezoidal basin, the ratio of the depth of the basin has no significant impact on the maximum wave elevation.
On Plane Wave Solutions in Lorentz-Violating Extensions of Gravity
Authors: Nascimento J. R. , Petrov A. Yu. , Vieira A. R.
Published: May 2021

In this paper, we obtain dispersion relations corresponding to plane wave solutions in Lorentz-breaking extensions of gravity with dimension 3, 4, 5 and 6 operators. We demonstrate that these dispersion relations display a usual Lorentz-invariant mode when the corresponding additive term involves higher derivatives.
Characterization of ETFDH and PHGDH Mutations in a Patient with Mild Glutaric Aciduria Type II and Serine Deficiency
Authors: Ali Amanat , Dhahouri Nahid Al , Almesmari Fatmah Saeed Ali , Fathalla Waseem Mahmoud , Jasmi Fatma Al
Published: May 2021

Glutaric aciduria type II (GA-II) is a rare autosomal recessive disease caused by defects in electron transfer flavoprotein (ETF), ultimately causing insufficiencies in multiple acyl-CoA dehydrogenase (MAD). 3-phosphoglycerate dehydrogenase (3-PHGDH) deficiency, is another rare autosomal disorder that appears due to a defect in the synthesis of L-serine amino acid. Several mutations of ETFDH and PHGDH genes have been associated with different forms of GA-II and serine deficiency, respectively. In this study, we report a unique case of GA-II with serine deficiency using biochemical, genetic, and in silico approaches. The proband of Syrian descent had positive newborn screening (NBS) for GA-II. At two years of age, the patient presented with developmental regression, ataxia, and intractable seizures. Results of amino acid profiling demonstrated extremely low levels of serine. Confirmatory tests for GA-II and whole exome sequencing (WES) were performed to determine the etiology of intractable seizure. Sequencing results indicated a previously reported homozygous missense mutation, c.679 C>A (p.Pro227Thr) in the ETFDH gene and a novel missense homozygous mutation c.1219 T>C (p.Ser407Pro) in the PHGDH gene. In silico tools predicted these mutations as deleterious. Here, the clinical and biochemical investigations indicate that ETFDH:p.Pro227Thr and PHGDH:p.Ser407Pro variants likely underlie the pathogenesis of GA-II and serine deficiency, respectively. This study indicates that two rare autosomal recessive disorders should be considered in consanguineous families, more specifically in those with atypical presentation.
Reducing Morbidity and Mortality Rates from COVID-19, Influenza and Pneumococcal Illness in Nursing Homes and Long-Term Care Facilities by Vaccination and Comprehensive Infection Control Interventions
Authors: Thomas Roger E.
Published: May 2021

The COVID-19 pandemic identifies the problems of preventing respiratory illnesses in seniors, especially frail multimorbidity seniors in nursing homes and Long-Term Care Facilities (LCTFs). Medline and Embase were searched for nursing homes, long-term care facilities, respiratory tract infections, disease transmission, infection control, mortality, systematic reviews and meta-analyses. For seniors, there is strong evidence to vaccinate against influenza, SARS-CoV-2 and pneumococcal disease, and evidence is awaited for effectiveness against COVID-19 variants and when to revaccinate. There is strong evidence to promptly introduce comprehensive infection control interventions in LCFTs: no admissions from inpatient wards with COVID-19 patients; quarantine and monitor new admissions in single-patient rooms; screen residents, staff and visitors daily for temperature and symptoms; and staff work in only one home. Depending on the vaccination situation and the current risk situation, visiting restrictions and meals in the residents’ own rooms may be necessary, and reduce crowding with individual patient rooms. Regional LTCF administrators should closely monitor and provide staff and PPE resources. The CDC COVID-19 tool measures 33 infection control indicators. Hand washing, social distancing, PPE (gowns, gloves, masks, eye protection), enhanced cleaning of rooms and high-touch surfaces need comprehensive implementation while awaiting more studies at low risk of bias. Individual ventilation with HEPA filters for all patient and common rooms and hallways is needed.
Agricultural Land-Use Changes in the Judean Region from the End of the Ottoman Empire to the End of the British Mandate: A Spatial Analysis
Authors: Schaffer Gad
Published: May 2021

Vines and olives are two important and widespread traditional agricultural crops that are also connected to the Judeo–Christian–Muslim tradition. The goal of the research was to demonstrate the importance of using cartographical sources to obtain a more accurate and complete view of the past. To this end, the aims were: (1) to reconstruct the former agricultural land-use in three periods, 1873–1874, 1917, and 1943–1945; (2) to analyze the different spatial physical factors that could explain the spatial distribution of traditional agricultural landscapes; (3) to identify the changes which took place between the three reconstructed timestamps. The research employed different cartographic sources and the implemented analyses were conducted using GIS tools and methods. The results show that, in the past, the distribution of vines and olive groves greatly depended on several physical geographic factors (climate, slopes, direction). Nonetheless, human factors such as political instability, cultural and religious beliefs contributed as well. Moreover, this research showed how GIS has advanced historical geography research. Lastly, the research demonstrated that obtaining the most complete view of the past can be achieved by a combination of sources together with the use of GIS tools and methods.
Assessing the Role of Calmodulin’s Linker Flexibility in Target Binding
Authors: Sun Bin , Kekenes-Huskey Peter M.
Published: May 2021

Calmodulin (CaM) is a highly-expressed Ca2+ binding protein known to bind hundreds of protein targets. Its binding selectivity to many of these targets is partially attributed to the protein’s flexible alpha helical linker that connects its N- and C-domains. It is not well established how its linker mediates CaM’s binding to regulatory targets yet. Insights into this would be invaluable to understanding its regulation of diverse cellular signaling pathways. Therefore, we utilized Martini coarse-grained (CG) molecular dynamics simulations to probe CaM/target assembly for a model system: CaM binding to the calcineurin (CaN) regulatory domain. The simulations were conducted assuming a ‘wild-type’ calmodulin with normal flexibility of its linker, as well as a labile, highly-flexible linker variant to emulate structural changes that could be induced, for instance, by post-translational modifications. For the wild-type model, 98% of the 600 simulations across three ionic strengths adopted a bound complex within 2 μs of simulation time; of these, 1.7% sampled the fully-bound state observed in the experimentally-determined crystallographic structure. By calculating the mean-first-passage-time for these simulations, we estimated the association rate to be ka= 8.7 × 108 M−1 s−1, which is similar to the diffusion-limited, experimentally-determined rate of 2.2 × 108 M−1 s−1. Furthermore, our simulations recapitulated its well-known inverse relationship between the association rate and the solution ionic strength. In contrast, although over 97% of the labile linker simulations formed tightly-bound complexes, only 0.3% achieved the fully-bound configuration. This effect appears to stem from a difference in the ensembles of extended and collapsed states which are controlled by the linker flexibility. Therefore, our simulations suggest that variations in the CaM linker’s propensity for alpha helical secondary structure can modulate the kinetics of target binding.
Solvates of New Arylpiperazine Salicylamide Derivative-a Multi-Technique Approach to the Description of 5 HTR Ligand Structure and Interactions
Authors: Pindelska Edyta , Marczewska-Rak Anna , Jaśkowska Jolanta , Madura Izabela D.
Published: May 2021

A new ligand for 5-HT1A and 5-HT7 receptors, an arylpiperazine salicylamide derivative with an inflexible spacer, is investigated to identify preferred fragments capable of creating essential intermolecular interactions in different solvates. To fully identify and characterize the obtained crystalline materials, various methods including powder and single-crystal X-ray diffraction, solid-state NMR, and thermal analysis were employed, supplemented by periodic ab initio calculations. The molecular conformation in different solvates, types, and hierarchy of intermolecular interactions as well as the crystal packing were investigated to provide data for future research focused on studying protein–ligand interactions. Based on various methods of crystal structure analysis, including the interaction energy calculation and programs using an artificial neural network, a salicylamide fragment was found to be crucial for intermolecular contacts, mostly of dispersion and electrostatic character. A supramolecular 2D kite-type layer of {4,4} topology was found to form in crystals. The closed voids between layers contain disordered solvents, very weakly interacting with the molecule and the layer. It has been postulated that the separation of the layers might be influenced by an increase in temperature or the size of the solvent; hence, only methanol and ethanol hemi-solvates could be obtained from a series of various alcohols.
The Ambivalent Role of Skin Microbiota and Adrenaline in Wound Healing and the Interplay between Them
Authors: Luqman Arif , Götz Friedrich
Published: May 2021

After skin injury, wound healing sets into motion a dynamic process to repair and replace devitalized tissues. The healing process can be divided into four overlapping phases: hemostasis, inflammation, proliferation, and maturation. Skin microbiota has been reported to participate in orchestrating the wound healing both in negative and positive ways. Many studies reported that skin microbiota can impose negative and positive effects on the wound. Recent findings have shown that many bacterial species on human skin are able to convert aromatic amino acids into so-called trace amines (TAs) and convert corresponding precursors into dopamine and serotonin, which are all released into the environment. As a stress reaction, wounded epithelial cells release the hormone adrenaline (epinephrine), which activates the β2-adrenergic receptor (β2-AR), impairing the migration ability of keratinocytes and thus re-epithelization. This is where TAs come into play, as they act as antagonists of β2-AR and thus attenuate the effects of adrenaline. The result is that not only TAs but also TA-producing skin bacteria accelerate wound healing. Adrenergic receptors (ARs) play a key role in many physiological and disease-related processes and are expressed in numerous cell types. In this review, we describe the role of ARs in relation to wound healing in keratinocytes, immune cells, fibroblasts, and blood vessels and the possible role of the skin microbiota in wound healing.
Solubility and Aggregation of Selected Proteins Interpreted on the Basis of Hydrophobicity Distribution
Authors: Ptak-Kaczor Magdalena , Banach Mateusz , Stapor Katarzyna , Fabian Piotr , Konieczny Leszek , Roterman Irena
Published: May 2021

Protein solubility is based on the compatibility of the specific protein surface with the polar aquatic environment. The exposure of polar residues to the protein surface promotes the protein’s solubility in the polar environment. The aquatic environment also influences the folding process by favoring the centralization of hydrophobic residues with the simultaneous exposure to polar residues. The degree of compatibility of the residue distribution, with the model of the concentration of hydrophobic residues in the center of the molecule, with the simultaneous exposure of polar residues is determined by the sequence of amino acids in the chain. The fuzzy oil drop model enables the quantification of the degree of compatibility of the hydrophobicity distribution observed in the protein to a form fully consistent with the Gaussian 3D function, which expresses an idealized distribution that meets the preferences of the polar water environment. The varied degrees of compatibility of the distribution observed with the idealized one allow the prediction of preferences to interactions with molecules of different polarity, including water molecules in particular. This paper analyzes a set of proteins with different levels of hydrophobicity distribution in the context of the solubility of a given protein and the possibility of complex formation.
Photoperiod Following Inoculation of Arabidopsis with Pyricularia oryzae (syn. Magnaporthe oryzae) Influences on the Plant–Pathogen Interaction
Authors: Shimizu Sayaka , Yamauchi Yuri , Ishikawa Atsushi
Published: May 2021

In plant–pathogen interactions, a proper light environment affects the establishment of defense responses in plants. In our previous experiments, we found that nonhost resistance (NHR) to Pyricularia oryzae Cav. in Arabidopsis thaliana (L.) Heynh. (Arabidopsis), in diurnal conditions, varies with the inoculation time. Moreover, we indicated that the circadian clock plays an important role in regulating time-of-day differences in NHR to P. oryzae in Arabidopsis. However, the involvement of photoperiod in regulating NHR was still not understood. To determine the photoperiod role, we performed the experiments in continuous light and darkness during the early Arabidopsis–P. oryzae interaction. We found that the light period after the inoculation in the evening enhanced the resistance to penetration. However, the dark period after the inoculation in the morning suppressed the penetration resistance. Furthermore, the genetic analysis indicated that jasmonic acid, reactive oxygen species, and tryptophan-derived metabolite(s) contribute to the photoperiod regulation of NHR in Arabidopsis. The present results denote that photoperiod plays an important role in regulating time-of-day differences in NHR to P. oryzae in Arabidopsis.
A Gene Expression Signature to Predict Nucleotide Excision Repair Defects and Novel Therapeutic Approaches
Authors: Wei Rongbin , Dai Hui , Zhang Jing , Shih David J. H. , Liang Yulong , Xiao Pengfeng , McGrail Daniel J. , Lin Shiaw-Yih
Published: May 2021

Nucleotide excision repair (NER) resolves DNA adducts, such as those caused by ultraviolet light. Deficient NER (dNER) results in a higher mutation rate that can predispose to cancer development and premature ageing phenotypes. Here, we used isogenic dNER model cell lines to establish a gene expression signature that can accurately predict functional NER capacity in both cell lines and patient samples. Critically, none of the identified NER deficient cell lines harbored mutations in any NER genes, suggesting that the prevalence of NER defects may currently be underestimated. Identification of compounds that induce the dNER gene expression signature led to the discovery that NER can be functionally impaired by GSK3 inhibition, leading to synergy when combined with cisplatin treatment. Furthermore, we predicted and validated multiple novel drugs that are synthetically lethal with NER defects using the dNER gene signature as a drug discovery platform. Taken together, our work provides a dynamic predictor of NER function that may be applied for therapeutic stratification as well as development of novel biological insights in human tumors.
Broad-Spectrum Bactericidal Activity of a Synthetic Random Copolymer Based on 2-Methoxy-6-(4-Vinylbenzyloxy)-Benzylammonium Hydrochloride
Authors: Schito Anna Maria , Piatti Gabriela , Caviglia Debora , Zuccari Guendalina , Alfei Silvana
Published: May 2021

Low-molecular-weight organic ammonium salts exert excellent antimicrobial effects by interacting lethally with bacterial membranes. Unfortunately, short-term functionality and high toxicity limit their clinical application. On the contrary, the equivalent macromolecular ammonium salts, derived from the polymerization of monomeric ammonium salts, have demonstrated improved antibacterial potency, a lower tendency to develop resistance, higher stability, long-term activity, and reduced toxicity. A water-soluble non-quaternary copolymeric ammonium salt (P7) was herein synthetized by copolymerizing 2-methoxy-6-(4-vinylbenzyloxy)-benzylammonium hydrochloride monomer with N, N-di-methyl-acrylamide. The antibacterial activity of P7 was assessed against several multidrug-resistant (MDR) clinical isolates of both Gram-positive and Gram-negative species. Except for colistin-resistant Pseudomonas aeruginosa, most isolates were susceptible to P7, also including some Gram-negative bacteria with a modified charge in the external membrane. P7 showed remarkable antibacterial activity against isolates of Enterococcus, Staphylococcus, Acinetobacter, and Pseudomonas, and on different strains of Escherichia coli and Stenotrophomonas maltophylia, regardless of their antibiotic resistance. The lowest minimal inhibitory concentrations (MICs) observed were 0.6–1.2 µM and the minimal bactericidal concentrations (MBC) were frequently overlapping with the MICs. In 24-h time–kill and turbidimetric studies, P7 displayed a rapid non-lytic bactericidal activity. P7 could therefore represent a novel and potent tool capable of counteracting infections sustained by several bacteria that are resistant to the presently available antibiotics.
Fitness Costs of Chlorantraniliprole Resistance Related to the SeNPF Overexpression in the Spodoptera exigua (Lepidoptera: Noctuidae)
Authors: Gong Changwei , Yao Xinge , Yang Qunfang , Wang Xuegui , Zhang Yuming , Wang Yumeng , Shen Litao
Published: May 2021

Spodopteraexigua, a multifeeding insect pest, has developed a high level of resistance to chlorantraniliprole, which is a benzoylurea insecticide that targets the ryanodine receptors (RyRs). Herein, the resistant strain (SE-Sel) and sensitive strain (SE-Sus) were obtained by bidirectional screening for six generations. The potential oviposited eggs and oviposition rate of the SE-Sel strain were dramatically lower than those of the SE-Sus strain; on the contrary, the weights of prepupae and preadult were significantly increased. As a post-mating response, the higher number of non-oviposited eggs in the SE-Sel strain was caused by a lower mating rate. In addition, the expression levels of vitellogenin (SeVg) and its receptor (SeVgR) in the SE-Sel strain were consistently lower than those in the SE-Sus strain. An RyRI4743M mutation, contributing to the resistance to chlorantraniliprole, was located in the S3 transmembrane segments and might have affected the release of calcium ions; it led to the upregulated expression of the neuropeptide SeNPF and its receptor SeNPFR, and the mating and oviposition rate were significantly recovered when the SeNPF was knocked down though RNA interference (RNAi) in the male adult of the SE-Sel strain. Moreover, the expression of the juvenile hormone-binding proteins SeJHBWDS3 and SeJHBAN in the male adult of the SE-Sel strain was significantly decreased, which proved the existence of a fitness cost from another angle. Therefore, these results indicate that the fitness cost accompanied by chlorantraniliprole resistance in S. exigua may be related to the decrease in mating desire due to SeNPF overexpression.
Molecular Imprinting Technology for Determination of Uric Acid
Authors: Ratautaite Vilma , Samukaite-Bubniene Urte , Plausinaitis Deivis , Boguzaite Raimonda , Balciunas Domas , Ramanaviciene Almira , Neunert Grażyna , Ramanavicius Arunas
Published: May 2021

The review focuses on the overview of electrochemical sensors based on molecularly imprinted polymers (MIPs) for the determination of uric acid. The importance of robust and precise determination of uric acid is highlighted, a short description of the principles of molecular imprinting technology is presented, and advantages over the others affinity-based analytical methods are discussed. The review is mainly concerned with the electro-analytical methods like cyclic voltammetry, electrochemical impedance spectroscopy, amperometry, etc. Moreover, there are some scattered notes to the other electrochemistry-related analytical methods, which are capable of providing additional information and to solve some challenges that are not achievable using standard electrochemical methods. The significance of these overviewed methods is highlighted. The overview of the research that is employing MIPs imprinted with uric acid is mainly targeted to address these topics: (i) type of polymers, which are used to design uric acid imprint structures; (ii) types of working electrodes and/or other parts of signal transducing systems applied for the registration of analytical signal; (iii) the description of the uric acid extraction procedures applied for the design of final MIP-structure; (iv) advantages and disadvantages of electrochemical methods and other signal transducing methods used for the registration of the analytical signal; (vi) overview of types of interfering molecules, which were analyzed to evaluate the selectivity; (vi) comparison of analytical characteristics such as linear range, limits of detection and quantification, reusability, reproducibility, repeatability, and stability. Some insights in future development of uric acid sensors are discussed in this review.