bluuebunny/crossref_metadata_2025 huggingface dataset:
The Propensity of the Human Liver to Form Large Lipid Droplets Is Associated with PNPLA3 Polymorphism, Reduced INSIG1 and NPC1L1 Expression and Increased Fibrogenetic Capacity
Authors: Ferri Flaminia , Carotti Simone , Carpino Guido , Mischitelli Monica , Cantafora Alfredo , Molinaro Antonio , Argenziano Maria Eva , Parisse Simona , Corsi Alessandro , Riminucci Mara , Lai Quirino , Mennini Gianluca , Spadetta Gustavo , Pugliese Francesco , Rossi Massimo , Morini Sergio , Gaudio Eugenio , Ginanni Corradini Stefano
Published: June 2021

In nonalcoholic steatohepatitis animal models, an increased lipid droplet size in hepatocytes is associated with fibrogenesis. Hepatocytes with large droplet (Ld-MaS) or small droplet (Sd-MaS) macrovesicular steatosis may coexist in the human liver, but the factors associated with the predominance of one type over the other, including hepatic fibrogenic capacity, are unknown. In pre-ischemic liver biopsies from 225 consecutive liver transplant donors, we retrospectively counted hepatocytes with Ld-MaS and Sd-MaS and defined the predominant type of steatosis as involving ≥50% of steatotic hepatocytes. We analyzed a donor Patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409 polymorphism, hepatic expression of proteins involved in lipid metabolism by RT-PCR, hepatic stellate cell (HSC) activation by α-SMA immunohistochemistry and, one year after transplantation, histological progression of fibrosis due to Hepatitis C Virus (HCV) recurrence. Seventy-four livers had no steatosis, and there were 98 and 53 with predominant Ld-MaS and Sd-MaS, respectively. In linear regression models, adjusted for many donor variables, the percentage of steatotic hepatocytes affected by Ld-MaS was inversely associated with hepatic expression of Insulin Induced Gene 1 (INSIG-1) and Niemann-Pick C1-Like 1 gene (NPC1L1) and directly with donor PNPLA3 variant M, HSC activation and progression of post-transplant fibrosis. In humans, Ld-MaS formation by hepatocytes is associated with abnormal PNPLA3-mediated lipolysis, downregulation of both the intracellular cholesterol sensor and cholesterol reabsorption from bile and increased hepatic fibrogenesis.
Natural Polyphenols in Metabolic Syndrome: Protective Mechanisms and Clinical Applications
Authors: Zhang Shiyao , Xu Mengyi , Zhang Wenxiang , Liu Chang , Chen Siyu
Published: June 2021

Metabolic syndrome (MetS) is a chronic disease, including abdominal obesity, dyslipidemia, hyperglycemia, and hypertension. It should be noted that the occurrence of MetS is closely related to oxidative stress-induced mitochondrial dysfunction, ectopic fat accumulation, and the impairment of the antioxidant system, which in turn further aggravates the intracellular oxidative imbalance and inflammatory response. As enriched anti-inflammatory and antioxidant components in plants, natural polyphenols exhibit beneficial effects, including improving liver fat accumulation and dyslipidemia, reducing blood pressure. Hence, they are expected to be useful in the prevention and management of MetS. At present, epidemiological studies indicate a negative correlation between polyphenol intake and MetS incidence. In this review, we summarized and discussed the most promising natural polyphenols (including flavonoid and non-flavonoid drugs) in the precaution and treatment of MetS, including their anti-inflammatory and antioxidant properties, as well as their regulatory functions involved in glycolipid homeostasis.
Modelling and Refining Neuronal Circuits with Guidance Cues: Involvement of Semaphorins
Authors: Limoni Greta
Published: June 2021

The establishment of neuronal circuits requires neurons to develop and maintain appropriate connections with cellular partners in and out the central nervous system. These phenomena include elaboration of dendritic arborization and formation of synaptic contacts, initially made in excess. Subsequently, refinement occurs, and pruning takes places both at axonal and synaptic level, defining a homeostatic balance maintained throughout the lifespan. All these events require genetic regulations which happens cell-autonomously and are strongly influenced by environmental factors. This review aims to discuss the involvement of guidance cues from the Semaphorin family.
Cascade of Inflammatory, Fibrotic Processes, and Stress-Induced Senescence in Chronic GVHD-Related Dry Eye Disease
Authors: Ogawa Yoko , Kawakami Yutaka , Tsubota Kazuo
Published: June 2021

Ocular graft-versus-host disease (GVHD) is a major complication after allogeneic hematopoietic stem cell transplantation. Ocular GVHD affects recipients’ visual function and quality of life. Recent advanced research in this area has gradually attracted attention from a wide range of physicians and ophthalmologists. This review highlights the mechanism of immune processes and the molecular mechanism, including several inflammation cascades, pathogenic fibrosis, and stress-induced senescence related to ocular GVHD, in basic spectrum topics in this area. How the disease develops and what kinds of cells participate in ocular GVHD are discussed. Although the classical immune process is a main pathological pathway in this disease, senescence-associated changes in immune cells and stem cells may also drive this disease. The DNA damage response, p16/p21, and the expression of markers associated with the senescence-associated secretory phenotype (SASP) are seen in ocular tissue in GVHD. Macrophages, T cells, and mesenchymal cells from donors or recipients that increasingly infiltrate the ocular surface serve as the source of increased secretion of IL-6, which is a major SASP driver. Agents capable of reversing the changes, including senolytic reagents or those that can suppress the SASP seen in GVHD, provide new potential targets for the treatment of GVHD. Creating innovative therapies for ocular GVHD is necessary to treat this intractable ocular disease.
RbfA Is Involved in Two Important Stages of 30S Subunit Assembly: Formation of the Central Pseudoknot and Docking of Helix 44 to the Decoding Center
Authors: Maksimova Elena M. , Korepanov Alexey P. , Kravchenko Olesya V. , Baymukhametov Timur N. , Myasnikov Alexander G. , Vassilenko Konstantin S. , Afonina Zhanna A. , Stolboushkina Elena A.
Published: June 2021

Ribosome biogenesis is a highly coordinated and complex process that requires numerous assembly factors that ensure prompt and flawless maturation of ribosomal subunits. Despite the increasing amount of data collected, the exact role of most assembly factors and mechanistic details of their operation remain unclear, mainly due to the shortage of high-resolution structural information. Here, using cryo-electron microscopy, we characterized 30S ribosomal particles isolated from an Escherichia coli strain with a deleted gene for the RbfA factor. The cryo-EM maps for pre-30S subunits were divided into six classes corresponding to consecutive assembly intermediates: from the particles with a completely unresolved head domain and unfolded central pseudoknot to almost mature 30S subunits with well-resolved body, platform, and head domains and partially distorted helix 44. The structures of two predominant 30S intermediates belonging to most populated classes obtained at 2.7 Å resolutions indicate that RbfA acts at two distinctive 30S assembly stages: early formation of the central pseudoknot including folding of the head, and positioning of helix 44 in the decoding center at a later stage. Additionally, it was shown that the formation of the central pseudoknot may promote stabilization of the head domain, likely through the RbfA-dependent maturation of the neck helix 28. An update to the model of factor-dependent 30S maturation is proposed, suggesting that RfbA is involved in most of the subunit assembly process.
Spatially Enriched Paralog Rearrangements Argue Functionally Diverse Ribosomes Arise during Cold Acclimation in Arabidopsis
Authors: Martinez-Seidel Federico , Beine-Golovchuk Olga , Hsieh Yin-Chen , Eshraky Kheloud El , Gorka Michal , Cheong Bo-Eng , Jimenez-Posada Erika V. , Walther Dirk , Skirycz Aleksandra , Roessner Ute , Kopka Joachim , Pereira Firmino Alexandre Augusto
Published: June 2021

Ribosome biogenesis is essential for plants to successfully acclimate to low temperature. Without dedicated steps supervising the 60S large subunits (LSUs) maturation in the cytosol, e.g., Rei-like (REIL) factors, plants fail to accumulate dry weight and fail to grow at suboptimal low temperatures. Around REIL, the final 60S cytosolic maturation steps include proofreading and assembly of functional ribosomal centers such as the polypeptide exit tunnel and the P-Stalk, respectively. In consequence, these ribosomal substructures and their assembly, especially during low temperatures, might be changed and provoke the need for dedicated quality controls. To test this, we blocked ribosome maturation during cold acclimation using two independent reil double mutant genotypes and tested changes in their ribosomal proteomes. Additionally, we normalized our mutant datasets using as a blank the cold responsiveness of a wild-type Arabidopsis genotype. This allowed us to neglect any reil-specific effects that may happen due to the presence or absence of the factor during LSU cytosolic maturation, thus allowing us to test for cold-induced changes that happen in the early nucleolar biogenesis. As a result, we report that cold acclimation triggers a reprogramming in the structural ribosomal proteome. The reprogramming alters the abundance of specific RP families and/or paralogs in non-translational LSU and translational polysome fractions, a phenomenon known as substoichiometry. Next, we tested whether the cold-substoichiometry was spatially confined to specific regions of the complex. In terms of RP proteoforms, we report that remodeling of ribosomes after a cold stimulus is significantly constrained to the polypeptide exit tunnel (PET), i.e., REIL factor binding and functional site. In terms of RP transcripts, cold acclimation induces changes in RP families or paralogs that are significantly constrained to the P-Stalk and the ribosomal head. The three modulated substructures represent possible targets of mechanisms that may constrain translation by controlled ribosome heterogeneity. We propose that non-random ribosome heterogeneity controlled by specialized biogenesis mechanisms may contribute to a preferential or ultimately even rigorous selection of transcripts needed for rapid proteome shifts and successful acclimation.
Diagnostics and Therapeutics in Targeting HER2 Breast Cancer: A Novel Approach
Authors: Vi Chris , Mandarano Giovanni , Shigdar Sarah
Published: June 2021

Breast cancer is one of the most commonly occurring cancers in women globally and is the primary cause of cancer mortality in females. BC is highly heterogeneous with various phenotypic expressions. The overexpression of HER2 is responsible for 15–30% of all invasive BC and is strongly associated with malignant behaviours, poor prognosis and decline in overall survival. Molecular imaging offers advantages over conventional imaging modalities, as it provides more sensitive and specific detection of tumours, as these techniques measure the biological and physiological processes at the cellular level to visualise the disease. Early detection and diagnosis of BC is crucial to improving clinical outcomes and prognosis. While HER2-specific antibodies and nanobodies may improve the sensitivity and specificity of molecular imaging, the radioisotope conjugation process may interfere with and may compromise their binding functionalities. Aptamers are single-stranded oligonucleotides capable of targeting biomarkers with remarkable binding specificity and affinity. Aptamers can be functionalised with radioisotopes without compromising target specificity. The attachment of different radioisotopes can determine the aptamer’s functionality in the treatment of HER2(+) BC. Several HER2 aptamers and investigations of them have been described and evaluated in this paper. We also provide recommendations for future studies with HER2 aptamers to target HER2(+) BC.
Three Complete Mitochondrial Genomes of Erotylidae (Coleoptera: Cucujoidea) with Higher Phylogenetic Analysis
Authors: Liu Jing , Wang Yuyu , Zhang Ruyue , Shi Chengmin , Lu Weicheng , Li Jing , Bai Ming
Published: June 2021

The family Erotylidae belongs to the superfamily Cucujoidea, which are phytophagous and mycophagous. So far, only two representative complete mitochondrial (mt) genomes of Erotylidae have been sequenced. Mitochondrial genomes of Tritoma metasobrina, Neotriplax arisana, and Episcapha opaca, which all belong to the subfamily Erotylinae, were sequenced using next-generation sequencing technology to better understand the diversity of mt genomes of Erotylidae. A comparative mt genomic analysis was conducted on the three sequenced representatives of Erotylinae and Languriinae sp. (Languriinae). The size of the complete mt genome of the 4 species ranged from 15,581 bp to 16,502 bp in length, including 37 genes (13 protein-coding genes, 22 transfer RNAs, and 2 ribosomal RNAs) and the control region. The arrangements of their mt genomes are highly consistent with other Coleoptera species. The start codons of two PCGs (ND1 and ND5) and the stop codons of one PCG (ATP8) were illustrated differences between Languriinae sp. and the other three species. All tRNAs of these 4 species exhibited cloverleaf secondary structures except that the dihydorouridine (DHU) arm of tRNASer(AGN) was absent. The phylogenetic analyses using both Bayesian inference (BI) and maximum likelihood (ML) methods all supported that Erotylidae as monophyletic. Erotylinae was monophyletic being the sister group to Xenocelinae. Languriinae was closely related to ‘Erotylinae-Xenocelinae’. Our results recovered Languriinae nested within Erotylidae.
Evaluation of Mosquito Attractant Candidates Using a High-Throughput Screening System for Aedes aegypti (L.), Culex quinquefasciatus Say. and Anopheles minimus Theobald (Diptera: Culicidae)
Authors: Kim Dae-Yun , Leepasert Theerachart , Bangs Michael J. , Chareonviriyaphap Theeraphap
Published: June 2021

Several types of olfactometers have been used to evaluate mosquito responses to agents that mimic natural volatiles that repel or attract. The Y-tube olfactometer has been widely used to study repellents and attractants, while the high-throughput screening system assay has only been used to study repellents. Whether the high-throughput screening system assay is suitable for evaluating attractants is unknown. We evaluated the responses to four lactic-acid-based mixtures and two non-lactic-acid-based chemical lure candidates using the high-throughput screening system (HITSS) for three mosquito species (laboratory strains and field populations of both Aedes aegypti (L.) and Culex quinquefasciatus Say.; laboratory strain of Anopheles minimus Theobald) under laboratory-controlled conditions. HITSS assay results showed that KU-lure #1 elicited the greatest percent attraction for pyrethroid-resistant and -susceptible Ae. aegypti. KU-lure #6 elicited the strongest attractive response for pyrethroid-susceptible and -resistant Cx. quinquefasciatus and pyrethroid-susceptible An. minimus. The response to the lures from each species was independent of the pyrethroid susceptibility status (Ae. aegypti, p = 0.825; Cx. quinquefasciatus, p = 0.056). However, a significant difference in attraction to KU-lure #6 was observed between diurnal and nocturnal mosquitoes (Cx. quinquefasciatus vs. Ae. aegypti, p = 0.014; An. minimus vs. Ae. aegypti, p = 0.001). The laboratory-level HITSS assay effectively selects potential lure candidates. Because the host-seeking behavior differs between mosquito species, further studies are needed to develop species-specific attractants. Additional studies in semi-field screen houses using commercial traps are necessary to evaluate the accuracy of these laboratory assay results.
New Treatments for Atopic Dermatitis Targeting Skin Barrier Repair via the Regulation of FLG Expression
Authors: Dębińska Anna
Published: June 2021

Atopic dermatitis (AD) is one of the most common chronic, inflammatory skin disorders with a complex etiology and a broad spectrum of clinical phenotypes. Despite its high prevalence and effect on the quality of life, safe and effective systemic therapies approved for long-term management of AD are limited. A better understanding of the pathogenesis of atopic dermatitis in recent years has contributed to the development of new therapeutic approaches that target specific pathophysiological pathways. Skin barrier dysfunction and immunological abnormalities are critical in the pathogenesis of AD. Recently, the importance of the downregulation of epidermal differentiation complex (EDC) molecules caused by external and internal stimuli has been extensively emphasized. The purpose of this review is to discuss the innovations in the therapy of atopic dermatitis, including biologics, small molecule therapies, and other drugs by highlighting regulatory mechanisms of skin barrier-related molecules, such as filaggrin (FLG) as a crucial pathway implicated in AD pathogenesis.
Does Unidirectional Block Exist after a Radiofrequency Line Creation? Insights from Ultra-High-Density Mapping (The UNIBLOCK Study)
Authors: Bun Sok-Sithikun , Da Costa Antoine , Guichard Jean-Baptiste , Khoueiry Ziad , Squara Fabien , Scarlatti Didier , Taghji Philippe , Moceri Pamela , Ferrari Emile
Published: June 2021

Background: Whether unidirectional conduction block (UB) can be observed after creation of a radiofrequency (RF) line is still debated. Previous studies reported a prevalence of 9 to 33% of UB, but the assessment was performed using a point-by-point recording across the line. Ultra-high-density (UHD) system may bring some new insights on the exact prevalence of UB. Purpose: A prospective study was conducted to assess the prevalence of UB and bidirectional block (BB) using UHD system after RF line creation. Methods: Patients referred for atrial RF ablation procedure were included in this multicenter prospective study. UHD maps were performed by pacing both sides of the created line. Results: A total of 80 maps were created in 40 patients (67 ± 12 years, 70% male) by pacing (mean cycle length 600 ± 57 ms) from both sides of the cavotricuspid isthmus line. After a 47 ± 17 min waiting time after the last RF application, UHD maps (mean number of 4842 ± 5010 electrograms, acquired during 6 ± 5 min) showed that BB was unambiguously confirmed on all of them. UB was not observed in any map. After a mean follow-up of 12 ± 4 months, 6 (14%) patients experienced an arrhythmia recurrence. Conclusion: After creation of an RF line, no case of UB was observed using UHD mapping, suggesting that the presence of a conduction block along a RF line is always associated with a block in the opposite direction.
Fujifilm SILVAMP TB-LAM for the Diagnosis of Tuberculosis in Nigerian Adults
Authors: Comella-del-Barrio Patricia , Bimba John S. , Adelakun Ramota , Kontogianni Konstantina , Molina-Moya Bárbara , Osazuwa Okoedoh , Creswell Jacob , Cuevas Luis E. , Domínguez José
Published: June 2021

There is a need for diagnostics for tuberculosis (TB) that are easy to use, able to screen non-sputum samples, and able to provide rapid results for the management of both immunocompromised and immunocompetent individuals. The Fujifilm SILVAMP TB LAM (FujiLAM) assay, a new non-sputum based point of need test for the diagnosis of TB, could potentially address most of these needs. We evaluated the performance of FujiLAM in HIV positive and HIV negative patients with presumptive TB attending three district hospitals in Nigeria. Consecutive patients were asked to provide urine samples on the spot, which were tested with FujiLAM. The results were compared against a positive culture and/or Xpert MTB/RIF as the reference standard. Forty-five patients had bacteriologically confirmed TB, and 159 had negative culture and Xpert MTB/RIF (no TB). The FujiLAM test was positive in 23 (sensitivity 65.7%, 95% CI = 48–80) HIV negative and seven (70%, 95% CI = 35–92) HIV positive patients with bacteriological confirmation of TB. FujiLAM was negative in 97 (specificity 99.0%, 95% CI = 94–100) HIV negative and 56 (93.3%, 95% CI = 83–98) HIV positive patients without TB. The FujiLAM test has good diagnostic accuracy for considering its application in both HIV positive and HIV negative patients with TB.
Physical Activity in Patients with Prader-Willi Syndrome—A Systematic Review of Observational and Interventional Studies
Authors: Bellicha Alice , Coupaye Muriel , Mosbah Héléna , Tauber Maithé , Oppert Jean-Michel , Poitou Christine
Published: June 2021

Physical activity (PA) is an important aspect of the management of patients with Prader-Willi syndrome (PWS). However, the day-to-day implementation of PA programs is particularly challenging in these patients. This systematic review aimed (1) to describe habitual PA and sedentary behavior and (2) to assess the effects of PA interventions and to describe their implementation process, in children and adults with PWS. A systematic search of controlled trials, single-group interventions, observational, and qualitative studies published up to December 2020 was performed. Twenty-five studies were included. Habitual PA was found to be lower in patients with PWS compared to controls without obesity or with non-syndromic obesity. Habitual PA was positively associated with lean body mass and bone parameters in children with PWS, and these finding were strengthened by intervention studies reporting an increase in both outcomes after a PA program. PA programs also improved physical function (muscle strength, walking distance, and coordination), without significant effect on weight and fat mass. Attendance to exercise sessions was usually high and no serious adverse effect was reported. In conclusion, supervised PA programs are beneficial for children and adults with PWS. Support should be provided to families to facilitate their implementation in real-life settings.
Is There an Association between Sleep Disorders and Diabetic Foot? A Scoping Review
Authors: Fernández-Torres Raúl , Ruiz-Muñoz María , Pérez-Belloso Ana J. , García-Romero Jerónimo , Gónzalez-Sánchez Manuel
Published: June 2021

Diabetic foot is associated with a low quality of life since physical disabilities, mood disturbances and psychological disorders are frequent. One of the most important biological processes to ensure quality of life is sleep. Sleep disorders can impair glycemic control in patients with diabetes mellitus or even cause long-term type 2 diabetes mellitus. The aim of this study is to carry out a scoping review about the association between sleep cycle disorders and diabetic foot. PubMed, Scopus, CINAHL, PEDro, Cochrane Library, SCIELO and EMBASE databases were chosen for the search and the following terms were used: “diabetic foot”,“sleep*”,“rest-activity”,“mood” and“behavior”. All the studies should include outcome variables about sleep and diabetic foot. Finally, 12 articles were selected, all of whichwere observational. The most frequent variables were those regarding diabetic foot ulcer aspects and diabetic neuropathy on one side, and obstructive sleep apnea, sleep duration and sleep quality on the other side. The results suggest that there is a possible association between obstructive sleep apnea and the presence or history of diabetic foot ulcers. No direct associations between sleep quality or sleep duration and diabetic foot or diabetic foot ulcer variables have been found.
Design and Comparative Study of Hybrid Propulsions for a River Ferry Operating on Short Cycles with High Power Demands
Authors: Bennabi Nacera , Menana Hocine , Charpentier Jean-Frederic , Billard Jean-Yves , Nottelet Benoit
Published: June 2021

Based on a multidisciplinary and configurable modeling approach, this work deals with the optimal choice and the design of a hybrid propulsion with the associated power management strategy to replace a conventional propulsion in a low tonnage river ferry operating on short cycles, with the aim of reducing its environmental impact and the costs over its entire lifetime. The considered ferry is used for the transport of people and vehicles crossing the Seine river, with an installed propulsive power of 330 KW. The operating cycle of the ferry and the energy consumption of its classical propulsion have been determined experimentally and then used as references in simulations for validation and comparison purposes. Two hybrid structures involving the use of batteries and supercapacitors were proposed and compared. It is shown that the hybridization leads to a substantial reduction in CO2 emissions. The supercapacitor- and battery-based hybrid structures lead respectively to 18% and 29.7% CO2 reduction compared to classical propulsion, representing, respectively, about 382 and 626 tons of CO2 reduction over 20 years of operation. Despite the fact that the use of batteries leads to a more significant reduction in CO2 emissions, the solution using supercapacitors is chosen following a technical-economic study over 20 years of operation.
IL17F: A Possible Risk Marker for Spondyloarthritis in HLA-B*27 Negative Brazilian Patients
Authors: Neves Janisleya Silva Ferreira , Visentainer Jeane Eliete Laguila , Reis Denise Manjurma da Silva , Rocha Loures Marco Antonio , Alves Hugo Vicentin , Zacarias Joana Maira Valentini , Sell Ana Maria
Published: June 2021

HLA-B*27 is an important marker for spondyloarthritis (SpA), however, many SpA patients are HLA-B*27 negative. Thus, the aim of this study was to investigate the influence of IL17, TNF and VDR gene polymorphisms in SpA patients who were HLA-B*27 negative. This case-control study was conducted in 158 patients [102 patients with ankylosing spondylitis (AS) and 56 with psoriatic arthritis (PsA)] and 184 controls. HLA-B*27 genotyping was performed using PCR-SSP and IL17A (rs2275913), IL17F (rs763780), TNF-308 (rs1800629), TNF-238 (rs361525), FokI C>T (rs2228570), TaqI C>T (rs731236), ApaI A>C (rs7975232), and BsmI C>T (rs1544410) using PCR-RFLP. Statistical analyses were performed by Chi-square and logistic regression using OpenEpi and SNPStats software. The IL17F C allele frequency was higher in patients with SpA, AS and PsA compared to controls. The IL17F T/C genotype frequency was higher in SpA patients in an overdominant inheritance model and when men and women were separately analyzed. IL17A_IL17F AC haplotype was significantly associated to the risk for SpA patients. As for VDR, the ApaI a/a was a potential risk factor for SpA in men. In conclusion, IL17F C variant contributed to the risk of SpA in Brazilian patients who were HLA-B*27 negative and could be a potential marker for SpA.
Application of Suitability Modeling in Establishing a New Bicycle–Pedestrian Path: The Case of the Abandoned Kanfanar–Rovinj Railway in Istria
Authors: Modesto Ariana , Kamenečki Monika , Tomić Reljić Dora
Published: June 2021

This paper presents research on the conversion of the abandoned Kanfanar–Rovinj railway into a bicycle–pedestrian path, with the aim of including it in the existing network of bicycle–pedestrian paths in the Istria County in Croatia. This would enable better connection of the repurposed railway corridor with the surrounding natural and cultural values and better use of the spatial potential, which would create more favorable conditions for the revitalization of the wider rural environment. In order to identify the existing potential of the area, as well as the impact of the proposed intervention on critical areas, a method of multicriteria analysis was used. The result of the analysis was a model of the suitability of the space, i.e., five value categories that make the space more or less suitable for accommodating new pedestrian and bicycle paths. In order to emphasize the importance of individual spatial contents in the modeling process, the method of weighted linear combination was used. Finally, the nature of the project and its potential impact on the environment have conditioned the selection of the appropriate aspect of the model and of the space’s suitability, which is further used for locating the new pedestrian and bicycle paths.
Applying the Fit-for-Purpose Land Administration Concept to South Africa
Authors: Williams-Wynn Christopher
Published: June 2021

What potential will the fit-for-purpose land administration concept have of working in the Republic of South Africa? This question is asked against the existence of a high-quality cadastre covering most of the South African landmass. However, a large proportion of the people living in South Africa live outside of this secure land tenure system. Many citizens and immigrants reside on communal land, in informal settlements, in resettled communities, in off-register housing schemes, and as farm dwellers, labour tenants and other occupants of commercial farms. Reasonable estimates suggest that there are more than 5 million land occupations that exist outside the formal land tenure system and hence outside the formal land administration system. This paper looks at the current bifurcated system and considers how the application of the fit-for-purpose land administration system can expand the existing cadastral system and provide security of tenure that is beneficial and acceptable to all. It demonstrates that, not only could it work, but it is also considered to be necessary. This paper uses South Africa as a case study to demonstrate how adjustments to institutional, legal and spatial frameworks will develop a fully inclusive, sufficiently accurate land administration system that fits the purpose for which it is envisioned. These country-specific proposals may well be of international interest to assist with the formulation of fit-for-purpose land administration systems being developed in other countries.
Planning Strategies of Wind Corridor Forests Utilizing the Properties of Cold Air
Authors: Sung Uk-Je , Eum Jeong-Hee , Son Jeong-Min , Oh Jeong-Hak
Published: June 2021

A wind corridor forest is defined as an urban forest for utilizing the functions of a wind corridor that allow “cool and fresh air (cold air)” generated in forests at night to flow to urban development areas. This study aims to provide planning strategies for implementing a wind corridor forest by analyzing current conditions in Haengbok City (HBC region), Sejong, South Korea. The HBC region had many wind-generating forests (WGF), wind-spreading forests (WSF), and wind-connecting forests (WCF), and secured the connections among the target areas of each wind corridor forest. Despite the favorable conditions for a wind corridor forest, cold air flow showed that there are regions with unfavorable wind conditions in the HBC region. In order to strengthen the functions of a wind corridor forests in the HBC region, four zones were distinguished according to the functional characteristics. Additionally, the planning strategies of a wind corridor forests suitable for each zone were provided, and the strategies for establishing a wind corridor forest were proposed. The results of this study can be used as the fundamental data for establishing guidelines for a wind corridor forest and utilized as resources for selecting regions suitable for a wind corridor forest.
Multispectral Sentinel-2 and SAR Sentinel-1 Integration for Automatic Land Cover Classification
Authors: De Fioravante Paolo , Luti Tania , Cavalli Alice , Giuliani Chiara , Dichicco Pasquale , Marchetti Marco , Chirici Gherardo , Congedo Luca , Munafò Michele
Published: June 2021

The study of land cover and land use dynamics are fundamental to understanding the radical changes that human activity is causing locally and globally and to analyse the continuous metamorphosis of landscape. In Europe, the Copernicus Program offers numerous territorial monitoring tools to users and decision makers, such as Sentinel data. This research aims at developing and implementing a land cover mapping and change detection methodology through the classification of Copernicus Sentinel-1 and Sentinel-2 satellite data. The goal is to create a versatile and economically sustainable algorithm capable of rapidly processing large amounts of data, allowing the creation of national-scale products with high spatial resolution and update frequency for operational purposes. Great attention was paid to compatibility with the main activities planned in the near future at the national and European level. In this sense, a land cover classification system consistent with the European specifications of the EAGLE group has been adopted. The methodology involves the definition of distinct sets of decision rules for each of the land cover macro-classes and for the land cover change classes. The classification refers to pixels’ spectral and backscatter characteristics, exploiting the main multi-temporal indices while proposing two new ones: the NDCI to distinguish between broad-leaved and needle-leaved trees, and the Burned Index (BI) to identify burned areas. This activity allowed for the production of a land cover map for 2018 and the change detection related to forest disturbances and land consumption for 2017–2018, reaching an overall accuracy of 83%.
Microsatellite Loci Reveal Genetic Diversity of Asian Callery Pear (Pyrus calleryana) in the Species Native Range and in the North American Cultivars
Authors: Sapkota Shiwani , Boggess Sarah L. , Trigiano Robert N. , Klingeman William E. , Hadziabdic Denita , Coyle David R. , Olukolu Bode A. , Kuster Ryan D. , Nowicki Marcin
Published: June 2021

Pyrus calleryana Decne. (Callery pear) includes cultivars that in the United States are popular ornamentals in commercial and residential landscapes. Last few decades, this species has increasingly naturalized across portions of the eastern and southern US. However, the mechanisms behind this plant’s spread are not well understood. The genetic relationship of present-day P.calleryana trees with their Asian P. calleryana forebears (native trees from China, Japan, and Korea) and the original specimens of US cultivars are unknown. We developed and used 18 microsatellite markers to analyze 147 Pyrus source samples and to articulate the status of genetic diversity within Asian P. calleryana and US cultivars. We hypothesized that Asian P. calleryana specimens and US cultivars would be genetically diverse and would show genetic relatedness. Our data revealed high genetic diversity, high gene flow, and presence of population structure in P. calleryana, potentially relating to the highly invasive capability of this species. Strong evidence for genetic relatedness between Asian P. calleryana specimens and US cultivars was also demonstrated. Our data suggest the source for P. calleryana that have become naturalized in US was China. These results will help understand the genetic complexity of invasive P. calleryana when developing management for escaped populations: In follow-up studies, we use the gSSRs developed here to analyze P. calleryana escape populations from across US.
Atomic Simulations of Packing Structures, Local Stress and Mechanical Properties for One Silicon Lattice with Single Vacancy on Heating
Authors: Dai Feng , Zhao Dandan , Zhang Lin
Published: June 2021

The effect of vacancy defects on the structure and mechanical properties of semiconductor silicon materials is of great significance to the development of novel microelectronic materials and the processes of semiconductor sensors. In this paper, molecular dynamics is used to simulate the atomic packing structure, local stress evolution and mechanical properties of a perfect lattice and silicon crystal with a single vacancy defect on heating. In addition, their influences on the change in Young’s modulus are also analyzed. The atomic simulations show that in the lower temperature range, the existence of vacancy defects reduces the Young’s modulus of the silicon lattice. With the increase in temperature, the local stress distribution of the atoms in the lattice changes due to the migration of the vacancy. At high temperatures, the Young’s modulus of the silicon lattice changes in anisotropic patterns. For the lattice with the vacancy, when the temperature is higher than 1500 K, the number and degree of distortion in the lattice increase significantly, the obvious single vacancy and its adjacent atoms contracting inward structure disappears and the defects in the lattice present complex patterns. By applying uniaxial tensile force, it can be found that the temperature has a significant effect on the elasticity–plasticity behaviors of the Si lattice with the vacancy.
A Comparative Study among New Hybrid Root Finding Algorithms and Traditional Methods
Authors: Badr Elsayed , Almotairi Sultan , Ghamry Abdallah El
Published: June 2021

In this paper, we propose a novel blended algorithm that has the advantages of the trisection method and the false position method. Numerical results indicate that the proposed algorithm outperforms the secant, the trisection, the Newton–Raphson, the bisection and the regula falsi methods, as well as the hybrid of the last two methods proposed by Sabharwal, with regard to the number of iterations and the average running time.
Ordering of Omics Features Using Beta Distributions on Montecarlo p-Values
Authors: Riffo-Campos Angela L. , Ayala Guillermo , Domingo Juan
Published: June 2021

The current trend in genetic research is the study of omics data as a whole, either combining studies or omics techniques. This raises the need for new robust statistical methods that can integrate and order the relevant biological information. A good way to approach the problem is to order the features studied according to the different kinds of data so a key point is to associate good values to the features that permit us a good sorting of them. These values are usually the p-values corresponding to a hypothesis which has been tested for each feature studied. The Montecarlo method is certainly one of the most robust methods for hypothesis testing. However, a large number of simulations is needed to obtain a reliable p-value, so the method becomes computationally infeasible in many situations. We propose a new way to order genes according to their differential features by using a score defined from a beta distribution fitted to the generated p-values. Our approach has been tested using simulated data and colorectal cancer datasets from Infinium methylationEPIC array, Affymetrix gene expression array and Illumina RNA-seq platforms. The results show that this approach allows a proper ordering of genes using a number of simulations much lower than with the Montecarlo method. Furthermore, the score can be interpreted as an estimated p-value and compared with Montecarlo and other approaches like the p-value of the moderated t-tests. We have also identified a new expression pattern of eighteen genes common to all colorectal cancer microarrays, i.e., 21 datasets. Thus, the proposed method is effective for obtaining biological results using different datasets. Our score shows a slightly smaller type I error for small sizes than the Montecarlo p-value. The type II error of Montecarlo p-value is lower than the one obtained with the proposed score and with a moderated p-value, but these differences are highly reduced for larger sample sizes and higher false discovery rates. Similar performances from type I and II errors and the score enable a clear ordering of the features being evaluated.
Prediction on Mechanical Properties of Non-Equiatomic High-Entropy Alloy by Atomistic Simulation and Machine Learning
Authors: Zhang Liang , Qian Kun , Schuller Björn W. , Shibuta Yasushi
Published: June 2021

High-entropy alloys (HEAs) with multiple constituent elements have been extensively studied in the past 20 years, due to their promising engineering application. Previous experimental and computational studies of HEAs focused mainly on equiatomic or near equiatomic HEAs. However, there is probably far more treasure in those non-equiatomic HEAs with carefully designed composition. In this study, the molecular dynamics (MD) simulation combined with machine learning (ML) methods was used to predict the mechanical properties of non-equiatomic CuFeNiCrCo HEAs. A database was established based on a tensile test of 900 HEA single-crystal samples by MD simulation. Eight ML models were investigated and compared for the binary classification learning tasks, ranging from shallow models to deep models. It was found that the kernel-based extreme learning machine (KELM) model outperformed others for the prediction of yield stress and Young’s modulus. The accuracy of the KELM model was further verified by the large-sized polycrystal HEA samples. The results show that computational simulation combined with ML methods is an efficient way to predict the mechanical performance of HEAs, which provides new ideas for accelerating the development of novel alloy materials for engineering applications.
Machine Learning Algorithms, Applied to Intact Islets of Langerhans, Demonstrate Significantly Enhanced Insulin Staining at the Capillary Interface of Human Pancreatic β Cells
Authors: Cottle Louise , Gilroy Ian , Deng Kylie , Loudovaris Thomas , Thomas Helen E. , Gill Anthony J. , Samra Jaswinder S. , Kebede Melkam A. , Kim Jinman , Thorn Peter
Published: June 2021

Pancreatic β cells secrete the hormone insulin into the bloodstream and are critical in the control of blood glucose concentrations. β cells are clustered in the micro-organs of the islets of Langerhans, which have a rich capillary network. Recent work has highlighted the intimate spatial connections between β cells and these capillaries, which lead to the targeting of insulin secretion to the region where the β cells contact the capillary basement membrane. In addition, β cells orientate with respect to the capillary contact point and many proteins are differentially distributed at the capillary interface compared with the rest of the cell. Here, we set out to develop an automated image analysis approach to identify individual β cells within intact islets and to determine if the distribution of insulin across the cells was polarised. Our results show that a U-Net machine learning algorithm correctly identified β cells and their orientation with respect to the capillaries. Using this information, we then quantified insulin distribution across the β cells to show enrichment at the capillary interface. We conclude that machine learning is a useful analytical tool to interrogate large image datasets and analyse sub-cellular organisation.
Towards Standards for Human Fecal Sample Preparation in Targeted and Untargeted LC-HRMS Studies
Authors: Hosseinkhani Farideh , Dubbelman Anne-Charlotte , Karu Naama , Harms Amy C. , Hankemeier Thomas
Published: June 2021

Gut microbiota and their metabolic products are increasingly being recognized as important modulators of human health. The fecal metabolome provides a functional readout of the interactions between human metabolism and the gut microbiota in health and disease. Due to the high complexity of the fecal matrix, sample preparation often introduces technical variation, which must be minimized to accurately detect and quantify gut bacterial metabolites. Here, we tested six different representative extraction methods (single-phase and liquid–liquid extractions) and compared differences due to fecal amount, extraction solvent type and solvent pH. Our results indicate that a minimum fecal (wet) amount of 0.50 g is needed to accurately represent the complex texture of feces. The MTBE method (MTBE/methanol/water, 3.6/2.8/3.5, v/v/v) outperformed the other extraction methods, reflected by the highest extraction efficiency for 11 different classes of compounds, the highest number of extracted features (97% of the total identified features in different extracts), repeatability (CV < 35%) and extraction recovery (≥70%). Importantly, optimization of the solvent volume of each step to the initial dried fecal material (µL/mg feces) offers a major step towards standardization, which enables confident assessment of the contributions of gut bacterial metabolites to human health.
Regulation of the Pseudomonas syringae Type III Secretion System by Host Environment Signals
Authors: O’Malley Megan R. , Anderson Jeffrey C.
Published: June 2021

Pseudomonas syringae are Gram-negative, plant pathogenic bacteria that use a type III secretion system (T3SS) to disarm host immune responses and promote bacterial growth within plant tissues. Despite the critical role for type III secretion in promoting virulence, T3SS-encoding genes are not constitutively expressed by P. syringae and must instead be induced during infection. While it has been known for many years that culturing P. syringae in synthetic minimal media can induce the T3SS, relatively little is known about host signals that regulate the deployment of the T3SS during infection. The recent identification of specific plant-derived amino acids and organic acids that induce T3SS-inducing genes in P. syringae has provided new insights into host sensing mechanisms. This review summarizes current knowledge of the regulatory machinery governing T3SS deployment in P. syringae, including master regulators HrpRS and HrpL encoded within the T3SS pathogenicity island, and the environmental factors that modulate the abundance and/or activity of these key regulators. We highlight putative receptors and regulatory networks involved in linking the perception of host signals to the regulation of the core HrpRS–HrpL pathway. Positive and negative regulation of T3SS deployment is also discussed within the context of P. syringae infection, where contributions from distinct host signals and regulatory networks likely enable the fine-tuning of T3SS deployment within host tissues. Last, we propose future research directions necessary to construct a comprehensive model that (a) links the perception of host metabolite signals to T3SS deployment and (b) places these host–pathogen signaling events in the overall context of P. syringae infection.
In Vitro Susceptibility to Miltefosine of Leishmania infantum (syn. L. chagasi) Isolates from Different Geographical Areas in Brazil
Authors: Espada Caroline Ricce , Levatti Erica V. de Castro , Boité Mariana Côrtes , Lamounier Dorcas , Alvar Jorge , Cupolillo Elisa , Costa Carlos Henrique Nery , Rode Joelle , Uliana Silvia R. B.
Published: June 2021

Treatment of visceral leishmaniasis in Brazil still relies on meglumine antimoniate, with less than ideal efficacy and safety, making new therapeutic tools an urgent need. The oral drug miltefosine was assayed in a phase II clinical trial in Brazil with cure rates lower than previously demonstrated in India. The present study investigated the susceptibility to miltefosine in 73 Brazilian strains of Leishmania infantum from different geographic regions, using intracellular amastigote and promastigote assays. The EC50 for miltefosine of 13 of these strains evaluated in intracellular amastigotes varied between 1.41 and 4.57 μM. The EC50 of the 73 strains determined in promastigotes varied between 5.89 and 23.7 μM. No correlation between in vitro miltefosine susceptibility and the presence of the miltefosine sensitive locus was detected among the tested strains. The relatively low heterogeneity in miltefosine susceptibility observed for the 73 strains tested in this study suggests the absence of decreased susceptibility to miltefosine in Brazilian L. infantum and does not exclude future clinical evaluation of miltefosine for VL treatment in Brazil.