bluuebunny/crossref_metadata_2025 huggingface dataset:
Note on the Equivalence of Special Norms on the Lebesgue Space
Authors: Kukushkin Maksim V.
Published: April 2021

In this paper, we consider a norm based on the infinitesimal generator of the shift semigroup in a direction. The relevance of such a focus is guaranteed by an abstract representation of a uniformly elliptic operator by means of a composition of the corresponding infinitesimal generator. The main result of the paper is a theorem establishing equivalence of norms in functional spaces. Even without mentioning the relevance of this result for the constructed theory, we claim it deserves to be considered itself.
Macronutrient Determinants of Obesity, Insulin Resistance and Metabolic Health
Authors: Wali Jibran A. , Solon-Biet Samantha M. , Freire Therese , Brandon Amanda E.
Published: April 2021

Obesity caused by the overconsumption of calories has increased to epidemic proportions. Insulin resistance is often associated with an increased adiposity and is a precipitating factor in the development of cardiovascular disease, type 2 diabetes, and altered metabolic health. Of the various factors contributing to metabolic impairments, nutrition is the major modifiable factor that can be targeted to counter the rising prevalence of obesity and metabolic diseases. However, the macronutrient composition of a nutritionally balanced “healthy diet” are unclear, and so far, no tested dietary intervention has been successful in achieving long-term compliance and reductions in body weight and associated beneficial health outcomes. In the current review, we briefly describe the role of the three major macronutrients, carbohydrates, fats, and proteins, and their role in metabolic health, and provide mechanistic insights. We also discuss how an integrated multi-dimensional approach to nutritional science could help in reconciling apparently conflicting findings.
177Lu-PSMA Therapy in Metastatic Castration-Resistant Prostate Cancer
Authors: Sanli Yasemin , Simsek Duygu Has , Sanli Oner , Subramaniam Rathan M. , Kendi Ayse Tuba
Published: April 2021

The aim of this narrative review is to evaluate the current status of 177Lu-PSMA (prostate specific membrane antigen) therapy for metastatic castration-resistant prostate cancer (mCRPC) in the light of the current literature. We also addressed patient preparation, therapy administration and side effect profiles. 177Lu-PSMA therapy efficacy was assessed by using prospective trials, meta-analyses and major retrospective trials. Predictors of efficacy were also mentioned. Although there are some different approaches regarding the use of 177Lu-PSMA therapy in different countries, this type of therapy is generally safe, with a low toxicity profile. From the oncological point of view, a PSA (prostate specific antigen) decline of ≥50% was seen in 10.6–69% of patients with mCRPC; whereas progression-free survival (PFS) was reported to be 3–13.7 months in different studies. Consequently, 177Lu-PSMA therapy is a promising treatment in patients with mCRPC, with good clinical efficacy, even in heavily pretreated patients with multiple lines of systemic therapy. Currently, there are ongoing clinical trials in the United States, including a phase III multicenter FDA registration trial.
A Computational Model for Pain Processing in the Dorsal Horn Following Axonal Damage to Receptor Fibers
Authors: Crodelle Jennifer , Maia Pedro D.
Published: April 2021

Computational modeling of the neural activity in the human spinal cord may help elucidate the underlying mechanisms involved in the complex processing of painful stimuli. In this study, we use a biologically-plausible model of the dorsal horn circuitry as a platform to simulate pain processing under healthy and pathological conditions. Specifically, we distort signals in the receptor fibers akin to what is observed in axonal damage and monitor the corresponding changes in five quantitative markers associated with the pain response. Axonal damage may lead to spike-train delays, evoked potentials, an increase in the refractoriness of the system, and intermittent blockage of spikes. We demonstrate how such effects applied to mechanoreceptor and nociceptor fibers in the pain processing circuit can give rise to dramatically distinct responses at the network/population level. The computational modeling of damaged neuronal assemblies may help unravel the myriad of responses observed in painful neuropathies and improve diagnostics and treatment protocols.
Main Features of the Timber Structure Building Industry Business Models
Authors: Gosselin Annie , Cimon Yan , Lehoux Nadia , Blanchet Pierre
Published: April 2021

The use of timber as structural building material is growing and a greater number of firms are looking to enter this raising market. Erecting a complex timber building usually involves combining the work of architects, structural engineers, builders, suppliers and/or supplier–builders, all of them having their own business models. The purpose of this research was to uncover the specific nature of business models in the timber structure building industry. First, a thorough mapping of these business models was undertaken. Second, underlying patterns were uncovered within these models. A triangulation method of secondary data, semi-structured interviews and participant observation was used to allow for an in-depth study of 23 stakeholder business models. The analysis shows that knowledge sharing appears as crucial and may be achieved through sustained collaboration. As a result, collaborative contract procurement modes seem to be the most appropriate for timber construction. Tight relationships with suppliers and supplier–builders also appear as prerequisites. Furthermore, stakeholder partnerships with universities appear common in the field, while prefabrication is increasing in popularity. These findings can be useful to grasp the prevailing business models in this industry given the sustained growth of the timber structure building market.
Positron Emission Tomography Imaging of Macrophages in Cancer
Authors: Parker Candace C. , Lapi Suzanne E.
Published: April 2021

Macrophages are large phagocytic cells that can be classified as a type of white blood cell and may be either mobile or stationary in tissues. The presence of macrophages in essentially every major disease makes them attractive candidates to serve as therapeutic targets and diagnostic biomarkers. Macrophages that are found in the microenvironment of solid tumors are referred to as tumor-associated macrophages (TAMs) and have been shown to influence chemoresistance, immune regulation, tumor initiation and tumor growth. The imaging of TAMs through Positron Emission Tomography (PET) has the potential to provide valuable information on cancer biology, tumor progression, and response to therapy. This review will highlight the versatility of macrophage imaging in cancer through the use of PET.
Lipase Catalyzed Synthesis of Enantiopure Precursors and Derivatives for β-Blockers Practolol, Pindolol and Carteolol
Authors: Gundersen Morten , Austli Guro , Løvland Sigrid , Hansen Mari , Rødseth Mari , Jacobsen Elisabeth
Published: April 2021

Sustainable methods for producing enantiopure drugs have been developed. Chlorohydrins as building blocks for several β-blockers have been synthesized in high enantiomeric purity by chemo-enzymatic methods. The yield of the chlorohydrins increased by the use of catalytic amount of base. The reason for this was found to be the reduced formation of the dimeric by-products compared to the use of higher concentration of the base. An overall reduction of reagents and reaction time was also obtained compared to our previously reported data of similar compounds. The enantiomers of the chlorohydrin building blocks were obtained by kinetic resolution of the racemate in transesterification reactions catalyzed by Candida antarctica Lipase B (CALB). Optical rotations confirmed the absolute configuration of the enantiopure drugs. The β-blocker (S)-practolol ((S)-N-(4-(2-hydroxy-3-(isopropylamino)propoxy)phenyl)acetamide) was synthesized with 96% enantiomeric excess (ee) from the chlorohydrin (R)-N-(4-(3-chloro-2 hydroxypropoxy)phenyl)acetamide, which was produced in 97% ee and with 27% yield. Racemic building block 1-((1H-indol-4-yl)oxy)-3-chloropropan-2-ol for the β-blocker pindolol was produced in 53% yield and (R)-1-((1H-indol-4-yl)oxy)-3-chloropropan-2-ol was produced in 92% ee. The chlorohydrin 7-(3-chloro-2-hydroxypropoxy)-3,4-dihydroquinolin-2(1H)-one, a building block for a derivative of carteolol was produced in 77% yield. (R)-7-(3-Chloro-2-hydroxypropoxy)-3,4-dihydroquinolin-2(1H)-one was obtained in 96% ee. The S-enantiomer of this carteolol derivative was produced in 97% ee in 87% yield. Racemic building block 5-(3-chloro-2-hydroxypropoxy)-3,4-dihydroquinolin-2(1H)-one, building block for the drug carteolol, was also produced in 53% yield, with 96% ee of the R-chlorohydrin (R)-5-(3-chloro-2-hydroxypropoxy)-3,4-dihydroquinolin-2(1H)-one. (S)-Carteolol was produced in 96% ee with low yield, which easily can be improved.
Cellular Senescence and Vitamin D Deficiency Play a Role in the Pathogenesis of Obesity-Associated Subclinical Atherosclerosis: Study of the Potential Protective Role of Vitamin D Supplementation
Authors: Bima Abdulhadi I. , Mahdi Abdullah S. , Al Fayez Fayza F. , Khawaja Taghreed M. , Abo El-Khair Salwa M. , Elsamanoudy Ayman Z.
Published: April 2021

The exact link between obesity, vitamin D deficiency, and their relation to cellular senescence in the pathogenesis of subclinical atherosclerosis is still under debate. Therefore, the current study aims to verify the possible role of vitamin D deficiency and cellular senescence in the pathogenesis of obesity-related subclinical atherosclerosis. Moreover, it aims to investigate the possible protective role of vitamin D supplementation. Fifty-seven male albino rats were enrolled in the study and classified into four groups: negative (10) and positive control groups (10), an obese model group (24), and a vitamin-D-supplemented obese group (13). Aortic tissue samples and fasting blood samples were collected. The following biochemical investigations were performed: serum cholesterol, triglycerides, HDL-C, LDL-C, ALT, AST, CPK, CK-MB, and hs-cTnt. HOMA-IR was calculated. Moreover, serum SMP-30, 25 (OH)Vitamin D3, and eNOS were determined by the ELISA technique. Aortic gene expression of eNOS, SMP-30, and P53 was estimated by real-time qRT-PCR. Serum 25(OH) D3 and SMP-30 were lower in the obese group. In addition, the obese group showed higher serum lipid profile, HOMA-IR, eNOS, ALT, AST, CPK, CK-MB, and hs-cTnt than the control groups, while decreased levels were found in the vitamin-D-treated obese group. Gene expression of eNOS and SMP-30 were in accordance with their serum levels. A positive correlation was found between vitamin D level and SMP-30. In conclusion, obesity is associated with vitamin D deficiency and enhanced cellular senescence. They could play a role in the pathogenesis of obesity-associated subclinical atherosclerosis and endothelial dysfunction. Vitamin D supplements could play a protective role against such obesity-related comorbidity.
Anti-Corrosion Performance of Polyaniline Coated Basalt Rockwool Wastes/Epoxy Resin Coatings
Authors: Fang Zhiqiang , Wang Guoqing , Xiong Yangkai , Li Jiang , Yang Yu , Huang Lei , Wang Peiqing , Liao Jianhe , Wang Aimin
Published: April 2021

Basalt rockwool wastes with large output, which are toxic and require expensive environmental treatment, are produced during the production of rock wool. Hence, it is urgent to find an effective method to reuse these materials. In this study, polyaniline (PANI)-coated basalt rockwool wastes (BRWs) were prepared as fillers to serve in coatings for the anticorrosion study. Results show that the PANI-coated BRW (PANI@BRW) had enhanced dispersion stability in several conventional solvents and improved the anticorrosion performance of the epoxy resin coating. A high protection efficiency of 97.7% could be obtained from the coating with 5% fillers after immersion for 30 days. This study not only provides a promising method of solving the issues caused by BRW, but also turns these wastes into valuable substances.
Combined Processing of Micro Cutters Using a Beam of Fast Argon Atoms in Plasma
Authors: Metel Alexander , Melnik Yury , Mustafaev Enver , Minin Ilya , Pivkin Petr
Published: April 2021

We present a new method for coating deposition on micro cutters without an increase in their cutting edges radii caused by the deposition. For this purpose, the cutting edges are sharpened before the coating deposition with a concentrated beam of fast argon atoms. The sharpening decreases the initial radius and, hence, limits its value after the coating deposition. The concentrated beam of fast argon atoms is generated using an immersed in the gas discharge plasma concave grid under a negative high voltage. Ions accelerated from the plasma by the grid pass through the grid holes and are concentrated in the focal point of the grid. As a result of the charge exchange in the space charge sheaths of the grid, they are transformed into fast atoms. A uniform sputtering by the fast atoms of the micro-cutter surface reduces the radius of its cutting edge.
Improving Business Performance by Employing Virtualization Technology: A Case Study in the Financial Sector
Authors: Lambropoulos Georgios , Mitropoulos Sarandis , Douligeris Christos
Published: April 2021

The financial crisis of the last decade has left many financial institutions with limited personnel and equipment resources. Thus, the IT departments of these institutions are being asked to explore novel approaches to resolve these constraints in a cost-effective and efficient manner. The goal of this paper is to measure the impact of modern enabling technologies, such as virtualization, in the process of replacing legacy infrastructures. This paper proposes an IT services upgrade plan approach for an organization by using modern technologies. For this purpose, research took place in an operating financial institution, which required a significant upgrade of both its service-level and its hardware infrastructure. A virtualization implementation and deployment assessment for the entire infrastructure was conducted and the resulting consolidated data are presented and analysed. The paper concludes with a five-year financial-based evaluation of the proposed approach with respect to the projection of expenditures, the return of investment and profitability.
Effect of Butyric Acid in the Proliferation and Migration of Junctional Epithelium in the Progression of Periodontitis: An In Vitro Study
Authors: Ishikawa Taichi , Sasaki Daisuke , Aizawa Ryo , Shimoyama Yu , Yamamoto Matsuo , Irié Tarou , Sasaki Minoru
Published: April 2021

Purpose: To elucidate the effects of butyric acid (BA), a metabolite of bacteria involved in periodontitis, and a possible enhancer of the junctional epithelial cells. Methods: A murine junctional epithelial cell line, JE-1, was used to assess the effects of sodium butyrate (NaB) as BA. Cell proliferation, migration and attachment were analyzed. Additionally, gene and promoter expression analysis was performed, i.e., cap analysis of gene expression (CAGE) and gene ontology (GO) term enrichment analysis. Results: NaB affected junctional epithelial cell proliferation, migration and attachment. A high concentration of NaB caused cell death and a low concentration tended to promote migration and adhesion. CAGE analysis revealed 75 upregulated and 96 downregulated genes in the cells after 0.2 mM NaB stimulation for 3 h. Regarding GO term enrichment, the genes upregulated >4-fold participated predominantly in cell migration and proliferation. The results of this study suggest that BA produced from periodontopathic bacteria is involved in periodontal tissue destruction at high concentrations. Furthermore, at low concentrations, BA potentially participates in periodontal disease progression by increasing proliferation, migration and attachment of the junctional epithelium and thereby increasing epithelial down-growth.
Human-Machine Cooperative Trajectory Planning for Semi-Autonomous Driving Based on the Understanding of Behavioral Semantics
Authors: Jiang Bohan , Li Xiaohui , Zeng Yujun , Liu Daxue
Published: April 2021

This paper presents a novel cooperative trajectory planning approach for semi-autonomous driving. The machine interacts with the driver at the decision level and the trajectory generation level. To minimize conflicts between the machine and the human, the trajectory planning problem is decomposed into a high-level behavior decision-making problem and a low-level trajectory planning problem. The approach infers the driver’s behavioral semantics according to the driving context and the driver’s input. The trajectories are generated based on the behavioral semantics and driver’s input. The feasibility of the proposed approach is validated by real vehicle experiments. The results prove that the proposed human–machine cooperative trajectory planning approach can successfully help the driver to avoid collisions while respecting the driver’s behavior.
Catalytic Decomposition of 2% Methanol in Methane over Metallic Catalyst by Fixed-Bed Catalytic Reactor
Authors: Awad Ali , Ahmed Israr , Qadir Danial , Khan Muhammad Saad , Idris Alamin
Published: April 2021

The structure and performance of promoted Ni/Al2O3 with Cu via thermocatalytic decomposition (TCD) of CH4 mixture (2% CH3OH) were studied. Mesoporous Cat-1 and Cat-2 were synthesized by the impregnation method. The corresponding peaks of nickel oxide and copper oxide in the XRD showed the presence of nickel and copper oxides as a mixed alloy in the calcined catalyst. Temperature program reduction (TPR) showed that Cu enhanced the reducibility of the catalyst as the peak of nickel oxide shifted toward a lower temperature due to the interaction strength of the metal particles and support. The impregnation of 10% Cu on Cat-1 drastically improved the catalytic performance and exhibited 68% CH4 conversion, and endured its activity for 6 h compared with Cat-1, which deactivated after 4 h. The investigation of the spent carbon showed that various forms of carbon were obtained as a by-product of TCD, including graphene fiber (GF), carbon nanofiber (CNF), and multi-wall carbon nanofibers (MWCNFs) on the active sites of Cat-2 and Cat-1, following various kinds of growth mechanisms. The presence of the D and G bands in the Raman spectroscopy confirmed the mixture of amorphous and crystalline morphology of the deposited carbon.
Impact of the Application of Fuel and Water Emulsion on CO and NOx Emission and Fuel Consumption in a Miniature Gas Turbine
Authors: Niszczota Paweł , Gieras Marian
Published: April 2021

Miniature gas turbines (MGT) are an important part of the production of electric energy in distributed systems. Due to the growing requirements for lower emissions and the increasing prices of hydrocarbon fuels, it is becoming more and more important to enhance the efficiency and improve the quality of the combustion process in gas turbines. One way to reduce NOx emissions is to add water to the fuel in the form of a water-based emulsion (FWE). This article presents the research results and the analysis of the impact of the use of FWE on CO and NOx emissions as well as on fuel consumption in MGT GTM-120. Experimental tests and numerical calculations were carried out using standard fuel (DF) and FWE with water content from 3% to 12%. It was found that the use of FWE leads to a reduction in NOx and CO emissions and reduction in the consumption of basic fuel. The maximum reduction in emissions by 12.32% and 35.16% for CO and NOx, respectively, and a reduction in fuel consumption by 5.46% at the computational operating point of the gas turbine were recorded.
A Survey on Over-The-Air Linearization Methods for MIMO Systems
Authors: Jordão Marina , Caldeirinha Rafael , Oliveira Arnaldo S. R. , Carvalho Nuno Borges
Published: April 2021

Transmitter antenna arrays are typically coupled to several RF chains, which imposes stringent requirements on the linearization of each power amplifier (PA) present in the system. For this and other reasons discussed in this work, Over-the-air (OTA) linearization methods are considered to linearize transmitter antenna arrays in 5G scenarios. However, several factors need to be considered when applying OTA linearization methods. In this paper, an extended critical review of validated OTA linearization methods is presented. The main goal is to point out and discuss the most prominent methods, in order to determine which one is the most suitable for a specific application. In particular, analysis for each method is performed and, subsequently, their benefits and the disadvantages are systematically discussed. This is sought to fill-in a gap in the scientific literarure and, thus, to help radio-frequency engineers in the implementation of OTA digital pre-distortion (DPD) techniques for multiple input multiple output (MIMO) systems.
Salicylic Acid-Induced Morpho-Physiological and Biochemical Changes Triggered Water Deficit Tolerance in Syzygium cumini L. Saplings
Authors: Zafar Zikria , Rasheed Fahad , Atif Rana Muhammad , Maqsood Muhammad , Gailing Oliver
Published: April 2021

Fruit tree culture is at the brink of disaster in arid to semi-arid regions due to low water availability. A pot experiment was carried out to analyze whether foliar application of salicylic acid (SA) can improve water stress tolerance in Syzygiumcumini. Saplings were subjected to control (CK, 90% of field capacity, FC), medium stress (MS, 60% of FC) and high stress (HS, 30% of FC) along with foliar application of 0.5 and 1.0 mM of SA. Results showed that soil water deficit significantly decreased leaf, stem and total dry weight, leaf gas exchange attributes and chlorophyll a, b. However, root dry weight and root/shoot ratio increased under MS and HS, respectively. Contrarily, foliar application of SA significantly improved chlorophyll a, b, leaf gas exchange attributes, and dry weight production under soil water deficit. Concentration of oxidants like hydrogen peroxide and superoxide radicals, along with malondialdehyde and electrolyte leakage increased under soil water deficit; however, decreased in plants sprayed with SA due to the increase in the concentration of antioxidant enzymes like superoxide dismutase, peroxidase, catalase and ascorbate peroxidase. Results suggest that the foliar application of SA can help improve water stress tolerance in Syzygiumcumini saplings; however, validation of the results under field conditions is necessary.
Reinforcement of Flexural Members with Basalt Fiber Mortar
Authors: Kurlapov Dmitry , Klyuev Sergey , Biryukov Yury , Vatin Nikolai , Biryukov Dmitry , Fediuk Roman , Vasilev Yuriy
Published: April 2021

Reconstruction of buildings and structures is becoming one of the main directions in the field of construction, and the design and production of works during reconstruction are significantly different from the ones of new buildings and structures. After carrying out a number of studies on the inspection of the technical condition of buildings in order to determine the effect of defects on the bearing capacity, the criteria for assessing the state of floor slab structures were identified. Conclusions on the state and further work of elements of reinforced concrete structures are considered. The authors achieve the aim of reinforcing flexural elements of reinforced concrete structures with fiber-reinforced mortar, which is especially important for floor elements with increased operational requirements. A technique for constructing a reinforcement layer using fiber-reinforced mortar from coarse basalt fiber has been developed. The parameters of basalt fiber in the reinforcement layer are substantiated. A method for solving problems of the operation of multilayer coatings under the influence of operational loads is used, in which the model prerequisites for describing the operation of layers are simplified, where the bearing layers are represented by classical Kirchhoff-Love plates. When solving problems, the maximum possible number of design features of flexural members is taken into account, in combination with appropriate experimental studies, the method allows us to consider all the variety of structures for reinforcing coatings and meet the needs of their practical application.
2-Piece Cork Stoppers as Alternative for Valorization of Thin Cork Planks: Analysis by LCA Methodology
Authors: Flor-Montalvo Francisco Javier , Ledesma Agustín Sánchez-Toledo , Cámara Eduardo Martínez , Jiménez-Macías Emilio , García-Alcaraz Jorge Luis , Blanco-Fernandez Julio
Published: April 2021

Natural stoppers are a magnificent closure for the production of aging wines and unique wines, whose application is limited by the availability of raw materials and more specifically of cork sheets of different thickness and quality. The growing demand for quality wine bottle closures leads to the search for alternative stopper production. The two-piece stopper is an alternative since it uses non-usable plates in a conventional way for the production of quality caps. The present study has analyzed the impact of the manufacture of these two-piece stoppers using different methodologies and for different dimensions by developing an LCA (Life Cycle Assessment), concluding that the process phases of the plate, its boiling, and its stabilization, are the phases with the greatest impact. Likewise, it is detected that the impacts in all phases are relatively similar (for one kg of net cork produced), although the volumetric difference between these stoppers represents a significant difference in impacts for each unit produced.
Assessment of Physicochemical Characteristics and Microbiological Quality in Broiler Chicken Breast Muscle (Pectoralis major) Subjected to Different Temperatures and Lengths of Cold Transportation
Authors: Hayat Muhammad Nizam , Kaka Ubedullah , Sazili Awis Qurni
Published: April 2021

Cold truck transportation is considered one of the most integral parts in a food processing chain. However, countless cases of product spoilage and food poisoning incidents have proven that temperature control during transport has been neglected. Literature on the impact of temperature during distribution is scarce. The objective of this study was to investigate the impact of various transportation temperatures and travel duration on the meat quality and microbial population of broiler chicken breast muscle. Sixty broiler chickens (42 days old) were slaughtered and eviscerated; they then had their breast muscles removed (each bird provided two breast muscle samples: left breast and right breast), which were wrapped in plastic film. All 120 packed boneless breasts (PBBs) were then placed at −18 °C for 24 h. After 24 h, the 60 PBB samples were subjected to transportation for 1 h at 4 °C (20 PBBs), 10 °C (20 PBBs), and 15 °C (20 PBBs) while the remaining 60 samples were transported for 5 h at 4 °C (20 PBBs), 10 °C (20 PBBs), and 15 °C (20 PBBs) before analyses. The samples transported at higher temperatures exhibited higher populations of coliform and Salmonella than those transported at lower temperatures. A significant impact of the transportation duration on the Salmonella population was only observed in samples transported at 4 °C for 5 h. However, a significant impact of transportation temperature on color was only recorded for the redness (a*) values, where the samples transported at higher temperatures exhibited higher redness (a*) values. Significant increases in lightness (L*) and yellowness (b*) values as well as decreases in redness (a*) and pH values were recorded in samples subjected to longer durations of transportation across all the temperatures observed in this study.
Classification of Botrytized Wines Based on Producing Technology Using Flow-Modulated Comprehensive Two-Dimensional Gas Chromatography
Authors: Vyviurska Olga , Koljančić Nemanja , Thai Ha Anh , Gorovenko Roman , Špánik Ivan
Published: April 2021

The enantiomeric ratio of chiral compounds is known as a useful tool to estimate wine quality as well as observe an influence of wine-producing technology. The incorporation of flow-modulated comprehensive two-dimensional gas chromatography in this type of analysis provides a possibility to improve the quality of results due to the enhancement of separation capacity and resolution. In this study, flow-modulated comprehensive two-dimensional gas chromatography was incorporated in enantioselective analysis to determine the influence of winemaking technology on specific features of botrytized wines. The samples included Tokaj essences (high-sugar wines), Tokaj botrytized wines and varietal wines (Furmint, Muscat Lunel, Lipovina) and wines maturated on grape peels. The obtained data was processed with hierarchic cluster analysis to reveal variations in composition and assess classification ability for botrytized wines. A significant difference between the samples was observed for the enantiomeric distribution of ethyl lactate and presence of monoterpene alcohols. The varietal wines were successfully separated from the other types, which showed more similar results and could be divided with additional parameters. We observed a correlation between the botrytized wines and the varietal wines fermented with grape skins. As to the essences produced from juice of botrytized grapes, the results were quite similar to those of the botrytized wines, even though monoterpenes were not detected in the extracts.
The Association between Poor Diet Quality, Physical Fatigability and Physical Function in the Oldest-Old from the Geisinger Rural Aging Study
Authors: Davis Brett , Liu Yi-Hsuan , Stampley James , Wood G. Craig , Mitchell Diane C. , Jensen Gordon L. , Gao Xiang , Glynn Nancy W. , Still Christopher D. , Irving Brian A.
Published: April 2021

More perceived physical fatigability and poor diet quality are associated with impairments in physical function in older adults. However, the degree to which more perceived fatigability explains the association between poor diet quality and low physical function is unknown. We examined this relationship in 122 (66F, 56M) of the oldest-old participants from the Geisinger Rural Aging Study (GRAS). We used 24-h dietary recalls to assess the Healthy Eating Index (HEI), the Pittsburgh Fatigability Scale (PFS, 0–50) to assess perceived physical fatigability, and the PROMIS Physical Function 20a* to assess physical function. We grouped participants into three age categories: 80–84 (n = 51), 85–89 (n = 51), and 90+ (n = 20) years. Multiple linear regression revealed that a lower HEI was associated with higher PFS Physical score after adjusting for age group, sex, body mass index, and the number of medical conditions (p = 0.001). Several macro- and micro-nutrient intakes were also lower in those reporting more (≥15) compared to less (<15) perceived physical fatigability. Mediation analysis revealed that PFS Physical scores explained ~65% (p = 0.001) of the association between HEI total score and PROMIS19 Physical Function score. Poor diet quality may contribute to more perceived physical fatigability, which could exacerbate impairments in the oldest-old’s physical function.
The Social Experiences and Uses of Post-War Modernist Urban Heritage Conservation and Regeneration: London’s Southbank Centre
Authors: Aelbrecht Patricia
Published: April 2021

Since the 1960s, post-war modernist heritage has been largely criticised and victimised by the public opinion because of its material failures and elitist social projects. Despite these critiques, post-war modernist heritage is being reassessed, revalued and in some places successfully rehabilitated. There is a growing recognition that most of the critiques have often been the result of subjective and biased value and taste judgments or incomplete assessments that neither considered the urban design nor the users’ experiences. This paper aims to contribute to these reassessments of post-war modernist urban heritage legacies. To do so, it places the user’s social experiences and uses, and the urban design at the centre of the analysis, by using a combination of ethnographic methods and urban design analysis and focusing on the public spaces of Southbank Centre in London, the UK’s largest and most iconic and contested post-war modernist ensemble with a long history of conservation and regeneration projects. Taken together, the findings demonstrate the importance of including the users’ social experiences and uses in the conservation and regeneration agendas if we want to achieve more objective and inclusive assessments.
Immune Checkpoints, Inhibitors and Radionuclides in Prostate Cancer: Promising Combinatorial Therapy Approach
Authors: Kgatle Mankgopo M. , Boshomane Tebatso M. G. , Lawal Ismaheel O. , Mokoala Kgomotso M. G. , Mokgoro Neo P. , Lourens Nico , Kairemo Kalevo , Zeevaart Jan Rijn , Vorster Mariza , Sathekge Mike M.
Published: April 2021

Emerging research demonstrates that co-inhibitory immune checkpoints (ICs) remain the most promising immunotherapy targets in various malignancies. Nonetheless, ICIs have offered insignificant clinical benefits in the treatment of advanced prostate cancer (PCa) especially when they are used as monotherapies. Current existing PCa treatment initially offers an improved clinical outcome and overall survival (OS), however, after a while the treatment becomes resistant leading to aggressive and uncontrolled disease associated with increased mortality and morbidity. Concurrent combination of the ICIs with radionuclides therapy that has rapidly emerged as safe and effective targeted approach for treating PCa patients may shift the paradigm of PCa treatment. Here, we provide an overview of the contextual contribution of old and new emerging inhibitory ICs in PCa, preclinical and clinical studies supporting the use of these ICs in treating PCa patients. Furthermore, we will also describe the potential of using a combinatory approach of ICIs and radionuclides therapy in treating PCa patients to enhance efficacy, durable cancer control and OS. The inhibitory ICs considered in this review are cytotoxic T-lymphocyte antigen 4 (CTLA4), programmed cell death 1 (PD1), V-domain immunoglobulin suppressor of T cell activation (VISTA), indoleamine 2,3-dioxygenase (IDO), T cell Immunoglobulin Domain and Mucin Domain 3 (TIM-3), lymphocyte-activation gene 3 (LAG-3), T cell immunoreceptor with Ig and ITIM domains (TIGIT), B7 homolog 3 (B7-H3) and B7-H4.
Nephrotoxicity of Herbal Products in Europe—A Review of an Underestimated Problem
Authors: Kiliś-Pstrusińska Katarzyna , Wiela-Hojeńska Anna
Published: April 2021

Currently in Europe, despite the many advances in production technology of synthetic drugs, the interest in natural herbal medicines continues to increase. One of the reasons for their popular use is the assumption that natural equals safe. However, herbal medicines contain pharmacologically active ingredients, some of which have been associated with adverse effects. Kidneys are particularly susceptible to injury induced by toxins, including poisonous constituents from medicinal plants. The most recognized herb-induced kidney injury is aristolochic acid nephropathy connected with misuse of certain Traditional Chinese herbal medicines. Data concerning nephrotoxicity of plant species of European origin are scarce. Here, we critically review significant data of the nephrotoxicity of several plants used in European phytotherapy, including Artemisia herba-alba, Glycyrrhiza glabra, Euphorbia paralias, and Aloe). Causative mechanisms and factors predisposing to intoxications from the use of herbs are discussed. The basic intention of this review is to improve pharmacovigilance of herbal medicine, especially in patients with chronic kidney diseases.
YABBY Genes in the Development and Evolution of Land Plants
Authors: Romanova Marina A. , Maksimova Anastasiia I. , Pawlowski Katharina , Voitsekhovskaja Olga V.
Published: April 2021

Mounting evidence from genomic and transcriptomic studies suggests that most genetic networks regulating the morphogenesis of land plant sporophytes were co-opted and modified from those already present in streptophyte algae and gametophytes of bryophytes sensu lato. However, thus far, no candidate genes have been identified that could be responsible for “planation”, a conversion from a three-dimensional to a two-dimensional growth pattern. According to the telome theory, “planation” was required for the genesis of the leaf blade in the course of leaf evolution. The key transcription factors responsible for leaf blade development in angiosperms are YABBY proteins, which until recently were thought to be unique for seed plants. Yet, identification of a YABBY homologue in a green alga and the recent findings of YABBY homologues in lycophytes and hornworts suggest that YABBY proteins were already present in the last common ancestor of land plants. Thus, these transcriptional factors could have been involved in “planation”, which fosters our understanding of the origin of leaves. Here, we summarise the current data on functions of YABBY proteins in the vegetative and reproductive development of diverse angiosperms and gymnosperms as well as in the development of lycophytes. Furthermore, we discuss a putative role of YABBY proteins in the genesis of multicellular shoot apical meristems and in the evolution of leaves in early divergent terrestrial plants.
CBCR: A Curriculum Based Strategy For Chromosome Reconstruction
Authors: Hovenga Van , Oluwadare Oluwatosin
Published: April 2021

In this paper, we introduce a novel algorithm that aims to estimate chromosomes’ structure from their Hi-C contact data, called Curriculum Based Chromosome Reconstruction (CBCR). Specifically, our method performs this three dimensional reconstruction using cis-chromosomal interactions from Hi-C data. CBCR takes intra-chromosomal Hi-C interaction frequencies as an input and outputs a set of xyz coordinates that estimate the chromosome’s three dimensional structure in the form of a .pdb file. The algorithm relies on progressively training a distance-restraint-based algorithm with a strategy we refer to as curriculum learning. Curriculum learning divides the Hi-C data into classes based on contact frequency and progressively re-trains the distance-restraint algorithm based on the assumed importance of each curriculum in predicting the underlying chromosome structure. The distance-restraint algorithm relies on a modification of a Gaussian maximum likelihood function that scales probabilities based on the importance of features. We evaluate the performance of CBCR on both simulated and actual Hi-C data and perform validation on FISH, HiChIP, and ChIA-PET data as well. We also compare the performance of CBCR to several current methods. Our analysis shows that the use of curricula affects the rate of convergence of the optimization while decreasing the computational cost of our distance-restraint algorithm. Also, CBCR is more robust to increases in data resolution and therefore yields superior reconstruction accuracy of higher resolution data than all other methods in our comparison.
Peripheral Nerve-Derived Stem Cell Spheroids Induce Functional Recovery and Repair after Spinal Cord Injury in Rodents
Authors: Lee Hye-Lan , Yeum Chung-Eun , Lee HyeYeong , Oh Jinsoo , Kim Jong-Tae , Lee Won-Jin , Ha Yoon , Yang Young-Il , Kim Keung-Nyun
Published: April 2021

Stem cell therapy is one of the most promising candidate treatments for spinal cord injury. Research has shown optimistic results for this therapy, but clinical limitations remain, including poor viability, engraftment, and differentiation. Here, we isolated novel peripheral nerve-derived stem cells (PNSCs) from adult peripheral nerves with similar characteristics to neural-crest stem cells. These PNSCs expressed neural-crest specific markers and showed multilineage differentiation potential into Schwann cells, neuroglia, neurons, and mesodermal cells. In addition, PNSCs showed therapeutic potential by releasing the neurotrophic factors, including glial cell-line-derived neurotrophic factor, insulin-like growth factor, nerve growth factor, and neurotrophin-3. PNSC abilities were also enhanced by their development into spheroids which secreted neurotrophic factors several times more than non-spheroid PNSCs and expressed several types of extra cellular matrix. These features suggest that the potential for these PNSC spheroids can overcome their limitations. In an animal spinal cord injury (SCI) model, these PNSC spheroids induced functional recovery and neuronal regeneration. These PNSC spheroids also reduced the neuropathic pain which accompanies SCI after remyelination. These PNSC spheroids may represent a new therapeutic approach for patients suffering from SCI.
Myocardial Accumulations of Reg3A, Reg3γ and Oncostatin M Are Associated with the Formation of Granulomata in Patients with Cardiac Sarcoidosis
Authors: Gajawada Praveen , Cetinkaya Ayse , von Gerlach Susanne , Kubin Natalia , Burger Heiko , Näbauer Michael , Grinninger Carola , Rolf Andreas , Schönburg Markus , Choi Yeong-Hoon , Kubin Thomas , Richter Manfred
Published: April 2021

Cardiac sarcoidosis (CS) is a poorly understood disease and is characterized by the focal accumulation of immune cells, thus leading to the formation of granulomata (GL). To identify the developmental principles of fatal GL, fluorescence microscopy and Western blot analysis of CS and control patients is presented here. CS is visualized macroscopically by positron emission tomography (PET)/ computed tomography (CT). A battery of antibodies is used to determine structural, cell cycle and inflammatory markers. GL consist of CD68+, CD163+ and CD206+ macrophages surrounded by T-cells within fibrotic areas. Cell cycle markers such as phospho-histone H3, phospho-Aurora and Ki67 were moderately present; however, the phosphorylated ERM (ezrin, radixin and moesin) and Erk1/2 proteins, strong expression of the myosin motor protein and the macrophage transcription factor PU.1 indicate highly active GL. Mild apoptosis is consistent with PI3 kinase and Akt activation. Massive amounts of the IL-1R antagonist reflect a mild activation of stress and inflammatory pathways in GL. High levels of oncostatin M and the Reg3A and Reg3γ chemokines are in accordance with macrophage accumulation in areas of remodeling cardiomyocytes. We conclude that the formation of GL occurs mainly through chemoattraction and less by proliferation of macrophages. Furthermore, activation of the oncostatin/Reg3 axis might help at first to wall-off substances but might initiate the chronic development of heart failure.
Cyberbullying Detection in Social Networks Using Bi-GRU with Self-Attention Mechanism
Authors: Fang Yong , Yang Shaoshuai , Zhao Bin , Huang Cheng
Published: April 2021

With the propagation of cyberbullying in social networks as a trending subject, cyberbullying detection has become a social problem that researchers are concerned about. Developing intelligent models and systems helps detect cyberbullying automatically. This work focuses on text-based cyberbullying detection because it is the commonly used information carrier in social networks and is the widely used feature in this regard studies. Motivated by the documented success of neural networks, we propose a complete model combining the bidirectional gated recurrent unit (Bi-GRU) and the self-attention mechanism. In detail, we introduce the design of a GRU cell and Bi-GRU’s advantage for learning the underlying relationships between words from both directions. Besides, we present the design of the self-attention mechanism and the benefit of this joining for achieving a greater performance of cyberbullying classification tasks. The proposed model could address the limitation of the vanishing and exploding gradient problems. We avoid using oversampling or downsampling on experimental data which could result in the overestimation of evaluation. We conduct a comparative assessment on two commonly used datasets, and the results show that our proposed method outperformed baselines in all evaluation metrics.
Discovery of Lebambromyia in Myanmar Cretaceous Amber: Phylogenetic and Biogeographic Implications (Insecta, Diptera, Phoroidea)
Authors: Badano Davide , Zhang Qingqing , Fratini Michela , Maugeri Laura , Bukreeva Inna , Longo Elena , Wilde Fabian , Yeates David K. , Cerretti Pierfilippo
Published: April 2021

Lebambromyia sacculifera sp. nov. is described from Late Cretaceous amber from Myanmar, integrating traditional observation techniques and X-ray phase contrast microtomography. Lebambromyia sacculifera is the second species of Lebambromyia after L. acrai Grimaldi and Cumming, described from Lebanese amber (Early Cretaceous), and the first record of this taxon from Myanmar amber, considerably extending the temporal and geographic range of this genus. The new specimen bears a previously undetected set of phylogenetically relevant characters such as a postpedicel sacculus and a prominent clypeus, which are shared with Ironomyiidae and Eumuscomorpha. Our cladistic analyses confirmed that Lebambromyia represented a distinct monophyletic lineage related to Platypezidae and Ironomyiidae, though its affinities are strongly influenced by the interpretation and coding of the enigmatic set of features characterizing these fossil flies.
CSF Dynamics for Shunt Prognostication and Revision in Normal Pressure Hydrocephalus
Authors: Lalou Afroditi Despina , Czosnyka Marek , Placek Michal M. , Smielewski Peter , Nabbanja Eva , Czosnyka Zofia
Published: April 2021

Background: Despite the quantitative information derived from testing of the CSF circulation, there is still no consensus on what the best approach could be in defining criteria for shunting and predicting response to CSF diversion in normal pressure hydrocephalus (NPH). Objective: We aimed to review the lessons learned from assessment of CSF dynamics in our center and summarize our findings to date. We have focused on reporting the objective perspective of CSF dynamics testing, without further inferences to individual patient management. Discussion: No single parameter from the CSF infusion study has so far been able to serve as an unquestionable outcome predictor. Resistance to CSF outflow (Rout) is an important biological marker of CSF circulation. It should not, however, be used as a single predictor for improvement after shunting. Testing of CSF dynamics provides information on hydrodynamic properties of the cerebrospinal compartment: the system which is being modified by a shunt. Our experience of nearly 30 years of studying CSF dynamics in patients requiring shunting and/or shunt revision, combined with all the recent progress made in producing evidence on the clinical utility of CSF dynamics, has led to reconsidering the relationship between CSF circulation testing and clinical improvement. Conclusions: Despite many open questions and limitations, testing of CSF dynamics provides unique perspectives for the clinician. We have found value in understanding shunt function and potentially shunt response through shunt testing in vivo. In the absence of infusion tests, further methods that provide a clear description of the pre and post-shunting CSF circulation, and potentially cerebral blood flow, should be developed and adapted to the bed-space.