bluuebunny/crossref_metadata_2025 huggingface dataset:
Gene Expression-Related Changes in Morphologies of Organelles and Cellular Component Organization in Mucopolysaccharidoses
Authors: Gaffke Lidia , Pierzynowska Karolina , Rintz Estera , Cyske Zuzanna , Giecewicz Izabela , Węgrzyn Grzegorz
Published: March 2021

Mucopolysaccharidoses (MPS) are inherited metabolic diseases characterized by accumulation of incompletely degraded glycosaminoglycans (GAGs) in lysosomes. Although primary causes of these diseases are mutations in genes coding for enzymes involved in lysosomal GAG degradation, it was demonstrated that storage of these complex carbohydrates provokes a cascade of secondary and tertiary changes affecting cellular functions. Potentially, this might lead to appearance of cellular disorders which could not be corrected even if the primary cause of the disease is removed. In this work, we studied changes in cellular organelles in MPS fibroblasts relative to control cells. All 11 types and subtypes of MPS were included into this study to obtain a complex picture of changes in organelles in this group of diseases. Two experimental approaches were employed, transcriptomic analyses and electron microscopic assessment of morphology of organelles. We analyzed levels of transcripts of genes grouped into two terms included into the QuickGO database, ‘Cellular component organization’ (GO:0016043) and ‘Cellular anatomical entity’ (GO:0110165), to find that number of transcripts with significantly changed levels in MPS fibroblasts vs. controls ranged from 109 to 322 (depending on MPS type) in GO:0016043, and from 70 to 208 in GO:0110165. This dysregulation of expression of genes crucial for proper structures and functions of various organelles was accompanied by severe changes in morphologies of lysosomes, nuclei, mitochondria, Golgi apparatus, and endoplasmic reticulum. Interestingly, some observed changes occurred in all/most MPS types while others were specific to particular disease types/subtypes. We suggest that severe changes in organelles in MPS cells might arise from dysregulation of expression of a battery of genes involved in organelles’ structures and functions. Intriguingly, normalization of GAG levels by using recombinant human enzymes specific to different MPS types corrected morphologies of some, but not all, organelles, while it failed to improve regulation of expression of selected genes. These results might suggest reasons for inability of enzyme replacement therapy to correct all MPS symptoms, particularly if initiated at advanced stages of the disease.
Rational Design of Adenylate Kinase Thermostability through Coevolution and Sequence Divergence Analysis
Authors: Chang Jian , Zhang Chengxin , Cheng Huaqiang , Tan Yan-Wen
Published: March 2021

Protein engineering is actively pursued in industrial and laboratory settings for high thermostability. Among the many protein engineering methods, rational design by bioinformatics provides theoretical guidance without time-consuming experimental screenings. However, most rational design methods either rely on protein tertiary structure information or have limited accuracies. We proposed a primary-sequence-based algorithm for increasing the heat resistance of a protein while maintaining its functions. Using adenylate kinase (ADK) family as a model system, this method identified a series of amino acid sites closely related to thermostability. Single- and double-point mutants constructed based on this method increase the thermal denaturation temperature of the mesophilic Escherichia coli (E. coli) ADK by 5.5 and 8.3 °C, respectively, while preserving most of the catalytic function at ambient temperatures. Additionally, the constructed mutants have improved enzymatic activity at higher temperature.
Preclinical Evaluation of 99mTc-ZHER2:41071, a Second-Generation Affibody-Based HER2-Visualizing Imaging Probe with a Low Renal Uptake
Authors: Oroujeni Maryam , Rinne Sara S. , Vorobyeva Anzhelika , Loftenius Annika , Feldwisch Joachim , Jonasson Per , Chernov Vladimir , Orlova Anna , Frejd Fredrik Y. , Tolmachev Vladimir
Published: March 2021

Radionuclide imaging of HER2 expression in tumours may enable stratification of patients with breast, ovarian, and gastroesophageal cancers for HER2-targeting therapies. A first-generation HER2-binding affibody molecule [99mTc]Tc-ZHER2:V2 demonstrated favorable imaging properties in preclinical studies. Thereafter, the affibody scaffold has been extensively modified, which increased its melting point, improved storage stability, and increased hydrophilicity of the surface. In this study, a second-generation affibody molecule (designated ZHER2:41071) with a new improved scaffold has been prepared and characterized. HER2-binding, biodistribution, and tumour-targeting properties of [99mTc]Tc-labelled ZHER2:41071 were investigated. These properties were compared with properties of the first-generation affibody molecules, [99mTc]Tc-ZHER2:V2 and [99mTc]Tc-ZHER2:2395. [99mTc]Tc-ZHER2:41071 bound specifically to HER2 expressing cells with an affinity of 58 ± 2 pM. The renal uptake for [99mTc]Tc-ZHER2:41071 and [99mTc]Tc-ZHER2:V2 was 25–30 fold lower when compared with [99mTc]Tc-ZHER2:2395. The uptake in tumour and kidney for [99mTc]Tc-ZHER2:41071 and [99mTc]Tc-ZHER2:V2 in SKOV-3 xenografts was similar. In conclusion, an extensive re-engineering of the scaffold did not compromise imaging properties of the affibody molecule labelled with 99mTc using a GGGC chelator. The new probe, [99mTc]Tc-ZHER2:41071 provided the best tumour-to-blood ratio compared to HER2-imaging probes for single photon emission computed tomography (SPECT) described in the literature so far. [99mTc]Tc-ZHER2:41071 is a promising candidate for further clinical translation studies.
Combined Application of Pan-AKT Inhibitor MK-2206 and BCL-2 Antagonist Venetoclax in B-Cell Precursor Acute Lymphoblastic Leukemia
Authors: Richter Anna , Fischer Elisabeth , Holz Clemens , Schulze Julia , Lange Sandra , Sekora Anett , Knuebel Gudrun , Henze Larissa , Roolf Catrin , Murua Escobar Hugo , Junghanss Christian
Published: March 2021

Aberrant PI3K/AKT signaling is a hallmark of acute B-lymphoblastic leukemia (B-ALL) resulting in increased tumor cell proliferation and apoptosis deficiency. While previous AKT inhibitors struggled with selectivity, MK-2206 promises meticulous pan-AKT targeting with proven anti-tumor activity. We herein, characterize the effect of MK-2206 on B-ALL cell lines and primary samples and investigate potential synergistic effects with BCL-2 inhibitor venetoclax to overcome limitations in apoptosis induction. MK-2206 incubation reduced AKT phosphorylation and influenced downstream signaling activity. Interestingly, after MK-2206 mono application tumor cell proliferation and metabolic activity were diminished significantly independently of basal AKT phosphorylation. Morphological changes but no induction of apoptosis was detected in the observed cell lines. In contrast, primary samples cultivated in a protective microenvironment showed a decrease in vital cells. Combined MK-2206 and venetoclax incubation resulted in partially synergistic anti-proliferative effects independently of application sequence in SEM and RS4;11 cell lines. Venetoclax-mediated apoptosis was not intensified by addition of MK-2206. Functional assessment of BCL-2 inhibition via Bax translocation assay revealed slightly increased pro-apoptotic signaling after combined MK-2206 and venetoclax incubation. In summary, we demonstrate that the pan-AKT inhibitor MK-2206 potently blocks B-ALL cell proliferation and for the first time characterize the synergistic effect of combined MK-2206 and venetoclax treatment in B-ALL.
Bcl-xL: A Focus on Melanoma Pathobiology
Authors: Lucianò Anna Maria , Pérez-Oliva Ana B. , Mulero Victoriano , Del Bufalo Donatella
Published: March 2021

Apoptosis is the main mechanism by which multicellular organisms eliminate damaged or unwanted cells. To regulate this process, a balance between pro-survival and pro-apoptotic proteins is necessary in order to avoid impaired apoptosis, which is the cause of several pathologies, including cancer. Among the anti-apoptotic proteins, Bcl-xL exhibits a high conformational flexibility, whose regulation is strictly controlled by alternative splicing and post-transcriptional regulation mediated by transcription factors or microRNAs. It shows relevant functions in different forms of cancer, including melanoma. In melanoma, Bcl-xL contributes to both canonical roles, such as pro-survival, protection from apoptosis and induction of drug resistance, and non-canonical functions, including promotion of cell migration and invasion, and angiogenesis. Growing evidence indicates that Bcl-xL inhibition can be helpful for cancer patients, but at present, effective and safe therapies targeting Bcl-xL are lacking due to toxicity to platelets. In this review, we summarized findings describing the mechanisms of Bcl-xL regulation, and the role that Bcl-xL plays in melanoma pathobiology and response to therapy. From these findings, it emerged that even if Bcl-xL plays a crucial role in melanoma pathobiology, we need further studies aimed at evaluating the involvement of Bcl-xL and other members of the Bcl-2 family in the progression of melanoma and at identifying new non-toxic Bcl-xL inhibitors.
Plumbagin, a Biomolecule with (Anti)Osteoclastic Properties
Authors: Sultanli Sevinj , Ghumnani Soni , Ashma Richa , Kubatzky Katharina F.
Published: March 2021

Plumbagin is a plant-derived naphthoquinone that is widely used in traditional Asian medicine due to its anti-inflammatory and anti-microbial properties. Additionally, plumbagin is cytotoxic for cancer cells due to its ability to trigger reactive oxygen species (ROS) formation and subsequent apoptosis. Since it was reported that plumbagin may inhibit the differentiation of bone resorbing osteoclasts in cancer-related models, we wanted to elucidate whether plumbagin interferes with cytokine-induced osteoclastogenesis. Using C57BL/6 mice, we unexpectedly found that plumbagin treatment enhanced osteoclast formation and that this effect was most pronounced when cells were pre-treated for 24 h with plumbagin before subsequent M-CSF/RANKL stimulation. Plumbagin caused a fast induction of NFATc1 signalling and mTOR-dependent activation of p70S6 kinase which resulted in the initiation of protein translation. In line with this finding, we observed an increase in RANK surface expression after Plumbagin stimulation that enhanced the responsiveness for subsequent RANKL treatment. However, in Balb/c mice and Balb/c-derived RAW264.7 macrophages, these findings could not be corroborated and osteoclastogenesis was inhibited. Our results suggest that the effects of plumbagin depend on the model system used and can therefore either trigger or inhibit osteoclast formation.
Indirect Measurements of Bridge Vibrations as an Experimental Tool Supporting Periodic Inspections
Authors: Ercolessi Stefano , Fabbrocino Giovanni , Rainieri Carlo
Published: March 2021

Recent collapses and malfunctions of European bridges threatened the service conditions of road networks and pointed out the need for robust procedures to mitigate the impact of material degradation and overloading of existing bridges. Condition assessment of bridges remains a challenging task, which could take advantage of cost-effective and reliable inspection strategies. The advances in sensors as well as Information and Communication Technologies (ICT) ensure a significant enhancement of the capabilities in recording and processing physical and mechanical data. The present paper focuses on the paradigm of indirect vibration measurements for modal parameter identification in operational conditions. It is very attractive because of the related opportunities of application of dynamic tests as a tool for periodic inspections while significantly mitigating their impact on the traffic flow. In this framework the instrumented vehicle acts as a dynamic measurement device for periodic inspections and provides valuable information on the structural response of the bridge at a low-cost. Vehicle-bridge interaction models are here applied to realistically simulate the traffic-induced vibration response of bridges and assess the accuracy of modal parameter estimates obtained from indirect vibration measurements characterized by different noise levels.
Acute Management Should Be Optimized in Patients with Less Specific Stroke Symptoms: Findings from a Retrospective Observational Study
Authors: Halúsková Simona , Herzig Roman , Krajíčková Dagmar , Hamza Abduljabar , Krajina Antonín , Chovanec Vendelín , Lojík Miroslav , Raupach Jan , Renc Ondřej , Šimůnek Libor , Vítková Eva , Sobíšek Lukáš , Vališ Martin
Published: March 2021

Anterior circulation stroke (ACS) is associated with typical symptoms, while posterior circulation stroke (PCS) may cause a wide spectrum of less specific symptoms. We aim to assess the correlation between the initial presentation of acute ischemic stroke (AIS) symptoms and the treatment timeline. Using a retrospective, observational, single-center study, the set consists of 809 AIS patients treated with intravenous thrombolysis (IVT) and/or endovascular treatment (EVT). We investigate the impact of baseline clinical AIS symptoms and the affected vascular territory on recanalization times in patients treated with IVT only and EVT (±IVT). Regarding the IVT-only group, increasing the National Institutes of Health Stroke Scale (NIHSS) score on admission and speech difficulties are associated with shorter (by 1.59 ± 0.76 min per every one-point increase; p = 0.036, and by 24.56 ± 8.42 min; p = 0.004, respectively) and nausea/vomiting with longer (by 43.72 ± 13.13 min; p = 0.001) onset-to-needle times, and vertigo with longer (by 8.58 ± 3.84 min; p = 0.026) door-to-needle times (DNT). Regarding the EVT (±IVT) group, coma is associated with longer (by 22.68 ± 6.05 min; p = 0.0002) DNT, anterior circulation stroke with shorter (by 47.32 ± 16.89 min; p = 0.005) onset-to-groin time, and drooping of the mouth corner with shorter (by 20.79 ± 6.02 min; p = 0.0006) door-to-groin time. Our results demonstrate that treatment is initiated later in strokes with less specific symptoms than in strokes with typical symptoms.
Sleeve Gastrectomy Is Associated with a Greater Reduction in Plasma Liver Enzymes Than Bypass Surgeries—A Registry-Based Two-Year Follow-Up Analysis
Authors: Azulai Shira , Grinbaum Ronit , Beglaibter Nahum , Eldar Shai Meron , Rubin Moshe , Ben-Haroush Schyr Rachel , Romano-Zelekha Orly , Ben-Zvi Danny
Published: March 2021

Bariatric surgeries may lead to an improvement in metabolic fatty liver disease, and a reduction in the levels of the hepatic enzyme Alanine Aminotransferase (ALT). We compared the effects of Sleeve Gastrectomy (SG), Roux en Y Gastric Bypass (RYGB) and One Anastomosis Gastric Bypass (OAGB) on the levels of ALT by analysis of two-year follow-up data from 4980 patients in the Israeli Bariatric Registry that included laboratory tests and demographic information. Pre-operative characteristics of patients, and particularly levels of liver enzymes, were similar across surgery types. Regression modeling and retrospective matching showed that SG was superior to RYGB and OAGB in reducing ALT levels, and in reducing the fraction of patients with abnormally high ALT levels. Two-year post-surgery, an increase in ALT levels from normal to abnormal levels was observed in 5% of SG patients, and in 18% and 23% of RYGB and OAGB patients. In conclusion, SG leads to a greater reduction in ALT levels compared with bypass surgeries and a lower incidence of post-surgical elevation of ALT levels. Further studies are required to identify the cause for the rise in liver enzymes, and to determine whether ALT levels correlate with liver pathology especially following bariatric surgery.
Ischemic Stroke and Heart Failure: Facts and Numbers. An Update
Authors: Barkhudaryan Anush , Doehner Wolfram , Scherbakov Nadja
Published: March 2021

Heart failure (HF) is a severe clinical syndrome accompanied by a number of comorbidities. Ischemic stroke occurs frequently in patients with HF as a complication of the disease. In the present review, we aimed to summarize the current state of research on the role of cardio–cerebral interactions in the prevalence, etiology, and prognosis of both diseases. The main pathophysiological mechanisms underlying the development of stroke in HF and vice versa are discussed. In addition, we reviewed the results of recent clinical trials investigating the prevalence and prevention of stroke in patients with HF.
Strength, Endocrine, and Body Composition Alterations across Four Blocks of Training in an Elite 400 m Sprinter
Authors: Batra Amit , Wetmore Alex B. , Hornsby W. Guy. , Lipinska Patrycja , Staniak Zbigniew , Surala Olga , Stone Michael H.
Published: March 2021

The ability to produce force rapidly has the potential to directly influence sprinting performance through changes in stride length and stride frequency. This ability is commonly referred to as the rate of force development (RFD). For this reason, many elite sprinters follow a combined program consisting of resistance training and sprint training. The purpose of this study was to investigate the strength, endocrine and body composition adaptations that occur during distinct phases of a block periodized training cycle in a 400 m Olympic level sprinter. The athlete is an elite level 400 m male sprinter (age 31 years, body mass: 74 kg, years of training: 15 and Personal Best (PB): 45.65 s). This athlete completed four distinct training phases of a block periodized training program (16 weeks) with five testing sessions consisting of testosterone:cortisol (T/C) profiles, body composition, vertical jump, and maximum strength testing. Large fluctuations in T/C were found following high volume training and the taper. Minor changes in body mass were observed with an abrupt decrease following the taper which coincided with a small increase in fat mass percentage. Jump height (5.7%), concentric impulse (9.4%), eccentric impulse (3.4%) and power ratio (18.7%) all increased substantially from T1 to T5. Relative strength increased 6.04% from T1 to T5. Lastly, our results demonstrate the effectiveness of a competitive taper in increasing physiological markers for performance as well as dynamic performance variables. Block periodization training was effective in raising the physical capabilities of an Olympic level 400 m runner which have been shown to directly transfer to sprinting performance.
Physical Drivers and Dominant Oceanographic Processes on the Uruguayan Margin (Southwestern Atlantic): A Review and a Conceptual Model
Authors: Burone Leticia , Franco-Fraguas Paula , Carranza Alvar , Calliari Danilo , Michaelovitch de Mahiques Michel , Gómez Mónica , Marin Yamandú , Gutiérrez Ofelia , Ortega Leonardo
Published: March 2021

The Uruguayan continental margin (UCM), located in the Southwestern Atlantic margin’s subtropical region, is positioned in a critical transitional region regarding the global ocean circulation (Río de la Plata (RdlP) outflow and Brazil-Malvinas Confluence), as also reflected in seafloor features (northernmost distribution of a large depositional contourite system and RdlP paleovalley). This complex oceanographic scenario occurring in a relatively small area highlights the advantage of considering the UCM as a natural laboratory for oceanographic research. The present work provides the first conceptual “control” model of the physical drivers (i.e., climate, geomorphology) and main oceanographic processes (i.e., hydrodynamics, sediment, and carbon dynamics) occurring along the UCM, reviewing and synthesizing available relevant information based on a functional integrated approach. Despite the conspicuous knowledge gaps on critical processes, a general picture of the system’s functioning is emerging for this complex biophysical setting. This includes conceptualizations of the actual controls, main processes, feedbacks, and interactions responsible for system dynamics. The structure adopted for developing our conceptual models allows permanent improvement by empirical testing of the working hypothesis and incorporating new information as scientific knowledge advances. These models can be used as a baseline for developing quantitative models and, as representations of relatively “pristine” conditions, for stressors models by identifying sources of stress and ecological responses of key system attributes under a transboundary approach.
Antioxidant Properties and Industrial Uses of Edible Polyporales
Authors: Quintero-Cabello Karen P. , Lugo-Flores Marco A. , Rivera-Palafox Patricia , Silva-Espinoza Brenda A. , González-Aguilar Gustavo A. , Esqueda Martín , Gaitán-Hernández Rigoberto , Ayala-Zavala J. Fernando
Published: March 2021

The content of antioxidant compounds varies within fungal species, and the Polyporales order has been recognized for this property. Numerous antioxidant compounds have been identified in Polyporales fungi, including phenolic compounds, β-glucans, ergosterol, ergothioneine, vitamin C, and tocopherols. Each compound contributes differently to the antioxidant potential of fungi. Besides the health benefits for rural communities caused by fungi consumption, their antioxidant composition attracts the food, cosmetic, and pharmaceutical industries’ interest. In this context, the present review compiles, analyzes, and discusses the bioactive composition of edible fungi of the Polyporales order and its contribution to total antioxidant capacity.
Volcanic Ash as a Sustainable Binder Material: An Extensive Review
Authors: Játiva Andrés , Ruales Evelyn , Etxeberria Miren
Published: March 2021

The construction industry is affected by the constant growth in the populations of urban areas. The demand for cement production has an increasing environmental impact, and there are urgent demands for alternative sustainable solutions. Volcanic ash (VA) is an abundant low-cost material that, because of its chemical composition and amorphous atomic structure, has been considered as a suitable material to replace Portland cement clinker for use as a binder in cement production. In the last decade, there has been interest in using alkali-activated VA material as an alternative material to replace ordinary Portland cement. In this way, a valuable product may be derived from a currently under-utilized material. Additionally, alkali-activated VA-based materials may be suitable for building applications because of their good densification behaviour, mechanical properties and low porosity. This article describes the most relevant findings from researchers around the world on the role of the chemical composition and mineral contents of VA on reactivity during the alkali-activation reaction; the effect of synthesis factors, which include the concentration of the alkaline activator, the solution-to-binder ratio and the curing conditions, on the properties of alkali-activated VA-based materials; and the mechanical performance and durability properties of these materials.
Evaluation on the Microstructure and Durability of High-Strength Concrete Containing Electric Arc Furnace Oxidizing Slag
Authors: Yuan Tian-Feng , Hong Se-Hee , Choi Jin-Seok , Yoon Young-Soo
Published: March 2021

The application of electric arc furnace oxidizing slag (EAS) in high strength concrete (HSC) as the cementitious material is investigated in this study. The microstructure and mechanical properties of HSC with four different replacement ratios of EAS were evaluated and HSC with two replacement ratios of ground granulated blast furnace slag (GBS) was used for performance comparison. The results show that the HSC with EAS replacement ratios smaller than 15% undergo similar hydration processes and result in a similar final product when compared with those of NC-NN. Increases in EAS replacement ratio cause a reduction in Ca(OH)2 content; this, in turn, leads to an increase in porosity and a reduction in compressive strength. In terms of shrinkage behavior under free conditions, mixtures with increasing replacement ratios of cementitious materials saw increasing shrinkage, with the HSC containing EAS being similar to the other specimens. The mixtures containing EAS saw a quite gradual decrease in their freezing and thawing resistance properties as the number of freeze–thaw cycles they underwent increased. However, the efficacy of HSC with less than 15% of EAS is similar to GBS; hence, EAS could replace cement in concrete for certain applications, which would lead to more environmental benefits.
Comparison of Hook and Straight Steel Fibers Addition on Malaysian Fly Ash-Based Geopolymer Concrete on the Slump, Density, Water Absorption and Mechanical Properties
Authors: Faris Meor Ahmad , Abdullah Mohd Mustafa Al Bakri , Muniandy Ratnasamy , Abu Hashim Mohammad Firdaus , Błoch Katarzyna , Jeż Bartłomiej , Garus Sebastian , Palutkiewicz Paweł , Mohd Mortar Nurul Aida , Ghazali Mohd Fathullah
Published: March 2021

Geopolymer concrete has the potential to replace ordinary Portland cement which can reduce carbon dioxide emission to the environment. The addition of different amounts of steel fibers, as well as different types of end-shape fibers, could alter the performance of geopolymer concrete. The source of aluminosilicate (fly ash) used in the production of geopolymer concrete may lead to a different result. This study focuses on the comparison between Malaysian fly ash geopolymer concrete with the addition of hooked steel fibers and geopolymer concrete with the addition of straight-end steel fibers to the physical and mechanical properties. Malaysian fly ash was first characterized by X-ray fluorescence (XRF) to identify the chemical composition. The sample of steel fiber reinforced geopolymer concrete was produced by mixing fly ash, alkali activators, aggregates, and specific amounts of hook or straight steel fibers. The steel fibers addition for both types of fibers are 0%, 0.5%, 1.0%, 1.5%, and 2.0% by volume percentage. The samples were cured at room temperature. The physical properties (slump, density, and water absorption) of reinforced geopolymer concrete were studied. Meanwhile, a mechanical performance which is compressive, as well as the flexural strength was studied. The results show that the pattern in physical properties of geopolymer concrete for both types of fibers addition is almost similar where the slump is decreased with density and water absorption is increased with the increasing amount of fibers addition. However, the addition of hook steel fiber to the geopolymer concrete produced a lower slump than the addition of straight steel fibers. Meanwhile, the addition of hook steel fiber to the geopolymer concrete shows a higher density and water absorption compared to the sample with the addition of straight steel fibers. However, the difference is not significant. Besides, samples with the addition of hook steel fibers give better performance for compressive and flexural strength compared to the samples with the addition of straight steel fibers where the highest is at 1.0% of fibers addition.
Laser-Assisted High Speed Machining of 316 Stainless Steel: The Effect of Water-Soluble Sago Starch Based Cutting Fluid on Surface Roughness and Tool Wear
Authors: Yasmin Farhana , Tamrin Khairul Fikri , Sheikh Nadeem Ahmed , Barroy Pierre , Yassin Abdullah , Khan Amir Azam , Mohamaddan Shahrol
Published: March 2021

Laser-assisted high speed milling is a subtractive machining method that employs a laser to thermally soften a difficult-to-cut material’s surface in order to enhance machinability at a high material removal rate with improved surface finish and tool life. However, this machining with high speed leads to high friction between workpiece and tool, and can result in high temperatures, impairing the surface quality. Use of conventional cutting fluid may not effectively control the heat generation. Besides, vegetable-based cutting fluids are invariably a major source of food insecurity of edible oils which is traditionally used as a staple food in many countries. Thus, the primary objective of this study is to experimentally investigate the effects of water-soluble sago starch-based cutting fluid on surface roughness and tool’s flank wear using response surface methodology (RSM) while machining of 316 stainless steel. In order to observe the comparison, the experiments with same machining parameters are conducted with conventional cutting fluid. The prepared water-soluble sago starch based cutting fluid showed excellent cooling and lubricating performance. Therefore, in comparison to the machining using conventional cutting fluid, a decrease of 48.23% in surface roughness and 38.41% in flank wear were noted using presented approach. Furthermore, using the extreme learning machine (ELM), the obtained data is modeled to predict surface roughness and flank wear and showed good agreement between observations and predictions.
Carbon Dot/Naphthalimide Based Ratiometric Fluorescence Biosensor for Hyaluronidase Detection
Authors: Raj Pushap , Lee Seon-yeong , Lee Tae Yoon
Published: March 2021

Bladder cancer is the leading cause of death in patients with genitourinary cancer. An elevated level of hyaluronidase (HAase) was found in bladder cancer, which acts as an important biomarker for the early diagnosis of bladder cancer. Hence, there is a need to develop a simple enzymatic assay for the early recognition of HAase. Herein, we report a simple, sensitive, and ratiometric fluorescence assay for HAase detection under physiological conditions. The fluorescence assay was constructed by the adsorption of cationic carbon dots and positively charged naphthalimide on negatively charged hyaluronic acid and the development of a Förster resonance energy transfer (FRET) mechanism from carbon dots to a naphthalimide fluorophores. The hyaluronidase enzyme cleaves the hyaluronic acid in this assay, and breaking down the FRET mechanism induces ratiometric changes. A detection limit of 0.09 U/mL was achieved, which is less than the HAase level found in normal human body fluids. Moreover, this assay may be used for diagnosing HAase-related diseases.
Applications of Additively Manufactured Tools in Abrasive Machining—A Literature Review
Authors: Deja Mariusz , Zieliński Dawid , Kadir Aini Zuhra Abdul , Humaira Siti Nur
Published: March 2021

High requirements imposed by the competitive industrial environment determine the development directions of applied manufacturing methods. 3D printing technology, also known as additive manufacturing (AM), currently being one of the most dynamically developing production methods, is increasingly used in many different areas of industry. Nowadays, apart from the possibility of making prototypes of future products, AM is also used to produce fully functional machine parts, which is known as Rapid Manufacturing and also Rapid Tooling. Rapid Manufacturing refers to the ability of the software automation to rapidly accelerate the manufacturing process, while Rapid Tooling means that a tool is involved in order to accelerate the process. Abrasive processes are widely used in many industries, especially for machining hard and brittle materials such as advanced ceramics. This paper presents a review on advances and trends in contemporary abrasive machining related to the application of innovative 3D printed abrasive tools. Examples of abrasive tools made with the use of currently leading AM methods and their impact on the obtained machining results were indicated. The analyzed research works indicate the great potential and usefulness of the new constructions of the abrasive tools made by incremental technologies. Furthermore, the potential and limitations of currently used 3D printed abrasive tools, as well as the directions of their further development are indicated.
Magnetoelectric Induced Switching of Perpendicular Exchange Bias Using 30-nm-Thick Cr2O3 Thin Film
Authors: Shiratsuchi Yu , Tao Yiran , Toyoki Kentaro , Nakatani Ryoichi
Published: March 2021

Magnetoelectric (ME) effect is a result of the interplay between magnetism and electric field and now, it is regarded as a principle that can be applied to the technique of controlling the antiferromagnetic (AFM) domain state. The ME-controlled AFM domain state can be read out by the magnetization of the adjacent ferromagnetic layer coupled with the ME AFM layer via exchange bias. In this technique, the reduction in the ME layer thickness is an ongoing challenge. In this paper, we demonstrate the ME-induced switching of exchange bias polarity using the 30-nm thick ME Cr2O3 thin film. Two typical switching processes, the ME field cooling (MEFC) and isothermal modes, are both explored. The required ME field for the switching in the MEFC mode suggests that the ME susceptibility (α33) is not deteriorated at 30 nm thickness regime. The isothermal change of the exchange bias shows the hysteresis with respect to the electric field, and there is an asymmetry of the switching field depending on the switching direction. The quantitative analysis of this asymmetry yields α33 at 273 K of 3.7 ± 0.5 ps/m, which is comparable to the reported value for the bulk Cr2O3.
A Non-Standard Finite Difference Scheme for Magneto-Hydro Dynamics Boundary Layer Flows of an Incompressible Fluid Past a Flat Plate
Authors: Fazio Riccardo , Jannelli Alessandra
Published: March 2021

This paper deals with a non-standard implicit finite difference scheme that is defined on a quasi-uniform mesh for approximate solutions of the Magneto-Hydro Dynamics (MHD) boundary layer flow of an incompressible fluid past a flat plate for a wide range of the magnetic parameter. The proposed approach allows imposing the given boundary conditions at infinity exactly. We show how to improve the obtained numerical results via a mesh refinement and a Richardson extrapolation. The obtained numerical results are favourably compared with those available in the literature.
Does COVID-19 Vaccination Warrant the Classical Principle “ofelein i mi vlaptin”?
Authors: Doulberis Michael , Papaefthymiou Apostolis , Kotronis Georgios , Gialamprinou Dimitra , Soteriades Elpidoforos S. , Kyriakopoulos Anthony , Chatzimichael Eleftherios , Kafafyllidou Kyriaki , Liatsos Christos , Chatzistefanou Ioannis , Anagnostis Paul , Semenin Vitalii , Ntona Smaragda , Gkolia Ioanna , Papazoglou Dimitrios David , Tsinonis Nikolaos , Papamichos Spyros , Kirbas Hristos , Zikos Petros , Niafas Dionisios , Kountouras Jannis
Published: March 2021

The current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic warrants an imperative necessity for effective and safe vaccination, to restrain Coronavirus disease 2019 (COVID-19) including transmissibility, morbidity, and mortality. In this regard, intensive medical and biological research leading to the development of an arsenal of vaccines, albeit incomplete preconditioned evaluation, due to emergency. The subsequent scientific gap raises some concerns in the medical community and the general public. More specifically, the accelerated vaccine development downgraded the value of necessary pre-clinical studies to elicit medium- and long-term beneficial or harmful consequences. Previous experience and pathophysiological background of coronaviruses’ infections and vaccine technologies, combined with the global vaccines’ application, underlined the obligation of a cautious and qualitative approach, to illuminate potential vaccination-related adverse events. Moreover, the high SARS-CoV-2 mutation potential and the already aggregated genetical alterations provoke a rational vagueness and uncertainty concerning vaccines’ efficacy against dominant strains and the respective clinical immunity. This review critically summarizes existing evidence and queries regarding SARS-CoV-2 vaccines, to motivate scientists’ and clinicians’ interest for an optimal, individualized, and holistic management of this unprecedented pandemic.
Conversion from Venovenous to Venoarterial Extracorporeal Membrane Oxygenation in Adults
Authors: Falk Lars , Fletcher-Sandersjöö Alexander , Hultman Jan , Broman Lars Mikael
Published: March 2021

No major study has been performed on the conversion from venovenous (VV) to venoarterial (VA) extracorporeal membrane oxygenation (ECMO) in adults. This single-center retrospective cohort study aimed to investigate the incidence, indication, and outcome in patients who converted from VV to VA ECMO. All adult patients (≥18 years) who commenced VV ECMO at our center between 2005 and 2018 were screened. Of 219 VV ECMO patients, 21% (n = 46) were converted to VA ECMO. The indications for conversion were right ventricular failure (RVF) (65%), cardiogenic shock (26%), and other (9%). In the converted patients, there was a significant increase in Sequential Organ Failure Assessment (SOFA) scores between admission 12 (9–13) and conversion 15 (13–17, p < 0.001). Compared to non-converted patients, converted patients also had a higher mortality rate (62% vs. 16%, p < 0.001) and a lower admission Respiratory Extracorporeal Membrane Oxygenation Survival Prediction (RESP) score (p < 0.001). Outcomes were especially unfavorable in those converted due to RVF. These results indicate that VA ECMO, as opposed to VV ECMO, should be considered as the first mode of choice in patients with respiratory failure and signs of circulatory impairment, especially in those with impaired RV function. For the remaining patients, Pre-admission RESP score, daily echocardiography, and SOFA score trajectories may help in the early identification of those where conversion from VV to VA ECMO is warranted. Multi-centric studies are warranted to validate these findings.
Regulation of K+ Conductance by a Hydrogen Bond in Kv2.1, Kv2.2, and Kv1.2 Channels
Authors: Zhang Yuchen , Zhang Xuefeng , Liu Cuiyun , Hu Changlong
Published: March 2021

The slow inactivation of voltage-gated potassium (Kv) channels plays an important role in controlling cellular excitability. Recently, the two hydrogen bonds (H-bonds) formed by W434-D447 and T439-Y445 have been reported to control the slow inactivation in Shaker potassium channels. The four residues are highly conserved among Kv channels. Our objective was to find the roles of the two H-bonds in controlling the slow inactivation of mammalian Kv2.1, Kv2.2, and Kv1.2 channels by point mutation and patch-clamp recording studies. We found that mutations of the residues equivalent to W434 and T439 in Shaker did not change the slow inactivation of the Kv2.1, Kv2.2, and Kv1.2 channels. Surprisingly, breaking of the inter-subunit H-bond formed by W366 and Y376 (Kv2.1 numbering) by various mutations resulted in the complete loss of K+ conductance of the three Kv channels. In conclusion, we found differences in the H-bonds controlling the slow inactivation of the mammalian Kv channels and Shaker channels. Our data provided the first evidence, to our knowledge, that the inter-subunit H-bond formed by W366 and Y376 plays an important role in regulating the K+ conductance of mammalian Kv2.1, Kv2.2, and Kv1.2 channels.
Testing the Applicability of 119Sn Mössbauer Spectroscopy for the Internal Stress Study in Ternary and Co-Doped Ni-Mn-Sn Metamagnetic Alloys
Authors: Unzueta I. , López-García J. , Sánchez-Alarcos V. , Recarte V. , Pérez-Landazábal J. I. , Rodríguez-Velamazán J. A. , Garitaonandia J. S. , García J. A. , Plazaola F.
Published: March 2021

The influence of both the Co addition and the internal stress on the atomic level magnetism is comparatively studied in Ni50Mn37Sn13 and Ni45Mn38Sn13Co4 alloys by magnetic measurements and 119Sn Mössbauer spectroscopy. The results show that the saturation magnetization and the hyperfine field follow the same temperature trend. The internal stress state is investigated by subjecting the samples to milling and annealing treatments, and tracking the singlet component revealed by 119Sn Mössbauer spectroscopy. Contrary to what was expected, in the Co-doped Ni-Mn-Sn sample the singlet component can be resolved between the milled and annealed states in both martensite and austenite phases. Therefore, the results demonstrate the feasibility of tracking the singlet component upon the structural recovery in Co-doped Ni-Mn-Sn alloys in a much wider range than in ternary alloys. In addition, it is concluded that the transferred dipolar field at Sn from the neighbor magnetic atoms depends very strongly on the stress field and on the microstructural order surrounding Sn atoms. The observed sensitivity of Sn Mössbauer probe atoms to slight microstructural distortions make 119Sn a powerful technique for the characterization of the stress present in Sn containing metamagnetic shape memory alloys.
The Composition and Diversity of the Gut Microbiota in Children Is Modifiable by the Household Dogs: Impact of a Canine-Specific Probiotic
Authors: Gómez-Gallego Carlos , Forsgren Mira , Selma-Royo Marta , Nermes Merja , Collado Maria Carmen , Salminen Seppo , Beasley Shea , Isolauri Erika
Published: March 2021

The development of the infant gut microbiota is initiated during pregnancy and continued through early life and childhood, guided by the immediate environment of the child. Our aim was to characterize the shared microbiota between dogs and children as well as to determine whether introduction to dogs of a dog-specific probiotic combination modifies the transfer process. We studied 31 children from allergic families with pet dog(s) and 18 control families without a dog. Altogether 37 dogs were randomized for a 4-week period in a double-blind design to receive canine-derived probiotic product containing a mixture of L. fermentum, L. plantarum, and L. rhamnosus, or placebo. Fecal samples from children and dogs were taken before and after the treatment. Distinctive gut microbiota composition was observed in children with dogs compared to those without a dog, characterized by higher abundance of Bacteroides and short-chain fatty acid producing bacteria such as Ruminococcus and Lachnospiraceae. Probiotic intervention in dogs had an impact on the composition of the gut microbiota in both dogs and children, characterized by a reduction in Bacteroides. We provide evidence for a direct effect of home environment and household pets on children microbiota and document that modification of dog microbiota by specific probiotics is reflected in children’s microbiota.
Activation of a Cryptic Manumycin-Type Biosynthetic Gene Cluster of Saccharothrix espanaensis DSM44229 by Series of Genetic Manipulations
Authors: Gorniaková Dominika , Petříček Miroslav , Kahoun David , Grabic Roman , Zelenka Tomáš , Chroňáková Alica , Petříčková Kateřina
Published: March 2021

(1) Background: Manumycins are small actinomycete polyketides with prominent cancerostatic and immunosuppressive activities via inhibition of various eukaryotic enzymes. Their overall activity towards human cells depends on the structural variability of both their polyketide chains, mainly the upper one. In our genetic screening project to find novel producers of anti-inflammatory manumycins, the strain Saccharothrix espanaensis DSM44229 was identified as containing a novel manumycin-type biosynthetic gene cluster (BGC). (2) Methods: The biosynthetic genes appeared to be silent under all assayed laboratory conditions. Several techniques were used to activate the BGC, including: (i) heterologous expression in various hosts, (ii) overexpression of putative pathway-specific regulatory genes, and (iii) overexpression of a bottleneck cyclizing aminolevulinate synthase gene in both natural and heterologous producers. (3) Results: Multiple novel manumycin-type compounds were produced at various levels by genetically-modified strains, sharing a tetraene lower chain structure with a colabomycin subgroup of manumycins, but possessing much shorter and saturated upper chains. (4) Conclusions: A cryptic manumycin-type BGC was successfully activated by genetic means to gain production of novel manumycin-type compounds for future comparative activity assays. Heterologously produced compounds were identical to those found after final activation of the BGC in the original strain, proving the intactness of the cloned BGC.
Mineralosphere Microbiome Leading to Changed Geochemical Properties of Sedimentary Rocks from Aiqigou Mud Volcano, Northwest China
Authors: Ma Ke , Ma Anzhou , Zheng Guodong , Ren Ge , Xie Fei , Zhou Hanchang , Yin Jun , Liang Yu , Zhuang Xuliang , Zhuang Guoqiang
Published: March 2021

The properties of rocks can be greatly affected by seepage hydrocarbons in petroleum-related mud volcanoes. Among them, the color of sedimentary rocks can reflect the changes of sedimentary environment and weathering history. However, little is known about the microbial communities and their biogeochemical significance in these environments. In this study, contrasting rock samples were collected from the Aiqigou mud volcano on the southern margin of the Junggar Basin in Northwest China as guided by rock colors indicative of redox conditions. The physicochemical properties and mineral composition are similar under the same redox conditions. For example, the content of chlorite, muscovite, quartz, and total carbon were higher, and the total iron was lower under reduced conditions compared with oxidized environments. High-throughput sequencing of 16S rRNA gene amplicons revealed that different functional microorganisms may exist under different redox conditions; microbes in oxidized conditions have higher diversity. Statistical analysis and incubation experiments indicated that the microbial community structure is closely related to the content of iron which may be an important factor for color stratification of continental sedimentary rocks in the Aiqigou mud volcano. The interactions between organics and iron-bearing minerals mediated by microorganisms have also been hypothesized.
The Effects of Dietary Supplementation of Lactococcus lactis Strain Plasma on Skin Microbiome and Skin Conditions in Healthy Subjects—A Randomized, Double-Blind, Placebo-Controlled Trial
Authors: Tsuji Ryohei , Yazawa Kamiyu , Kokubo Takeshi , Nakamura Yuumi , Kanauchi Osamu
Published: March 2021

(1) Background: Lactococcus lactis strain Plasma (LC-Plasma) is a unique strain which directly activates plasmacytoid dendritic cells, resulting in the prevention against broad spectrum of viral infection. Additionally, we found that LC-Plasma intake stimulated skin immunity and prevents Staphylococcus aureus epicutaneous infection. The aim of this study was to investigate the effect of LC-Plasma dietary supplementation on skin microbiome, gene expression in the skin, and skin conditions in healthy subjects. (2) Method: A randomized, double-blind, placebo-controlled, parallel-group trial was conducted. Seventy healthy volunteers were enrolled and assigned into two groups receiving either placebo or LC-Plasma capsules (approximately 1 × 1011 cells/day) for 8 weeks. The skin microbiome was analyzed by NGS and qPCR. Gene expression was analyzed by qPCR and skin conditions were diagnosed by dermatologists before and after intervention. (3) Result: LC-Plasma supplementation prevented the decrease of Staphylococcus epidermidis and Staphylococcus pasteuri and overgrowth of Propionibacterium acnes. In addition, LC-Plasma supplementation suggested to increase the expression of antimicrobial peptide genes but not tight junction genes. Furthermore, the clinical scores of skin conditions were ameliorated by LC-Plasma supplementation. (4) Conclusions: Our findings provided the insights that the dietary supplementation of LC-Plasma might have stabilizing effects on seasonal change of skin microbiome and skin conditions in healthy subjects.