bluuebunny/crossref_metadata_2025 huggingface dataset:
RAP-011 Rescues the Disease Phenotype in a Cellular Model of Congenital Dyserythropoietic Anemia Type II by Inhibiting the SMAD2-3 Pathway
Authors: De Rosa Gianluca , Andolfo Immacolata , Marra Roberta , Manna Francesco , Rosato Barbara Eleni , Iolascon Achille , Russo Roberta
Published: August 2020

Congenital dyserythropoietic anemia type II (CDA II) is a hypo-productive anemia defined by ineffective erythropoiesis through maturation arrest of erythroid precursors. CDA II is an autosomal recessive disorder due to loss-of-function mutations in SEC23B. Currently, management of patients with CDA II is based on transfusions, splenectomy, or hematopoietic stem-cell transplantation. Several studies have highlighted benefits of ACE-011 (sotatercept) treatment of ineffective erythropoiesis, which acts as a ligand trap against growth differentiation factor (GDF)11. Herein, we show that GDF11 levels are increased in CDA II, which suggests sotatercept as a targeted therapy for treatment of these patients. Treatment of stable clones of SEC23B-silenced erythroleukemia K562 cells with the iron-containing porphyrin hemin plus GDF11 increased expression of pSMAD2 and reduced nuclear localization of the transcription factor GATA1, with subsequent reduced gene expression of erythroid differentiation markers. We demonstrate that treatment of these SEC23B-silenced K562 cells with RAP-011, a “murinized” ortholog of sotatercept, rescues the disease phenotype by restoring gene expression of erythroid markers through inhibition of the phosphorylated SMAD2 pathway. Our data also demonstrate the effect of RAP-011 treatment in reducing the expression of erythroferrone in vitro, thus suggesting a possible beneficial role of the use of sotatercept in the management of iron overload in patients with CDA II.
α1AMP-Activated Protein Kinase Protects against Lipopolysaccharide-Induced Endothelial Barrier Disruption via Junctional Reinforcement and Activation of the p38 MAPK/HSP27 Pathway
Authors: Angé Marine , Castanares-Zapatero Diego , De Poortere Julien , Dufeys Cécile , Courtoy Guillaume E. , Bouzin Caroline , Quarck Rozenn , Bertrand Luc , Beauloye Christophe , Horman Sandrine
Published: August 2020

Vascular hyperpermeability is a determinant factor in the pathophysiology of sepsis. While, AMP-activated protein kinase (AMPK) is known to play a role in maintaining endothelial barrier function in this condition. Therefore, we investigated the underlying molecular mechanisms of this protective effect. α1AMPK expression and/or activity was modulated in human dermal microvascular endothelial cells using either α1AMPK-targeting small interfering RNA or the direct pharmacological AMPK activator 991, prior to lipopolysaccharide (LPS) treatment. Western blotting was used to analyze the expression and/or phosphorylation of proteins that compose cellular junctions (zonula occludens-1 (ZO-1), vascular endothelial cadherin (VE-Cad), connexin 43 (Cx43)) or that regulate actin cytoskeleton (p38 MAPK; heat shock protein 27 (HSP27)). Functional endothelial permeability was assessed by in vitro Transwell assays, and quantification of cellular junctions in the plasma membrane was assessed by immunofluorescence. Actin cytoskeleton remodeling was evaluated through actin fluorescent staining. We consequently demonstrate that α1AMPK deficiency is associated with reduced expression of CX43, ZO-1, and VE-Cad, and that the drastic loss of CX43 is likely responsible for the subsequent decreased expression and localization of ZO-1 and VE-Cad in the plasma membrane. Moreover, α1AMPK activation by 991 protects against LPS-induced endothelial barrier disruption by reinforcing cortical actin cytoskeleton. This is due to a mechanism that involves the phosphorylation of p38 MAPK and HSP27, which is nonetheless independent of the small GTPase Rac1. This results in a drastic decrease of LPS-induced hyperpermeability. We conclude that α1AMPK activators that are suitable for clinical use may provide a specific therapeutic intervention that limits sepsis-induced vascular leakage.
Dr. Louis Isaac Woolf: At the Forefront of Newborn Screening and the Diet to Treat Phenylketonuria—Biography to Mark His 100th Birthday †
Authors: Alonso-Fernández José
Published: August 2020

In mid 2019, the author reminded the (International Society for Neonatal Screening) ISNS of the happy occasion of the 100th birthday of one of the living pioneers of neonatal screening, Professor Louis Isaac Woolf [...]
Nutritional Relationship between Bemisia tabaci and Its Primary Endosymbiont, Portiera aleyrodidarum, during Host Plant Acclimation
Authors: Hu Fang-Yu , Tsai Chi-Wei
Published: August 2020

Plant sap-sucking insects commonly have established mutualistic relationships with endosymbiotic bacteria that can provide nutrients lacking in their diet. Bemisia tabaci harbors one primary endosymbiont, Portiera aleyrodidarum, and up to seven secondary endosymbionts, including Hamiltonella defensa and Rickettsia sp. Portiera aleyrodidarum is already known to play a critical role in providing necessary nutrients for B. tabaci. In the present study, the relationship among B. tabaci, its primary endosymbiont, and the host plant were examined through the effects of host plant shifting and acclimation. Bemisia tabaci was transferred from Chinese kale to four different host plants, and the effects on both its performance and the expression levels of nutrient-related genes of P. aleyrodidarum were analyzed. The results showed that host shifting from Chinese kale to cotton plants led to a decrease in the performance of B. tabaci in the first generation, which was restored after 10 generations of acclimation. Furthermore, the expression levels of essential amino acid biosynthesis genes of P. aleyrodidarum were found to be differentially regulated after B. tabaci had acclimated to the cotton plants. Host plant shifting and acclimation to cucumber, poinsettia, and tomato plants did not affect the fecundity of B. tabaci and the expression levels of most examined genes. We speculate that P. aleyrodidarum may help B. tabaci improve its performance and acclimate to new hosts and that P. aleyrodidarum has a close nutritional relationship with its host during host plant acclimation.
Diverse Diets with Consistent Core Microbiome in Wild Bee Pollen Provisions
Authors: Dew Rebecca M. , McFrederick Quinn S. , Rehan Sandra M.
Published: August 2020

Bees collect pollen from flowers for their offspring, and by doing so contribute critical pollination services for our crops and ecosystems. Unlike many managed bee species, wild bees are thought to obtain much of their microbiome from the environment. However, we know surprisingly little about what plant species bees visit and the microbes associated with the collected pollen. Here, we addressed the hypothesis that the pollen and microbial components of bee diets would change across the range of the bee, by amplicon sequencing pollen provisions of a widespread small carpenter bee, Ceratina calcarata, across three populations. Ceratina calcarata was found to use a diversity of floral resources across its range, but the bacterial genera associated with pollen provisions were very consistent. Acinetobacter, Erwinia, Lactobacillus, Sodalis, Sphingomonas and Wolbachia were among the top ten bacterial genera across all sites. Ceratina calcarata uses both raspberry (Rubus) and sumac (Rhus) stems as nesting substrates, however nests within these plants showed no preference for host plant pollen. Significant correlations in plant and bacterial co-occurrence differed between sites, indicating that many of the most common bacterial genera have either regional or transitory floral associations. This range-wide study suggests microbes present in brood provisions are conserved within a bee species, rather than mediated by climate or pollen composition. Moving forward, this has important implications for how these core bacteria affect larval health and whether these functions vary across space and diet. These data increase our understanding of how pollinators interact with and adjust to their changing environment.
The Real-Life Journey of Elderly Patients in Soft Tissue and Bone Sarcomas: A Retrospective Analysis from a Sarcoma Referral Center
Authors: Ferraresi Virginia , Vari Sabrina , Rossi Barbara , Maggi Gabriella , Giannarelli Diana , Persichetti Agnese , Petrongari Maria Grazia , Cercato Maria Cecilia , Annovazzi Alessio , Anelli Vincenzo , Pescarmona Edoardo , Baldi Jacopo , Zoccali Carmine , Pellegrini Domenicangela , Cognetti Francesco , Biagini Roberto
Published: August 2020

The high complexity of multimodality treatment frequently results in undertreatment of elderly sarcoma patients, and this may be one of the factors that influence their prognosis. We describe the real-life approach to a population of patients aged over 70 with both soft tissue (STS) and bone sarcomas (BS) followed by our Sarcoma Disease Management Team from 2012 to 2017. One-hundred and twenty-three patients with a median age of 77 years (range: 70–92) were identified. STS were the most common histological subtypes (94%) and the grade was high in 79/123 patients (64%). At diagnosis, 88% of patients had localized disease (LD) and 12% were metastatic (MD). Overall, 96% of patients with LD underwent surgery, 46/54 (85%) with high grade STS patients underwent complementary radiotherapy, and 10/54 (19%) received adjuvant treatments. Twelve out of 33 patients who relapsed (36%) underwent local therapies. Seventeen (52%) and eight (24%) patients were treated with first-line and second-line medical treatments, respectively. Tolerability to systemic treatments was fairly good. Overall, 21% of the patients with advanced disease were candidates for best supportive care alone. Our case series of elderly patients with both STS and BS shows that personalized multidisciplinary treatment can nevertheless be offered to this frail population in order to control the evolution of disease.
Chronic Spontaneous Urticaria and Type 1 Diabetes Mellitus—Does Quality of Life Impairment Always Reflect Health Danger?
Authors: Brzoza Zenon , Nabrdalik Katarzyna , Moos Lukasz , Kwiendacz Hanna , Badura-Brzoza Karina , Jarolim Hanna , Kapeluszna Katarzyna , Gumprecht Janusz
Published: August 2020

Background and aims: Chronic spontaneous urticaria (CSU) and diabetes mellitus type 1 (T1DM) may compromise the quality of life (QoL). We decided to compare the QoL of T1DM patients to those suffering from CSU. Materials and methods: Sixty-six patients with well-controlled T1DM (male 52%) in the mean age of (SD) 36.3 (11.09) years and 51 patients with CSU (male 33%) in the mean age of (SD) 35.8 (8.53) years were enrolled in this observational study. All the participants completed a Short-Form 36 (SF-36) QoL. Results: The QoL related to social functioning was significantly worse among CSU patients. There were differences related to gender found in the group of patients with T1DM—where men tended to declare a better quality of life than women (p = 0.015)—especially in the area of energy/fatigue and pain. It appeared that due to physical and emotional problems occurring in married patients, the QoL is lower in T1DM group in comparison to the CSU one. Conclusions: The patients with CSU presented significantly worse social functioning compared to the ones with T1DM. This fact proves the QoL impairment level is not always related to the level of health danger. The differences in the QoL related to gender and marital status found among T1DM patients point to the necessity for further exploration in a larger group of patients. Due to the fact that optimal disease management should ensure patient’s good emotional well-being, there is a need for additional psychological and social care for patients from those two groups.
Three and Five-Year Mortality in Ovarian Cancer after Minimally Invasive Compared to Open Surgery: A Systematic Review and Meta-Analysis
Authors: Jochum Floriane , Vermel Muriel , Faller Emilie , Boisrame Thomas , Lecointre Lise , Akladios Cherif
Published: August 2020

As regards ovarian cancer, the use of minimally invasive surgery has steadily increased over the years. Reluctance persists, however, about its oncological outcomes. The main objective of this meta-analysis was to compare the three and five-year mortality of patients operated by minimally invasive surgery (MIS) for ovarian cancer to those operated by conventional open surgery (OPS), as well as their respective perioperative outcomes. PubMed, Cochrane library and CinicalTrials.gov were systematically searched, using the terms laparoscopy, laparoscopic or minimally invasive in combination with ovarian cancer or ovarian carcinoma. We finally included 19 observational studies with a total of 7213 patients. We found no statistically significant difference for five-year (relative risk (RR) = 0.89, 95% CI 0.53–1.49, p = 0.62)) and three-year mortality (RR = 0.95, 95% CI 0.80–1.12, p = 0.52) between the patients undergoing MIS and those operated by OPS. When five and three-year recurrences were analyzed, no statistically significant differences were also observed. Analysis in early and advanced stages subgroups showed no significant difference for survival outcomes, suggesting oncological safety of MIS in all stages. Whether the surgery was primary or interval debulking surgery in advanced ovarian cancer, did not influence the comparative results on mortality or recurrence. Although the available studies are retrospective, and mostly carry a high risk for bias and confounding, an overwhelming consistency of the evidence suggests the likely effectiveness of MIS in selected cases of ovarian cancer, even in advanced stages. To validate the use of MIS, the development of future randomized interventional studies should be a priority.
Assessment of Solitary Pulmonary Nodules Based on Virtual Monochrome Images and Iodine-Dependent Images Using a Single-Source Dual-Energy CT with Fast kVp Switching
Authors: Zegadło Arkadiusz , Żabicka Magdalena , Kania-Pudło Marta , Maliborski Artur , Różyk Aleksandra , Sośnicki Witold
Published: August 2020

With lung cancer being the most common malignancy diagnosed worldwide, lung nodule assessment has proved to be one of big challenges of modern medicine. The aim of this study was to examine the usefulness of Dual Energy Computed Tomography (DECT) in solitary pulmonary nodule (SPN) assessment. Between January 2017 and June 2018; 65 patients (42 males and 23 females) underwent DECT scans in the late arterial phase (AP) and venous phase (VP). We concluded that imaging at an energy level of 65 keV was the most accurate in detecting malignancy in solitary pulmonary nodules (SPNs) measuring ≤30 mm in diameter on virtual monochromatic maps. Both virtual monochromatic images and iodine concentration maps prove to be highly useful in differentiating benign and malignant pulmonary nodules. As for iodine concentration maps, the analysis of venous phase images resulted in the highest clinical usefulness. To summarize, DECT may be a useful tool in the differentiation of benign and malignant SPNs. A single-phase DECT examination with scans acquired 90 s after contrast media injection is recommended.
A Survey of Computer Vision Methods for 2D Object Detection from Unmanned Aerial Vehicles
Authors: Cazzato Dario , Cimarelli Claudio , Sanchez-Lopez Jose Luis , Voos Holger , Leo Marco
Published: August 2020

The spread of Unmanned Aerial Vehicles (UAVs) in the last decade revolutionized many applications fields. Most investigated research topics focus on increasing autonomy during operational campaigns, environmental monitoring, surveillance, maps, and labeling. To achieve such complex goals, a high-level module is exploited to build semantic knowledge leveraging the outputs of the low-level module that takes data acquired from multiple sensors and extracts information concerning what is sensed. All in all, the detection of the objects is undoubtedly the most important low-level task, and the most employed sensors to accomplish it are by far RGB cameras due to costs, dimensions, and the wide literature on RGB-based object detection. This survey presents recent advancements in 2D object detection for the case of UAVs, focusing on the differences, strategies, and trade-offs between the generic problem of object detection, and the adaptation of such solutions for operations of the UAV. Moreover, a new taxonomy that considers different heights intervals and driven by the methodological approaches introduced by the works in the state of the art instead of hardware, physical and/or technological constraints is proposed.
Risk Management: Rethinking Fashion Supply Chain Management for Multinational Corporations in Light of the COVID-19 Outbreak
Authors: McMaster May , Nettleton Charlie , Tom Christeen , Xu Belanda , Cao Cheng , Qiao Ping
Published: August 2020

Through an international business risk management lens, the widespread and catalytic implications of the 2020 COVID-19 pandemic on the supply chains (SCs) of fashion multinational corporations (MNC) are analyzed to contribute to existing research on supply chain management (SCM). While a movement towards agile, networked supply chain models had been in consideration for many firms prior to the outbreak, the pandemic highlights issues inherent in supply chains that employ concentrated production. We examined the current state of fashion supply chains, risks that have arisen historically and recently, and existing risk mitigation methods. We found that while lean supply chain management is primarily favored for its cost and waste reduction advantages, the structure is limited by the lack of supply chain transparency that results as well as the increasing demand volatility observed even before the COVID-19 outbreak. Although this problem might exist in the agile supply chain, agile supply chains combat this by focusing on enhancing communication and buyer-supplier relationships to improve information exchange. However, this structure also entails an associated increase in inventory and inventory costs. The COVID-19 pandemic has caused supply and demand disruptions which have resonating effects on supply chain activities and management, indicating a need to build flexibility to mitigate epidemic and demand risks. To address this, several strategies that firms can adopt to control for such risks are outlined and key areas for further research are identified which consider parties both upstream and downstream of the fashion supply chain.
Experimental and Numerical Evaluation on Deformation and Fracture Mechanism of Cast Duplex Stainless Steel Tubular Specimen
Authors: Li Zhenhua , Wang Xinyu , Chen Tao , Feng Fan , Liu Pan , Lu Yonghao
Published: August 2020

The deformation behavior and fracture mechanism of cast duplex stainless steel tubular specimens under different tensile stages were investigated through experimental and numerical evaluation. The results showed that the axial stress was redistributed due to the necking of the tubular specimen, the axial stress near the internal wall was larger than those near the external wall, and its maximum axial stress was distributed between the internal wall and the center of the wall thickness. Microcracks and voids were initiated under the maximum shear stress along the δ/γ phase interface and propagated to the ferrite interior. The voids were connected and merged into the main crack through the propagation of the microcracks. Moreover, the main crack first propagated to the internal wall and then rapidly propagated to the external wall. The fracture morphology can be divided into three types: shear lip zones that can be found on both the internal and external walls, and shear lip zones that can be found on either only the internal wall or the external wall.
Compostable Polylactide and Cellulose Based Packaging for Fresh-Cut Cherry Tomatoes: Performance Evaluation and Influence of Sterilization Treatment
Authors: Rapisarda Marco , Patanè Cristina , Pellegrino Alessandra , Malvuccio Angelo , Rizzo Valeria , Muratore Giuseppe , Rizzarelli Paola
Published: August 2020

For food packaging, plastic materials display large appeal, mostly due to their versatility, mechanical, optical and barrier properties. However, they play an important role in environmental concerns and waste management issue. Compostable bioplastics represent alternative materials designed for a lower environmental impact. In this work, a biobased compostable packaging, constituted by polylactide (PLA) trays and NatureFlex™ film, was evaluated for fresh-cut cherry tomato. A comparative analysis was accomplished using traditional packaging materials, that is, polyethylene terephtalate (PET) trays and polypropylene (PP Coex) film. Structural stability under food contact conditions, mechanical and physical-chemical properties were investigated. Tensile mechanical properties, puncture resistance, contact angle (CA) and attenuated total reflection Fourier-transform infrared spectroscopy (ATR-FTIR), before and after UV or radiofrequency (RF) sterilization treatment, were evaluated. UV irradiation method resulted the less invasive one. Therefore, oxygen and water vapor transmission rate (OTR and WVTR), overall chemical migration test, biodegradation assessment by biochemical oxygen demand (BOD) according to ISO 14851 and disintegration test by ISO 20200 were carried out to establish the further influence of UV sterilization on the packaging. Overall, data showed that the biobased compostable packaging for a prolonged shelf-life of fresh-cut cherry tomato has better properties that were surprisingly enhanced by the UV treatment.
Leachable Poly(Trimethylene Carbonate)/CaCO3 Composites for Additive Manufacturing of Microporous Vascular Structures
Authors: Guo Zhengchao , Grijpma Dirk , Poot André
Published: August 2020

The aim of this work was to fabricate microporous poly(trimethylene carbonate) (PTMC) vascular structures by stereolithography (SLA) for applications in tissue engineering and organ models. Leachable CaCO3 particles with an average size of 0.56 μm were used as porogens. Composites of photocrosslinkable PTMC and CaCO3 particles were cast on glass plates, crosslinked by ultraviolet light treatment and leached in watery HCl solutions. In order to obtain interconnected pore structures, the PTMC/CaCO3 composites had to contain at least 30 vol % CaCO3. Leached PTMC films had porosities ranging from 33% to 71% and a pore size of around 0.5 μm. The mechanical properties of the microporous PTMC films matched with those of natural blood vessels. Resins based on PTMC/CaCO3 composites with 45 vol % CaCO3 particles were formulated and successfully used to build vascular structures of various shapes and sizes by SLA. The intrinsic permeabilities of the microporous PTMC films and vascular structures were at least one order of magnitude higher than reported for the extracellular matrix, indicating no mass transfer limitations in the case of cell seeding.
Effect of Immiscible Secondary Fluid on Particle Dynamics and Coffee Ring Characteristics during Suspension Drying
Authors: Jung Kevin Injoe , Park Baek Sung , Lee Seong Jae , Noh Seung Man , Jung Hyun Wook
Published: August 2020

Particle motion and coffee ring patterns in water-borne suspensions of polystyrene (PS) particle added with small amounts of secondary hydrophobic decalin are investigated during the drying of the suspension droplets, mainly employing light scattering methods. Very tiny secondary fluid insertions via high-speed agitation effectively link the particles through hydrophobic dissolution leading to the formation of multimodal particulate clusters, with resistance to the outward capillary flow and suppression of coffee ring formation after drying. The impact of decalin on particles is corroborated by actual images acquired from an optical profiler and a scanning electron microscope (SEM). The average particle motion inside the suspension changed by decalin was expressed in terms of mean square displacement (MSD) based on diffusing wave spectroscopy (DWS). Employing multispeckle diffusing wave spectroscopy (MSDWS), the rapid motion or β-relaxation of particles in various suspensions with and without decalin is quantified in early lag time during the drying of droplets. The change in particle dynamics during suspension drop drying, when adding a small secondary fluid, plays a key role in tuning coffee ring patterns.
Experimental Investigations Regarding the Structural Damage Monitoring of Strands Wire Rope within Mechanical Systems
Authors: Debeleac Carmen , Nastac Silviu , Musca (Anghelache) Gina Diana
Published: August 2020

This paper deals with the area of structural damage monitoring of steel strands wire ropes embedded into various equipment and mechanical systems. Of the currently available techniques and methods for wire ropes health monitoring, the authors focused on the group of techniques based on operational dynamics investigation of such systems. Beyond the capability and efficiency of both occasionally and continuously monitoring application, the dynamics-based methods are able to provide additional information regarding the structural integrity and functional operability of the entire ensemble embedding the wire ropes. This paper presents the results gained by the authors using a laboratory setup that can simulate the operational condition usually used for regular applications of wire ropes. The investigations were conducted on three directions of acquired signals post-processing. Firstly, the classical fast Fourier transform was used to evaluate the potential changes within the spectral distribution of transitory response. The other two directions involved high-order spectral analyses in terms of bi-spectrum and Wigner–Ville distribution and multi-scale analysis based methods such as complex wavelet cross-correlation and complex wavelet coherency. The results indicate that each direction of analysis can provide suitable information regarding potential wire rope damage, but the ensemble of post-processing methods offers supplementary precision.
Coordination in Coupled Arrays of Stiff Filaments—Modelling and Simulation
Authors: Spinello Davide
Published: August 2020

We present the mechanical model of an array of elastic filaments and simulate the response with different mechanical couplings. This class of systems is inspired by robust and elegant solutions for locomotion mechanics that have emerged in several small-scale biological entities in the form of beating protrusions, such as cellular cilia and eukaryotic flagella. The collective dynamics of cilia arrays reveals important features such as array alignments, two-phase asymmetric beating of individual filaments, and the emergence of metachronal coordination, which make them suitable for bio-inspired terrestrial and aquatic locomotion. The model presented here is the basis for further developments towards the design of terrestrial and aquatic locomotion systems for general purpose robotic devices.
Towards a Better Basis Search through a Surrogate Model-Based Epistasis Minimization for Pseudo-Boolean Optimization
Authors: Kim Yong-Hoon , Yoon Yourim , Kim Yong-Hyuk
Published: August 2020

Epistasis, which indicates the difficulty of a problem, can be used to evaluate the basis of the space in which the problem lies. However, calculating epistasis may be challenging as it requires all solutions to be searched. In this study, a method for constructing a surrogate model, based on deep neural networks, that estimates epistasis is proposed for basis evaluation. The proposed method is applied to the Variant-OneMax problem and the NK-landscape problem. The method is able to make successful estimations on a similar level to basis evaluation based on actual epistasis, while significantly reducing the computation time. In addition, when compared to the epistasis-based basis evaluation, the proposed method is found to be more efficient.
Microstructure and Mechanical Properties of an Extruded 6005A Al Alloy Composite Reinforced with TiC Nanosized Particles and Strengthened by Precipitation Hardening
Authors: Feijoo Iria , Merino Pedro , Pena Gloria , Rey Pilar , Cabeza Marta
Published: August 2020

High-energy ball milling was carried out to disperse 3 vol% TiC nanoparticles (ex situ reinforcement) in a high-pressure inert gas-atomised prealloyed micron-sized 6005A Al alloy (AA6005A), with a Si/Mg atomic ratio of 1.32 powder matrix. Nanocomposite powders were consolidated by hot extrusion in strip shape at 500 °C, followed by a T6 ageing heat treatment. The microstructural features of the consolidated and precipitation hardening nanocomposites specimens were studied using X-ray diffractometry (DRX), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and electron backscatter diffraction (EBSD). The consolidated nanocomposites consisted of approximately equiaxed grains of different grain sizes with a high fraction of high-angle grain boundaries with average misorientation angles of approximately 35°. The nanocomposites showed remarkably higher hardness, Young’s modulus, yield, and ultimate strengths at room temperature than the extruded profiles of unreinforced milled AA6005A powders obtained through refinement of the Al alloy grain structure and a strong particle–matrix bonding, although with a drop in their ductility. The consolidated nanocomposite showed a weak response to industrial ageing heat treatment, as demonstrated by microstructural analyses and mechanical tests.
Comparative Genome Analysis of Bacillus sporothermodurans with Its Closest Phylogenetic Neighbor, Bacillus oleronius, and Bacillus cereus and Bacillus subtilis Groups
Authors: Owusu-Darko Rodney , Allam Mushal , Ismail Arshad , Ferreira Carlos A. S. , Oliveira Sílvia D. de , Buys Elna M.
Published: August 2020

Bacillus sporothermodurans currently possesses one of the most highly heat-resistant spores (HRS), which can withstand ultra-high temperature (UHT) processing. Determination of multiple whole genome sequences of B. sporothermodurans provided an opportunity to perform the first comparative genome analysis between strains and with B. oleronius, B. cereus, and B. subtilis groups. In this study, five whole genome sequences of B. sporothermodurans strains, including those belonging to the HRS clone (SAD and BR12) normally isolated from UHT milk, were compared with the aforementioned Bacillus species for gene clusters responsible for heat resistance. In the phylogenomic analysis, B. sporothermodurans, with its closest phylogenetic neighbor, B. oleronius, clustered with B. thermoamylovorans and B. thermotolerans. Heat shock proteins GrpE, GroES, GroEL, and DnaK presented identical sequences for all B. sporothermodurans strains, indicating that differences in functional efficiency are not involved in the thermal resistance variations. However, comparing all species evaluated, B. sporothermodurans exhibited a different gene configuration in the chromosomal region of the heat shock protein GrpE. Furthermore, only B. sporothermodurans strains presented the stage II sporulation protein P gene located in this region. Multisequence alignment and phylogenetic analysis of the ClpB protein showed differences for HRS and non-HRS strains. The study identified ClpC, ClpE, and ClpX as the three ATPases putatively involved in protein disaggregation in B. sporothermodurans. Bacillussporothermodurans exhibits high homology with other Bacillus species in the DnaK, DnaJ, GroEL, and GroES cluster of genes involved in heat resistance. The data presented here pave the way to select and evaluate the phenotypic effects of genes putatively involved in heat resistance.
Far-Off Resonance: Multiwavelength Raman Spectroscopy Probing Amide Bands of Amyloid-β-(37–42) Peptide
Authors: Talaikis Martynas , Strazdaitė Simona , Žiaunys Mantas , Niaura Gediminas
Published: August 2020

Several neurodegenerative diseases, like Alzheimer’s and Parkinson’s are linked with protein aggregation into amyloid fibrils. Conformational changes of native protein into the β-sheet structure are associated with a significant change in the vibrational spectrum. This is especially true for amide bands which are inherently sensitive to the secondary structure of a protein. Raman amide bands are greatly intensified under resonance conditions, in the UV spectral range, allowing for the selective probing of the peptide backbone. In this work, we examine parallel β-sheet forming GGVVIA, the C-terminus segment of amyloid-β peptide, using UV–Vis, FTIR, and multiwavelength Raman spectroscopy. We find that amide bands are enhanced far from the expected UV range, i.e., at 442 nm. A reasonable two-fold relative intensity increase is observed for amide II mode (normalized according to the δCH2/δCH3 vibration) while comparing 442 and 633 nm excitations; an increase in relative intensity of other amide bands was also visible. The observed relative intensification of amide II, amide S, and amide III modes in the Raman spectrum recorded at 442 nm comparing with longer wavelength (633/785/830 nm) excited spectra allows unambiguous identification of amide bands in the complex Raman spectra of peptides and proteins containing the β-sheet structure.
Workers’ Exposure Assessment during the Production of Graphene Nanoplatelets in R&D Laboratory
Authors: Bellagamba Irene , Boccuni Fabio , Ferrante Riccardo , Tombolini Francesca , Marra Fabrizio , Sarto Maria Sabrina , Iavicoli Sergio
Published: August 2020

Widespread production and use of engineered nanomaterials in industrial and research settings raise concerns about their health impact in the workplace. In the last years, graphene-based nanomaterials have gained particular interest in many application fields. Among them, graphene nanoplatelets (GNPs) showed superior electrical, optical and thermal properties, low-cost and availability. Few and conflicting results have been reported about toxicity and potential effects on workers’ health, during the production and handling of these nanostructures. Due to this lack of knowledge, systematic approaches are needed to assess risks and quantify workers’ exposure to GNPs. This work applies a multi-metric approach to assess workers’ exposure during the production of GNPs, based on the Organization for Economic Cooperation and Development (OECD) methodology by integrating real-time measurements and personal sampling. In particular, we analyzed the particle number concentration, the average diameter and the lung deposited surface area of airborne nanoparticles during the production process conducted by thermal exfoliation in two different ways, compared to the background. These results have been integrated by electron microscopic and spectroscopic analysis on the filters sampled by personal impactors. The study identifies the process phases potentially at risk for workers and reports quantitative information about the parameters that may influence the exposure in order to propose recommendations for a safer design of GNPs production process.
Cellulose Nanocrystals/Graphene Hybrids—A Promising New Class of Materials for Advanced Applications
Authors: Trache Djalal , Thakur Vijay Kumar , Boukherroub Rabah
Published: August 2020

With the growth of global fossil-based resource consumption and the environmental concern, there is an urgent need to develop sustainable and environmentally friendly materials, which exhibit promising properties and could maintain an acceptable level of performance to substitute the petroleum-based ones. As elite nanomaterials, cellulose nanocrystals (CNC) derived from natural renewable resources, exhibit excellent physicochemical properties, biodegradability and biocompatibility and have attracted tremendous interest nowadays. Their combination with other nanomaterials such as graphene-based materials (GNM) has been revealed to be useful and generated new hybrid materials with fascinating physicochemical characteristics and performances. In this context, the review presented herein describes the quickly growing field of a new emerging generation of CNC/GNM hybrids, with a focus on strategies for their preparation and most relevant achievements. These hybrids showed great promise in a wide range of applications such as separation, energy storage, electronic, optic, biomedical, catalysis and food packaging. Some basic concepts and general background on the preparation of CNC and GNM as well as their key features are provided ahead.
Core-Shell Magnetic Nanoparticles for Highly Sensitive Magnetoelastic Immunosensor
Authors: Campanile Raffaele , Scardapane Emanuela , Forente Antonio , Granata Carmine , Germano Roberto , Di Girolamo Rocco , Minopoli Antonio , Velotta Raffaele , Della Ventura Bartolomeo , Iannotti Vincenzo
Published: August 2020

A magnetoelastic (ME) biosensor for wireless detection of analytes in liquid is described. The ME biosensor was tested against human IgG in the range 0–20 μg∙mL−1. The sensing elements, anti-human IgG produced in goat, were immobilized on the surface of the sensor by using a recently introduced photochemical immobilization technique (PIT), whereas a new amplification protocol exploiting gold coated magnetic nanoparticles (core-shell nanoparticles) is demonstrated to significantly enhance the sensitivity. The gold nanoflowers grown on the magnetic core allowed us to tether anti-human IgG to the nanoparticles to exploit the sandwich detection scheme. The experimental results show that the 6 mm × 1 mm × 30 μm ME biosensor with an amplification protocol that uses magnetic nanoparticles has a limit of detection (LOD) lower than 1 nM, works well in water, and has a rapid response time of few minutes. Therefore, the ME biosensor is very promising for real-time wireless detection of pathogens in liquids and for real life diagnostic purpose.
Disposable Stochastic Sensors Based on Nanolayer Deposition(s) of Silver and AgC Composite on Plastic for the Assay of α-amylase in Whole Blood and Saliva
Authors: Stefan-van Staden Raluca-Ioana , Moscalu-Lungu Alexandrina , Badulescu Marius
Published: August 2020

Nanolayer deposition(s) of Ag and AgC composite on a plastic substrate was used to design disposable stochastic sensors. Three shapes of nanocoatings were tested. The first shape was obtained by deposition of a nanofilm of Ag on the plastic material; the second shape was obtained by deposition of a composite AgC nanolayer on the plastic material; the third shape was obtained by nanolayer deposition of a composite material of AgC on the top of the Ag nanofilm deposited on the plastic material. α-Cyclodextrin was used to modify the active surface of the sensor. Wide linear concentration ranges were obtained as follows: for de-assay of α-amylase in whole blood: 1.00 × 10−7–1.00 × 103 U mL−1 and for the assay of α-amylase in saliva: 1.5 × 10−15–1.5 × 102 U mL−1. α-Amylase was reliably determined from whole blood and saliva samples using the proposed disposable stochastic sensors.
UV-Induced Nanoparticles-Formation, Properties and Their Potential Role in Origin of Life
Authors: Nejdl Lukas , Zemankova Kristyna , Havlikova Martina , Buresova Michaela , Hynek David , Xhaxhiu Kledi , Mravec Filip , Matouskova Martina , Adam Vojtech , Ferus Martin , Kapus Jakub , Vaculovicova Marketa
Published: August 2020

Inorganic nanoparticles might have played a vital role in the transition from inorganic chemistry to self-sustaining living systems. Such transition may have been triggered or controlled by processes requiring not only versatile catalysts but also suitable reaction surfaces. Here, experimental results showing that multicolor quantum dots might have been able to participate as catalysts in several specific and nonspecific reactions, relevant to the prebiotic chemistry are demonstrated. A very fast and easy UV-induced formation of ZnCd quantum dots (QDs) with a quantum yield of up to 47% was shown to occur 5 min after UV exposure of the solution containing Zn(II) and Cd(II) in the presence of a thiol capping agent. In addition to QDs formation, xanthine activity was observed in the solution. The role of solar radiation to induce ZnCd QDs formation was replicated during a stratospheric balloon flight.
Circadian Variation in Human Milk Composition, a Systematic Review
Authors: Italianer Merel F. , Naninck Eva F. G. , Roelants Jorine A. , van der Horst Gijsbertus T. J. , Reiss Irwin K. M. , Goudoever Johannes B. van , Joosten Koen F. M. , Chaves Inês , Vermeulen Marijn J.
Published: August 2020

Background: Breastfeeding is considered the most optimal mode of feeding for neonates and mothers. Human milk changes over the course of lactation in order to perfectly suit the infant’s nutritional and immunological needs. Its composition also varies throughout the day. Circadian fluctuations in some bioactive components are suggested to transfer chronobiological information from mother to child to assist the development of the biological clock. This review aims to give a complete overview of studies examining human milk components found to exhibit circadian variation in their concentration. Methods: We included studies assessing the concentration of a specific human milk component more than once in 24 h. Study characteristics, including gestational age, lactational stage, sampling strategy, analytical method, and outcome were extracted. Methodological quality was graded using a modified Newcastle-Ottawa Scale (NOS). Results: A total of 83 reports assessing the circadian variation in the concentration of 71 human milk components were included. Heterogeneity among studies was high. The methodological quality varied widely. Significant circadian variation is found in tryptophan, fats, triacylglycerol, cholesterol, iron, melatonin, cortisol, and cortisone. This may play a role in the child’s growth and development in terms of the biological clock.
The Interaction of Fluorinated Glycomimetics with DC-SIGN: Multiple Binding Modes Disentangled by the Combination of NMR Methods and MD Simulations
Authors: Martínez J. Daniel , Infantino Angela S. , Valverde Pablo , Diercks Tammo , Delgado Sandra , Reichardt Niels-Christian , Ardá Ana , Cañada Francisco Javier , Oscarson Stefan , Jiménez-Barbero Jesús
Published: August 2020

Fluorinated glycomimetics are frequently employed to study and eventually modulate protein–glycan interactions. However, complex glycans and their glycomimetics may display multiple binding epitopes that enormously complicate the access to a complete picture of the protein–ligand complexes. We herein present a new methodology based on the synergic combination of experimental 19F-based saturation transfer difference (STD) NMR data with computational protocols, applied to analyze the interaction between DC-SIGN, a key lectin involved in inflammation and infection events with the trifluorinated glycomimetic of the trimannoside core, ubiquitous in human glycoproteins. A novel 2D-STD-TOCSYreF NMR experiment was employed to obtain the experimental STD NMR intensities, while the Complete Relaxation Matrix Analysis (CORCEMA-ST) was used to predict that expected for an ensemble of geometries extracted from extensive MD simulations. Then, an in-house built computer program was devised to find the ensemble of structures that provide the best fit between the theoretical and the observed STD data. Remarkably, the experimental STD profiles obtained for the ligand/DC-SIGN complex could not be satisfactorily explained by a single binding mode, but rather with a combination of different modes coexisting in solution. Therefore, the method provides a precise view of those ligand–receptor complexes present in solution.
Uncovering the Exosomes Diversity: A Window of Opportunity for Tumor Progression Monitoring
Authors: Maisano Domenico , Mimmi Selena , Russo Rossella , Fioravanti Antonella , Fiume Giuseppe , Vecchio Eleonora , Nisticò Nancy , Quinto Ileana , Iaccino Enrico
Published: August 2020

Cells can communicate through special “messages in the bottle”, which are recorded in the bloodstream inside vesicles, namely exosomes. The exosomes are nanovesicles of 30–100 nm in diameter that carry functionally active biological material, such as proteins, messanger RNA (mRNAs), and micro RNA (miRNAs). Therefore, they are able to transfer specific signals from a parental cell of origin to the surrounding cells in the microenvironment and to distant organs through the circulatory and lymphatic stream. More and more interest is rising for the pathological role of exosomes produced by cancer cells and for their potential use in tumor monitoring and patient follow up. In particular, the exosomes could be an appropriate index of proliferation and cancer cell communication for monitoring the minimal residual disease, which cannot be easily detectable by common diagnostic and monitoring techniques. The lack of unequivocal markers for tumor-derived exosomes calls for new strategies for exosomes profile characterization aimed at the adoption of exosomes as an official tumor biomarker for tumor progression monitoring.
In Vitro Release Study of the Polymeric Drug Nanoparticles: Development and Validation of a Novel Method
Authors: Weng Jingwen , Tong Henry H. Y. , Chow Shing Fung
Published: August 2020

The in vitro release study is a critical test to assess the safety, efficacy, and quality of nanoparticle-based drug delivery systems, but there is no compendial or regulatory standard. The variety of testing methods makes direct comparison among different systems difficult. We herein proposed a novel sample and separate (SS) method by combining the United States Pharmacopeia (USP) apparatus II (paddle) with well-validated centrifugal ultrafiltration (CU) technique that efficiently separated the free drug from nanoparticles. Polymeric drug nanoparticles were prepared by using a four-stream multi-inlet vortex mixer with d-α-tocopheryl polyethylene glycol 1000 succinate as a stabilizer. Itraconazole, cholecalciferol, and flurbiprofen were selected to produce three different nanoparticles with particle size <100 nm. By comparing with the dialysis membrane (DM) method and the SS methods using syringe filters, this novel SS + CU technique was considered the most appropriate in terms of the accuracy and repeatability to provide the in vitro release kinetics of nanoparticles. Interestingly, the DM method appeared to misestimate the release kinetics of nanoparticles through separate mechanisms. This work offers a superior analytical technique for studying in vitro drug release from polymeric nanoparticles, which could benefit the future development of in vitro-in vivo correlation of polymeric nanoparticles.
Procedure for the Selection of Rubber Compound in Rubber-Metal Springs for Vibration Isolation
Authors: Banić Milan , Stamenković Dušan , Miltenović Aleksandar , Jovanović Dragan , Tica Milan
Published: August 2020

The selection of a rubber compound has a determining influence on the final characteristics of rubber-metal springs. Therefore, the correct selection of a rubber compound is a key factor for development of rubber-metal vibration isolation springs with required characteristics. The procedure for the selection of the rubber compound for vibration isolation of rubber-metal springs has been proposed, so that the rubber-metal elements have the necessary characteristics, especially in terms of deflection. The procedure is based on numerical simulation of spring deflection with Bergström-Boyce constitutive model in virtual experiment, with a goal to determine which parameters of the constitutive model will lead to spring required deflection. The procedure was verified by case study defined to select rubber compound for a rubber–metal spring used in railway engineering.