bluuebunny/crossref_metadata_2025 huggingface dataset:
Utility of Magnetic Resonance Imaging for Differentiating Necrotizing Fasciitis from Severe Cellulitis: A Magnetic Resonance Indicator for Necrotizing Fasciitis (MRINEC) Algorithm
Authors: Kim Min-Chul , Kim Sujin , Cho Eun Been , Lee Guen Young , Choi Seong-Ho , Kim Seon Ok , Chung Jin-Won
Published: September 2020

We developed a new magnetic resonance indicator for necrotizing fasciitis (MRINEC) algorithm for differentiating necrotizing fasciitis (NF) from severe cellulitis (SC). All adults with suspected NF between 2010 and 2018 in a tertiary hospital in South Korea were enrolled. Sixty-one patients were diagnosed with NF and 28 with SC. Among them, 34 with NF and 15 with SC underwent magnetic resonance imaging (MRI). The MRINEC algorithm, a two-step decision tree including T2 hyperintensity of intermuscular deep fascia and diffuse T2 hyperintensity of deep peripheral fascia, diagnosed NF with 94% sensitivity (95% confidence interval (CI), 80–99%) and 60% specificity (95% CI, 32–84%). The algorithm accurately diagnosed all 15 NF patients with a high (≥8) laboratory risk indicator for necrotizing fasciitis (LRINEC) score. Among the five patients with an intermediate (6–7) LRINEC score, sensitivity and specificity were 100% (95% CI, 78–100%) and 0% (95% CI, 0–84%), respectively. Finally, among the 29 patients with a low (≤5) LRINEC score, the algorithm had a sensitivity and specificity of 88% (95% CI, 62–98%) and 69% (95% CI, 39–91%), respectively. The MRINEC algorithm may be a useful adjuvant method for diagnosing NF, especially when NF is suspected in patients with a low LRINEC score.
Can Adenosine Fight COVID-19 Acute Respiratory Distress Syndrome?
Authors: Falcone Carmela , Caracciolo Massimo , Correale Pierpaolo , Macheda Sebastiano , Vadalà Eugenio Giuseppe , La Scala Stefano , Tescione Marco , Danieli Roberta , Ferrarelli Anna , Tarsitano Maria Grazia , Romano Lorenzo , De Lorenzo Antonino
Published: September 2020

Coronavirus disease 2019 (COVID-19) patients can develop interstitial pneumonia, which, in turn, can evolve into acute respiratory distress syndrome (ARDS). This is accompanied by an inflammatory cytokine storm. severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) has proteins capable of promoting the cytokine storm, especially in patients with comorbidities, including obesity. Since currently no resolutive therapy for ARDS has been found and given the scientific literature regarding the use of adenosine, its application has been hypothesized. Through its receptors, adenosine is able to inhibit the acute inflammatory process, increase the protection capacity of the epithelial barrier, and reduce the damage due to an overactivation of the immune system, such as that occurring in cytokine storms. These features are known in ischemia/reperfusion models and could also be exploited in acute lung injury with hypoxia. Considering these hypotheses, a COVID-19 patient with unresponsive respiratory failure was treated with adenosine for compassionate use. The results showed a rapid improvement of clinical conditions, with negativity of SARS-CoV2 detection.
Mycosynthesis of ZnO Nanoparticles Using Trichoderma spp. Isolated from Rhizosphere Soils and Its Synergistic Antibacterial Effect against Xanthomonas oryzae pv. oryzae
Authors: Shobha Balagangadharaswamy , Lakshmeesha Thimappa Ramachandrappa , Ansari Mohammad Azam , Almatroudi Ahmad , Alzohairy Mohammad A. , Basavaraju Sumanth , Alurappa Ramesha , Niranjana Siddapura Ramachandrappa , Chowdappa Srinivas
Published: September 2020

The Plant Growth Promoting Fungi (PGPF) is used as a source of biofertilizers due to their production of secondary metabolites and beneficial effects on plants. The present work is focused on the co-cultivation of Trichoderma spp. (T. harzianum (PGT4), T. reesei (PGT5) and T. reesei (PGT13)) and the production of secondary metabolites from mono and co-culture and mycosynthesis of zinc oxide nanoparticles (ZnO NPs), which were characterized by a UV visible spectrophotometer, Powder X-ray Diffraction (PXRD), Fourier Transform Infrared Spectroscopy (FTIR) and Scanning Electron Microscopy (SEM) with Energy Dispersive Spectroscopy (EDAX) and Transmission Electron Microscope (TEM) and Selected Area (Electron) Diffraction (SAED) patterns. The fungal secondary metabolite crude was extracted from the mono and co-culture of Trichoderma spp. And were analyzed by GC-MS, which was further subjected for antibacterial activity against Xanthomonas oryzae pv. Oryzae, the causative organism for Bacterial Leaf Blight (BLB) in rice. Our results showed that the maximum zone of inhibition was recorded from the co-culture of Trichoderma spp. rather than mono cultures, which indicates that co-cultivation of beneficial fungi can stimulate the synthesis of novel secondary metabolites better than in monocultures. ZnO NPs were synthesized from fungal secondary metabolites of mono cultures of Trichoderma harzianum (PGT4), Trichoderma reesei (PGT5), Trichoderma reesei (PGT13) and co-culture (PGT4 + PGT5 + PGT13). These ZnO NPs were checked for antibacterial activity against Xoo, which was found to be of a dose-dependent manner. In summary, the biosynthesized ZnO NPs and secondary metabolites from co-culture of Trichoderma spp. are ecofriendly and can be used as an alternative for chemical fertilizers in agriculture.
ATAC-Seq Identifies Chromatin Landscapes Linked to the Regulation of Oxidative Stress in the Human Fungal Pathogen Candida albicans
Authors: Jenull Sabrina , Tscherner Michael , Mair Theresia , Kuchler Karl
Published: September 2020

Human fungal pathogens often encounter fungicidal stress upon host invasion, but they can swiftly adapt by transcriptional reprogramming that enables pathogen survival. Fungal immune evasion is tightly connected to chromatin regulation. Hence, fungal chromatin modifiers pose alternative treatment options to combat fungal infections. Here, we present an assay for transposase-accessible chromatin using sequencing (ATAC-seq) protocol adapted for the opportunistic pathogen Candida albicans to gain further insight into the interplay of chromatin accessibility and gene expression mounted during fungal adaptation to oxidative stress. The ATAC-seq workflow not only facilitates the robust detection of genomic regions with accessible chromatin but also allows for the precise modeling of nucleosome positions in C. albicans. Importantly, the data reveal genes with altered chromatin accessibility in upstream regulatory regions, which correlate with transcriptional regulation during oxidative stress. Interestingly, many genes show increased chromatin accessibility without change in gene expression upon stress exposure. Such chromatin signatures could predict yet unknown regulatory factors under highly dynamic transcriptional control. Additionally, de novo motif analysis in genomic regions with increased chromatin accessibility upon H2O2 treatment shows significant enrichment for Cap1 binding sites, a major factor of oxidative stress responses in C. albicans. Taken together, the ATAC-seq workflow enables the identification of chromatin signatures and highlights the dynamics of regulatory mechanisms mediating environmental adaptation of C. albicans.
Comprehensive Custom NGS Panel Validation for the Improvement of the Stratification of B-Acute Lymphoblastic Leukemia Patients
Authors: Montaño Adrián , Hernández-Sánchez Jesús , Forero-Castro Maribel , Matorra-Miguel María , Lumbreras Eva , Miguel Cristina , Santos Sandra , Ramírez-Maldonado Valentina , Fuster José Luís , de Las Heras Natalia , García-de Coca Alfonso , Sierra Magdalena , Dávila Julio , de la Fuente Ignacio , Olivier Carmen , Olazabal Juan , Martínez Joaquín , Vega-García Nerea , González Teresa , Hernández-Rivas Jesús María , Benito Rocío
Published: September 2020

Background: B-acute lymphoblastic leukemia (B-ALL) is a hematological neoplasm of the stem lymphoid cell of the B lineage, characterized by the presence of genetic alterations closely related to the course of the disease. The number of alterations identified in these patients grows as studies of the disease progress, but in clinical practice, the conventional techniques frequently used are only capable of detecting the most common alterations. However, techniques, such as next-generation sequencing (NGS), are being implemented to detect a wide spectrum of new alterations that also include point mutations. Methods: In this study, we designed and validated a comprehensive custom NGS panel to detect the main genetic alterations present in the disease in a single step. For this purpose, 75 B-ALL diagnosis samples from patients previously characterized by standard-of-care diagnostic techniques were sequenced. Results: The use of the custom NGS panel allowed the correct detection of the main genetic alterations present in B-ALL patients, including the presence of an aneuploid clone in 14 of the samples and some of the recurrent fusion genes in 35 of the samples. The panel was also able to successfully detect a number of secondary alterations, such as single nucleotide variants (SNVs) and copy number variations (CNVs) in 66 and 46 of the samples analyzed, respectively, allowing for further refinement of the stratification of patients. The custom NGS panel could also detect alterations with a high level of sensitivity and reproducibility when the findings obtained by NGS were compared with those obtained from other conventional techniques. Conclusions: The use of this custom NGS panel allows us to quickly and efficiently detect the main genetic alterations present in B-ALL patients in a single assay (SNVs and insertions/deletions (INDELs), recurrent fusion genes, CNVs, aneuploidies, and single nucleotide polymorphisms (SNPs) associated with pharmacogenetics). The application of this panel would thus allow us to speed up and simplify the molecular diagnosis of patients, helping patient stratification and management.
Biomarkers for Alzheimer’s Disease (AD) and the Application of Precision Medicine
Authors: Lukiw Walter J. , Vergallo Andrea , Lista Simone , Hampel Harald , Zhao Yuhai
Published: September 2020

An accurate diagnosis of Alzheimer’s disease (AD) currently stands as one of the most difficult and challenging in all of clinical neurology. AD is typically diagnosed using an integrated knowledge and assessment of multiple biomarkers and interrelated factors. These include the patient’s age, gender and lifestyle, medical and genetic history (both clinical- and family-derived), cognitive, physical, behavioral and geriatric assessment, laboratory examination of multiple AD patient biofluids, especially within the systemic circulation (blood serum) and cerebrospinal fluid (CSF), multiple neuroimaging-modalities of the brain’s limbic system and/or retina, followed up in many cases by post-mortem neuropathological examination to finally corroborate the diagnosis. More often than not, prospective AD cases are accompanied by other progressive, age-related dementing neuropathologies including, predominantly, a neurovascular and/or cardiovascular component, multiple-infarct dementia (MID), frontotemporal dementia (FTD) and/or strokes or ‘mini-strokes’ often integrated with other age-related neurological and non-neurological disorders including cardiovascular disease and cancer. Especially over the last 40 years, enormous research efforts have been undertaken to discover, characterize, and quantify more effectual and reliable biological markers for AD, especially during the pre-clinical or prodromal stages of AD so that pre-emptive therapeutic treatment strategies may be initiated. While a wealth of genetic, neurobiological, neurochemical, neuropathological, neuroimaging and other diagnostic information obtainable for a single AD patient can be immense: (i) it is currently challenging to integrate and formulate a definitive diagnosis for AD from this multifaceted and multidimensional information; and (ii) these data are unfortunately not directly comparable with the etiopathological patterns of other AD patients even when carefully matched for age, gender, familial genetics, and drug history. Four decades of AD research have repeatedly indicated that diagnostic profiles for AD are reflective of an extremely heterogeneous neurological disorder. This commentary will illuminate the heterogeneity of biomarkers for AD, comment on emerging investigative approaches and discuss why ‘precision medicine’ is emerging as our best paradigm yet for the most accurate and definitive prediction, diagnosis, and prognosis of this insidious and lethal brain disorder.
Using SERVQUAL Method to Assess Tourist Service Quality by the Example of the Silesian Museum Established on the Post-Mining Area
Authors: Kowalska Natalia , Ostręga Anna
Published: September 2020

The increasing role of the tourism industry in the global economy and the growing competition makes it necessary to ensure constant performance and continually improve quality. The paper draws attention to the necessity of conducting research on tourist attraction quality also in post-industrial areas which have become attractive tourist sites. It is emphasised that industrial tourism is a new yet quickly developing phenomenon in Poland, which compels managers to differentiate their service range and improve quality standards. The paper employs the SERVQUAL (SERvice QUALity) method to assess the quality of tourist services as a theoretical instrument to measure overall visitor satisfaction. The subject of the research was the Silesian Museum, which is result of reclamation and revitalisation of the inactive “Katowice” Hard Coal Mine. The article presents an empirical verification of the methodology which was modified for the purposes of the research subject. The Museum is considered to be one of the most important cultural centres and a crucial element of the social life of the Silesia region where mining activity has been carried out for centuries. Thirty young people from different continents participated in the survey. The results demonstrated that the expectations of the visitors were not met in three cases only which suggests a very high quality of the Silesian Museum. Moreover, the presented results show increasing capabilities and opportunities to maintain a high quality of services in the studied facility. The findings indicate that the appropriately modified SERVQUAL methodology is a valuable and simple tool to evaluate visitor satisfaction. The results of the evaluation of the Silesian Museum services will be presented to the facility managers. Further research will be carried out after the improvement and implementation of the next stage of the Museum’s development.
Reframing Native Knowledge, Co-Managing Native Landscapes: Ethnographic Data and Tribal Engagement at Yosemite National Park
Authors: Bloom Rochelle , Deur Douglas
Published: September 2020

Several Native American communities assert traditional ties to Yosemite Valley, and special connections to the exceptional landmarks and natural resources of Yosemite National Park. However, tribal claims relating to this highly visible park with its many competing constituencies—such as tribal assertions of traditional ties to particular landscapes or requests for access to certain plant gathering areas—often require supporting documentation from the written record. Addressing this need, academic researchers, the National Park Service and park-associated tribes collaborated in a multi-year effort to assemble a comprehensive ethnographic database containing most available written accounts of Native American land and resource use in Yosemite National Park. To date, the database includes over 13,000 searchable and georeferenced entries from historical accounts, archived ethnographic notebooks, tribal oral history transcripts and more. The Yosemite National Park Ethnographic Database represents a progressive tool for identifying culturally significant places and resources in Yosemite—a tool already being used by both cultural and natural resource managers within the National Park Service as well as tribal communities considering opportunities for future collaborative management of their traditional homelands within Yosemite National Park. We conclude that the organization of such data, including inherent ambiguities and contradictions, periodically updated with data provided by contemporary Tribal members, offers a rich, multivocal and dynamic representation of cultural traditions linked to specific park lands and resources. Indeed, some Yosemite tribal members celebrate the outcomes as revelatory, and as a partial antidote to their textual erasure from dispossessed lands. In practice however, as with any database, we find that this approach still risks ossifying data and reinforcing hegemonic discourses relating to cultural stasis, ethnographic objectivity and administrative power. By critically engaging these contradictions, we argue that one can still navigate pathways forward—bringing Native voices more meaningfully into the management of parks and other protected spaces, and providing a template useful at other parks for collaboration toward shared conservation goals.
Correlation between Expression Profiles of Key Signaling Genes in Colorectal Cancer Samples from Type 2 Diabetic and Non-Diabetic Patients
Authors: Elek Zsuzsanna , Rónai Zsolt , Keszler Gergely , Harsányi László , Kontsek Endre , Herold Zoltán , Herold Magdolna , Somogyi Anikó , Bánlaki Zsófia
Published: September 2020

Several lines of epidemiological and biochemical evidence support the association of type 2 diabetes mellitus (T2DM) and colorectal cancer (CRC). T2DM has been shown to impinge on the transcriptome of colon tumor cells, promoting their proliferation and invasion. In order to gain insight into diabetes-specific modulation of colon cancer signaling, we analyzed gene expression patterns of more than five hundred genes encoding signaling proteins on TaqMan OpenArray panels from colonoscopic colorectal tumor samples of type 2 diabetic and non-diabetic patients. In total, 48 transcripts were found to be differentially expressed in tumors of T2DM patients as compared to healthy colon samples. Enrichment analysis with the g:GOSt (Gene Ontology Statistics) functional profiling tool revealed that the underlying genes can be classified into five signaling pathways (in decreasing order of significance: Wnt (wingless-type)/β-catenin; Hippo; TNF (tumor necrosis factor); PI3K/Akt (phosphoinositide-3 kinase/protein kinase B), and platelet activation), implying that targeted downregulation of these signaling cascades might help combat CRC in diabetic patients. Transcript levels of some of the differentially expressed genes were also measured from surgically removed diabetic and non-diabetic CRC specimens by individual qPCR (quantitative real-time PCR) assays using the adjacent normal tissue mRNA levels as an internal control. The most significantly altered genes in diabetic tumor samples were largely different from those in non-diabetic ones, implying that T2DM profoundly alters the expression of signaling genes and presumably the biological characteristics of CRC.
Effect of Annealing on the Microstructure and SERS Performance of Mo-48.2% Ag Films
Authors: Sun Haoliang , Lian Xinxin , Lv Yuanjiang , Liu Yuanhao , Xu Chao , Dai Jiwei , Wu Yilin , Wang Guangxin
Published: September 2020

Mo-48.2% Ag films were fabricated by direct current (DC) magnetron sputtering and annealed in an argon atmosphere. The effects of annealing on the surface morphology, resistivity and surface-enhanced Raman scattering (SERS) performance of Mo-48.2% Ag films were investigated. Results show a mass of polyhedral Ag particles grown on the annealed Mo-48.2% Ag films’ surface, which are different from that of as-deposited Mo-Ag film. Moreover, the thickness and the resistivity of Mo-48.2% Ag films gradually decrease as the annealing temperature increases. Furthermore, finite-difference time-domain (FDTD) simulations proved that the re-deposition Ag layer increases the “hot spots” between adjacent Ag nanoparticles, thereby greatly enhancing the local electromagnetic (EM) field. The Ag layer/annealed Mo-48.2% Ag films can identify crystal violet (CV) with concentration lower than 5 × 10−10 M (1 mol/L = 1 M), which indicated that this novel type of particles/films can be applied as ultrasensitive SERS substrates.
Electrodialytic Desalination of Tobacco Sheet Extract: Membrane Fouling Mechanism and Mitigation Strategies
Authors: Ge Shaolin , Zhang Zhao , Yan Haiyang , Irfan Muhammad , Xu Yingbo , Li Wei , Wang Huangying , Wang Yaoming
Published: September 2020

In the papermaking industry (reconstituted tobacco), a large number of tobacco stems, dust, and fines are discharged in the wastewater. This high salinity wastewater rich in ionic constituents and nicotine is difficult to be degraded by conventional biological treatment and is a serious threat that needs to be overcome. Electrodialysis (ED) has proved a feasible technique to remove the inorganic components in the papermaking wastewater. However, the fouling in ion exchange membranes causes deterioration of membranes, which causes a decrease in the flux and an increase in the electrical resistance of the membranes. In this study, the fouling potential of the membranes was analyzed by comparing the properties of the pristine and fouled ion exchange membranes. The physical and chemical properties of the ion exchange membranes were investigated in terms of electrical resistance, water content, and ion exchange capacity, as well as studied by infrared spectroscopy (IR) spectra, scanning electron microscopy (SEM), and energy dispersive spectroscopy (EDS) analyses. The results indicated that the membrane fouling is caused by two different mechanisms. For the anion exchange membranes, the fouling is mainly caused by the charged organic anions. For the cation exchange membrane, the fouling is caused by minerals such as Ca2+ and Mg2+. These metal ions reacted with OH− ions generated by water dissociation and precipitated on the membrane surface. The chemical cleaning with alkaline and acid could mitigate the fouling potential of the ion exchange membranes.
Ceramic Microfiltration Membranes in Wastewater Treatment: Filtration Behavior, Fouling and Prevention
Authors: Hakami Mohammed Wali , Alkhudhiri Abdullah , Al-Batty Sirhan , Zacharof Myrto-Panagiota , Maddy Jon , Hilal Nidal
Published: September 2020

Nowadays, integrated microfiltration (MF) membrane systems treatment is becoming widely popular due to its feasibility, process reliability, commercial availability, modularity, relative insensitivity in case of wastewater of various industrial sources as well as raw water treatment and lower operating costs. The well thought out, designed and implemented use of membranes can decrease capital cost, reduce chemical usage, and require little maintenance. Due to their resistance to extreme operating conditions and cleaning protocols, ceramic MF membranes are gradually becoming more employed in the drinking water and wastewater treatment industries when compared with organic and polymeric membranes. Regardless of their many advantages, during continuous operation these membranes are susceptible to a fouling process that can be detrimental for successful and continuous plant operations. Chemical and microbial agents including suspended particles, organic matter particulates, microorganisms and heavy metals mainly contribute to fouling, a complex multifactorial phenomenon. Several strategies, such as chemical cleaning protocols, turbulence promoters and backwashing with air or liquids are currently used in the industry, mainly focusing around early prevention and treatment, so that the separation efficiency of MF membranes will not decrease over time. Other strategies include combining coagulation with either inorganic or organic coagulants, with membrane treatment which can potentially enhance pollutants retention and reduce membrane fouling.
A Review of Recent Advances in Depression Techniques for Flotation Separation of Cu–Mo Sulfides in Porphyry Copper Deposits
Authors: Park Ilhwan , Hong Seunggwan , Jeon Sanghee , Ito Mayumi , Hiroyoshi Naoki
Published: September 2020

Porphyry copper deposits (PCDs) are some of the most important sources of copper (Cu) and molybdenum (Mo). Typically, the separation and recovery of chalcopyrite (CuFeS2) and molybdenite (MoS2), the major Cu and Mo minerals, respectively, in PCDs are achieved by two-step flotation involving (1) bulk flotation to separate Cu–Mo concentrates and tailings (e.g., pyrite, silicate, and aluminosilicate minerals) and (2) Cu–Mo flotation to separate chalcopyrite and molybdenite. In Cu–Mo flotation, chalcopyrite is depressed using Cu depressants, such as NaHS, Na2S, Nokes reagent (P2S5 + NaOH), and NaCN, meaning that it is recovered as tailings, while molybdenite is floated and recovered as froth product. Although conventionally used depressants are effective in the separation of Cu and Mo, they have the potential to emit toxic and deadly gases such as H2S and HCN when operating conditions are not properly controlled. To address these problems caused by the use of conventional depressants, many studies aimed to develop alternative methods of depressing either chalcopyrite or molybdenite. In this review, recent advances in chalcopyrite and molybdenite depressions for Cu–Mo flotation separation are reviewed, including alternative organic and inorganic depressants for Cu or Mo, as well as oxidation-treatment technologies, such as ozone (O3), plasma, hydrogen peroxide (H2O2), and electrolysis, which create hydrophilic coatings on the mineral surface.
A Comprehensive Review on the Corrosion Pathways of Titanium Dental Implants and Their Biological Adverse Effects
Authors: Souza Júlio C. M. , Apaza-Bedoya Karin , Benfatti Cesar A. M. , Silva Filipe S. , Henriques Bruno
Published: September 2020

The main aim of this work was to perform a comprehensive review of findings reported by previous studies on the corrosion of titanium dental implants and consequent clinical detrimental effects to the patients. Most studies were performed by in vitro electrochemical tests and complemented with microscopic techniques to evaluate the corrosion behavior of the protective passive oxide film layer, namely TiO2. Results revealed that bacterial accumulation, dietary, inflammation, infection, and therapeutic solutions decrease the pH of the oral environment leading to the corrosion of titanium. Some therapeutic products used as mouthwash negatively affect the corrosion behavior of the titanium oxide film and promote changes on the implant surface. In addition, toothpaste and bleaching agents, can amplify the chemical reactivity of titanium since fluor ions interacting with the titanium oxide film. Furthermore, the number of in vivo studies is limited although corrosion signs have been found in retrieved implants. Histological evaluation revealed titanium macro- and micro-scale particles on the peri-implant tissues. As a consequence, progressive damage of the dental implants and the evolution of inflammatory reactions depend on the size, chemical composition, and concentration of submicron- and nanoparticles in the surrounding tissues and internalized by the cells. In fact, the damage of the implant surfaces results in the loss of material that compromises the implant surfaces, implant-abutment connections, and the interaction with soft tissues. The corrosion can be an initial trigger point for the development of biological or mechanical failures in dental implants.
A Review of Factors Affecting the Mechanical Properties of Maraging Steel 300 Fabricated via Laser Powder Bed Fusion
Authors: Mooney Barry , Kourousis Kyriakos
Published: September 2020

Maraging steel is an engineering alloy which has been widely employed in metal additive manufacturing. This paper examines manufacturing and post-processing factors affecting the properties of maraging steel fabricated via laser powder bed fusion (L-PBF). It covers the review of published research findings on how powder quality feedstock, processing parameters, laser scan strategy, build orientation and heat treatment can influence the microstructure, density and porosity, defects and residual stresses developed on L-PBF maraging steel, with a focus on the maraging steel 300 alloy. This review offers an evaluation of the resulting mechanical properties of the as-built and heat-treated maraging steel 300, with a focus on anisotropic characteristics. Possible directions for further research are also identified.
The Microfluidic Trainer: Design, Fabrication and Validation of a Tool for Testing and Improving Manual Skills
Authors: Costa Francesco , Falzetti Luigi , Baldini Nicola , Avnet Sofia
Published: September 2020

Microfluidic principles have been widely applied for more than 30 years to solve biological and micro-electromechanical problems. Despite the numerous advantages, microfluidic devices are difficult to manage as their handling comes with several technical challenges. We developed a new portable tool, the microfluidic trainer (MT), that assesses the operator handling skills and that may be used for maintaining or improving the ability to inject fluid in the inlet of microfluidic devices for in vitro cell culture applications. After several tests, we optimized the MT tester cell to reproduce the real technical challenges of a microfluidic device. In addition to an exercise path, we included an overfilling indicator and a correct infilling indicator at the inlet (control path). We manufactured the MT by engraving a 3 mm-high sheet of methacrylate with 60W CO2 laser plotter to create multiple capillary paths. We validated the device by enrolling 21 volunteers (median age 33) to fill both the MT and a commercial microfluidic device. The success rate obtained with MT significantly correlated with those of a commercial microfluidic culture plate, and its 30 min-continuous use for three times significantly improved the performance. Overall, our data demonstrate that MT is a valid assessment tool of individual performances in using microfluidic devices and may represent a low-cost solution to training, improve or warm up microfluidic handling skills.
Application of Miniature FBG-MEMS Pressure Sensor in Penetration Process of Jacked Pile
Authors: Liu Xueying , Wang Yonghong , Zhang Mingyi
Published: September 2020

In order to study the penetration mechanism of jacked piles in viscous soil foundation, the stress variation law of the pile–soil interface was obtained by installing silicon piezoresistive earth pressure and pore water pressure sensors, and fiber Bragg grating (FBG) sensors in a model pile body, and the penetration characteristics of jacked piles in homogeneous viscous soil were defined. The test results show that: Fiber Bragg grating and silicon piezoresistive sensing technology can better meet the requirements of testing the characteristics of jacked pile in viscous soil. The ratio of pile lateral resistance to pile end resistance varies when pile is jacked in homogeneous viscous soil. In the early stage of pile jacking, the ratio of pile lateral resistance is small, and in the later stage of pile jacking, the ratio of pile lateral resistance increases, but the ratio of pile end resistance is still higher than that of pile lateral resistance. The ratio of the effective stress to the total radial stress is high, and the variation law of the two is consistent with the depth. The total radial stress, pore water pressure, and effective radial stress all exhibit the degradation phenomenon, and the degradation degree decreases gradually with the increase in penetration depth at the same depth. The ratio of excess pore water pressure to overburden weight decreases with the increase in depth, and the maximum value is 87%. The research results can provide a reference for the engineering practice of jacked pile in viscous soil foundation.
Revealing the Plastic Mode of Time-Dependent Deformation of a LiTaO3 Single Crystal by Nanoindentation
Authors: Zhou Shengyun , Huang Xianwei , Lu Congda , Liu Yunfeng , Zhang Taihua , Ma Yi
Published: September 2020

Recently, instrumental nanoindentation has been widely applied to detect time-dependent plastic deformation or creep behavior in numerous materials, particularly thin films and heterogeneous materials. However, deformation mechanism at nanoindentation holding stage has not been well revealed hitherto. In the current work, nanoindentation holding tests with high loads were performed on a brittle LiTaO3 single crystal. The surface morphologies of residual impressions with various holding times were investigated. It was indicated that generation of secondary cracks and propagation of both main and secondary cracks were the dominating mechanism for time-dependent plastic deformation at the initial holding stage, and the density and length of cracks were invariable at the steady-state holding stage, which suggested a nonlocalized plastic deformation beneath the indenter. It could be concluded that time-dependent plastic deformation of brittle ceramic under nanoindentation is composed of instant cracking as the continuation of loading sequence and homogeneous creep flow by high shear-compression stress at room temperature.
Antibiotic-Resistant Escherichia coli and Sequence Type 131 in Fecal Colonization in Dogs in Taiwan
Authors: Chen Jenn-Wei , Huang Han Hsiang , Chang Szu-Min , Scaria Joy , Chiu Yu-Lung , Chen Chih-Ming , Ko Wen-Chien , Wang Jiun-Ling
Published: September 2020

Background: Most drug-resistant Escherichia coli isolates in dogs come from diseased dogs. Prior to this study, the prevalence and risk factors of fecal carriage drug-resistant E. coli and epidemic clone sequence type (ST) 131 (including subtypes) isolates in dogs were unknown. Methods: Rectal swabs were used for E. coli isolation from 299 non-infectious dogs in a veterinary teaching hospital in Taiwan. Antibiotic resistance and multiplex PCR analyses of E. coli for major STs were performed. Result: There were 43.1% cefazolin-resistant, 22.1% fluoroquinolone-resistant, and 9.4% extended-spectrum beta-lactamase-producing E. coli in our cohort. In the phylogenetic study, B2 was the predominant group (30.1%). The cefazolin-resistant group and ciprofloxacin-resistant group had greater antibiotic exposure in the last 14 days (p < 0.05). The age, sex, and dietary habits of the antibiotic-resistant and -susceptible groups were similar. In the seven isolates of ST131 in fecal colonization, the most predominant subtypes were FimH41 and FimH22. Conclusion: Recent antibiotic exposure was related to the fecal carriage of antibiotic-resistant E. coli isolates. Three major subtypes (FimH41, H22, and H30) of ST131 can thus be found in fecal carriage in dogs in Taiwan.
Central Asian Rodents as Model Animals for Leishmania major and Leishmania donovani Research
Authors: Vojtkova Barbora , Spitzova Tatiana , Votypka Jan , Lestinova Tereza , Kominkova Iveta , Hajkova Michaela , Santos-Mateus David , Miles Michael A. , Volf Petr , Sadlova Jovana
Published: September 2020

The clinical manifestation of leishmaniases depends on parasite species, host genetic background, and immune response. Manifestations of human leishmaniases are highly variable, ranging from self-healing skin lesions to fatal visceral disease. The scope of standard model hosts is insufficient to mimic well the wide disease spectrum, which compels the introduction of new model animals for leishmaniasis research. In this article, we study the susceptibility of three Asian rodent species (Cricetulus griseus, Lagurus lagurus, and Phodopus sungorus) to Leishmania major and L. donovani. The external manifestation of the disease, distribution, as well as load of parasites and infectiousness to natural sand fly vectors, were compared with standard models, BALB/c mice and Mesocricetus auratus. No significant differences were found in disease outcomes in animals inoculated with sand fly- or culture-derived parasites. All Asian rodent species were highly susceptible to L. major. Phodopus sungorus showed the non-healing phenotype with the progressive growth of ulcerative lesions and massive parasite loads. Lagurus lagurus and C. griseus represented the healing phenotype, the latter with high infectiousness to vectors, mimicking best the character of natural reservoir hosts. Both, L. lagurus and C. griseus were also highly susceptible to L. donovani, having wider parasite distribution and higher parasite loads and infectiousness than standard model animals.
Updated Taxonomy of Pectobacterium Genus in the CIRM-CFBP Bacterial Collection: When Newly Described Species Reveal “Old” Endemic Population
Authors: Portier Perrine , Pédron Jacques , Taghouti Géraldine , Dutrieux Cécile , Barny Marie-Anne
Published: September 2020

Bacterial collections are invaluable tools for microbiologists. However, their practical use is compromised by imprecise taxonomical assignation of bacterial strains. This is particularly true for soft rotting plant pathogens of the Pectobacterium genus. We analysed the taxonomic status of 265 Pectobacterium strains deposited at CIRM-CFBP collection from 1944 to 2020. This collection gathered Pectobacterium strains isolated in 27 countries from 32 plant species representing 17 botanical families or from nonhost environments. The MLSA approach completed by genomic analysis of 15 strains was performed to update the taxonomic status of these 265 strains. The results showed that the CIRM-CFBP Pectobacterium collection harboured at least one strain of each species, with the exception of P. polonicum. Yet, seven strains could not be assigned to any of the described species and may represent at least two new species. Surprisingly, P. versatile, recently described in 2019, is the most prevalent species among CIRM-CFBP strains. An analysis of P. versatile strains revealed that this species is pandemic and isolated from various host plants and environments. At the opposite, other species gathered strains isolated from only one botanical family or exclusively from a freshwater environment. Our work also revealed new host plants for several Pectobacterium spp.
Colistin and Isavuconazole Interact Synergistically In Vitro against Aspergillus nidulans and Aspergillus niger
Authors: Schwarz Patrick , Djenontin Elie , Dannaoui Eric
Published: September 2020

The in vitro interactions of isavuconazole in combination with colistin were evaluated against 55 clinical Aspergillus species isolates belonging to the five most important species (Aspergillus flavus, Aspergillus fumigatus, Aspergillus nidulans, Aspergillus niger, and Aspergillus terreus) responsible for human aspergillosis by a microdilution checkerboard technique based on the European Committee on Antimicrobial Susceptibility Testing (EUCAST) reference method for antifungal susceptibility testing. Selected isolates (A. nidulans, n = 10; A. niger, n = 15) were additionally evaluated by an agar diffusion assay using isavuconazole gradient concentration strips with or without colistin incorporated Roswell Parc Memorial Institute (RPMI) agar. Interpretation of the checkerboard results was done by the fractional inhibitory concentration index. Using the checkerboard method, combination isavuconazole–colistin was synergistic for 100% of the 15 A. nidulans isolates and for 60% of the 20 A. niger isolates. No interactions were found for any of the other isolates. By agar diffusion assay, minimal inhibitory concentrations (MICs) in combination decreased compared to isavuconazole alone for 92% of the isolates. No interactions were found for any A. nidulans isolates, but synergy was observed for 40% of the A. niger isolates. A poor essential agreement of EUCAST and gradient concentration strip MICs at ± 2 log2 dilutions with 0% was obtained. Antagonistic interactions were never observed regardless of the technique used.
Synthesis of Fly Ash-Based Geopolymers: Effect of Calcite Addition and Mechanical Activation
Authors: Kalinkin Alexander M. , Gurevich Basya I. , Myshenkov Mikhail S. , Chislov Mikhail V. , Kalinkina Elena V. , Zvereva Irina A. , Cherkezova-Zheleva Zara , Paneva Daniela , Petkova Vilma
Published: September 2020

Blends of fly ash and natural calcite, mechanically activated for 0–400 s in a planetary mill, were used to synthesize geopolymers at ambient temperature. The calcite content in the blends was 0–10 wt.%. Sodium hydroxide solution was used as an alkaline agent. Mechanical activation of the raw material considerably enhanced its reactivity with respect to the alkaline agent, as was observed using Fourier-transform infrared spectroscopy, isothermal conduction calorimetry, thermogravimetry coupled with mass spectrometry analysis of the evolved gas, and SEM/EDS. The addition of calcite to the fly ash improved the compressive strength of the geopolymers, especially during the early age of curing. For 7 d aged geopolymers based on the 90% fly ash + 10% calcite blend, the strength was 8.0-, 3.5- and 2.9-fold higher than that for the geopolymers based on the unblended fly ash for 30 s, 180 s and 400 s mechanical activation time, respectively. Using Mössbauer spectroscopy, it was revealed that iron present in the fly ash did not play a significant part in the geopolymerization process. The dominant reaction product was sodium containing aluminosilicate hydrogel (N-A-S-H gel). Calcite was found to transform, to a small extent, to vaterite and Ca(OH)2 in the course of the geopolymerization.
The Origin of Hydrocarbon Gases in the Lovozero Nepheline-Syenite Massif (Kola Peninsula, NW Russia), as Revealed from He and Ar Isotope Evidence
Authors: Nivin Valentin
Published: September 2020

The occurrence of hydrocarbon gases (HCG) in unusually high concentrations for magmatic complexes, in the Lovozero and some other alkaline massifs, is of both geochemical and practical interest. The nature of these gases, despite the long history of research, remains the subject of debate. As an approach to solving this problem, we studied the coupled distribution of occluded HCG and the recognized tracers of various geological processes, such as helium and argon isotopes. The extraction of the gas components trapped in fluid micro-inclusions was carried out by the mechanical crushing of rock and mineral samples. A positive correlation was found between the 3He/4He and CH4/C2H6 ratios, whereas a negative correlation of the latter was found with the 36Ar concentration, which in turn was directly related, in varying degrees, to the content of HCG and most strongly with pentanes. Conjugacy of the processes of the heavier gaseous hydrocarbons, a loss of the deep component of the fluid phase and dilution of it with the atmogenic component was established. In the absence of a correlation between CH4 and 3He, the value of the CH4/3He ratio in the Lovozero gas substantially exceeded the estimates of it in gases of a mantle origin, and mainly corresponded to the crustal values. However, in some samples, a small fraction of mantle methane was allowed. The peculiarities of the relationships between hydrocarbon gases and the isotopes of noble gases indicate a sequential process of abiogenic generation and transformation of HCG at the magmatic and post-magmatic stages during the formation of the Lovozero massif. The obtained results confirm the usefulness of this approach in solving the origin of reduced gases in alkaline igneous systems.
Cytotoxic Properties of 1,3,4-Thiadiazole Derivatives—A Review
Authors: Janowska Sara , Paneth Agata , Wujec Monika
Published: September 2020

During recent years, small molecules containing five-member heterocyclic moieties have become the subject of considerable growing interest for designing new antitumor agents. One of them is 1,3,4-thiadiazole. This study is an attempt to collect the 1,3,4-thiadiazole and its derivatives, which can be considered as potential anticancer agents, reported in the literature in the last ten years.
Effects of Combined Admistration of Imatinib and Sorafenib in a Murine Model of Liver Fibrosis
Authors: Pesce Antonio , Ciurleo Rosella , Bramanti Alessia , Armeli Iapichino Eliana Concetta , Petralia Maria Cristina , Magro Gaetano Giuseppe , Fagone Paolo , Bramanti Placido , Nicoletti Ferdinando , Mangano Katia
Published: September 2020

Liver fibrosis is defined as excessive extracellular matrix deposition in the hepatic parenchyma as a consequence of complex interactions among matrix-producing hepatic stellate cells (HSCs) and liver-resident and infiltrating cells. In addition to the liver, the process of fibrosis may represent end-stage disease of several diseases including kidneys, lungs, spleens, heart, muscles and at certain extent, the central nervous system and the peripheral nerves. To date, antifibrotic treatment of fibrosis represents an unconquered area for drug development. The aim of the present study was to test the efficacy of a new drug combination for the treatment of hepatic fibrosis in order to provide a proof-of-concept for the use of therapeutic agents in clinical practice. For this purpose, we have studied the effects of the PDGF inhibitor imatinib and the angiogenesis inhibitor sorafenib, administered alone or in combination, in reducing the progression of the fibrogenetic process in a pre-clinical model of liver damage induced in mice by repeated administration of Concanavalin A (ConA), resembling long-tern autoimmune hepatitis. Our results suggest that treatments with imatinib and sorafenib can modulate potently and, in a superimposable fashion, the fibrinogenic process when administered alone. However, and in agreement with the computational data presently generated, they only exert partial overlapping antifibrotic effects in modulating the main pathways involved in the process of liver fibrosis, without significant additive or synergist effects, when administered in combination.
Design, Synthesis and Bioactivity Evaluation of 4,6-Disubstituted Pyrido[3,2-d]pyrimidine Derivatives as Mnk and HDAC Inhibitors
Authors: Xing Kun , Zhang Jian , Han Yu , Tong Tong , Liu Dan , Zhao Linxiang
Published: September 2020

Both HDACs and Mnks play important role in translating multiple oncogenic signaling pathways during oncogenesis. As HDAC and Mnk are highly expressed in a variety of tumors; thus simultaneous inhibit HDAC and Mnk can increase the inhibition of tumor cell proliferation and provide a new way of inhibiting tumor growth. Based on the previous work and the merge pharmacophore method; we designed and synthesized a series of 4,6-disubstituted pyrido[3,2-d]pyrimidine derivatives as HDAC and Mnk dual inhibitors. Among them; compound A12 displayed good HDAC and Mnk inhibitory activity. In vitro antiproliferative assay; compound A12 exhibited the best antiproliferative activity against human prostate cancer PC-3 cells. Docking study revealed that the pyrido[3,2-d]pyrimidine framework and hydroxamic acid motif of compound A12 were essential for maintaining the activity of HDAC and Mnk. These result indicated that A12 was a potent Mnk /HDAC inhibitor and will be further researched.