bluuebunny/crossref_metadata_2025 huggingface dataset:
Proteomic Profiling of the First Human Dental Pulp Mesenchymal Stem/Stromal Cells from Carbonic Anhydrase II Deficiency Osteopetrosis Patients
Authors: Alkhayal Zikra , Shinwari Zakia , Gaafar Ameera , Alaiya Ayodele
Published: December 2020

Osteopetrosis is a hereditary disorder characterized by sclerotic, thick, weak, and brittle bone. The biological behavior of mesenchymal cells obtained from osteopetrosis patients has not been well-studied. Isolated mesenchymal stem/stromal cells from dental pulp (DP-MSSCs) of recently extracted deciduous teeth from osteopetrosis (OP) patients and healthy controls (HCs) were compared. We evaluated whether the dental pulp of OP patients has a population of MSSCs with similar multilineage differentiation capability to DP-MSSCs of healthy subjects. Stem/progenitor cells were characterized using immunohistochemistry, flow cytometry, and proteomics. Our DP-MSSCs were strongly positive for CD44, CD73, CD105, and CD90. DP-MSSCs obtained from HC subjects and OP patients showed similar patterns of proliferation and differentiation as well as gene expression. Proteomic analysis identified 1499 unique proteins with 94.3% similarity in global protein fingerprints of HCs and OP patients. Interestingly, we observed subtle differences in expressed proteins of osteopetrosis disease-related in pathways, including MAPK, ERK 1/2, PI3K, and integrin, rather than in the stem cell signaling network. Our findings of similar protein expression signatures in DP-MSSCs of HC and OP patients are of paramount interest, and further in vivo validation study is needed. There is the possibility that OP patients could have their exfoliating deciduous teeth banked for future use in regenerative dentistry.
“I Want to Experience the Past”: Lessons from a Visitor Survey on How Immersive Technologies Can Support Historic Interpretation
Authors: Ress Stella A. , Cafaro Francesco
Published: December 2020

This paper utilizes a visitor survey conducted at an open-air museum in New Harmony, Indiana to discuss design guidelines for immersive technologies that support historic interpretation–specifically, the visitor’s ability to experience the past. We focus on three themes that emerged from the survey: (1) Visitors at this site skewed older, with nearly a quarter over 70; (2) Despite literature suggesting the opposite, visitors at New Harmony liked to learn from a tour guide; and, (3) Visitors said they wanted to “experience the past.” The very notion of a single “experience” of the past, however, is complicated at New Harmony and other historic sites because they interpret multiple periods of significance. Ultimately, our findings suggest immersive technologies must be suited for older visitors, utilize the tour guide, and facilitate visitors’ ability to “experience the past” in such a way that they feel immersed in multiple timelines at the same site.
Indigenous Knowledge about Consumption of Edible Insects in South Africa
Authors: Hlongwane Zabentungwa T. , Slotow Rob , Munyai Thinandavha C.
Published: December 2020

Consumption of edible insects is an indigenous practice that has played an essential role in human nutrition across Africa. The traditional use of insects forms an important part of food culture in Africa, and insects are consumed either as a delicacy, emergency, or staple source of food. However, indigenous knowledge about insect consumption is being lost because recent generations have adopted western methods and paid less attention to traditional practices. We conducted 500 questionnaires in five local municipalities in Kwazulu-Natal (KZN), and 122 questionnaires in four local municipalities in Vhembe district in Limpopo, South Africa, to document indigenous knowledge about edible insects’ consumption, collection, and preparation methods used in Limpopo and KZN. Eight insect species belonging to five insect orders were used as food in Limpopo and KZN, with mopane worms (94%) and termites (70%) being the most preferred species by respondents in Limpopo and KZN, respectively. Ninety-five percent of the respondents occasionally consumed insects in Limpopo, while only 28% did so in KZN. Nutritional benefits and tradition were the main reasons for consuming insects. Edible insects are a nutritious diet and play an important role in people’s livelihoods in rural areas. However, there was a notable decline in entomophagy, particularly in KZN. The decline may be related to occidental acculturation, discomfort associated with eating insects, and declining insect availability. To promote entomophagy, the authorities should encourage people to include edible insects in their diets because of their nutritional value. In addition, edible insect flour should be incorporated in food products such as biscuits, bread, energy bars, cereal, and cookies to promote acceptability.
Intelligence and Creativity: Mapping Constructs on the Space-Time Continuum
Authors: Corazza Giovanni Emanuele , Lubart Todd
Published: December 2020

This theoretical article proposes a unified framework of analysis for the constructs of intelligence and creativity. General definitions for intelligence and creativity are provided, allowing fair comparisons between the two context-embedded constructs. A novel taxonomy is introduced to classify the contexts in which intelligent and/or creative behavior can be embedded, in terms of the tightness vs. looseness of the relevant conceptual space S and available time T. These two dimensions are used to form what is identified as the space-time continuum, containing four quadrants: tight space and tight time, loose space and tight time, tight space and loose time, loose space and loose time. The intelligence and creativity constructs can be mapped onto the four quadrants and found to overlap more or less, depending on the context characteristics. Measurement methodologies adapted to the four different quadrants are discussed. The article concludes with a discussion about future research directions based on the proposed theoretical framework, in terms of theories and hypotheses on intelligence and creativity, of eminent personalities and personality traits, as well as its consequences for developmental, educational, and professional environments.
Large-Scale Laboratory Experiments on Mussel Dropper Lines in Ocean Surface Waves
Authors: Gieschen Rebekka , Schwartpaul Christian , Landmann Jannis , Fröhling Lukas , Hildebrandt Arndt , Goseberg Nils
Published: December 2020

The rapid growth of marine aquaculture around the world accentuates issues of sustainability and environmental impacts of large-scale farming systems. One potential mitigation strategy is to relocate to more energetic offshore locations. However, research regarding the forces which waves and currents impose on aquaculture structures in such conditions is still scarce. The present study aimed at extending the knowledge related to live blue mussels (Mytilus edulis), cultivated on dropper lines, by unique, large-scale laboratory experiments in the Large Wave Flume of the Coastal Research Center in Hannover, Germany. Nine-months-old live dropper lines and a surrogate of 2.0 m length each are exposed to regular waves with wave heights between 0.2 and 1.0 m and periods between 1.5 and 8.0 s. Force time histories are recorded to investigate the inertia and drag characteristics of live mussel and surrogate dropper lines. The surrogate dropper line was developed from 3D scans of blue mussel dropper lines, using the surface descriptor Abbott–Firestone Curve as quality parameter. Pull-off tests of individual mussels are conducted that reveal maximum attachment strength ranges of 0.48 to 10.55 N for mussels that had medium 3.04 cm length, 1.60 cm height and 1.25 cm width. Mean drag coefficients of CD = 3.9 were found for live blue mussel lines and CD = 3.4 for the surrogate model, for conditions of Keulegan–Carpenter number (KC) 10 to 380, using regular wave tests.
Drug Resistance-Associated Mutations in ERG11 of Multidrug-Resistant Candida auris in a Tertiary Care Hospital of Eastern Saudi Arabia
Authors: AlJindan Reem , AlEraky Doaa M. , Mahmoud Nehal , Abdalhamid Baha , Almustafa Mashael , AbdulAzeez Sayed , Borgio J. Francis
Published: December 2020

Candida auris is an emerging multi-drug resistant pathogen with high mortality rate; nosocomial infections have been reported worldwide, causing a major challenge for clinicians and microbiological laboratories. The study aims to describe new cases of C. auris and detect drug resistance-associated mutations of C. auris by the sequencing of ERG11 and FKS1 genes. A total of six specimens were collected from blood, urine, ear swab, and groin screening samples. Isolates were incubated for 48 h on Sabouraud Dextrose agar (SDA) at 42 °C, then confirmed by MALDI-TOF MS. Furthermore, antifungal susceptibility testing was performed using the Vitek 2 system to detect Minimum Inhibitory Concentrations (MICs) of six antifungals. Sequences of 18S rRNA gene and ITS regions from isolates and phylogenetic analysis were performed. Gene sequencing was analysed to detect drug resistance-associated mutations by FKS1 and ERG11 genes sequencing. All C. auris isolates were confirmed by MALDI-TOF MS, and evolutionary analyses using sequences of 18S rRNA gene and ITS region. Antifungal susceptibility testing showed that all isolates were resistant to fluconazole. Sequencing of ERG11 and FKS1 genes from the isolates revealed the presence of two (F132Y and K143R) drug resistance-associated mutations in ERG11, however, FKS1 gene was devoid of mutations. The study sheds light on a public health threat of an emerging pathogen, and the hospital implemented strict contact screening and infection control precautions to prevent C. auris infection. Finally, there is a critical need to monitor the antifungal resistance in different geographical areas and implementation of efficient guidelines for treatment.
Aspergillus fumigatus and Its Allergenic Ribotoxin Asp f I: Old Enemies but New Opportunities for Urine-Based Detection of Invasive Pulmonary Aspergillosis Using Lateral-Flow Technology
Authors: Davies Genna , Singh Oski , Prattes Juergen , Hoenigl Martin , Sheppard Paul W. , Thornton Christopher R.
Published: December 2020

Invasive pulmonary aspergillosis (IPA) caused by Aspergillus fumigatus is a life-threatening lung disease of immunocompromised patients. Diagnosis currently relies on non-specific chest CT, culture of the fungus from invasive lung biopsy, and detection of the cell wall carbohydrate galactomannan (GM) in serum or in BAL fluids recovered during invasive bronchoscopy. Urine provides an ideal bodily fluid for the non-invasive detection of pathogen biomarkers, with current urine-based immunodiagnostics for IPA focused on GM. Surrogate protein biomarkers might serve to improve disease detection. Here, we report the development of a monoclonal antibody (mAb), PD7, which is specific to A. fumigatus and related species in the section Fumigati, and which binds to its 18 kDa ribotoxin Asp f I. Using PD7, we show that the protein is secreted during hyphal development, and so represents an ideal candidate for detecting invasive growth. We have developed a lateral-flow device (Afu-LFD®) incorporating the mAb which has a limit of detection of ~15 ng Asp f I/mL urine. Preliminary evidence of the test’s diagnostic potential is demonstrated with urine from a patient with acute lymphoid leukaemia with probable IPA. The Afu-LFD® therefore provides a potential novel opportunity for non-invasive urine-based detection of IPA caused by A. fumigatus.
An Optimized Ustilago maydis for Itaconic Acid Production at Maximal Theoretical Yield
Authors: Becker Johanna , Hosseinpour Tehrani Hamed , Ernst Philipp , Blank Lars Mathias , Wierckx Nick
Published: December 2020

Ustilago maydis, a member of the Ustilaginaceae family, is a promising host for the production of several metabolites including itaconic acid. This dicarboxylate has great potential as a bio-based building block in the polymer industry, and is of special interest for pharmaceutical applications. Several itaconate overproducing Ustilago strains have been generated by metabolic and morphology engineering. This yielded stabilized unicellular morphology through fuz7 deletion, reduction of by-product formation through deletion of genes responsible for itaconate oxidation and (glyco)lipid production, and the overexpression of the regulator of the itaconate cluster ria1 and the mitochondrial tricarboxylate transporter encoded by mttA from Aspergillusterreus. In this study, itaconate production was further optimized by consolidating these different optimizations into one strain. The combined modifications resulted in itaconic acid production at theoretical maximal yield, which was achieved under biotechnologically relevant fed-batch fermentations with continuous feed.
Auditory Processing of Gender Agreement across Relative Clauses by Spanish Heritage Speakers
Authors: Vergara Daniel , Socarrás Gilda
Published: December 2020

Processing research on Spanish gender agreement has focused on L2 learners’ and—to a lesser extent—heritage speakers’ sensitivity to gender agreement violations. This research has been mostly carried out in the written modality, which places heritage speakers at a disadvantage as they are more frequently exposed to Spanish auditorily. This study contributes to the understanding of the differences between heritage and L2 grammars by examining the processing of gender agreement in the auditory modality and its impact on comprehension. Twenty Spanish heritage speakers and 20 intermediate L2 learners listened to stimuli containing two nouns with gender mismatches in the main clause, and an adjective in the relative clause that only agreed in gender with one of the nouns. We measured noun-adjective agreement accuracy through participants’ responses to an auditory task. Our results show that heritage speakers are more accurate than L2 learners in the auditory processing of gender agreement information for comprehension. Additionally, heritage speakers’ accuracy is modulated by their Spanish language proficiency and age of onset. Participants also exhibit higher accuracies in cases in which the adjective agrees with the first noun. We argue that this is an ambiguity resolution strategy influenced by the experimental task.
Food Logistics 4.0: Opportunities and Challenges
Authors: Jagtap Sandeep , Bader Farah , Garcia-Garcia Guillermo , Trollman Hana , Fadiji Tobi , Salonitis Konstantinos
Published: December 2020

Food Logistics 4.0 is a term derived from Industry 4.0 focusing on all the aspects of food logistics management based on cyber-physical systems. It states that real-time information and the interconnectivity of things, supplemented with novel technologies will revolutionise and improve the way food logistics is carried out. It has tremendous potential in terms of bringing transparency, swift delivery of food at reduced cost, flexibility, and capability to deliver the right quality product at the right place and at the right time. This paper discusses the vital technologies within Food Logistics 4.0 and the opportunities and challenges in this regard. It focuses primarily on food logistics, including resource planning, warehouse management, transportation management, predictive maintenance, and data security. Internet of Things, Blockchain, Robotics and Automation and artificial intelligence are some of the technologies discussed.
Self-Supported Reduced Graphene Oxide Membrane and Its Cu2+ Adsorption Capability
Authors: Yu Yangjinghua , Wang Zhong , Sun Runjun , Chen Zhihua , Liu Meicheng , Zhou Xiang , Yao Mu , Wang Guohe
Published: December 2020

Graphene stratiform membrane materials have been recently applied to heavy metal removal in aqueous systems via adsorption due to their high mechanical strength, chemical stability, and other properties. We applied reduced graphene oxide (rGO) alone as an adsorbent to remove heavy metal ions from wastewater. Self-supported rGO membrane was prepared using a green reduction method with sodium hydrosulfite. We used the Raman spectra to observe the structure of the rGO membrane. The morphology of the self-supported membrane was measured by a scanning electron microscope. The Cu2+ adsorption performance was measured in terms of pH, reaction time, metal ion concentration, and temperature. The maximum Cu2+ adsorption capacity of the rGO membrane was found to be 149.25 mg/g. The adsorption process followed a pseudo-second-order kinetic model, and adsorption isotherms were simulated by the Freundlich model.
Effects of Elevated Temperatures on the Properties of Cement Mortars with the Iron Oxides Concentrate
Authors: Borucka-Lipska Jolanta , Brzozowski Piotr , Błyszko Jarosław , Bednarek Roman , Horszczaruk Elżbieta
Published: December 2020

Using the waste materials in the production of the building materials limits the storage of the wastes, burdensome for the environment and landscape, and makes possible to manufacture the materials and products with the use of the less volume of the raw materials. Cement concretes and mortars as the basic building materials offer the broad prospects of utilization of the recyclable or waste materials. The wastes from the iron ore processing are the solid wastes resulting from the process of enrichment of the ore concentrate. The paper presents the results of testing three mortars, in which a part of fine aggregate was replaced with the iron oxide concentrate (IOC) resulting from such a process. IOC has been used as a substitute of 10%, 20% and 30% (by mass) of the fine aggregate. The effect of the concentrate on the mechanical performance of the mortars at the high temperature (up to 600 °C) was also investigated. The IOC is a neutral material, not affecting chemically the process of cement hydration. The addition of IOC slightly improves the strength of the cement mortars (by 5% to 10%). In the case of the larger amount (20–30%) of the addition, the use of superplasticizer is necessary. The IOC significantly improves the high temperature resistance of the cement mortars (300 °C). The cement mortars containing 30% of the IOC addition keep 80% of the initial flexural and compressive strength when exposed to the temperature 450 °C.
Additive Manufacturing of β-Tricalcium Phosphate Components via Fused Deposition of Ceramics (FDC)
Authors: Esslinger Steffen , Grebhardt Axel , Jaeger Jonas , Kern Frank , Killinger Andreas , Bonten Christian , Gadow Rainer
Published: December 2020

Bone defects introduced by accidents or diseases are very painful for the patient and their treatment leads to high expenses for the healthcare systems. When a bone defect reaches a critical size, the body is not able to restore this defect by itself. In this case a bone graft is required, either an autologous one taken from the patient or an artificial one made of a bioceramic material such as calcium phosphate. In this study β-tricalcium phosphate (β-TCP) was dispersed in a polymer matrix containing poly(lactic acid) (PLA) and poly(ethylene glycole) (PEG). These compounds were extruded to filaments, which were used for 3D printing of cylindrical scaffolds via Fused Deposition of Ceramics (FDC) technique. After shaping, the printed parts were debindered and sintered. The components combined macro- and micropores with a pore size of 1 mm and 0.01 mm, respectively, which are considered beneficial for bone healing. The compressive strength of sintered cylindrical scaffolds exceeded 72 MPa at an open porosity of 35%. The FDC approach seems promising for manufacturing patient specific bioceramic bone grafts.
A Novel Camera-Based Measurement System for Roughness Determination of Concrete Surfaces
Authors: Özcan Barış , Schwermann Raimund , Blankenbach Jörg
Published: December 2020

Determining the roughness of technical surfaces is an important task in many engineering disciplines. In civil engineering, for instance, the repair and reinforcement of building component parts (such as concrete structures) requires a certain surface roughness in order to ensure the bond between a coating material and base concrete. The sand patch method is so far the state-of-the-art for the roughness measurement of concrete structures. Although the method is easy to perform, it suffers from considerable drawbacks. Consequently, more sophisticated measurement systems are required. In a research project, we developed a novel camera-based alternative, which comes with several advantages. The measurement system consists of a mechanical cross slide that guides an industrial camera over a surface to be measured. Images taken by the camera are used for 3D reconstruction. Finally, the reconstructed point clouds are used to estimate roughness. In this article, we present our measurement system (including the hardware and the self-developed software for 3D reconstruction). We further provide experiments to camera calibration and evaluation of our system on concrete specimens. The resulting roughness estimates for the concrete specimens show a strong linear correlation to reference values obtained by the sand patch method.
Artificial Neural Network Algorithms for 3D Printing
Authors: Mahmood Muhammad Arif , Visan Anita Ioana , Ristoscu Carmen , Mihailescu Ion N.
Published: December 2020

Additive manufacturing with an emphasis on 3D printing has recently become popular due to its exceptional advantages over conventional manufacturing processes. However, 3D printing process parameters are challenging to optimize, as they influence the properties and usage time of printed parts. Therefore, it is a complex task to develop a correlation between process parameters and printed parts’ properties via traditional optimization methods. A machine-learning technique was recently validated to carry out intricate pattern identification and develop a deterministic relationship, eliminating the need to develop and solve physical models. In machine learning, artificial neural network (ANN) is the most widely utilized model, owing to its capability to solve large datasets and strong computational supremacy. This study compiles the advancement of ANN in several aspects of 3D printing. Challenges while applying ANN in 3D printing and their potential solutions are indicated. Finally, upcoming trends for the application of ANN in 3D printing are projected.
Comparison of Three Manufacturing Techniques for Sustainable Porous Clay Ceramics
Authors: Andreola Fernanda , Lancellotti Isabella , Sergi Rachele , Cannillo Valeria , Barbieri Luisa
Published: December 2020

This study proposes different manufacturing techniques (manual pelletization, powder pressing, and “shell scaffold”) to obtain lightweight clay ceramics containing recovery raw materials. The sintering in an electrical furnace (1000 °C, 1 h processing time) was conducted by traditional firing from room temperature, for pressed and shell-scaffold samples, while the flash heating (i.e., samples directly put at 1000 °C) was used only for the pellets. The porous materials (porosity 40–80%), functionalized with nutrients (K and P) in amounts to confer the fertilizer capability, gave suitable results in terms of pH (6.7–8.15) and electrical conductivity (0.29–1.33 mS/cm). Thus, such materials can be considered as feasible lightweight clay ceramics, with a positive effect on the soil. These findings permit us to hypothesize a potential use in green roofs or in agronomic applications.
A Semi-Analytical Model for the Heat Generation during Hybrid Metal Extrusion and Bonding (HYB)
Authors: Leoni Francesco , Grong Øystein , Ferro Paolo , Berto Filippo
Published: December 2020

Hybrid Metal Extrusion and Bonding (HYB) is a novel solid-state welding method for metals and alloys that utilises continuous extrusion as a technique to enable aluminium filler metal additions. In the present study, a new semi-analytical model for the heat generation during aluminium butt welding is presented. As a starting point, the classical Rosenthal thin plate solution for the pseudo-steady-state temperature distribution around a fully penetrating line source is invoked. Then, the associated heat generation is calculated by considering the individual contributions from the tip of the rotating pin, the pin shoulder, and the filler metal additions on the net power input. In a calibrated form, the model yields thermal efficiency factors that are in close agreement with those obtained from more sophisticated finite element analyses but with considerably less computational effort.
Planar Graphs with the Distance of 6--Cycles at Least 2 from Each Other Are DP-3-Colorable
Authors: Zhao Yueying , Miao Lianying
Published: December 2020

DP-coloring as a generalization of list coloring was introduced by Dvořák and Postle recently. In this paper, we prove that every planar graph in which the distance between 6−-cycles is at least 2 is DP-3-colorable, which extends the result of Yin and Yu [Discret. Math. 2019, 342, 2333–2341].
Wiener Complexity versus the Eccentric Complexity
Authors: Knor Martin , Škrekovski Riste
Published: December 2020

Let wG(u) be the sum of distances from u to all the other vertices of G. The Wiener complexity, CW(G), is the number of different values of wG(u) in G, and the eccentric complexity, Cec(G), is the number of different eccentricities in G. In this paper, we prove that for every integer c there are infinitely many graphs G such that CW(G)−Cec(G)=c. Moreover, we prove this statement using graphs with the smallest possible cyclomatic number. That is, if c≥0 we prove this statement using trees, and if c<0 we prove it using unicyclic graphs. Further, we prove that Cec(G)≤2CW(G)−1 if G is a unicyclic graph. In our proofs we use that the function wG(u) is convex on paths consisting of bridges. This property also promptly implies the already known bound for trees Cec(G)≤CW(G). Finally, we answer in positive an open question by finding infinitely many graphs G with diameter 3 such that Cec(G)<CW(G).
Application of Multi-Objective Evolutionary Algorithms for Planning Healthy and Balanced School Lunches
Authors: Ramos-Pérez Juan-Manuel , Miranda Gara , Segredo Eduardo , León Coromoto , Rodríguez-León Casiano
Published: December 2020

A multi-objective formulation of the Menu Planning Problem, which is termed the Multi-objective Menu Planning Problem, is presented herein. Menu planning is of great interest in the health field due to the importance of proper nutrition in today’s society, and particularly, in school canteens. In addition to considering the cost of the meal plan as the classic objective to be minimized, we also introduce a second objective aimed at minimizing the degree of repetition of courses and food groups that a particular meal plan consists of. The motivation behind this particular multi-objective formulation is to offer a meal plan that is not only affordable but also varied and balanced from a nutritional standpoint. The plan is designed for a given number of days and ensures that the specific nutritional requirements of school-age children are satisfied. The main goal of the current work is to demonstrate the multi-objective nature of the said formulation, through a comprehensive experimental assessment carried out over a set of multi-objective evolutionary algorithms applied to different instances. At the same time, we are also interested in validating the multi-objective formulation by performing quantitative and qualitative analyses of the solutions attained when solving it. Computational results show the multi-objective nature of the said formulation, as well as that it allows suitable meal plans to be obtained.
Marine-Derived Secondary Metabolites as Promising Epigenetic Bio-Compounds for Anticancer Therapy
Authors: Conte Mariarosaria , Fontana Elisabetta , Nebbioso Angela , Altucci Lucia
Published: December 2020

Sessile organisms such as seaweeds, corals, and sponges continuously adapt to both abiotic and biotic components of the ecosystem. This extremely complex and dynamic process often results in different forms of competition to ensure the maintenance of an ecological niche suitable for survival. A high percentage of marine species have evolved to synthesize biologically active molecules, termed secondary metabolites, as a defense mechanism against the external environment. These natural products and their derivatives may play modulatory roles in the epigenome and in disease-associated epigenetic machinery. Epigenetic modifications also represent a form of adaptation to the environment and confer a competitive advantage to marine species by mediating the production of complex chemical molecules with potential clinical implications. Bioactive compounds are able to interfere with epigenetic targets by regulating key transcriptional factors involved in the hallmarks of cancer through orchestrated molecular mechanisms, which also establish signaling interactions of the tumor microenvironment crucial to cancer phenotypes. In this review, we discuss the current understanding of secondary metabolites derived from marine organisms and their synthetic derivatives as epigenetic modulators, highlighting advantages and limitations, as well as potential strategies to improve cancer treatment.
Sodium-Glucose Cotransporter-2 Inhibitors for Treatment of Nonalcoholic Fatty Liver Disease: A Meta-Analysis of Randomized Controlled Trials
Authors: Mantovani Alessandro , Petracca Graziana , Csermely Alessandro , Beatrice Giorgia , Targher Giovanni
Published: December 2020

Recent randomized controlled trials (RCTs) tested the efficacy of sodium-glucose cotransporter-2 (SGLT-2) inhibitors to specifically treat nonalcoholic fatty liver disease (NAFLD). We systematically searched three electronic databases (up to 31 October 2020) for identifying placebo-controlled or head-to-head RCTs that used SGLT-2 inhibitors for treatment of NAFLD. No published RCTs with paired liver biopsy data were available for the meta-analysis. Primary outcome measures were changes in serum liver enzyme levels and liver fat content on imaging techniques. Overall, we included a total of twelve RCTs testing the efficacy of dapagliflozin (n = six RCTs), empagliflozin (n = three RCTs), ipragliflozin (n = two RCTs) or canagliflozin (n = one RCT) to specifically treat NAFLD for a median period of 24 weeks with aggregate data on 850 middle-aged overweight or obese individuals with NAFLD (90% with type 2 diabetes). Compared to placebo/reference therapy, treatment with SGLT-2 inhibitors significantly decreased serum alanine aminotransferase (weighted mean differences (WMD): −10.0 IU/L, 95%CI −12.2 to −7.79 IU/L; I2 = 10.5%) and gamma-glutamyltransferase levels (WMD: −14.49 IU/L, 95%CI −19.35 to −9.63 IU/L, I2 = 38.7%), as well as the absolute percentage of liver fat content on magnetic resonance-based techniques (WMD: −2.05%, 95%CI −2.61 to −1.48%; I2 = 0%). In conclusion, SGLT-2 inhibitors seem to be a promising treatment option for NAFLD.
An Ascophyllum nodosum-Derived Biostimulant Protects Model and Crop Plants from Oxidative Stress
Authors: Staykov Nikola S. , Angelov Mihail , Petrov Veselin , Minkov Pavel , Kanojia Aakansha , Guinan Kieran J. , Alseekh Saleh , Fernie Alisdair R. , Sujeeth Neerakkal , Gechev Tsanko S.
Published: December 2020

Abiotic stresses, which at the molecular level leads to oxidative damage, are major determinants of crop yield loss worldwide. Therefore, considerable efforts are directed towards developing strategies for their limitation and mitigation. Here the superoxide-inducing agent paraquat (PQ) was used to generate oxidative stress in the model species Arabidopsis thaliana and the crops tomato and pepper. Pre-treatment with the biostimulant SuperFifty (SF) effectively and universally suppressed PQ-induced leaf lesions, H2O2 build up, cell destruction and photosynthesis inhibition. To further investigate the stress responses and SF-induced protection at the molecular level, we investigated the metabolites by GC-MS metabolomics. PQ induced specific metabolic changes such as accumulation of free amino acids (AA) and stress metabolites. These changes were fully prevented by the SF pre-treatment. Moreover, the metabolic changes of the specific groups were tightly correlating with their phenotypic characteristics. Overall, this study presents physiological and metabolomics data which shows that SF protects against oxidative stress in all three plant species.
Technological Challenges in the Development of Optogenetic Closed-Loop Therapy Approaches in Epilepsy and Related Network Disorders of the Brain
Authors: Vandekerckhove Bram , Missinne Jeroen , Vonck Kristl , Bauwens Pieter , Verplancke Rik , Boon Paul , Raedt Robrecht , Vanfleteren Jan
Published: December 2020

Epilepsy is a chronic, neurological disorder affecting millions of people every year. The current available pharmacological and surgical treatments are lacking in overall efficacy and cause side-effects like cognitive impairment, depression, tremor, abnormal liver and kidney function. In recent years, the application of optogenetic implants have shown promise to target aberrant neuronal circuits in epilepsy with the advantage of both high spatial and temporal resolution and high cell-specificity, a feature that could tackle both the efficacy and side-effect problems in epilepsy treatment. Optrodes consist of electrodes to record local field potentials and an optical component to modulate neurons via activation of opsin expressed by these neurons. The goal of optogenetics in epilepsy is to interrupt seizure activity in its earliest state, providing a so-called closed-loop therapeutic intervention. The chronic implantation in vivo poses specific demands for the engineering of therapeutic optrodes. Enzymatic degradation and glial encapsulation of implants may compromise long-term recording and sufficient illumination of the opsin-expressing neural tissue. Engineering efforts for optimal optrode design have to be directed towards limitation of the foreign body reaction by reducing the implant’s elastic modulus and overall size, while still providing stable long-term recording and large-area illumination, and guaranteeing successful intracerebral implantation. This paper presents an overview of the challenges and recent advances in the field of electrode design, neural-tissue illumination, and neural-probe implantation, with the goal of identifying a suitable candidate to be incorporated in a therapeutic approach for long-term treatment of epilepsy patients.
Built-In Self-Test (BIST) Methods for MEMS: A Review
Authors: Hantos Gergely , Flynn David , Desmulliez Marc P. Y.
Published: December 2020

A novel taxonomy of built-in self-test (BIST) methods is presented for the testing of micro-electro-mechanical systems (MEMS). With MEMS testing representing 50% of the total costs of the end product, BIST solutions that are cost-effective, non-intrusive and able to operate non-intrusively during system operation are being actively sought after. After an extensive review of the various testing methods, a classification table is provided that benchmarks such methods according to four performance metrics: ease of implementation, usefulness, test duration and power consumption. The performance table provides also the domain of application of the method that includes field test, power-on test or assembly phase test. Although BIST methods are application dependent, the use of the inherent multi-modal sensing capability of most sensors offers interesting prospects for effective BIST, as well as built-in self-repair (BISR).
Analysis of Arbuscular Mycorrhizal Fungal Inoculant Benchmarks
Authors: Basiru Sulaimon , Mwanza Hopkins Pachalo , Hijri Mohamed
Published: December 2020

Growing evidence showed that efficient acquisition and use of nutrients by crops is controlled by root-associated microbiomes. Efficient management of this system is essential to improving crop yield, while reducing the environmental footprint of crop production. Both endophytic and rhizospheric microorganisms can directly promote crop growth, increasing crop yield per unit of soil nutrients. A variety of plant symbionts, most notably the arbuscular mycorrhizal fungi (AMF), nitrogen-fixing bacteria, and phosphate-potassium-solubilizing microorganisms entered the era of large-scale applications in agriculture, horticulture, and forestry. The purpose of this study is to compile data to give a complete and comprehensive assessment and an update of mycorrhizal-based inoculant uses in agriculture in the past, present, and future. Based on available data, 68 mycorrhizal products from 28 manufacturers across Europe, America, and Asia were examined on varying properties such as physical forms, arbuscular mycorrhizal fungal composition, number of active ingredients, claims of purpose served, mode of application, and recommendation. Results show that 90% of the products studied are in solid formula—powder (65%) and granular (25%), while only 10% occur in liquid formula. We found that 100% of the products are based on the Glomeraceae of which three species dominate among all the products in the order of Rhizophagus irregularis (39%), Funneliformis mosseae (21%), Claroideoglomus etunicatum (16%). Rhizophagus clarus is the least common among all the benchmark products. One third of the products is single species AMF and only 19% include other beneficial microbes. Of the sampled products, 44% contain AMF only while the rest are combined with varying active ingredients. Most of the products (84%) claimed to provide plant nutrient benefits. Soil application dominates agricultural practices of the products and represents 47%. A substantial amount of the inoculants were applied in cereal production. Recommended application doses varied extensively per plant, seed and hectare. AMF inoculant seed coating accounted for 26% of the products’ application and has great potential for increased inoculation efficiency over large-scale production due to minimum inoculum use. More applied research should also be conducted on the possible combination of AMF with other beneficial microbes.
Advanced Geomechanical Model to Predict the Impact of CO2-Induced Microstructural Alterations on the Cohesive-Frictional Behavior of Mt. Simon Sandstone
Authors: Akono Ange-Therese , Werth Charles , Shi Zhuofan , Jessen Kristian , Tsotsis Theodore
Published: December 2020

We investigated the influence of CO2-induced geochemical reactions on the cohesive-frictional properties of host rock within the context of CO2 storage in a saline aquifer and focused on the Mt. Simon sandstone. The research objective was to model geo-mechanical changes due to host rock exposure to CO2-saturated brine while accounting for heterogeneity, double-scale porosity, and granular structure. We formulated a three-level multi-scale model for host rocks. We conducted scanning electron microscopy analyses to probe the microstructure and grid nanoindentation to measure the mechanical response. We derived new nonlinear strength upscaling solutions to correlate the effective strength characteristics and the macroscopic yield surface to the micro-structure at the nano-, micro-, and meso-scales. Specifically, our theoretical model links CO2-induced microstructural alterations to a reduction in the size of the yield surface, and a drop in the value of the friction coefficient. In turn, regarding the Illinois Basin Decatur Project, the CO2-induced drop in friction coefficient is linked to an increase in the risk of fault slip and a higher probability of induced microseismicity during and after the end of CO2 underground injection operations. The theoretical model presented is essential for the geo-mechanical modeling of CO2 underground injection operations at multiple length-scales.
Effects of the Japanese 2016 Kumamoto Earthquake on Nitrate Content in Groundwater Supply
Authors: Nakagawa Kei , Shimada Jun , Yu Zhi-Qiang , Ide Kiyoshi , Berndtsson Ronny
Published: December 2020

The 2016 Kumamoto earthquake had a significant impact on groundwater levels and quality. In some areas, the groundwater level increased significantly due to the release of groundwater from upstream mountainous regions. Conversely, the groundwater level in other areas greatly decreased due to the creation of new fracture networks by the earthquake. There were also significant changes in certain groundwater quality variables. In this study, we used clustering based SOM (self-organizing maps) analysis to improve the understanding of earthquake effects on groundwater quality. We were especially interested in effects on groundwater used for drinking purposes and in nitrate concentration. For this purpose, we studied groundwater nitrate (NO3− + NO2−–N) concentrations for the period 2012–2017. Nitrate concentration changes were classified into seven typical SOM clusters. The clusters were distributed in three representative geographical regions: a high concentration region (>4 mg/L), a low concentration region (<1.6 mg/L) with minimal anthropogenic loading area, and an intermediate concentration region (2–4 mg/L). Depending on these regions, the nitrate concentration changes just before and after the earthquake had both increasing and decreasing trends between 2015–2017. This points to complex physiographical relationships for release of stored upstream groundwater, promotion of infiltration of shallow soil water/groundwater, and nitrate concentration as affected by earthquakes. We present an analysis of these complex relationships and a discussion of causes of nitrate concentration changes due to earthquakes.
New Geochemical and Mineralogical Data on Rocks and Ores of the NE Flank of the Oktyabr’skoe Deposit (Norilsk Area) and a View on Their Origin
Authors: Krivolutskaya Nadezhda , Bychkova Yana , Gongalsky Bronislav , Kubrakova Irina , Tyutyunnik Oksana , Dekunova Elena , Taskaev Vladimir
Published: December 2020

The Oktyabr’skoe deposit in the Norilsk ore district is the largest platinum-copper-nickel deposit in the world. It contains a huge main orebody (2.4 km3) of massive sulfide ores and some smaller sulfide bodies. Almost all publications on this deposit are devoted to the main orebody. However, to solve the problems of the deposit genesis, it is necessary to take into account the geological structure of the entire area and the composition of all orebodies. For the first time we present data on the inner structure, geochemical and mineralogical characteristics of the intrusive body, and related the disseminated and massive sulfide ores (orebody number C-5) in the northeastern flank of the deposit. The intrusion studied in the core of the borehole RG-2 consists of several horizons including the following rock varieties (from bottom to top): olivine gabbro-dolerites, taxitic gabbro-dolerites, picritic gabbro-dolerites, troctolites, olivine-free gabbro-dolerites, ferrogabbro, and leucogabbro. The intrusion shows a strong differentiated inner structure where high-Mg rocks (up to 25 wt.% MgO troctolites and picritic gabbro-dolerites) in the bottom are associated with low-Mg rocks (6–7 wt.%, gabbro-dolerites, leucogabbro, ferrogabbro) without intermediate differentiated members (8–12 wt.% MgO olivine gabbro-dolerites). Rocks are characterized by low TiO2 content (≤1 wt.%). Taxitic gabbro-dolerites, picritic gabbro-dolerites, and troctolites contain disseminated sulfide chalcopyrite-pyrrhotite mineralization (32 m thick). Cu and Ni concentrations reach up 0.74 and 0.77 wt.%, respectively. Massive ores (27 m) occur in the bottom part of the intrusion. The ores consist of pentlandite, chalcopyrite and pyrrhotite, the latter mineral dominates. Their chemical composition is stable: Cu/Ni ~1, Pd/Pt varies from 5 to 6. The C-5 orebody is similar to the C-3 orebody in terms of mineral and chemical compositions, and differ from the nearby the C-4 orebody which is characterized by a Cu/Ni ratio changing from 5 to 8. On the basis of geochemical and mineralogical data, it is assumed that orebodies C-3 and C-5 are associated with one intrusion, while the orebody number C-4 is related to another intrusive body. Thus, the deposit has a more complex structure and includes several more intrusions than is usually considered.
SYN-View: A Phylogeny-Based Synteny Exploration Tool for the Identification of Gene Clusters Linked to Antibiotic Resistance
Authors: Stahlecker Jason , Mingyar Erik , Ziemert Nadine , Mungan Mehmet Direnç
Published: December 2020

The development of new antibacterial drugs has become one of the most important tasks of the century in order to overcome the posing threat of drug resistance in pathogenic bacteria. Many antibiotics originate from natural products produced by various microorganisms. Over the last decades, bioinformatical approaches have facilitated the discovery and characterization of these small compounds using genome mining methodologies. A key part of this process is the identification of the most promising biosynthetic gene clusters (BGCs), which encode novel natural products. In 2017, the Antibiotic Resistant Target Seeker (ARTS) was developed in order to enable an automated target-directed genome mining approach. ARTS identifies possible resistant target genes within antibiotic gene clusters, in order to detect promising BGCs encoding antibiotics with novel modes of action. Although ARTS can predict promising targets based on multiple criteria, it provides little information about the cluster structures of possible resistant genes. Here, we present SYN-view. Based on a phylogenetic approach, SYN-view allows for easy comparison of gene clusters of interest and distinguishing genes with regular housekeeping functions from genes functioning as antibiotic resistant targets. Our aim is to implement our proposed method into the ARTS web-server, further improving the target-directed genome mining strategy of the ARTS pipeline.
Structural Diversity of Peptoids: Tube-Like Structures of Macrocycles
Authors: Herlan Claudine Nicole , Sommer Katharina , Weis Patrick , Nieger Martin , Bräse Stefan
Published: December 2020

Peptoids, or poly-N-substituted glycines, are characterised by broad structural diversity. Compared to peptides, they are less restricted in rotation and lack backbone-derived H bonding. Nevertheless, certain side chains force the peptoid backbone into distinct conformations. Designable secondary structures like helices or nanosheets arise from this knowledge. Herein, we report the copper-catalysed alkyne-azide cycloaddition (CuAAC) of macrocycles to form innovative tube-like tricyclic peptoids, giving access to host–guest chemistry or storage applications. Different linker systems make the single tubes tuneable in size and enable modifications within the gap. An azobenzene linker, which is reversibly switchable in conformation, was successfully incorporated and allowed for light-triggered changes of the entire tricyclic structure.
Chemical Composition and Antibacterial Activity of Lippia multiflora Moldenke Essential Oil from Different Regions of Angola
Authors: Samba Nsevolo , Aitfella-Lahlou Radhia , Nelo Mpazu , Silva Lucia , Coca. Rui , Rocha Pedro , López Rodilla Jesus Miguel
Published: December 2020

The purpose of the study was to determine the chemical composition and antibacterial activity of Lippia multiflora Moldenke essential oils (EOs) collected in different regions of Angola. Antibacterial activity was evaluated using the agar wells technique and vapour phase test. Analysis of the oils by GC/MS identified thirty-five components representing 67.5 to 100% of the total oils. Monoterpene hydrocarbons were the most prevalent compounds, followed by oxygenated monoterpenes. The content of the compounds varied according to the samples. The main components were Limonene, Piperitenone, Neral, Citral, Elemol, p-cymene, Transtagetone, and Artemisia ketone. Only one of the eleven samples contained Verbenone as the majority compound. In the vapour phase test, a single oil was the most effective against all the pathogens studied. The principal component analysis (PCA) and hierarchical cluster analysis (HCA) of components of the selected EOs and inhibition zone diameter values of agar wells technique allowed us to identify a variability between the plants from the two provinces, but also intraspecific variability between sub-groups within a population. Each group of essential oils constituted a chemotype responsible for their bacterial inhibition capacity. The results presented here suggest that Angolan Lippia multiflora Moldenke has antibacterial properties and could be a potential source of antimicrobial agents for the pharmaceutical and food industry.