bluuebunny/crossref_metadata_2025 huggingface dataset:
Recent Developments in Understanding Biochar’s Physical–Chemistry
Authors: Conte Pellegrino , Bertani Roberta , Sgarbossa Paolo , Bambina Paola , Schmidt Hans-Peter , Raga Roberto , Lo Papa Giuseppe , Chillura Martino Delia Francesca , Lo Meo Paolo
Published: March 2021

Biochar is a porous material obtained by biomass thermal degradation in oxygen-starved conditions. It is nowadays applied in many fields. For instance, it is used to synthesize new materials for environmental remediation, catalysis, animal feeding, adsorbent for smells, etc. In the last decades, biochar has been applied also to soils due to its beneficial effects on soil structure, pH, soil organic carbon content, and stability, and, therefore, soil fertility. In addition, this carbonaceous material shows high chemical stability. Once applied to soil it maintains its nature for centuries. Consequently, it can be considered a sink to store atmospheric carbon dioxide in soils, thereby mitigating the effects of global climatic changes. The literature contains plenty of papers dealing with biochar’s environmental effects. However, a discrepancy exists between studies dealing with biochar applications and those dealing with the physical-chemistry behind biochar behavior. On the one hand, the impression is that most of the papers where biochar is tested in soils are based on trial-and-error procedures. Sometimes these give positive results, sometimes not. Consequently, it appears that the scientific world is divided into two factions: either supporters or detractors. On the other hand, studies dealing with biochar’s physical-chemistry do not appear helpful in settling the factions’ problem. This review paper aims at collecting all the information on physical-chemistry of biochar and to use it to explain biochar’s role in different fields of application.
Roles of Nitrocompounds in Inhibition of Foodborne Bacteria, Parasites, and Methane Production in Economic Animals
Authors: Teng Po-Yun , Kim Woo Kyun
Published: March 2021

Nitrocompounds are derivatives of hydrocarbons, alcohols, fatty acids, and esters, consisting one or more nitro functional groups. Either natural sources of nitrocompounds or synthetic chemicals have been applied in animal diets to investigate their effects on economic animals, since conjugates of 3-nitropropanol and 3-nitropropionic acid were isolated from Astragalus oblongifolius. In this review, emphasis will be placed on nitrocompounds’ antimicrobial activity, toxicity, metabolisms and mechanisms of actions. Nitrocompounds can be metabolized by ruminal microbials, such as Denitrobacterium detoxificans, or alcohol dehydrogenase in the liver. Moreover, it has been found that nitrocompounds are capable of inhibiting pathogens, parasites, methane and ammonia production; however, overdose of nitrocompounds could cause methemoglobinemia or interfere with energy production in mitochondria by inhibiting succinate dehydrogenase.
Influence of Different Light Spectrums on Behaviour and Welfare in Laying Hens
Authors: Wichman Anette , De Groot Rosan , Håstad Olle , Wall Helena , Rubene Diana
Published: March 2021

Artificial commercial lighting used in animal production facilities can have negative influences on visual abilities, behaviour and welfare of domestic fowl. This study examined the effects of natural-derived light spectrums on behaviour, production and welfare of laying hens reared from hatching into adulthood. Comparisons were made of frequency of a range of behaviours associated with activity, aggression and comfort in birds kept in control light (commercial standard), daylight (full spectrum, including ultraviolet (UV) wavelengths and forest light (forest understorey, including UV). In addition, bird preferences for different lights, feather damage and egg production were monitored. The results showed that the behavioural repertoire of birds changed with age, while the effects of light treatment were subtle. Some evidence was found that birds preferred either daylight or forest light to control light, suggesting that inclusion of UV contributed to the preference. Daylight and forest light were associated with more active behaviours, and daylight with better plumage and later start of lay. Thus natural-like light may have beneficial effects on domestic fowl, but the differences between broad-spectrum light sources are rather small.
Machine Learning-Based Prediction and Optimisation System for Laser Shock Peening
Authors: Mathew Jino , Kshirsagar Rohit , Zabeen Suraiya , Smyth Niall , Kanarachos Stratis , Langer Kristina , Fitzpatrick Michael E.
Published: March 2021

Laser shock peening (LSP) as a surface treatment technique can improve the fatigue life and corrosion resistance of metallic materials by introducing significant compressive residual stresses near the surface. However, LSP-induced residual stresses are known to be dependent on a multitude of factors, such as laser process variables (spot size, pulse width and energy), component geometry, material properties and the peening sequence. In this study, an intelligent system based on machine learning was developed that can predict the residual stress distribution induced by LSP. The system can also be applied to “reverse-optimise” the process parameters. The prediction system was developed using residual stress data derived from incremental hole drilling. We used artificial neural networks (ANNs) within a Bayesian framework to develop a robust prediction model validated using a comprehensive set of case studies. We also studied the relative importance of the LSP process parameters using Garson’s algorithm and parametric studies to understand the response of the residual stresses in laser peening systems as a function of different process variables. Furthermore, this study critically evaluates the developed machine learning models while demonstrating the potential benefits of implementing an intelligent system in prediction and optimisation strategies of the laser shock peening process.
Fracture Behaviour of Concrete with Reactive Magnesium Oxide as Alternative Binder
Authors: Forero J. A. , Bravo M. , Pacheco J. , de Brito J. , Evangelista L.
Published: March 2021

This research evaluates the fracture behavior of concrete with reactive magnesium oxide (MgO). Replacing cement with MgO is an attractive option for the concrete industry, mainly due to sustainability benefits and reduction of shrinkage. Four different MgO’s from Australia, Canada, and Spain were used in the concrete mixes, as a partial substitute of cement, at 5%, 10%, and 20% (by weight). The fracture toughness (KI) intensity factor and the stress–strain softening parameters of the wedge split test were evaluated after 28 days. The experimental results showed that the replacement of cement with MgO reduced the fracture energy between 13% and 53%. Moreover, the fracture energy was found to be correlated with both compressive strength and modulus of elasticity. A well-defined relationship between these properties is important for an adequate prediction of the non-linear behavior of reinforced concrete structures made with partial replacement of cement with MgO.
Peening Natural Aging of Aluminum Alloy by Ultra-High-Temperature and High-Pressure Cavitation
Authors: Yoshimura Toshihiko , Iwamoto Masayoshi , Ogi Takayuki , Kato Fumihiro , Ijiri Masataka , Kikuchi Shoichi
Published: March 2021

The peening solution treatment was performed on AC4CH aluminum alloy by ultra-high-temperature and high-pressure cavitation (UTPC) processing, and the peening natural aging was examined. Furthermore, peening artificial aging treatment by low-temperature and low-pressure cavitation (LTPC) was performed, and the time course of peening natural aging and peening artificial aging were compared and investigated. It was found that when the AC4CH alloy is processed for an appropriate time by UTPC processing, compressive residual stress is applied and natural aging occurs. In addition, the UTPC processing conditions for peening natural aging treatment with high compressive residual stress and surface hardness were clarified. After peening artificial aging by LTPC processing, the compressive residual stress decreases slightly over time, but the compression residual stress becomes constant by peening natural aging through UTPC treatment. In contrast, it was found that neither natural nor artificial peening natural aging occurs after processing for a short time.
End-to-End Deep Reinforcement Learning for Decentralized Task Allocation and Navigation for a Multi-Robot System
Authors: Elfakharany Ahmed , Ismail Zool Hilmi
Published: March 2021

In this paper, we present a novel deep reinforcement learning (DRL) based method that is used to perform multi-robot task allocation (MRTA) and navigation in an end-to-end fashion. The policy operates in a decentralized manner mapping raw sensor measurements to the robot’s steering commands without the need to construct a map of the environment. We also present a new metric called the Task Allocation Index (TAI), which measures the performance of a method that performs MRTA and navigation from end-to-end in performing MRTA. The policy was trained on a simulated gazebo environment. The centralized learning and decentralized execution paradigm was used for training the policy. The policy was evaluated quantitatively and visually. The simulation results showed the effectiveness of the proposed method deployed on multiple Turtlebot3 robots.
Evolving a Multi-Classifier System for Multi-Pitch Estimation of Piano Music and Beyond: An Application of Cartesian Genetic Programming
Authors: Miragaia Rolando , Fernández Francisco , Reis Gustavo , Inácio Tiago
Published: March 2021

This paper presents a new method with a set of desirable properties for multi-pitch estimation of piano recordings. We propose a framework based on a set of classifiers to analyze audio input and to identify piano notes present in a given audio signal. Our system’s classifiers are evolved using Cartesian genetic programming: we take advantage of Cartesian genetic programming to evolve a set of mathematical functions that act as independent classifiers for piano notes. Two significant improvements are described: the use of a harmonic mask for better fitness values and a data augmentation process for improving the training stage. The proposed approach achieves competitive results using F-measure metrics when compared to state-of-the-art algorithms. Then, we go beyond piano and show how it can be directly applied to other musical instruments, achieving even better results. Our system’s architecture is also described to show the feasibility of its parallelization and its implementation as a real-time system. Our methodology is also a white-box optimization approach that allows for clear analysis of the solutions found and for researchers to learn and test improvements based on the new findings.
The Equivalence between Successive Approximations and Matricial Load Flow Formulations
Authors: Herrera-Briñez María Camila , Montoya Oscar Danilo , Alvarado-Barrios Lazaro , Chamorro Harold R.
Published: March 2021

This paper shows the equivalence of the matricial form of the classical backward/forward load flow formulation for distribution networks with the recently developed successive approximations (SA) load flow approach. Both formulations allow solving the load flow problem in meshed and radial distribution grids even if these are operated with alternating current (AC) or direct current (DC) technologies. Both load flow methods are completely described in this research to make a fair comparison between them and demonstrate their equivalence. Numerical comparisons in the 33- and 69-bus test feeder with radial topology show that both methods have the same number of iterations to find the solution with a convergence error defined as 1×10−10.
Influence of Digester Temperature on Methane Yield of Organic Fraction of Municipal Solid Waste (OFMSW)
Authors: Sailer Gregor , Silberhorn Martin , Eichermüller Johanna , Poetsch Jens , Pelz Stefan , Oechsner Hans , Müller Joachim
Published: March 2021

This study evaluates the anaerobic digestion (AD) of the organic fraction of municipal solid waste (OFMSW) and digested sewage sludge (DSS) at lowered temperatures. AD batch tests for CH4 yield determination were carried out with DSS as inoculum between 23 and 40 °C. All results were related to organic dry matter and calculated for standard conditions (1013 hPa, 0 °C). The AD experiments at 40 °C and at 35 °C delivered specific CH4 yields of 325 ± 6 mL/g and 268 ± 27 mL/g for OFMSW alone. At lower temperatures, specific CH4 yields of 364 ± 25 mL/g (25 °C) and 172 ± 21 mL/g (23 °C) were reached. AD at 25 °C could be beneficial regarding energy input (heating costs) and energy output (CH4 yield). Plant operators could increase AD efficiencies by avoiding heating costs. The co-digestion of OFMSW together with DSS could lead to further synergies such as better exploitation of the energy potentials of DSS, but the digestate utilization could become problematic due to hygienic requirements. Efficiency potentials through lowered operating temperatures are limited. In further research, lowered process temperatures could be applied in the AD of energy crops due to large numbers of existing plants.
Research on a Piezoelectric Pump with Flexible Valves
Authors: Huang Weiqing , Lai Liyi , Chen Zhenlin , Chen Xiaosheng , Huang Zhi , Dai Jietao , Zhang Fan , Zhang Jianhui
Published: March 2021

Imitating the structure of the venous valve and its characteristics of passive opening and closing with changes in heart pressure, a piezoelectric pump with flexible valves (PPFV) was designed. Firstly, the structure and the working principle of the PPFV were introduced. Then, the flexible valve, the main functional component of the pump, was analyzed theoretically. Finally, an experimental prototype was manufactured and its performance was tested. The research proves that the PPFV can achieve a smooth transition between valved and valveless by only changing the driving signal of the piezoelectric (PZT) vibrator. The results demonstrate that when the driving voltage is 100 V and the frequency is 25 Hz, the experimental flow rate of the PPFV is about 119.61 mL/min, and the output pressure is about 6.16 kPa. This kind of pump can realize the reciprocal conversion of a large flow rate, high output pressure, and a small flow rate, low output pressure under the electronic control signal. Therefore, it can be utilized for fluid transport and pressure transmission at both the macro-level and the micro-level, which belongs to the macro–micro combined component.
Analyzing and Visualizing Spatiotemporal Patterns of El Niño Teleconnections Using Attribute Trajectories
Authors: Zhang Long , Van Schaeybroeck Bert , Caluwaerts Steven , Termonia Piet , Van de Weghe Nico
Published: March 2021

El Niño influences the global climate through teleconnections that are not constant in space and time. In order to study and visualize the spatiotemporal patterns of the El Niño teleconnections, a new method inspired by the concept of attribute trajectories is proposed. The coordinates of the trajectories are the normalized anomalies of the relevant meteorological variables in El Niño. The data structures called flocks are extracted from the trajectories to indicate the regions that are subject to the same type of El Niño teleconnection for a certain period. It is then shown how these structures can be used to get a detailed, spatiotemporal picture of the dynamics of the El Niño teleconnections. The comparison between the flocks of the same temporal scale reveals the general dynamics of the teleconnection, while the analysis among the flocks of different temporal scales indicates the relationship between the coverage and their duration. As an illustration of this method, the spatiotemporal patterns of the anomalous temperature increase caused by El Niño are presented and discussed at the monthly and seasonal scales. This study demonstrates the capability of the proposed method in analyzing and visualizing the spatiotemporal patterns of the teleconnections.
A Tree-Ring-Based Precipitation Reconstruction since 1760 CE from Northeastern Tibetan Plateau, China
Authors: Chen Youping , Chen Feng , Zhang Heli
Published: March 2021

Hydroclimatic conditions and related water resources change in the Tibetan Plateau is one of the main concerns for future sustainable development in China. This study presents a 254-year precipitation reconstruction from August of the previous year to June of the current year for the northeastern Tibetan Plateau based on tree-ring width data of tree-ring cores of Picea crassifolia from three sampling sites. The precipitation reconstruction explained 51.4% of the variance in instrumental precipitation during the calibration period 1958–2013. Dry periods with precipitation below the 254-year average value occurred during 1848–1865, 1873–1887, 1898–1923, and 1989–2003, and wet periods (precipitation above the mean) occurred during 1769–1785, 1798–1833, 1924–1938, 1957–1968, and 2004–2013. Spatial correlation analyses with the precipitation gridded dataset showed that our reconstruction contains some strong regional-scale precipitation signals for the upper Yellow River Basin. Our precipitation reconstruction also agreed in general with other dendroclimatic precipitation reconstructions from surrounding regions. In addition, reconstructed precipitation changes were consistent with the streamflow variation of the Yellow River.
A Review of Genetic Abnormalities in Unicentric and Multicentric Castleman Disease
Authors: Butzmann Alexandra , Kumar Jyoti , Sridhar Kaushik , Gollapudi Sumanth , Ohgami Robert S.
Published: March 2021

Castleman disease (CD) is a rare lymphoproliferative disorder known to represent at least four distinct clinicopathologic subtypes. Large advancements in our clinical and histopathologic description of these diverse diseases have been made, resulting in subtyping based on number of enlarged lymph nodes (unicentric versus multicentric), according to viral infection by human herpes virus 8 (HHV-8) and human immunodeficiency virus (HIV), and with relation to clonal plasma cells (POEMS). In recent years, significant molecular and genetic abnormalities associated with CD have been described. However, we continue to lack a foundational understanding of the biological mechanisms driving this disease process. Here, we review all cases of CD with molecular abnormalities described in the literature to date, and correlate cytogenetic, molecular, and genetic abnormalities with disease subtypes and phenotypes. Our review notes complex karyotypes in subsets of cases, specific mutations in PDGFRB N666S in 10% of unicentric CD (UCD) and NCOA4 L261F in 23% of idiopathic multicentric CD (iMCD) cases. Genes affecting chromatin organization and abnormalities in methylation are seen more commonly in iMCD while abnormalities within the mitogen-activated protein kinase (MAPK) and interleukin signaling pathways are more frequent in UCD. Interestingly, there is a paucity of genetic studies evaluating HHV-8 positive multicentric CD (HHV-8+ MCD) and POEMS-associated CD. Our comprehensive review of genetic and molecular abnormalities in CD identifies subtype-specific and novel pathways which may allow for more targeted treatment options and unique biologic therapies.
Understanding the Hedgehog Signaling Pathway in Acute Myeloid Leukemia Stem Cells: A Necessary Step toward a Cure
Authors: Lainez-González Daniel , Serrano-López Juana , Alonso-Domínguez Juan Manuel
Published: March 2021

A better understanding of how signaling pathways govern cell fate is fundamental to advances in cancer development and treatment. The initialization of different tumors and their maintenance are caused by the deregulation of different signaling pathways and cancer stem cell maintenance. Quiescent stem cells are resistant to conventional chemotherapeutic treatments and, consequently, are responsible for disease relapse. In this review we focus on the conserved Hedgehog (Hh) signaling pathway which is involved in regulating the cell cycle of hematopoietic and leukemic stem cells. Thus, we examine the role of the Hh signaling pathway in normal and leukemic stem cells and dissect its role in acute myeloid leukemia. We explain not only the connection between illness and the signaling pathway but also evaluate innovative therapeutic approaches that could affect the outcome of patients with acute myeloid leukemia. We found that many aspects of the Hedgehog signaling pathway remain unknown. The role of Hh has only been proven in embryo and hematopoietic stem cell development. Further research is needed to elucidate the role of GLI transcription factors for therapeutic targeting. Glasdegib, an SMO inhibitor, has shown clinical activity in acute myeloid leukemia; however, its mechanism of action is not clear.
AP-64, Encoded by C5orf46, Exhibits Antimicrobial Activity against Gram-Negative Bacteria
Authors: Zhong Kunhong , Wang Yuelong , Wang Zeng , Zhang Zongliang , Zhao Shasha , Li Hexian , Huang Jianhan , Guo Wenhao , Zheng Xi , Guo Gang , Zhou Liangxue , Yang Hui , Tong Aiping
Published: March 2021

Antimicrobial peptides (AMPs), which are evolutionarily conserved components of the innate immune response, contribute to the first line of defense against microbes in the skin and at mucosal surfaces. Here, we report the identification of a human peptide, encoded by the chromosome 5 open reading frame 46 (C5orf46) gene, as a type of AMP, which we termed antimicrobial peptide with 64 amino acid residues (AP-64). AP-64 is an anionic amphiphilic peptide lacking cysteines (MW = 7.2, PI = 4.54). AP-64 exhibited significant antibacterial activity against Gram-negative bacteria, including Escherichia coli DH5α, Escherichia coli O157:H7, Vibrio cholerae, and Pseudomonas aeruginosa. Moreover, AP-64 was efficient in combating Escherichia coli O157:H7 infections in a mouse model and exhibited cytotoxic effects against human T-cell lymphoma Jurkat and B-cell lymphoma Raji cells. We also observed that Gm94, encoded by mouse C5orf46 homologous gene, closely resembles AP-64 in its antibacterial properties. Compared with other human AMPs, AP-64 has distinct characteristics, including a longer sequence length, absence of cysteine residues, a highly anionic character, and cell toxicity. Together, this study identified that AP-64 is an AMP worthy of further investigation.
Antitumoral Activity of the MEK Inhibitor Trametinib (TMT212) Alone and in Combination with the CDK4/6 Inhibitor Ribociclib (LEE011) in Neuroendocrine Tumor Cells In Vitro
Authors: Jin Xi-Feng , Spöttl Gerald , Maurer Julian , Nölting Svenja , Auernhammer Christoph Josef
Published: March 2021

Objectives: This study assessed the antitumoral activity of the MEK inhibitor trametinib (TMT212) and the ERK1/2 inhibitor SCH772984, alone and in combination with the CDK4/6 inhibitor ribociclib (LEE011) in human neuroendocrine tumor (NET) cell lines in vitro. Methods: Human NET cell lines BON1, QGP-1, and NCI-H727 were treated with trametinib or SCH772984, alone and in combination with ribociclib, to assess cell proliferation, cell cycle distribution, and protein signaling using cell proliferation, flow cytometry, and Western blot assays, respectively. Results: Trametinib and SCH772984, alone and in combination with ribociclib, significantly reduced NET cell viability and arrested NET cells at the G1 phase of the cell cycle in all three cell lines tested. In addition, trametinib also caused subG1 events and apoptotic PARP cleavage in QGP1 and NCI-H727 cells. A western blot analysis demonstrated the use of trametinib alone and trametinib in combination with ribociclib to decrease the expression of pERK, cMyc, Chk1, pChk2, pCDK1, CyclinD1, and c-myc in a time-dependent manner in NCI-H727 and QGP-1 cells. Conclusions: MEK and ERK inhibition causes antiproliferative effects in human NET cell lines in vitro. The combination of the MEK inhibitor trametinib (TMT212) with the CDK4/6 inhibitor ribociclib (LEE011) causes additive antiproliferative effects. Future preclinical and clinical studies of MEK inhibition in NETs should be performed.
The Importance of Mitochondrial Pyruvate Carrier in Cancer Cell Metabolism and Tumorigenesis
Authors: Ruiz-Iglesias Ainhoa , Mañes Santos
Published: March 2021

Pyruvate is a key molecule in the metabolic fate of mammalian cells; it is the crossroads from where metabolism proceeds either oxidatively or ends with the production of lactic acid. Pyruvate metabolism is regulated by many enzymes that together control carbon flux. Mitochondrial pyruvate carrier (MPC) is responsible for importing pyruvate from the cytosol to the mitochondrial matrix, where it is oxidatively phosphorylated to produce adenosine triphosphate (ATP) and to generate intermediates used in multiple biosynthetic pathways. MPC activity has an important role in glucose homeostasis, and its alteration is associated with diabetes, heart failure, and neurodegeneration. In cancer, however, controversy surrounds MPC function. In some cancers, MPC upregulation appears to be associated with a poor prognosis. However, most transformed cells undergo a switch from oxidative to glycolytic metabolism, the so-called Warburg effect, which, amongst other possibilities, is induced by MPC malfunction or downregulation. Consequently, impaired MPC function might induce tumors with strong proliferative, migratory, and invasive capabilities. Moreover, glycolytic cancer cells secrete lactate, acidifying the microenvironment, which in turn induces angiogenesis, immunosuppression, and the expansion of stromal cell populations supporting tumor growth. This review examines the latest findings regarding the tumorigenic processes affected by MPC.
Municipality and Adjusted Gross Income Influence Outcome of Patients Diagnosed with Pancreatic Cancer in a Newly Developed Cancer Center in Mercer County New Jersey, USA, a Single Center Study
Authors: Doria Cataldo , De Deyne Patrick , Dolan Sherry , Chung Jooyeun , Yatcilla Karen , Zarifian Ladan , Remstein Rona , Schwartz Eric
Published: March 2021

Socioeconomic status (SES) correlates directly to ZIP code. Mercer County is not atypical as a collection of a dozen municipalities with a suburban/metropolitan population of 370,430 in the immediate vicinity of a major medical center. The purpose of this study for Mercer County, New Jersey, USA is to determine whether a patient’s ZIP code is related to the outlook of pancreatic cancer defined as staging at diagnosis, prevalence, overall survival, type of insurance, and recurrence. Our hypothesis was that specific variables such as socio-economic status or race could be linked to the outcome of patients with pancreatic cancer. We interrogated a convenience sample from our cancer center registry and obtained 479 subjects diagnosed with pancreatic cancer in 1998-2018. We selected 339 subjects by ZIP code, representing the plurality of the cases in our catchment area. The outcome variable was overall survival; predictor variables were socio-economic status (SES), recurrence, insurance, type of treatment, gender, cancer stage, age, and race. We converted ZIP code to municipality and culled data using adjusted gross income (AGI, FY 2017). Comparative statistical analysis was performed using chi-square tests for nominal and ordinal variables, and a two-way ANOVA test was used for continuous variables; the p-value was set at 0.05. Our analysis confirmed that overall survival was significantly higher for Whites and for individuals who live in a municipality with a high SES. Tumor stage at the time of diagnosis was not different among race and SES; however, statistically significant differences for race or SES existed in the type of treatment received, with disparities found in those who received radiation therapy and surgery but not chemotherapy. The data may point to a lack of access to specific care modalities that subsequently may lead to lower survival in an underserved population. Access to care, optimal nutritional status, overall fitness, and co-morbidities could play a major role and confound the results. Our study suggests that low SES has a negative impact on overall pancreatic cancer survival. Surgery for pancreatic cancer should be appropriately decentralized to those community cancer centers that possess the expertise and the infrastructure to carry out specialized treatments regardless of race, ethnicity, SES, and insurance.
Organizing Multi-Enzyme Systems into Programmable Materials for Biocatalysis
Authors: Seo Min-Ju , Schmidt-Dannert Claudia
Published: March 2021

Significant advances in enzyme discovery, protein and reaction engineering have transformed biocatalysis into a viable technology for the industrial scale manufacturing of chemicals. Multi-enzyme catalysis has emerged as a new frontier for the synthesis of complex chemicals. However, the in vitro operation of multiple enzymes simultaneously in one vessel poses challenges that require new strategies for increasing the operational performance of enzymatic cascade reactions. Chief among those strategies is enzyme co-immobilization. This review will explore how advances in synthetic biology and protein engineering have led to bioinspired co-localization strategies for the scaffolding and compartmentalization of enzymes. Emphasis will be placed on genetically encoded co-localization mechanisms as platforms for future autonomously self-organizing biocatalytic systems. Such genetically programmable systems could be produced by cell factories or emerging cell-free systems. Challenges and opportunities towards self-assembling, multifunctional biocatalytic materials will be discussed.
Constitutive Cell Proliferation Regulating Inhibitor of Protein Phosphatase 2A (CIP2A) Mediates Drug Resistance to Erlotinib in an EGFR Activating Mutated NSCLC Cell Line
Authors: Saafan Hisham , Alahdab Ahmad , Michelet Robin , Gohlke Linus , Ziemann Janine , Holdenrieder Stefan , McLaughlin Katie-May , Wass Mark N. , Cinatl Jindrich , Michaelis Martin , Kloft Charlotte , Ritter Christoph A
Published: March 2021

Exploring mechanisms of drug resistance to targeted small molecule drugs is critical for an extended clinical benefit in the treatment of non-small cell lung cancer (NSCLC) patients carrying activating epidermal growth factor receptor (EGFR) mutations. Here, we identified constitutive cell proliferation regulating inhibitor of protein phosphatase 2A (CIP2A) in the HCC4006rErlo0.5 NSCLC cell line adapted to erlotinib as a model of acquired drug resistance. Constitutive CIP2A resulted in a constitutive activation of Akt signaling. The proteasome inhibitor bortezomib was able to reduce CIP2A levels, which resulted in an activation of protein phosphatase 2A and deactivation of Akt. Combination experiments with erlotinib and bortezomib revealed a lack of interaction between the two drugs. However, the effect size of bortezomib was higher in HCC4006rErlo0.5, compared to the erlotinib-sensitive HCC4006 cells, as indicated by an increase in Emax (0.911 (95%CI 0.867–0.954) vs. 0.585 (95%CI 0.568–0.622), respectively) and decrease in EC50 (52.4 µM (95%CI 46.1–58.8 µM) vs. 73.0 µM (95%CI 60.4–111 µM), respectively) in the concentration–effect model, an earlier onset of cell death induction, and a reduced colony surviving fraction (0.38 ± 0.18 vs. 0.95 ± 0.25, respectively, n = 3, p < 0.05). Therefore, modulation of CIP2A with bortezomib could be an interesting approach to overcome drug resistance to erlotinib treatment in NSCLC.
Angiotensin II-Induced Cardiac Effects Are Modulated by Endocannabinoid-Mediated CB1 Receptor Activation
Authors: Miklós Zsuzsanna , Wafa Dina , Nádasy György L. , Tóth Zsuzsanna E. , Besztercei Balázs , Dörnyei Gabriella , Laska Zsófia , Benyó Zoltán , Ivanics Tamás , Hunyady László , Szekeres Mária
Published: March 2021

Angiotensin II (Ang II) has various cardiac effects and causes vasoconstriction. Ang II activates the type-1 angiotensin receptor—Gq/11 signaling pathway resulting in the release of 2-arachidonoylglycerol (2-AG). We aimed to investigate whether cardiac Ang II effects are modulated by 2-AG-release and to identify the role of type-1 cannabinoid receptors (CB1R) in these effects. Expression of CB1R in rat cardiac tissue was confirmed by immunohistochemistry. To characterize short-term Ang II effects, increasing concentrations of Ang II (10−9–10−7 M); whereas to assess tachyphylaxis, repeated infusions of Ang II (10−7 M) were administered to isolated Langendorff-perfused rat hearts. Ang II infusions caused a decrease in coronary flow and ventricular inotropy, which was more pronounced during the first administration. CB agonist 2-AG and WIN55,212-2 administration to the perfusate enhanced coronary flow. The flow-reducing effect of Ang II was moderated in the presence of CB1R blocker O2050 and diacylglycerol-lipase inhibitor Orlistat. Our findings indicate that Ang II-induced cardiac effects are modulated by simultaneous CB1R-activation, most likely due to 2-AG-release during Ang II signalling. In this combined effect, the response to 2-AG via cardiac CB1R may counteract the positive inotropic effect of Ang II, which may decrease metabolic demand and augment Ang II-induced coronary vasoconstriction.
Regulation of TGFβ Signalling by TRPV4 in Chondrocytes
Authors: Woods Steven , Humphreys Paul A. , Bates Nicola , Richardson Sophie Alice , Kuba Shweta Yogesh , Brooks Imogen R. , Cain Stuart A. , Kimber Susan J.
Published: March 2021

The growth factor TGFβ and the mechanosensitive calcium-permeable cation channel TRPV4 are both important for the development and maintenance of many tissues. Although TRPV4 and TGFβ both affect core cellular functions, how their signals are integrated is unknown. Here we show that pharmacological activation of TRPV4 significantly increased the canonical response to TGFβ stimulation in chondrocytes. Critically, this increase was only observed when TRPV4 was activated after, but not before TGFβ stimulation. The increase was prevented by pharmacological TRPV4 inhibition or knockdown and is calcium/CamKII dependent. RNA-seq analysis after TRPV4 activation showed enrichment for the TGFβ signalling pathway and identified JUN and SP1 as key transcription factors involved in this response. TRPV4 modulation of TGFβ signalling represents an important pathway linking mechanical signalling to tissue development and homeostasis.
Optimization of Yb2O3-Gd2O3-Y2O3 Co-Doped ZrO2 Agglomerated and Calcined Powders for Air Plasma Spraying
Authors: Yan Zheng , Peng Haoran , Yuan Kang , Zhang Xin
Published: March 2021

Yb2O3-Gd2O3-Y2O3 co-doped ZrO2 (YGYZ) is considered to be a promising material in thermal barrier coating (TBC) applications. In this study, 2Yb2O3-2Gd2O3-6Y2O3-90ZrO2 (mol.%) (10YGYZ) feedstock candidates for air plasma spraying (APS) were prepared by calcination of agglomerated powders at 1100, 1200, 1300, 1400, and 1500 °C for 3 h, respectively. Incomplete solid solution was observed in calcined powders at 1100, 1200 and 1300 °C, and the 1500 °C calcined powder exhibited poor flowability due to intense sintering effect. The 1400 °C calcined powders were eventually determined to be the optimized feedstock for proper phase structure (cubic phase), great flowability, suitable apparent density and particle size distribution, etc. 10YGYZ TBCs with the optimized feedstock were prepared by APS, exhibiting pure c phase and good chemical uniformity. Controllable preparation of coatings with different porosity (i.e., 7%–9% and 12%–14%) was realized by stand-off distance adjustment.
Hyaluronic Acid-Coated MTX-PEI Nanoparticles for Targeted Rheumatoid Arthritis Therapy
Authors: Zhong Shenghui , Liu Peng , Ding Jinsong , Zhou Wenhu
Published: March 2021

Methotrexate (MTX) is an anchor drug for the treatment of rheumatoid arthritis (RA); however, long-term and high-dose usage of MTX for patients can cause many side effects and toxic reactions. To address these difficulties, selectively delivering MTX to the inflammatory site of a joint is promising in the treatment of RA. In this study, we prepared MTX-PEI@HA nanoparticles (NPs), composed of hyaluronic acid (HA) as the hydrophilic negative electrical shell, and MTX-linked branched polyethyleneimine (MTX-PEI) NPs as the core. MTX-PEI@HA NPs were prepared in the water phase by a one-pot method. The polymeric NPs were selectively internalized via CD44 receptor-mediated endocytosis in the activated macrophages. In the in vivo mice mode study, treatment with MTX-PEI@HA NPs mitigated inflammatory arthritis with notable safety at a high dose of MTX. We highlight the distinct advantages of aqueous-synthesized NPs coated with HA for arthritis-selective targeted delivery, thus verifying MTX-PEI@HA NPs as a promising MTX-based nanoplatform for treatment of RA.
Isotope Effect in Thermal Conductivity of Polycrystalline CVD-Diamond: Experiment and Theory
Authors: Inyushkin Alexander V. , Taldenkov Alexander N. , Ralchenko Victor G. , Bolshakov Andrey P. , Khomich Alexander V.
Published: March 2021

We measured the thermal conductivity κ(T) of polycrystalline diamond with natural (natC) and isotopically enriched (12C content up to 99.96 at.%) compositions over a broad temperature T range, from 5 to 410 K. The high quality polycrystalline diamond wafers were produced by microwave plasma chemical vapor deposition in CH4-H2 mixtures. The thermal conductivity of 12C diamond along the wafer, as precisely determined using a steady-state longitudinal heat flow method, exceeds much that of the natC sample at T>60 K. The enriched sample demonstrates the value of κ(298K)=25.1±0.5 W cm−1 K−1 that is higher than the ever reported conductivity of natural and synthetic single crystalline diamonds with natural isotopic composition. A phenomenological theoretical model based on the full version of Callaway theory of thermal conductivity is developed which provides a good approximation of the experimental data. The role of different resistive scattering processes, including due to minor isotope 13C atoms, defects, and grain boundaries, is estimated from the data analysis. The model predicts about a 37% increase of thermal conductivity for impurity and dislocation free polycrystalline chemical vapor deposition (CVD)-diamond with the 12C-enriched isotopic composition at room temperature.
Electromyographic Patterns of Masticatory Muscles in Relation to Active Myofascial Trigger Points of the Upper Trapezius and Temporomandibular Disorders
Authors: Zieliński Grzegorz , Byś Aleksandra , Szkutnik Jacek , Majcher Piotr , Ginszt Michał
Published: March 2021

The presented study aimed to analyze and compare the electromyographic patterns of masticatory muscles in subjects with active myofascial trigger points (MTrPs) within upper trapezius, patients with temporomandibular disorders (TMDs) and healthy adults. Based on the diagnostic criteria of MTrPs according to Travell & Simons and the Research Diagnostic Criteria for Temporomandibular Disorders, 167 people were qualified for the study. Subjects were divided into 3 groups: with active MTrPs in the upper trapezius, with diagnosed temporomandibular disorders (TMDs) and healthy adults. Measurements of the bioelectric activity of the temporalis anterior (TA) and masseter muscle (MM) were carried out using the BioEMG III ™. Based on statistical analysis, significantly lower values of TA resting activity were observed among controls in comparison to MTrPs (1.49 μV vs. 2.81 μV, p = 0.00) and TMDs (1.49 μV vs. 2.97 μV, p = 0.01). The POC index values at rest differed significantly between MTrPs and TMDs (86.61% vs. 105%, p = 0.04). Controls presented different electromyographic patterns within AcI in comparison to both MTrPs (4.90 vs. −15.51, p = 0.00) and TMDs (4.90 vs. −16.49, p = 0.00). During clenching, the difference between MTrPs and TMDs was observed within MVC TA (91.82% vs. 116.98%, p = 0.02). TMDs showed differences within AcI in comparison to both MTrPs group (−42.52 vs. 20.42, p = 0.01) and controls (−42.52 vs. 3.07, p = 0.00). During maximum mouth opening, differences between MTrPs and TMDs were observed within the bioelectric activity of masseter muscle (16.45 μV vs. 10.73 μV, p = 0.01), AsI MM (0.67 vs. 11.12, p = 0.04) and AcI (13.04 vs. −3.89, p = 0.01). Both the presence of MTrPs in the upper trapezius and TMDs are related to changes in electromyographic patterns of masticatory muscles.
Modeling the Contribution of Male Testosterone Levels to the Duration of Positive COVID Testing among Hospitalized Male COVID-19 Patients
Authors: Salciccia Stefano , Eisenberg Michael L. , Maggi Martina , Lai Silvia , Mastroianni Claudio Maria , Pasculli Patrizia , Ciardi Maria Rosa , Canale Vittorio , Ferro Matteo , Busetto Gian Maria , De Berardinis Ettore , Ricciuti Gian Piero , Sciarra Alessandro , Del Giudice Francesco
Published: March 2021

Background: A growing body of evidence is emerging suggesting testosterone can affect all cells involved in the immune response to both bacterial and viral infections, and the testosterone effect on the immune response could explain the greater susceptibility of men to infections including COVID-19. We aimed to explore the predictive role of male serum total testosterone (TT) levels on the time till viral negativity testing among hospitalized COVID-19 patients. Methods: The univariate effect of risk factors for the duration of COVID-19 viral positivity was evaluated using the log-rank test and Kaplan–Meier estimates. A multivariable Cox regression model was developed to test the role of TT levels and the subsequent odds for shorter viral positivity intervals. Results: Increasing serum TT levels and the need for an oxygen administration strategy were independently predictive for respectively reduced and increased days to negativization (Hazard Ratio [HR]: 1.39, 95% CI: 0.95–2.03 and HR: 0.19, 95% CI: 0.03–1.18). Conclusion: Baseline higher TT levels for male COVID-19 patients at hospital admission are associated with shorter durations of positive COVID-19 testing and thus viral clearance. Our preliminary findings might play a relevant to help pandemic control strategies if these will be verified in future larger multicentric and possibly randomized trials.
Nestin Expression Is Associated with Relapses in Head and Neck Lesions
Authors: Pérez-Sayáns Mario , Chamorro-Petronacci Cintia M , Baltazar Fátima , Pires Fabio Ramoa , Ínsua Ángel , Suárez-Quintanilla Juan A , Suárez-Peñaranda José M
Published: March 2021

Background: The aim was to investigate the clinical significance of nestin immunohistochemical expression in head and neck area lesions and to study its role in patient survival and recurrence. Methods: 39 (44.3%) nasosinus, 37 (42%) major salivary gland (6 submandibular and 31 parotid) and 12 (13.6%) oral cavity lesions of paraffin-embedded samples were retrospectively included. Results: The expression was categorized into grades, negative for 55 (62.5%) cases, grade 1 in 10 cases (11.4%), grade 2 in 12 cases (13.6%), and grade 3 in 11 cases (12.5%); 100% of pleomorphic adenomas were positive for nestin with grade 3 intensity, 100% of polyps and inverted papillomas were negative (p < 0.001). The lowest estimate of disease-free-survival (DFS) was for grade 1 expression, with 50 months, confidence interval (CI): 95% 13.3–23.9 months and the highest for grade 3 expression, 167.9 months (CI: 95% 32.1–105 months; Log-Rank = 14.846, p = 0.002). ROC (receiver operating characteristic) curves revealed that the positivity for nestin (+/−) in relation to malignancy, presented a sensitivity of 50.98%, a specificity of 81.08%, with an area under the curve of 0.667 (p = 0.009). Conclusions: Nestin could be a useful marker to detect the presence of stem cells in head and neck tumors that have a role in tumor initiation and progression.
Utilizing Dynamic Phosphorous-31 Magnetic Resonance Spectroscopy for the Early Detection of Acute Compartment Syndrome: A Pilot Study on Rats
Authors: Ohta Hiroki , Vo Nhat-Minh Van , Hata Junichi , Terawaki Koshiro , Shirakawa Takako , Okano Hirotaka James
Published: March 2021

Introduction: Disasters, including terrorism and earthquakes, are significant threats to people and may lead to many people requiring rescue. The longer the rescue takes, the higher the chances of an individual contracting acute compartment syndrome (ACS). ACS is fatal if diagnosed too late, and early diagnosis and treatment are essential. Objective: To assess the ability of dynamic phosphorus magnetic resonance spectroscopy (31P-MRS) in the early detection of muscular damage in ACS. Materials and Methods: Six ACS model rats were used for serial 31P-MRS scanning (9.4 Tesla). Skeletal muscle metabolism, represented by the levels of phosphocreatine (PCr), inorganic phosphate (Pi), and adenosine triphosphate (ATP), was assessed. The PCr/(Pi + PCr) ratio, which decreases with ischemia, was compared with simultaneously sampled plasma creatine phosphokinase (CPK), a muscle damage marker. Results: The PCr/(Pi + PCr) ratio significantly decreased after inducing ischemia (from 0.86 ± 0.10 to 0.18 ± 0.06; p < 0.05), while CPK did not change significantly (from 89 ± 29.46 to 241.50 ± 113.28; p > 0.05). The intracellular and arterial pH index decreased over time, revealing significant differences at 120 min post-ischemia (from 7.09 ± 0.01 to 6.43 ± 0.13, and from 7.47 ± 0.03 to 7.39 ± 0.04, respectively). In the reperfusion state, the spectra and pH did not return to the original values. Conclusions: The dynamic 31P-MRS technique can rapidly detect changes in muscle bioenergetics. This technique is a promising non-invasive method for determining early muscular damage in ACS.
Classical Dynamics of Rydberg States of Muonic-Electronic Helium and Helium-Like Ions in a Weak Electric Field: Counter-Intuitive Linear Stark Effect
Authors: Oks Eugene
Published: March 2021

According to the existing paradigm, helium atoms and helium-like ions (hereafter, heliumic systems) in a relatively weak external static electric field do not exhibit the linear Stark effect—in distinction to hydrogen atoms and hydrogen-like ions. In the present paper we consider the classical dynamics of a muonic-electronic heliumic system in Rydberg states–starting from the concept from our previous paper. We show that there are two states of the system where the averaged electric dipole moment is non-zero. Consequently, in these states the heliumic system should exhibit the linear Stark effect even in a vanishingly small electric field, which is a counter-intuitive result. We also demonstrate the possibility of controlling the overall precession of the electronic orbit by an external electric field. In particular, we show the existence of a critical value of the external electric field that would “kill” the precession and make the electronic orbit stationary. This is another counter-intuitive result. We calculate analytically the value of the critical field and show that it is typically smaller or even much smaller than 1 V/cm.
Structure of Investor Networks and Financial Crises
Authors: Baltakys Kęstutis , Le Viet Hung , Kanniainen Juho
Published: March 2021

In this paper, we ask whether the structure of investor networks, estimated using shareholder registration data, is abnormal during a financial crises. We answer this question by analyzing the structure of investor networks through several most prominent global network features. The networks are estimated from data on marketplace transactions of all publicly traded securities executed in the Helsinki Stock Exchange by Finnish stock shareholders between 1995 and 2016. We observe that most of the feature distributions were abnormal during the 2008–2009 financial crisis, with statistical significance. This paper provides evidence that the financial crisis was associated with a structural change in investors’ trade time synchronization. This indicates that the way how investors use their private information channels changes depending on the market conditions.