bluuebunny/crossref_metadata_2025 huggingface dataset:
Discovery, characterization and functional improvement of kumamonamide as a novel plant growth inhibitor that disturbs plant microtubules
Authors: Ishida Takashi , Yoshimura Haruna , Takekawa Masatsugu , Higaki Takumi , Ideue Takashi , Hatano Masaki , Igarashi Masayuki , Tani Tokio , Sawa Shinichiro , Ishikawa Hayato
Published: March 2021

The discovery and useful application of natural products can help improve human life. Chemicals that inhibit plant growth are broadly utilized as herbicides to control weeds. As various types of herbicides are required, the identification of compounds with novel modes of action is desirable. In the present study, we discovered a novel N-alkoxypyrrole compound, kumamonamide from Streptomyces werraensis MK493-CF1 and established a total synthesis procedure. Resulted in the bioactivity assays, we found that kumamonamic acid, a synthetic intermediate of kumamonamide, is a potential plant growth inhibitor. Further, we developed various derivatives of kumamonamic acid, including a kumamonamic acid nonyloxy derivative (KAND), which displayed high herbicidal activity without adverse effects on HeLa cell growth. We also detected that kumamonamic acid derivatives disturb plant microtubules; and additionally, that KAND affected actin filaments and induced cell death. These multifaceted effects differ from those of known microtubule inhibitors, suggesting a novel mode of action of kumamonamic acid, which represents an important lead for the development of new herbicides.
Standardization of esophageal adenocarcinoma in vitro model and its applicability for model drug testing
Authors: Tratnjek Larisa , Sibinovska Nadica , Kralj Slavko , Makovec Darko , Kristan Katja , Kreft Mateja Erdani
Published: March 2021

FLO-1 cell line represents an important tool in esophageal adenocarcinoma (EAC) research as a verified and authentic cell line to study the disease pathophysiology and antitumor drug screenings. Since in vitro characteristics of cells depend on the microenvironment and culturing conditions, we performed a thorough characterization of the FLO-1 cell line under different culturing conditions with the aim of (1) examining the effect of serum-free growth medium and air–liquid interface (A–L) culturing, which better reflect physiological conditions in vivo and (2) investigating the differentiation potential of FLO-1 cells to mimic the properties of the in vivo esophageal epithelium. Our study shows that the composition of the media influenced the morphological, ultrastructural and molecular characteristics of FLO-1 cells, such as the expression of junctional proteins. Importantly, FLO-1 cells formed spheres at the A–L interface, recapitulating key elements of tumors in the esophageal tube, i.e., direct contact with the gas phase and three-dimensional architecture. On the other hand, FLO-1 models exhibited high permeability to model drugs and zero permeability markers, and low transepithelial resistance, and therefore poorly mimicked normal esophageal epithelium. In conclusion, the identified effect of culture conditions on the characteristics of FLO-1 cells should be considered for standardization, data reproducibility and validity of the in vitro EAC model. Moreover, the sphere-forming ability of FLO-1 cells at the A–L interface should be considered in EAC tumor biology and anticancer drug studies as a reliable and straightforward model with the potential to increase the predictive efficiency of the current in vitro approaches.
Terahertz radiation generation from metallic electronic structure manipulated by inhomogeneous DC-fields
Authors: Lin H. , Liu C. P.
Published: March 2021

We propose a feasible, high-efficiency scheme of primary terahertz (THz) radiation source through manipulating electronic structure (ES) of a metallic film by targeted-designed DC-fields configuration. The DC magnetic field is designed to be of a spatially inhomogeneous strength profile, and its direction is designed to be normal to the film, and the direction of the DC electric field is parallel to the film. Strict quantum theory and numerical results indicate that the ES under such a field configuration will change from a 3D Fermi sphere into a highly-degenerate structure whose density-of-state curve has pseudogap near Fermi surface. Wavefunctions’ shapes in this new ES are space-asymmetric, and the width of pseudogap near Fermi surface, as well as magnitudes of transition matrix element, can be handily controlled by adjusting parameter values of DC fields. Under available parameter values, the width of the pseudogap can be at milli-electron-volt level (corresponding to THz radiation frequency), and the magnitude of oscillating dipole can be at $$10^{-9} C*m$$

10

-
9

C

∗
m

-level. In room-temperature environment, phonon in metal can pump the ES to achieve population inversion.
Ultra-small and highly dispersive iron oxide hydroxide as an efficient catalyst for oxidation reactions: a Swiss-army-knife catalyst
Authors: Amini Mojtaba , Mousazade Younes , Zand Zahra , Bagherzadeh Mojtaba , Najafpour Mohammad Mahdi
Published: March 2021

Ultra-small and highly dispersive (< 10 nm) iron oxide hydroxide is characterized by some methods. The compound is an efficient and stable catalyst for alcohol oxidation, organic sulfide oxidation, and epoxidation of alkenes in the presence of H2O2. The electrochemical oxygen-evolution reaction of the iron oxide hydroxide is also tested under acidic, neutral, and alkaline conditions. In the presence of the iron oxide hydroxide, excellent conversions (75–100%) and selectivities of substrates (92–97%), depending on the nature of the sulfide, were obtained. Benzylalcohols having electron-donating and-withdrawing substituents in the aromatic ring were oxidized to produce the corresponding aldehydes with excellent conversion (65–89%) and selectivity (96–100%) using this iron oxide hydroxide. The conversion of styrene and cyclooctene toward the epoxidation in the presence of this catalyst are 60 and 53%, respectively. Water oxidation for the catalysts was investigated at pH 2, 6.7, 12, and 14. The onset of OER at pH 14 is observed with a 475 mV overpotential. At 585 mV overpotential, a current density of more than 0.18 mA/cm2and a turnover frequency of 1.5/h is observed. Operando high-resolution visible spectroscopy at pH 14, similar to previously reported investigations, shows that Fe(IV)=O is an intermediate for water oxidation.
Thigmotaxis in a virtual human open field test
Authors: Gromer Daniel , Kiser Dominik P. , Pauli Paul
Published: March 2021

Animal models are used to study neurobiological mechanisms in mental disorders. Although there has been significant progress in the understanding of neurobiological underpinnings of threat-related behaviors and anxiety, little progress was made with regard to new or improved treatments for mental disorders. A possible reason for this lack of success is the unknown predictive and cross-species translational validity of animal models used in preclinical studies. Re-translational approaches, therefore, seek to establish cross-species translational validity by identifying behavioral operations shared across species. To this end, we implemented a human open field test in virtual reality and measured behavioral indices derived from animal studies in three experiments ($$\textit{N}=31$$

N
=
31

, $$\textit{N}=30$$

N
=
30

, and $$\textit{N}=80$$

N
=
80

). In addition, we investigated the associations between anxious traits and such behaviors. Results indicated a strong similarity in behavior across species, i.e., participants in our study—like rodents in animal studies—preferred to stay in the outer region of the open field, as indexed by multiple behavioral parameters. However, correlational analyses did not clearly indicate that these behaviors were a function of anxious traits of participants. We conclude that the realized virtual open field test is able to elicit thigmotaxis and thus demonstrates cross-species validity of this aspect of the test. Modulatory effects of anxiety on human open field behavior should be examined further by incorporating possible threats in the virtual scenario and/or by examining participants with higher anxiety levels or anxiety disorder patients.
The phylogeographic history of Krascheninnikovia reflects the development of dry steppes and semi-deserts in Eurasia
Authors: Seidl Anna , Tremetsberger Karin , Pfanzelt Simon , Blattner Frank R. , Neuffer Barbara , Friesen Nikolai , Hurka Herbert , Shmakov Alexander , Batlai Oyuntsetseg , Žerdoner Čalasan Anže , Vesselova Polina V. , Bernhardt Karl-Georg
Published: March 2021

Constituting one of Earth’s major biomes, steppes are characterised by naturally treeless extra-tropical vegetation. The formation of the Eurasian steppe belt, the largest steppe region in the world, began in Central Asia during the Neogene. In the glacial stages of the Pleistocene, steppe displaced forest vegetation, which in turn recolonised the area during the warmer interglacial periods, thus affecting the distribution of plants adapted to these habitats. Krascheninnikovia ceratoides (Chenopodiaceae) is a plant characteristic of dry steppe and semi-desert formations. Earlier studies showed that the ancestor of this autochthonous steppe element originated in Central Asia during the Miocene/Pliocene, i.e., in the same region and at the same time as the first appearance of steppe vegetation. However, as the extant lineages of Krascheninnikovia ceratoides diversified only 2.2 ± 0.9 Mya, it may represent a modern element of current dry steppe and semi-desert formations, rather than a component of the first steppe precursors of the Miocene. As such, it may have capitalised on the climatic conditions of the cold stages of the Quaternary to expand its range and colonise suitable habitats outside of its area of origin. To test this hypothesis, phylogeographic methods were applied to high-resolution genotyping-by-sequencing data. Our results indicate that Krascheninnikovia originated in western Central Asia and the Russian Altai, then spread to Europe in the West, and reached North America in the East. The populations of eastern Central Asia and North America belong to the same clade and are genetically clearly distinct from the Euro-Siberian populations. Among the populations west of the Altai Mountains, the European populations are genetically distinct from all others, which could be the result of the separation of populations east and west of the Urals caused by the Pleistocene transgressions of the Caspian Sea.
Identification of extracellular matrix proteins secreted by human dermal fibroblasts cultured in 3D electrospun scaffolds
Authors: Malakpour-Permlid Atena , Buzzi Irina , Hegardt Cecilia , Johansson Fredrik , Oredsson Stina
Published: March 2021

The appreciation that cell interactions in tissues is dependent on their three dimensional (3D) distribution has stimulated the development of 3D cell culture models. We constructed an artificial 3D tumour by culturing human breast cancer JIMT-1 cells and human dermal fibroblasts (HDFs) in a 3D network of electrospun polycaprolactone fibres. Here, we investigate ECM components produced by the cells in the artificial 3D tumour, which is an important step in validating the model. Immunostaining and confocal fluorescence microscopy show that the ECM proteins fibronectin, collagen I, and laminin are deposited throughout the entire 3D structure. Secreted soluble factors including matrix metalloproteinases (MMPs) and interleukine-6 (IL-6) were analysed in collected medium and were found to be mainly derived from the HDFs. Treatment with transforming growth factor-β1 (TGF-β1), a major cytokine found in a tumour, significantly alters the MMP activity and IL-6 concentration. In addition, TGF-β1 treatment, changes the morphology of the HDFs to become more elongated and with increased linearized actin filaments compared to non-treated HDFs. Collectively, these novel findings suggest that the artificial 3D tumour displays a clear cell distribution and ECM deposition that resembles a tumour environment in vivo, suggesting an innovative biological model to study a human tumour.
Palaeoproteomics confirm earliest domesticated sheep in southern Africa ca. 2000 BP
Authors: Coutu Ashley N. , Taurozzi Alberto J. , Mackie Meaghan , Jensen Theis Zetner Trolle , Collins Matthew J. , Sealy Judith
Published: March 2021

We used palaeoproteomics and peptide mass fingerprinting to obtain secure species identifications of key specimens of early domesticated fauna from South Africa, dating to ca. 2000 BP. It can be difficult to distinguish fragmentary remains of early domesticates (sheep) from similar-sized local wild bovids (grey duiker, grey rhebok, springbok—southern Africa lacks wild sheep) based on morphology alone. Our analysis revealed a Zooarchaeology by Mass Spectrometry (ZooMS) marker (m/z 1532) present in wild bovids and we demonstrate through LC–MS/MS that it is capable of discriminating between wild bovids and caprine domesticates. We confirm that the Spoegrivier specimen dated to 2105 ± 65 BP is indeed a sheep. This is the earliest directly dated evidence of domesticated animals in southern Africa. As well as the traditional method of analysing bone fragments, we show the utility of minimally destructive sampling methods such as PVC eraser and polishing films for successful ZooMS identification. We also show that collagen extracted more than 25 years ago for the purpose of radiocarbon dating can yield successful ZooMS identification. Our study demonstrates the importance of developing appropriate regional frameworks of comparison for future research using ZooMS as a method of biomolecular species identification.
Distinct DNA methylation patterns associated with treatment resistance in metastatic castration resistant prostate cancer
Authors: Peter Madonna R. , Bilenky Misha , Davies Alastair , Isserlin Ruth , Bader Gary D. , Fleshner Neil E. , Hirst Martin , Zoubeidi Amina , Bapat Bharati
Published: March 2021

Androgens are a major driver of prostate cancer (PCa) and continue to be a critical treatment target for advanced disease, which includes castration therapy and antiandrogens. However, resistance to these therapies leading to metastatic castration-resistant prostate cancer (mCRPC), and the emergence of treatment-induced neuroendocrine disease (tNEPC) remains an ongoing challenge. Instability of the DNA methylome is well established as a major hallmark of PCa development and progression. Therefore, investigating the dynamics of the methylation changes going from the castration sensitive to the tNEPC state would provide insights into novel mechanisms of resistance. Using an established xenograft model of CRPC, genome-wide methylation analysis was performed on cell lines representing various stages of PCa progression. We confirmed extensive methylation changes with the development of CRPC and tNEPC using this model. This included key genes and pathways associated with cellular differentiation and neurodevelopment. Combined analysis of methylation and gene expression changes further highlighted genes that could potentially serve as therapeutic targets. Furthermore, tNEPC-related methylation signals from this model were detectable in circulating cell free DNA (cfDNA) from mCRPC patients undergoing androgen-targeting therapies and were associated with a faster time to clinical progression. These potential biomarkers could help with identifying patients with aggressive disease.
Group contribution and atomic contribution models for the prediction of various physical properties of deep eutectic solvents
Authors: Haghbakhsh Reza , Raeissi Sona , Duarte Ana Rita C.
Published: March 2021

The urgency of advancing green chemistry from labs and computers into the industries is well-known. The Deep Eutectic Solvents (DESs) are a promising category of novel green solvents which simultaneously have the best advantages of liquids and solids. Furthermore, they can be designed or engineered to have the characteristics desired for a given application. However, since they are rather new, there are no general models available to predict the properties of DESs without requiring other properties as input. This is particularly a setback when screening is required for feasibility studies, since a vast number of DESs are envisioned. For the first time, this study presents five group contribution (GC) and five atomic contribution (AC) models for densities, refractive indices, heat capacities, speeds of sound, and surface tensions of DESs. The models, developed using the most up-to-date databank of various types of DESs, simply decompose the molecular structure into a number of predefined groups or atoms. The resulting AARD% of densities, refractive indices, heat capacities, speeds of sound and surface tensions were, respectively, 1.44, 0.37, 3.26, 1.62, and 7.59% for the GC models, and 2.49, 1.03, 9.93, 4.52 and 7.80% for the AC models. Perhaps, even more importantly for designer solvents, is the predictive capability of the models, which was also shown to be highly reliable. Accordingly, very simple, yet highly accurate models are provided that are global for DESs and needless of any physical property information, making them useful predictive tools for a category of green solvents, which is only starting to show its potentials in green technology.
Identification of resistance loci against new pathotypes of Plasmodiophora brassicae in Brassica napus based on genome-wide association mapping
Authors: Dakouri Abdulsalam , Lamara Mebarek , Karim Md. Masud , Wang Jinghe , Chen Qilin , Gossen Bruce D. , Strelkov Stephen E. , Hwang Sheau-Fang , Peng Gary , Yu Fengqun
Published: March 2021

Genetic resistance is a successful strategy for management of clubroot (Plasmodiophora brassicae) of brassica crops, but resistance can break down quickly. Identification of novel sources of resistance is especially important when new pathotypes arise. In the current study, the reaction of 177 accessions of Brassica napus to four new, virulent pathotypes of P. brassicae was assessed. Each accession was genotyped using genotyping by sequencing to identify and map novel sources of clubroot resistance using mixed linear model (MLM) analysis. The majority of accessions were highly susceptible (70–100 DSI), but a few accessions exhibited strong resistance (0–20 DSI) to pathotypes 5X (21 accessions), 3A (8), 2B (7), and 3D (15), based on the Canadian Clubroot Differential system. In total, 301,753 SNPs were mapped to 19 chromosomes. Population structure analysis indicated that the 177 accessions belong to seven major populations. SNPs were associated with resistance to each pathotype using MLM. In total, 13 important SNP loci were identified, with 9 SNPs mapped to the A-genome and 4 to the C-genome. The SNPs were associated with resistance to pathotypes 5X (2 SNPs), 3A (4), 2B (5) and 3D (6). A Blast search of 1.6 Mb upstream and downstream from each SNP identified 13 disease-resistance genes or domains. The distance between a SNP locus and the nearest resistance gene ranged from 0.04 to 0.74 Mb. The resistant lines and SNP markers identified in this study can be used to breed for resistance to the most prevalent new pathotypes of P. brassicae in Canada.
Origin and diffusion of human Y chromosome haplogroup J1-M267
Authors: Sahakyan Hovhannes , Margaryan Ashot , Saag Lauri , Karmin Monika , Flores Rodrigo , Haber Marc , Kushniarevich Alena , Khachatryan Zaruhi , Bahmanimehr Ardeshir , Parik Jüri , Karafet Tatiana , Yunusbayev Bayazit , Reisberg Tuuli , Solnik Anu , Metspalu Ene , Hovhannisyan Anahit , Khusnutdinova Elza K. , Behar Doron M. , Metspalu Mait , Yepiskoposyan Levon , Rootsi Siiri , Villems Richard
Published: March 2021

Human Y chromosome haplogroup J1-M267 is a common male lineage in West Asia. One high-frequency region—encompassing the Arabian Peninsula, southern Mesopotamia, and the southern Levant—resides ~ 2000 km away from the other one found in the Caucasus. The region between them, although has a lower frequency, nevertheless demonstrates high genetic diversity. Studies associate this haplogroup with the spread of farming from the Fertile Crescent to Europe, the spread of mobile pastoralism in the desert regions of the Arabian Peninsula, the history of the Jews, and the spread of Islam. Here, we study past human male demography in West Asia with 172 high-coverage whole Y chromosome sequences and 889 genotyped samples of haplogroup J1-M267. We show that this haplogroup evolved ~ 20,000 years ago somewhere in northwestern Iran, the Caucasus, the Armenian Highland, and northern Mesopotamia. The major branch—J1a1a1-P58—evolved during the early Holocene ~ 9500 years ago somewhere in the Arabian Peninsula, the Levant, and southern Mesopotamia. Haplogroup J1-M267 expanded during the Chalcolithic, the Bronze Age, and the Iron Age. Most probably, the spread of Afro-Asiatic languages, the spread of mobile pastoralism in the arid zones, or both of these events together explain the distribution of haplogroup J1-M267 we see today in the southern regions of West Asia.
Evaluation of the gut microbiome in association with biological signatures of inflammation in murine polytrauma and shock
Authors: Appiah Sandra A. , Foxx Christine L. , Langgartner Dominik , Palmer Annette , Zambrano Cristian A. , Braumüller Sonja , Schaefer Evan J. , Wachter Ulrich , Elam Brooke L. , Radermacher Peter , Stamper Christopher E. , Heinze Jared D. , Salazar Stephanie N. , Luthens Amalia K. , Arnold Andrea L. , Reber Stefan O. , Huber-Lang Markus , Lowry Christopher A. , Halbgebauer Rebecca
Published: March 2021

Severe injuries are frequently accompanied by hemorrhagic shock and harbor an increased risk for complications. Local or systemic inflammation after trauma/hemorrhage may lead to a leaky intestinal epithelial barrier and subsequent translocation of gut microbiota, potentially worsening outcomes. To evaluate the extent with which trauma affects the gut microbiota composition, we performed a post hoc analysis of a murine model of polytrauma and hemorrhage. Four hours after injury, organs and plasma samples were collected, and the diversity and composition of the cecal microbiome were evaluated using 16S rRNA gene sequencing. Although cecal microbial alpha diversity and microbial community composition were not found to be different between experimental groups, norepinephrine support in shock animals resulted in increased alpha diversity, as indicated by higher numbers of distinct microbial features. We observed that the concentrations of proinflammatory mediators in plasma and intestinal tissue were associated with measures of microbial alpha and beta diversity and the presence of specific microbial drivers of inflammation, suggesting that the composition of the gut microbiome at the time of trauma, or shortly after trauma exposure, may play an important role in determining physiological outcomes. In conclusion, we found associations between measures of gut microbial alpha and beta diversity and the severity of systemic and local gut inflammation. Furthermore, our data suggest that four hours following injury is too early for development of global changes in the alpha diversity or community composition of the intestinal microbiome. Future investigations with increased temporal-spatial resolution are needed in order to fully elucidate the effects of trauma and shock on the gut microbiome, biological signatures of inflammation, and proximal and distal outcomes.
Recovering wasted nutrients from shrimp farming through the combined culture of polychaetes and halophytes
Authors: Jerónimo Daniel , Lillebø Ana Isabel , Cremades Javier , Cartaxana Paulo , Calado Ricardo
Published: March 2021

The bioremediation and biomass production of organic extractive organisms (polychaetes Arenicola marina, Hediste diversicolor and halophyte Salicornia ramosissima) was assessed in an integrated multi-trophic aquaculture (IMTA) framework. Culture trials were performed outdoors using the nutient rich effluent from a shrimp farm employing recirculated aquaculture systems. Similar bioremediation efficiencies were obtained in cultures using a single polyculture tank (1 T) or two trophic levels separated tanks (2 T; ≈ 0.3 and 0.6 m2 operational area, respectively), with a reduction of 74–87% for particulate organic matter (POM), 56–64% for dissolved inorganic nitrogen (DIN) and 60–65% for dissolved inorganic phosphorus (DIP). Hediste diversicolor adapted well to culture conditions, reaching densities up to 5.000 ind. m−2 (≈ 78–98 g m−2). Arenicola marina failed to cope with water temperature that exceeded the species thermal limits, displaying a survival < 10% (20 °C often pointed as the maximum thermal threshold for this species). Productivity of S. ramosissima with 1 T was about twice that obtained with 2 T (≈ 150–170 and ≈ 60–90 g FW m−2 edible aboveground biomass, respectively). The yellowish coloration of cultured plants was likely due to the chemical oxidation and rapid sand filtration pre-treatment applied to the brackish groundwater used in the aquaculture facility, that removed iron (and probably other essential elements). Overall, 1 T design combining H. diversicolor and S. ramosissima displayed the best bioremediation performance and biomass production, while also allowing reducing in half the operational area required to implement this IMTA framework.
Imaging the transmembrane and transendothelial sodium gradients in gliomas
Authors: Khan Muhammad H. , Walsh John J. , Mihailović Jelena M. , Mishra Sandeep K. , Coman Daniel , Hyder Fahmeed
Published: March 2021

Under normal conditions, high sodium (Na+) in extracellular (Na+e) and blood (Na+b) compartments and low Na+ in intracellular milieu (Na+i) produce strong transmembrane (ΔNa+mem) and weak transendothelial (ΔNa+end) gradients respectively, and these manifest the cell membrane potential (Vm) as well as blood–brain barrier (BBB) integrity. We developed a sodium (23Na) magnetic resonance spectroscopic imaging (MRSI) method using an intravenously-administered paramagnetic polyanionic agent to measure ΔNa+mem and ΔNa+end. In vitro 23Na-MRSI established that the 23Na signal is intensely shifted by the agent compared to other biological factors (e.g., pH and temperature). In vivo 23Na-MRSI showed Na+i remained unshifted and Na+b was more shifted than Na+e, and these together revealed weakened ΔNa+mem and enhanced ΔNa+end in rat gliomas (vs. normal tissue). Compared to normal tissue, RG2 and U87 tumors maintained weakened ΔNa+mem (i.e., depolarized Vm) implying an aggressive state for proliferation, whereas RG2 tumors displayed elevated ∆Na+end suggesting altered BBB integrity. We anticipate that 23Na-MRSI will allow biomedical explorations of perturbed Na+ homeostasis in vivo.
Impact of device scaling on the electrical properties of MoS2 field-effect transistors
Authors: Arutchelvan Goutham , Smets Quentin , Verreck Devin , Ahmed Zubair , Gaur Abhinav , Sutar Surajit , Jussot Julien , Groven Benjamin , Heyns Marc , Lin Dennis , Asselberghs Inge , Radu Iuliana
Published: March 2021

Two-dimensional semiconducting materials are considered as ideal candidates for ultimate device scaling. However, a systematic study on the performance and variability impact of scaling the different device dimensions is still lacking. Here we investigate the scaling behavior across 1300 devices fabricated on large-area grown MoS2 material with channel length down to 30 nm, contact length down to 13 nm and capacitive effective oxide thickness (CET) down to 1.9 nm. These devices show best-in-class performance with transconductance of 185 μS/μm and a minimum subthreshold swing (SS) of 86 mV/dec. We find that scaling the top-contact length has no impact on the contact resistance and electrostatics of three monolayers MoS2 transistors, because edge injection is dominant. Further, we identify that SS degradation occurs at short channel length and can be mitigated by reducing the CET and lowering the Schottky barrier height. Finally, using a power performance area (PPA) analysis, we present a roadmap of material improvements to make 2D devices competitive with silicon gate-all-around devices.
Antibacterial activity testing methods for hydrophobic patterned surfaces
Authors: Perez-Gavilan Ana , de Castro Joana Vieira , Arana Ainara , Merino Santos , Retolaza Aritz , Alves Sofia A. , Francone Achille , Kehagias Nikolaos , Sotomayor-Torres Clivia M. , Cocina Donato , Mortera Renato , Crapanzano Salvatore , Pelegrín Carlos Javier , Garrigos María Carmen , Jiménez Alfonso , Galindo Begoña , Araque Mari Carmen , Dykeman Donna , Neves Nuno M. , Marimón Jose Maria
Published: March 2021

One strategy to decrease the incidence of hospital-acquired infections is to avoid the survival of pathogens in the environment by the development of surfaces with antimicrobial activity. To study the antibacterial behaviour of active surfaces, different approaches have been developed of which ISO 22916 is the standard. To assess the performance of different testing methodologies to analyse the antibacterial activity of hydrophobic surface patterned plastics as part of a Horizon 2020 European research project. Four different testing methods were used to study the antibacterial activity of a patterned film, including the ISO 22916 standard, the immersion method, the touch-transfer inoculation method, and the swab inoculation method, this latter developed specifically for this project. The non-realistic test conditions of the ISO 22916 standard showed this method to be non-appropriate in the study of hydrophobic patterned surfaces. The immersion method also showed no differences between patterned films and smooth controls due to the lack of attachment of testing bacteria on both surfaces. The antibacterial activity of films could be demonstrated by the touch-transfer and the swab inoculation methods, that more precisely mimicked the way of high-touch surfaces contamination, and showed to be the best methodologies to test the antibacterial activity of patterned hydrophobic surfaces. A new ISO standard would be desirable as the reference method to study the antibacterial behaviour of patterned surfaces.
Risk and mortality of aspiration pneumonia in Parkinson’s disease: a nationwide database study
Authors: Won Jun Hee , Byun Seong Jun , Oh Byung-Mo , Park Sang Jun , Seo Han Gil
Published: March 2021

This retrospective cohort study investigated the risk and mortality rate due to aspiration pneumonia in patients with Parkinson’s disease (PD) using a nationwide database. We identified 10,159 newly diagnosed PD patients between 2004 and 2006, and four age- and sex-matched controls for each PD patient from the National Health Insurance Service database in Korea. We analyzed the relative risk of aspiration pneumonia and mortality after the first occurrence of aspiration pneumonia until 2017. Throughout the study period, PD patients showed a higher incidence of aspiration pneumonia than their matched controls (3.01 vs. 0.59 events per 1,000 person-years), and they were at an increased risk of aspiration pneumonia (hazard ratio = 4.21; 95% confidence interval, 3.87–4.58). After the first occurrence of aspiration pneumonia, the mortality rate of PD patients was 23.9% after one month, 65.2% after 1 year, and 91.8% after 5 years, while that of controls was 30.9%, 67.4%, and 88.9%, respectively. Patients with PD are at an increased risk of aspiration pneumonia, and approximately two-thirds of the patients die within a year after experiencing aspiration pneumonia. Further studies are warranted to prevent aspiration pneumonia and implement proper treatments to prevent death after aspiration pneumonia in patients with PD.
Efficacy of combination treatment using YHO-1701, an orally active STAT3 inhibitor, with molecular-targeted agents on cancer cell lines
Authors: Taniguchi Keisuke , Konishi Hiroaki , Yoshinaga Akiko , Tsugane Momomi , Takahashi Hiroyuki , Nishisaka Fukiko , Shishido Yoshiyuki , Asai Akira
Published: March 2021

Signal transducer and activator of transcription 3 (STAT3) plays a critical role in regulating cell growth, survival, and metastasis. STAT3 signaling is constitutively activated in various types of hematologic or solid malignancies. YHO-1701 has been developed as an orally available STAT3 inhibitor. Herein, YHO-1701 in combination with molecular-targeted agents was evaluated. Additive or synergistic effects were observed in a broad spectrum of “combination treatment + cell line” pairs. Of particular interest was the synergistic effect observed when YHO-1701 was combined with imatinib or dasatinib [breakpoint cluster region-abelson (BCR-ABL) inhibitors], osimertinib [epidermal growth factor receptor (EGFR) inhibitor], crizotinib, alectinib, or ceritinib [anaplastic lymphoma kinase (ALK) inhibitors]. The results further showed a close relationship between these synergistic effects and the cellular levels of the key molecules involved in the target pathways for YHO-1701 and each combination drug. The combination of YHO-1701 with alectinib resulted in significantly greater antitumor activity without exhibiting body weight loss in an NCI-H2228 [echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion] xenograft mouse model. Our results strongly suggest that the logical strategy in combination with the novel STAT3 inhibitor YHO-1701 and other mechanistically different targeted agents, could be a promising approach in future clinical settings.
Implication of O2 dynamics for both N2O and CH4 emissions from soil during biological soil disinfestation
Authors: Wang Chen , Ma Xuehong , Wang Gang , Li Guitong , Zhu Kun
Published: March 2021

Soil O2 dynamics have significant influences on greenhouse gas emissions during soil management practice. In this study, we deployed O2-specific planar optodes to visualize spatiotemporal distribution of O2 in soils treated with biological soil disinfestation (BSD). This study aimed to reveal the role of anoxia development on emissions of N2O and CH4 from soil amended with crop residues during BSD period. The incorporation of crop residues includes wheat straw only, wheat straw with biochar and early straw incorporation. The anoxia in soil developed very fast within 3 days, while the O2 in headspace decreased much slower and it became anaerobic after 5 days, which was significantly affected by straw and biochar additions. The N2O emissions were positively correlated with soil hypoxic fraction. The CH4 emissions were not significant until the anoxia dominated in both soil and headspace. The co-application of biochar with straw delayed the anoxia development and extended the hypoxic area in soil, resulting in lower emissions of N2O and CH4. Those results highlight that the soil O2 dynamic was the key variable triggering the N2O and CH4 productions. Therefore, detailed information of soil O2 availability could be highly beneficial for optimizing the strategies of organic amendments incorporation in the BSD technique.
PPV distribution of sidewalls induced by underground cavern blasting excavation
Authors: Luo Yi , Wei Xiaoqing , Huang Junhong , Zhang Guang , Bian Xing , Li Xinping
Published: March 2021

The peak particle velocity (PPV) is an important indicator for predicting blasting excavation disturbances. However, the PPV distribution in the deep underground space is significantly different from that on the outdoor ground. Therefore, it is difficult to predict the underground PPV by Sadovsky’s vibration formula. The PPV sidewall distribution characteristics were studied during site blasting in an underground cavern in the Taohuazui mine in China, and a similar numerical model was used to verify the site test data. We derived a PPV prediction formula for the underground cavern sidewall surrounding rock using a mechanical analysis model of a simply supported plate and beam in combination with dimensional analysis. The model considered derived boundary constraints, comparison with site measured data, the value predicted by Sadovsky’s vibration formula, and numerical simulation results. The results showed that the PPV distribution on the middle 1/3 section of the underground cavern sidewall showed a “platform” or “bulge” different from the curve from Sadovsky’s vibration formula. The PPV amplification coefficient in this section was distributed in a drum shape. The PPV prediction formula for the middle section of the sidewall derived in this paper was highly consistent with the data measured on-site and the numerical simulation results. The mechanical analysis model with a simply supported plate and beam included an underground cavern sidewall length–height ratio of 5 and effectively supplemented the PPV prediction formula for the middle section of the traditional underground cavern sidewall.
Mid infrared polarization engineering via sub-wavelength biaxial hyperbolic van der Waals crystals
Authors: Dixit Saurabh , Sahoo Nihar Ranjan , Mall Abhishek , Kumar Anshuman
Published: March 2021

Mid-infrared (IR) spectral region is of immense importance for astronomy, medical diagnosis, security and imaging due to the existence of the vibrational modes of many important molecules in this spectral range. Therefore, there is a particular interest in miniaturization and integration of IR optical components. To this end, 2D van der Waals (vdW) crystals have shown great potential owing to their ease of integration with other optoelectronic platforms and room temperature operation. Recently, 2D vdW crystals of $$\alpha$$
α
-$$\hbox {MoO}_{3}$$

MoO
3

and $$\alpha$$
α
-$$\hbox {V}_2 \hbox {O}_5$$

V
2

O
5

have been shown to possess the unique phenomenon of natural in-plane biaxial hyperbolicity in the mid-infrared frequency regime at room temperature. Here, we report a unique application of this in-plane hyperbolicity for designing highly efficient, lithography free and extremely subwavelength mid-IR photonic devices for polarization engineering. In particular, we show the possibility of a significant reduction in the device footprint while maintaining an enormous extinction ratio from $$\alpha$$
α
-$$\hbox {MoO}_{3}$$

MoO
3

and $$\alpha$$
α
-$$\hbox {V}_2$$

V
2

$$\hbox {O}_5$$

O
5

based mid-IR polarizers. Furthermore, we investigate the application of sub-wavelength thin films of these vdW crystals towards engineering the polarization state of incident mid-IR light via precise control of polarization rotation, ellipticity and relative phase. We explain our results using natural in-plane hyperbolic anisotropy of $$\alpha$$
α
-$$\hbox {MoO}_{3}$$

MoO
3

and $$\alpha$$
α
-$$\hbox {V}_2$$

V
2

$$\hbox {O}_5$$

O
5

via both analytical and full-wave electromagnetic simulations. This work provides a lithography free alternative for miniaturized mid-infrared photonic devices using the hyperbolic anisotropy of $$\alpha$$
α
-$$\hbox {MoO}_{3}$$

MoO
3

and $$\alpha$$
α
-$$\hbox {V}_2$$

V
2

$$\hbox {O}_5$$

O
5

.
Improved biodiesel production from waste cooking oil with mixed methanol–ethanol using enhanced eggshell-derived CaO nano-catalyst
Authors: Erchamo Yeshimebet Simeon , Mamo Tadios Tesfaye , Workneh Getachew Adam , Mekonnen Yedilfana Setarge
Published: March 2021

In this report, the utilization of mixed methanol–ethanol system for the production of biodiesel from waste cooking oil (WCO) using enhanced eggshell-derived calcium oxide (CaO) nano-catalyst was investigated. CaO nano-catalyst was produced by calcination of eggshell powder at 900 °C and followed by hydration-dehydration treatment to improve its catalytic activity. The particle size, morphology, and elemental composition of a catalyst were characterized by using XRD, SEM, and EDX techniques, respectively. After hydration-dehydration the shape of a catalyst was changed from a rod-like to honeycomb-like porous microstructure. Likewise, average particle size was reduced from 21.30 to 13.53 nm, as a result, its surface area increases. The main factors affecting the biodiesel yield were investigated, accordingly, an optimal biodiesel yield of 94% was obtained at 1:12 oil to methanol molar ratio, 2.5 wt% catalyst loading, 60 °C, and 120-min reaction time. A biodiesel yield of 88% was obtained using 6:6 equimolar ratio of methanol to ethanol, the yield even increased to 91% by increasing the catalyst loading to 3.5 wt%. Moreover, by slightly increasing the share of methanol in the mixture, at 8:4 ratio, the maximum biodiesel yield could reach 92%. Therefore, we suggest the utilization of methanol–ethanol mixture as a reactant and eggshell-derived CaO as a catalyst for enhanced conversion of WCO into biodiesel. It is a very promising approach for the development of low-cost and environmentally friendly technology. Properties of the biodiesel were also found in good agreement with the American (ASTM D6571) fuel standards.
Exclusion of patients living with HIV from cancer immune checkpoint inhibitor trials
Authors: Vora Kruti B. , Ricciuti Biagio , Awad Mark M.
Published: March 2021

Emerging retrospective and prospective studies indicate that immune checkpoint inhibitors (ICIs) can be safe and effective cancer treatments among people living with human immunodeficiency virus (PLWH), however this high-cancer-risk population has often been excluded from groundbreaking cancer ICI trials. Our study aimed to characterize the current rate of exclusion and conditional inclusion of PLWH in cancer ICI trials by tumor type, trial phase, and year. ClinicalTrials.gov cancer ICI trials with planned starts between 1/1/2019 and 10/20/2020 were identified. Based on trial eligibility criteria, trials were categorized as “excluded” if PLWH could not enroll, “conditionally included” if only PLWH with adequate immune function were allowed, or “included/not specified” if HIV was not mentioned in the eligibility criteria. Trials from 2014 were separately collected for comparison over time. The number of trials excluding PLWH were compared to the included/not specified group using Fisher’s exact test. Of 809 trials analyzed from 2019 to 2020, 74.4% excluded, 6.9% conditionally included, and 18.7% included/did not specify PLWH. Early phase trials excluded PLWH more frequently than late phase trials. The 2019–2020 trial cohort showed no significant change in exclusion of PLWH compared to 2014. Despite increasing evidence for safe and effective ICI use for PLWH, most cancer ICI trials exclude PLWH and few studies permit PLWH to participate, even if HIV is well-controlled.
Similar major cardiovascular outcomes between pure statin and ezetimibe-statin in comparable intensity for type 2 diabetes with extremely atherosclerotic risks
Authors: Kao Yu-Cheng , Chen Tien-Hsing , Liu Chi-Hung , Hwang Jawl-Shan , Hsiao Ching-Chung , Lin Yu-Sheng , Mao Chun-Tai , Hung Ming-Jui , Li Yan-Rong
Published: March 2021

Atorvastatin 40 mg (ATOR 40) and ezetimibe 10 mg/simvastatin 20 mg (EZ-SIM 20) have similar reductions of low-density lipoprotein cholesterol (LDL-C) but cardiovascular (CV) outcomes between these two therapies are unclear. Our real-world cohort study is to test the hypothesis of pleiotropic effects of purely higher dose statin on CV outcomes beyond similar reductions of LDL-C, especially for extremely CV risk patients. Between January 1, 2007 and December 31, 2013, a total of 3,372 patients with type 2 diabetes mellitus (T2DM) admitted due to acute coronary syndrome (ACS) or acute ischemic stroke (AIS) were selected as the study cohort from the Taiwan National Health Insurance Research Database. Clinical outcomes were evaluated by ATOR 40 group (n = 1686) matched with EZ-SIM 20 group (n = 1686). Primary composite outcome includes CV death, non-fatal myocardial infarction, and non-fatal stroke. Secondary composite outcome includes hospitalization for unstable angina (HUA), percutaneous coronary intervention (PCI), and coronary artery bypass grafting (CABG). With a mean follow-up of 2.4 years, no significant difference of primary composite outcome was observed between ATOR 40 and EZ-SIM 20 groups (subdistribution hazard ratio [SHR], 1.09; 95% confidence interval [CI], 0.95–1.25). Nevertheless, ATOR 40 group had lower risks of HUA (SHR, 0.50; 95% CI, 0.35–0.72), PCI (SHR, 0.82; 95% CI, 0.69–0.97) and CABG (SHR, 0.62; 95% CI, 0.40–0.97) than EZ-SIM 20 group. For T2DM patients after ACS or AIS, ATOR 40 and EZ-SIM 20 had similar major CV outcomes, which still supported the main driver for CV risk reductions is LDL-C lowering.
Characterization of design grammar of peptides for regulating liquid droplets and aggregates of FUS
Authors: Kamagata Kiyoto , Chiba Rika , Kawahata Ichiro , Iwaki Nanako , Kanbayashi Saori , Maeda Kana , Takahashi Hiroto , Hirano Atsushi , Fukunaga Koji , Ikeda Keisuke , Kameda Tomoshi
Published: March 2021

Liquid droplets of aggregation-prone proteins, which become hydrogels or form amyloid fibrils, are a potential target for drug discovery. In this study, we proposed an experiment-guided protocol for characterizing the design grammar of peptides that can regulate droplet formation and aggregation. The protocol essentially involves investigation of 19 amino acid additives and polymerization of the identified amino acids. As a proof of concept, we applied this protocol to fused in sarcoma (FUS). First, we evaluated 19 amino acid additives for an FUS solution and identified Arg and Tyr as suppressors of droplet formation. Molecular dynamics simulations suggested that the Arg additive interacts with specific residues of FUS, thereby inhibiting the cation–π and electrostatic interactions between the FUS molecules. Second, we observed that Arg polymers promote FUS droplet formation, unlike Arg monomers, by bridging the FUS molecules. Third, we found that the Arg additive suppressed solid aggregate formation of FUS, while Arg polymer enhanced it. Finally, we observed that amyloid-forming peptides induced the conversion of FUS droplets to solid aggregates of FUS. The developed protocol could be used for the primary design of peptides controlling liquid droplets and aggregates of proteins.
Different triggers for the two pulses of mass extinction across the Permian and Triassic boundary
Authors: Li Guoshan , Liao Wei , Li Sheng , Wang Yongbiao , Lai Zhongping
Published: March 2021

Widespread ocean anoxia has been proposed to cause biotic mass extinction across the Permian–Triassic (P–Tr) boundary. However, its temporal dynamics during this crisis period are unclear. The Liangfengya section in the South China Block contains continuous marine sedimentary and fossil records. Two pulses of biotic extinction and two mass extinction horizons (MEH 1 & 2) near the P–Tr boundary were identified and defined based on lithology and fossils from the section. The data showed that the two pulses of extinction have different environmental triggers. The first pulse occurred during the latest Permian, characterized by disappearance of algae, large foraminifers, and fusulinids. Approaching the MEH 1, multiple layers of volcanic clay and yellowish micritic limestone occurred, suggesting intense volcanic eruptions and terrigenous influx. The second pulse occurred in the earliest Triassic, characterized by opportunist-dominated communities of low diversity and high abundance, and resulted in a structural marine ecosystem change. The oxygen deficiency inferred by pyrite framboid data is associated with biotic declines above the MEH 2, suggesting that the anoxia plays an important role.