bluuebunny/crossref_metadata_2025 huggingface dataset:
Distinct late Pleistocene subtropical-tropical divergence revealed by fifteen low-copy nuclear genes in a dominant species in South-East China
Authors: Ye Jun-Wei , Li De-Zhu
Published: February 2021

In East Asia, genetic divergence is usually considered to be correlated to different floristic regions, however, subtropical-tropical divergence is largely ignored, compared to widely explored temperate-subtropical divergence. Lindera aggregata (Lauraceae), a dominant species in South-East China was selected to address this issue. Fifteen low-copy nuclear genes (LCGs) and four chloroplast DNA (cpDNA) fragments were used to detect its evolutionary history. In LCGs, STRUCTURE and dated Bayesian phylogeny analyses detect distinct subtropical-tropical divergence since late Pleistocene. Approximate Bayesian calculation (ABC) further supports the distinct subtropical-tropical divergence, and close related Taiwan and South China populations are diverged at the last interglacial. Isolation by distance, isolation by environment and isolation by resistance analyses suggest the current climatic difference rather than geographical distance contributes to the genetic differentiation. Principle component analysis shows populations of tropical cluster occur in warmer area with higher precipitation. Ancestral area reconstruction based on Bayesian phylogeny indicates that ancestral L. aggregata populations are distributed in tropical region. In cpDNA, although unique haplotypes are found in tropical region, distinct subtropical-tropical divergence is absent. In conclusion, distinct late Pleistocene subtropical-tropical divergence of L. aggregata is triggered by climate. It is likely that L. aggregata is originated in Southwest-South China and experienced hierarchical dispersal from south to north. The South China Sea land bridge has dual role in connecting or isolating Taiwan and mainland populations since the last glaciation.
Subseasonal relationship between Arctic and Eurasian surface air temperature
Authors: Kim Hye-Jin , Son Seok-Woo , Moon Woosok , Kug Jong-Seong , Hwang Jaeyoung
Published: February 2021

The subseasonal relationship between Arctic and Eurasian surface air temperature (SAT) is re-examined using reanalysis data. Consistent with previous studies, a significant negative correlation is observed in cold season from November to February, but with a local minimum in late December. This relationship is dominated not only by the warm Arctic-cold Eurasia (WACE) pattern, which becomes more frequent during the last two decades, but also by the cold Arctic-warm Eurasia (CAWE) pattern. The budget analyses reveal that both WACE and CAWE patterns are primarily driven by the temperature advection associated with sea level pressure anomaly over the Ural region, partly cancelled by the diabatic heating. It is further found that, although the anticyclonic anomaly of WACE pattern mostly represents the Ural blocking, about 20% of WACE cases are associated with non-blocking high pressure systems. This result indicates that the Ural blocking is not a necessary condition for the WACE pattern, highlighting the importance of transient weather systems in the subseasonal Arctic-Eurasian SAT co-variability.
Music-based biofeedback to reduce tibial shock in over-ground running: a proof-of-concept study
Authors: Van den Berghe Pieter , Lorenzoni Valerio , Derie Rud , Six Joren , Gerlo Joeri , Leman Marc , De Clercq Dirk
Published: February 2021

Methods to reduce impact in distance runners have been proposed based on real-time auditory feedback of tibial acceleration. These methods were developed using treadmill running. In this study, we extend these methods to a more natural environment with a proof-of-concept. We selected ten runners with high tibial shock. They used a music-based biofeedback system with headphones in a running session on an athletic track. The feedback consisted of music superimposed with noise coupled to tibial shock. The music was automatically synchronized to the running cadence. The level of noise could be reduced by reducing the momentary level of tibial shock, thereby providing a more pleasant listening experience. The running speed was controlled between the condition without biofeedback and the condition of biofeedback. The results show that tibial shock decreased by 27% or 2.96 g without guided instructions on gait modification in the biofeedback condition. The reduction in tibial shock did not result in a clear increase in the running cadence. The results indicate that a wearable biofeedback system aids in shock reduction during over-ground running. This paves the way to evaluate and retrain runners in over-ground running programs that target running with less impact through instantaneous auditory feedback on tibial shock.
TNFR1-d2 carrying the p.(Thr79Met) pathogenic variant is a potential novel actor of TNFα/TNFR1 signalling regulation in the pathophysiology of TRAPS
Authors: Rittore Cécile , Méchin Déborah , Sanchez Elodie , Marinèche Léa , Ea Vuthy , Soler Stephan , Vereecke Marion , Mallavialle Aude , Richard Eric , Duroux-Richard Isabelle , Apparailly Florence , Touitou Isabelle , Grandemange Sylvie
Published: February 2021

Binding of tumour necrosis factor α (TNFα) to its receptor (TNFR1) is critical for both survival and death cellular pathways. TNFα/TNFR1 signalling is complex and tightly regulated at different levels to control cell fate decisions. Previously, we identified TNFR1-d2, an exon 2-spliced transcript of TNFRSF1A gene encoding TNFR1, whose splicing may be modulated by polymorphisms associated with inflammatory disorders. Here, we investigated the impact of TNFRSF1A variants involved in TNFR-associated periodic syndrome (TRAPS) on TNFR1-d2 protein expression and activity. We found that TNFR1-d2 could be translated by using an internal translation initiation codon and a de novo internal ribosome entry site (IRES), which resulted in a putative TNFR1 isoform lacking its N-terminal region. The kinetic of assembly of TNFR1-d2 clusters at the cell surface was reduced as compared with full-length TNFR1. Although co-localized with the full-length TNFR1, TNFR1-d2 neither activated nuclear factor (NF)-κB signalling, nor interfered with TNFR1-induced NF-κB activation. Translation of TNFR1-d2 carrying the severe p.(Thr79Met) pathogenic variant (also known as T50M) was initiated at the mutated codon, resulting in an elongated extracellular domain, increased speed to form preassembled clusters in absence of TNFα, and constitutive NF-κB activation. Overall, TNFR1-d2 might reflect the complexity of the TNFR1 signalling pathways and could be involved in TRAPS pathophysiology of patients carrying the p.(Thr79Met) disease-causing variant.
A/H1N1 hemagglutinin antibodies show comparable affinity in vaccine-related Narcolepsy type 1 and control and are unlikely to contribute to pathogenesis
Authors: Lind Alexander , Marzinotto Ilaria , Brigatti Cristina , Ramelius Anita , Piemonti Lorenzo , Lampasona Vito
Published: February 2021

An increased incidence of narcolepsy type 1 (NT1) was observed in Scandinavia following the 2009–2010 influenza Pandemrix vaccination. The association between NT1 and HLA-DQB1*06:02:01 supported the view of the vaccine as an etiological agent. A/H1N1 hemagglutinin (HA) is the main antigenic determinant of the host neutralization antibody response. Using two different immunoassays, the Luciferase Immunoprecipitation System (LIPS) and Radiobinding Assay (RBA), we investigated HA antibody levels and affinity in an exploratory and in a confirmatory cohort of Swedish NT1 patients and healthy controls vaccinated with Pandemrix. HA antibodies were increased in NT1 patients compared to controls in the exploratory (LIPS p = 0.0295, RBA p = 0.0369) but not in the confirmatory cohort (LIPS p = 0.55, RBA p = 0.625). HA antibody affinity, assessed by competition with Pandemrix vaccine, was comparable between patients and controls (LIPS: 48 vs. 39 ng/ml, p = 0.81; RBA: 472 vs. 491 ng/ml, p = 0.65). The LIPS assay also detected higher HA antibody titres as associated with HLA-DQB1*06:02:01 (p = 0.02). Our study shows that following Pandemrix vaccination, HA antibodies levels and affinity were comparable NT1 patients and controls and suggests that HA antibodies are unlikely to play a role in NT1 pathogenesis.
Association between EBV serological patterns and lymphocytic profile of SjS patients support a virally triggered autoimmune epithelitis
Authors: Barcelos Filipe , Martins Catarina , Monteiro Ricardo , Cardigos Joana , Prussiani Tiziano , Sítima Miguel , Alves Nuno , Vaz-Patto José , Cunha-Branco Jaime , Borrego Luís-Miguel
Published: February 2021

Sjögren's syndrome (SjS) is characterized by lymphocytic infiltration of exocrine glands, i.e. autoimmune epithelitis. Lymphocytes are central in SjS pathogenesis, with B-cell hyperactivity mediated by T-cells. B-cells are main targets of Epstein-Barr virus (EBV) infection, a frequently-suggested trigger for SjS. We aimed to evaluate how the EBV infection modulates B and T-cell subsets in SjS, including as controls Rheumatoid arthritis patients (RA) and healthy participants (HC). SjS patients presented decreased CXCR5+T-cells, although IL21-secreting Tfh and Tfc cells were increased. Tfc were positively correlated with ESSDAI scores, suggesting their relevant role in SjS pathogenesis. As previously described, SjS patients showed expanded circulating naïve B-cell compartments. SjS patients had a higher incidence of EBV-EA-D-IgG+ antibodies, characteristic of recent EBV-infection/reactivation. SjS patients with past infection or recent infection/reactivation showed increased CXCR3+Th1 and CXCR3+Tfh1 cells compared to those without active infection. SjS patients with a recent infection/reactivation profile presented increased transitional B-cells compared to patients with past infection and increased plasmablasts, compared to those without infection. Our results suggest EBV-infection contributes to B and T-cell differentiation towards the effector phenotypes typical of SjS. Local lymphocyte activation at ectopic germinal centres, mediated by Tfh and Tfc, can be EBV-driven, perpetuating autoimmune epithelitis, which leads to gland destruction in SjS.
The look ahead trace back optimizer for genomic selection under transparent and opaque simulators
Authors: Amini Fatemeh , Franco Felipe Restrepo , Hu Guiping , Wang Lizhi
Published: February 2021

Recent advances in genomic selection (GS) have demonstrated the importance of not only the accuracy of genomic prediction but also the intelligence of selection strategies. The look ahead selection algorithm, for example, has been found to significantly outperform the widely used truncation selection approach in terms of genetic gain, thanks to its strategy of selecting breeding parents that may not necessarily be elite themselves but have the best chance of producing elite progeny in the future. This paper presents the look ahead trace back algorithm as a new variant of the look ahead approach, which introduces several improvements to further accelerate genetic gain especially under imperfect genomic prediction. Perhaps an even more significant contribution of this paper is the design of opaque simulators for evaluating the performance of GS algorithms. These simulators are partially observable, explicitly capture both additive and non-additive genetic effects, and simulate uncertain recombination events more realistically. In contrast, most existing GS simulation settings are transparent, either explicitly or implicitly allowing the GS algorithm to exploit certain critical information that may not be possible in actual breeding programs. Comprehensive computational experiments were carried out using a maize data set to compare a variety of GS algorithms under four simulators with different levels of opacity. These results reveal how differently a same GS algorithm would interact with different simulators, suggesting the need for continued research in the design of more realistic simulators. As long as GS algorithms continue to be trained in silico rather than in planta, the best way to avoid disappointing discrepancy between their simulated and actual performances may be to make the simulator as akin to the complex and opaque nature as possible.
Air pollution exposure is linked with methylation of immunoregulatory genes, altered immune cell profiles, and increased blood pressure in children
Authors: Prunicki Mary , Cauwenberghs Nicholas , Lee Justin , Zhou Xiaoying , Movassagh Hesam , Noth Elizabeth , Lurmann Fred , Hammond S. Katharine , Balmes John R. , Desai Manisha , Wu Joseph C. , Nadeau Kari C.
Published: February 2021

Ambient air pollution exposure is associated with cardiovascular dysregulation and immune system alterations, yet no study has investigated both simultaneously in children. Understanding the multifaceted impacts may provide early clues for clinical intervention prior to actual disease presentation. We therefore determined the associations between exposure to multiple air pollutants and both immunological outcomes (methylation and protein expression of immune cell types associated with immune regulation) and cardiovascular outcomes (blood pressure) in a cohort of school-aged children (6–8 years; n = 221) living in a city with known elevated pollution levels. Exposure to fine particular matter (PM2.5), carbon monoxide (CO), and ozone (O3) was linked to altered methylation of most CpG sites for genes Foxp3, IL-4, IL-10 and IFN-g, all involved in immune regulation (e.g. higher PM2.5 exposure 1 month prior to the study visit was independently associated with methylation of the IL-4 CpG24 site (est = 0.16; P = 0.0095). Also, immune T helper cell types (Th1, Th2 and Th17) were associated with short-term exposure to PM2.5, O3 and CO (e.g. Th1 cells associated with PM2.5 at 30 days: est = − 0.34, P < 0.0001). Both B cells (est = − 0.19) and CD4+ cells (est = 0.16) were associated with 1 day NO2 exposure (P ≤ 0.031), whereas CD4+ and CD8+ cells were associated with chronic exposure to PAH456, NOx and/or NO2 (P ≤ 0.038 for all). Finally, diastolic BP (DBP) was inversely associated with long-term exposures to both CO and PAH456, and both systolic and pulse pressure were associated with short-term NO2 and chronic NOx exposure. Our findings demonstrate links between air pollution exposure and methylation of immunoregulatory genes, immune cell profiles and blood pressure, suggesting that even at a young age, the immune and cardiovascular systems are negatively impacted by exposure to air pollution.
Chemosensitizing activity of peptide from Lentinus squarrosulus (Mont.) on cisplatin-induced apoptosis in human lung cancer cells
Authors: Khine Hnin Ei Ei , Ecoy Gea Abigail Uy , Roytrakul Sittiruk , Phaonakrop Narumon , Pornputtapong Natapol , Prompetchara Eakachai , Chanvorachote Pithi , Chaotham Chatchai
Published: February 2021

The limitations of cisplatin, a standard chemotherapy for lung cancer, have been documented with serious adverse effects and drug resistance. To address the need for novel therapy, this study firstly reveals the potential of peptide fromLentinus squarrosulus(Mont.) as a chemotherapeutic adjuvant for cisplatin treatment. The purified peptide fromL. squarrosulusaqueous extracts was obtained after eluting with 0.4 M NaCl through FPLC equipped with anion exchange column. Preincubation for 24 h with 5 µg/mL of the peptide at prior to treatment with 5 µM cisplatin significantly diminished %cell viability in various human lung cancer cells but not in human dermal papilla and proximal renal cells. Flow cytometry indicated the augmentation of cisplatin-induced apoptosis in lung cancer cells pretreated with peptide fromL. squarrosulus. Preculture with the peptide dramatically inhibited colony formation in lung cancer cells derived after cisplatin treatment. Strong suppression on integrin-mediated survival was evidenced with the diminution of integrins (β1, β3, β5, α5, αV) and down-stream signals (p-FAK/FAK, p-Src/Src, p-Akt/Akt) consequence with alteration of p53, Bax, Blc-2 and Mcl-1 in cisplatin-treated lung cancer cells preincubated with peptide fromL. squarrosulus. These results support the development ofL. squarrosuluspeptide as a novel combined chemotherapy with cisplatin for lung cancer treatment.
Overexpression of aberrant Wnt5a and its effect on acquisition of malignant phenotypes in adult T-cell leukemia/lymphoma (ATL) cells
Authors: Nakano Kazumi , Chihara Yohei , Kobayashi Seiichiro , Iwanaga Masako , Utsunomiya Atae , Watanabe Toshiki , Uchimaru Kaoru
Published: February 2021

Wnt5a is a ligand of the non-canonical Wnt signaling pathway involved in cell differentiation, motility, and inflammatory response. Adult T-cell leukemia/lymphoma (ATL) is one of the most aggressive T-cell malignancies caused by infection of human T-cell leukemia virus type1 (HTLV-1). Among subtypes of ATL, acute-type ATL cells are particularly resistant to current multidrug chemotherapies and show remarkably high cell-proliferative and invasive phenotypes. Here we show a dramatic increase of WNT5A gene expression in acute-type ATL cells compared with those of indolent-type ATL cells. Treatment with IWP-2 or Wnt5a-specific knockdown significantly suppressed cell growth of ATL-derived T-cell lines. We demonstrated that the overexpression of c-Myb and FoxM1 was responsible for the synergistic activation of the WNT5A promoter. Also, a WNT5A transcript variant without the exon4 (the ΔE4-WNT5A mRNA), encoding ΔC-Wnt5 (1-136aa of 380aa), is overexpressed in acute-type ATL cells. The ΔC-Wnt5a is secreted extracellularly and enhances cellular migration/invasion to a greater extent compared with wildtype (WT)-Wnt5a. Moreover, the ΔC-Wnt5a secretion was not suppressed by IWP-2, indicating that this mutant Wnt5a is secreted via a different pathway from the WT-Wnt5a. Taken together, synergistic overexpression of the ΔC-Wnt5a by c-Myb and FoxM1 may be responsible for the malignant phenotype of acute-type ATL cells.
Structure based pharmacophore modeling, virtual screening, molecular docking and ADMET approaches for identification of natural anti-cancer agents targeting XIAP protein
Authors: Opo Firoz A. Dain Md , Rahman Mohammed M. , Ahammad Foysal , Ahmed Istiak , Bhuiyan Mohiuddin Ahmed , Asiri Abdullah M.
Published: February 2021

X-linked inhibitor of apoptosis protein (XIAP) is a member of inhibitor of apoptosis protein (IAP) family responsible for neutralizing the caspases-3, caspases-7, and caspases-9. Overexpression of the protein decreased the apoptosis process in the cell and resulting development of cancer. Different types of XIAP antagonists are generally used to repair the defective apoptosis process that can eliminate carcinoma from living bodies. The chemically synthesis compounds discovered till now as XIAP inhibitors exhibiting side effects, which is making difficulties during the treatment of chemotherapy. So, the study has design to identifying new natural compounds that are able to induce apoptosis by freeing up caspases and will be low toxic. To identify natural compound, a structure-based pharmacophore model to the protein active site cavity was generated following by virtual screening, molecular docking and molecular dynamics (MD) simulation. Initially, seven hit compounds were retrieved and based on molecular docking approach four compounds has chosen for further evaluation. To confirm stability of the selected drug candidate to the target protein the MD simulation approach were employed, which confirmed stability of the three compounds. Based on the finding, three newly obtained compounds namely Caucasicoside A (ZINC77257307), Polygalaxanthone III (ZINC247950187), and MCULE-9896837409 (ZINC107434573) may serve as lead compounds to fight against the treatment of XIAP related cancer, although further evaluation through wet lab is necessary to measure the efficacy of the compounds.
An LDV based method to quantify the error of PC-MRI derived Wall Shear Stress measurement
Authors: Castagna Marco , Levilly Sébastien , Paul-Gilloteaux Perrine , Moussaoui Saïd , Rousset Jean-Marc , Bonnefoy Félicien , Idier Jérôme , Serfaty Jean-Michel , Le Touzé David
Published: February 2021

Wall Shear Stress (WSS) has been demonstrated to be a biomarker of the development of atherosclerosis. In vivo assessment of WSS is still challenging, but 4D Flow MRI represents a promising tool to provide 3D velocity data from which WSS can be calculated. In this study, a system based on Laser Doppler Velocimetry (LDV) was developed to validate new improvements of 4D Flow MRI acquisitions and derived WSS computing. A hydraulic circuit was manufactured to allow both 4D Flow MRI and LDV velocity measurements. WSS profiles were calculated with one 2D and one 3D method. Results indicated an excellent agreement between MRI and LDV velocity data, and thus the set-up enabled the evaluation of the improved performances of 3D with respect to the 2D-WSS computation method. To provide a concrete example of the efficacy of this method, the influence of the spatial resolution of MRI data on derived 3D-WSS profiles was investigated. This investigation showed that, with acquisition times compatible with standard clinical conditions, a refined MRI resolution does not improve WSS assessment, if the impact of noise is unreduced. This study represents a reliable basis to validate with LDV WSS calculation methods based on 4D Flow MRI.
Increasing benthic vent formation: a threat to Japan’s ancient lake
Authors: Kumagai Michio , Robarts Richard D. , Aota Yasuaki
Published: February 2021

An autonomous underwater vehicle (AUV) was deployed in Lake Biwa from 2000 to 2012. In December 2009, ebullition of turbid water was first found in the deepest area (> 90 m) of the North Basin. Follow-up investigations in April and December 2010 and January 2012 confirmed the existence of benthic vents similar to the vents observed in other deep lakes. Importantly, vent numbers per unit travel distance in Lake Biwa dramatically increased from only two vents (0.37 vents km−1) in December 2009 to 54 vents (5.28 vents km−1) in January 2012, which could be related to recent tectonic activity in Japan, e.g., the M9.1 Tohoku earthquake in March 2011 and slow earthquakes along the Nankai Trough from 2006 to 2018. Continuous back-up investigations from 2014 to 2019 revealed additional benthic vents in the same area. The sudden increase in benthic vent activity (liquid and gaseous ebullitions) have significant potential to alter lake biogeochemistry and, ultimately, degrade Japan’s major drinking water source and may be a harbinger of major crustal change in the near future.
Direct evidence of electronic ferroelectricity in YbFe2O4 using neutron diffraction and nonlinear spectroscopy
Authors: Fujiwara K. , Fukada Y. , Okuda Y. , Seimiya R. , Ikeda N. , Yokoyama K. , Yu H. , Koshihara S. , Okimoto Y.
Published: February 2021

We report the first observation of room temperature spontaneous electric polarization in an electronic ferroelectric material, a YbFe2O4 single crystal. The observation was based on second harmonic generation (SHG), a nonlinear optical process. Tensor analysis of the SHG signal revealed that this material has a polar charge superstructure with Cm symmetry. This result settles the long-term discussion on the uncertainty about electronic ferroelectric properties, including the charge order structure. We present a complete picture of the polar charge ordering of this material via consistent results from two different characterization methods. The SHG signal shows the same temperature dependence as the superlattice signal observed in neutron diffraction experiments. These results prove ferroelectric coupling to electron ordering in YbFe2O4, which results in electronic ferroelectricity which is enabled by the real space ordering of iron cations with different valences. The existence of electronic ferroelectricity holds promise for future electronics technologies where devices run a thousand times faster than frequency of the present CPU (a few gigahertz) embedded in smartphones, etc.
Retinal ganglion cell dysfunction in mice following acute intraocular pressure is exacerbated by P2X7 receptor knockout
Authors: Wang Anna Y. M. , Wong Vickie H. Y. , Lee Pei Ying , Bui Bang V. , Dudczig Stefanie , Vessey Kirstan A. , Fletcher Erica L.
Published: February 2021

There is increasing evidence for the vulnerability of specific retinal ganglion cell (RGC) types in those with glaucoma and in animal models. In addition, the P2X7-receptor (P2X7-R) has been suggested to contribute to RGC death following stimulation and elevated IOP, though its role in RGC dysfunction prior to death has not been examined. Therefore, we examined the effect of an acute, non-ischemic intraocular pressure (IOP) insult (50 mmHg for 30 min) on RGC function in wildtype mice and P2X7-R knockout (P2X7-KO) mice. We examined retinal function using electroretinogram recordings and individual RGC responses using multielectrode arrays, 3 days following acute IOP elevation. Immunohistochemistry was used to examine RGC cell death and P2X7-R expression in several RGC types. Acute intraocular pressure elevation produced pronounced dysfunction in RGCs; whilst other retinal neuronal responses showed lesser changes. Dysfunction at 3 days post-injury was not associated with RGC loss or changes in receptive field size. However, in wildtype animals, OFF-RGCs showed reduced spontaneous and light-elicited activity. In the P2X7-KO, both ON- and OFF-RGC light-elicited responses were reduced. Expression of P2X7-R in wildtype ON-RGC dendrites was higher than in other RGC types. In conclusion, OFF-RGCs were vulnerable to acute IOP elevation and their dysfunction was not rescued by genetic ablation of P2X7-R. Indeed, knockout of P2X7-R also caused ON-RGC dysfunction. These findings aid our understanding of how pressure affects RGC function and suggest treatments targeting the P2X7-R need to be carefully considered.
Seepage field characteristic and stability analysis of tailings dam under action of chemical solution
Authors: Wang Guangjin , Hu Bin , Tian Sen , Ai Min , Liu Wenlian , Kong Xiangyun
Published: February 2021

As one of the important influencing factors of tailings dam stability, seepage field distribution within the dam is often affected by the tailings mineral characteristics. While the alkalinity or acidity of reservoir water and long term immersion will partially change the physical and mechanical properties of tailings. This study carried out permeability tests of tailings under the action of chemical solution. On this basis, a three dimensional (3D) model was constructed to analyze the velocity field and effective saturation within the tailings dam. Moreover, the dam section along the valley bottom was selected as the basic section in calculation, so as to analyze the changes in infiltration point and buried depth of the phreatic line under different permeability coefficient ratios. The results suggest that, under the action of acid-alkaline solution, the permeability coefficients of tailings reduced, and the stronger solution acidity-alkalinity resulted in the longer action time and more obvious change; under the action of chemical solution, the fluid flow velocity in the dam gradually decreased, and the drat beach length in the reservoir gradually shortened. Besides, when the upper layer permeability coefficients of tailings was lower than that of the lower layer, the dam phreatic line had a shallow buried depth and a high infiltration point.
Modern dolomite formation caused by seasonal cycling of oxygenic phototrophs and anoxygenic phototrophs in a hypersaline sabkha
Authors: Diloreto Zach A. , Garg Sanchit , Bontognali Tomaso R. R. , Dittrich Maria
Published: February 2021

The “Dolomite Problem” has been a controversy for over a century, owing to massive assemblages of low-temperature dolomite in ancient rocks with little dolomite forming today despite favorable geochemical conditions. Experiments show that microbes and their exopolymeric substances (EPS) nucleate dolomite. However, factors controlling ancient abundances of dolomite can still not be explained. To decode the enigma of ancient dolomite, we examined a modern dolomite forming environment, and found that a cyclic shift in microbial community between cyanobacteria and anoxygenic phototrophs creates EPS suited to dolomite precipitation. Specifically, EPS show an increased concentration of carboxylic functional groups as microbial composition cycles from cyanobacterial to anoxygenic phototroph driven communities at low-and high- salinity, respectively. Comparing these results to other low-T forming environments suggests that large turnover of organic material under anoxic conditions is an important driver of the process. Consequently, the shift in atmospheric oxygen throughout Earth’s history may explain important aspects of “The Dolomite Problem”. Our results provide new context for the interpretation of dolomite throughout Earth’s history.
Inverse relation between structural flexibility and IgE reactivity of Cor a 1 hazelnut allergens
Authors: Führer Sebastian , Kamenik Anna S. , Zeindl Ricarda , Nothegger Bettina , Hofer Florian , Reider Norbert , Liedl Klaus R. , Tollinger Martin
Published: February 2021

A major proportion of allergic reactions to hazelnuts (Corylus avellana) are caused by immunologic cross-reactivity of IgE antibodies to pathogenesis-related class 10 (PR-10) proteins. Intriguingly, the four known isoforms of the hazelnut PR-10 allergen Cor a 1, denoted as Cor a 1.0401–Cor a 1.0404, share sequence identities exceeding 97% but possess different immunologic properties. In this work we describe the NMR solution structures of these proteins and provide an in-depth study of their biophysical properties. Despite sharing highly similar three-dimensional structures, the four isoforms exhibit remarkable differences regarding structural flexibility, hydrogen bonding and thermal stability. Our experimental data reveal an inverse relation between structural flexibility and IgE-binding in ELISA experiments, with the most flexible isoform having the lowest IgE-binding potential, while the isoform with the most rigid backbone scaffold displays the highest immunologic reactivity. These results point towards a significant entropic contribution to the process of antibody binding.
Experimental demonstrations of unconditional security in a purely classical regime
Authors: Ham Byoung S.
Published: February 2021

So far, unconditional security in key distribution processes has been confined to quantum key distribution (QKD) protocols based on the no-cloning theorem of nonorthogonal bases. Recently, a completely different approach, the unconditionally secured classical key distribution (USCKD), has been proposed for unconditional security in the purely classical regime. Unlike QKD, both classical channels and orthogonal bases are key ingredients in USCKD, where unconditional security is provided by deterministic randomness via path superposition-based reversible unitary transformations in a coupled Mach–Zehnder interferometer. Here, the first experimental demonstration of the USCKD protocol is presented.
RETRACTED ARTICLE: Establishment of an Acanthamoeba keratitis mouse model confirmed by amoebic DNA amplification
Authors: Kang Heekyoung , Sohn Hae-Jin , Park A-Young , Ham A-Jeong , Lee Jeong-Heon , Oh Young-Hwan , Chwae Yong-Joon , Kim Kyongmin , Park Sun , Yang Hongseok , Jung Suk-Yul , Kim Jong-Hyun , Shin Ho-Joon
Published: February 2021

Acanthamoeba castellanii, the causative agent of Acanthamoeba keratitis (AK), occurs mainly in contact lens users with poor eye hygiene. The findings of many in vitro studies of AK, as well as the testing of therapeutic drugs, need validation in in vivo experiments. BALB/c mice were used in this study to establish in vivo AK model. A. castellanii cell suspensions (equal mixtures of trophozoites and cysts) were loaded onto 2-mm contact lens pieces and inserted into mouse eyes that were scratched using an ophthalmic surgical blade under anesthesia and the eyelids of the mice were sutured. The AK signs were grossly observed and PCR was performed using P-FLA primers to amplify the Acanthamoeba 18S-rRNA gene from mouse ocular tissue. The experimental AK mouse model was characterized by typical hazy blurring and melting of the mouse cornea established on day 1 post-inoculation. AK was induced with at least 0.3 × 105
A. castellanii cells (optimal number, 5 × 104), and the infection persisted for two months. The PCR products amplified from the extracted mouse eye DNA confirmed the development of Acanthamoeba-induced keratitis during the infection periods. In conclusion, the present AK mouse model may serve as an important in vivo model for the development of various therapeutic drugs against AK.
Antagonizing the spindle assembly checkpoint silencing enhances paclitaxel and Navitoclax-mediated apoptosis with distinct mechanistic
Authors: Henriques Ana C. , Silva Patrícia M. A. , Sarmento Bruno , Bousbaa Hassan
Published: February 2021

Antimitotic drugs arrest cells in mitosis through chronic activation of the spindle assembly checkpoint (SAC), leading to cell death. However, drug-treated cancer cells can escape death by undergoing mitotic slippage, due to premature mitotic exit. Therefore, overcoming slippage issue is a promising chemotherapeutic strategy to improve the effectiveness of antimitotics. Here, we antagonized SAC silencing by knocking down the MAD2-binding protein p31comet, to delay mitotic slippage, and tracked cancer cells treated with the antimitotic drug paclitaxel, over 3 days live-cell time-lapse analysis. We found that in the absence of p31comet, the duration of mitotic block was increased in cells challenged with nanomolar concentrations of paclitaxel, leading to an additive effects in terms of cell death which was predominantly anticipated during the first mitosis. As accumulation of an apoptotic signal was suggested to prevent mitotic slippage, when we challenged p31comet-depleted mitotic-arrested cells with the apoptosis potentiator Navitoclax (previously called ABT-263), cell fate was shifted to accelerated post-mitotic death. We conclude that inhibition of SAC silencing is critical for enhancing the lethality of antimitotic drugs as well as that of therapeutic apoptosis-inducing small molecules, with distinct mechanisms. The study highlights the potential of p31comet as a target for antimitotic therapies.
Conservation priorities in an endangered estuarine seahorse are informed by demographic history
Authors: Mkare Thomas Kalama , Jansen van Vuuren Bettine , Teske Peter R.
Published: February 2021

Historical demographic events shape genetic diversity that remains evident in the genomes of contemporary populations. In the case of species that are of conservation concern, this information helps to unravel evolutionary histories that can be critical in guiding conservation efforts. The Knysna seahorse, Hippocampus capensis, is the world’s most endangered seahorse species, and it presently survives in only three estuaries on the South African south coast. Factors that contributed to the species becoming endangered are unclear; additionally, the lack of information on whether the three populations should be managed separately because of potential long-term isolation hampers effective management efforts. In the present study, we reconstructed the seahorses’ demographic history using a suite of microsatellite loci. We found that the largest population (Knysna Estuary) has colonised the other estuaries relatively recently (< 450 years ago), and that its population size is comparatively large and stable. Neither of the other two populations shows signs of long-term reductions in population size. The high conservation status of the species is thus a result of its limited range rather than historical population declines. Our findings indicate that the long-term survival of H. capensis depends primarily on the successful management of the Knysna population, although the other estuaries may serve as reservoirs of genetic diversity.
Sophisticated viral quasispecies with a genotype-related pattern of mutations in the hepatitis B X gene of HBeAg-ve chronically infected patients
Authors: Cortese Maria Francesca , González Carolina , Gregori Josep , Casillas Rosario , Carioti Luca , Guerrero-Murillo Mercedes , Riveiro-Barciela Mar , Godoy Cristina , Sopena Sara , Yll Marçal , Quer Josep , Rando Ariadna , Lopez-Martinez Rosa , Pacín Ruiz Beatriz , García-García Selene , Esteban-Mur Rafael , Tabernero David , Buti Maria , Rodríguez-Frías Francisco
Published: February 2021

Patients with HBeAg-negative chronic infection (CI) have not been extensively studied because of low viremia. The HBx protein, encoded by HBX, has a key role in viral replication. Here, we analyzed the viral quasispecies at the 5′ end of HBX in CI patients and compared it with that of patients in other clinical stages. Fifty-eight HBeAg-negative patients were included: 16 CI, 19 chronic hepatitis B, 16 hepatocellular carcinoma and 6 liver cirrhosis. Quasispecies complexity and conservation were determined in the region between nucleotides 1255 and 1611. Amino acid changes detected were tested in vitro. CI patients showed higher complexity in terms of mutation frequency and nucleotide diversity and higher quasispecies conservation (p < 0.05). A genotype D-specific pattern of mutations (A12S/P33S/P46S/T36D-G) was identified in CI (median frequency, 81.7%), which determined a reduction in HBV DNA release of up to 1.5 log in vitro. CI patients showed a more complex and conserved viral quasispecies than the other groups. The genotype-specific pattern of mutations could partially explain the low viremia observed in these patients.
Early risk assessment for COVID-19 patients from emergency department data using machine learning
Authors: Heldt Frank S. , Vizcaychipi Marcela P. , Peacock Sophie , Cinelli Mattia , McLachlan Lachlan , Andreotti Fernando , Jovanović Stojan , Dürichen Robert , Lipunova Nadezda , Fletcher Robert A. , Hancock Anne , McCarthy Alex , Pointon Richard A. , Brown Alexander , Eaton James , Liddi Roberto , Mackillop Lucy , Tarassenko Lionel , Khan Rabia T.
Published: February 2021

Since its emergence in late 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic with more than 55 million reported cases and 1.3 million estimated deaths worldwide. While epidemiological and clinical characteristics of COVID-19 have been reported, risk factors underlying the transition from mild to severe disease among patients remain poorly understood. In this retrospective study, we analysed data of 879 confirmed SARS-CoV-2 positive patients admitted to a two-site NHS Trust hospital in London, England, between January 1st and May 26th, 2020, with a majority of cases occurring in March and April. We extracted anonymised demographic data, physiological clinical variables and laboratory results from electronic healthcare records (EHR) and applied multivariate logistic regression, random forest and extreme gradient boosted trees. To evaluate the potential for early risk assessment, we used data available during patients’ initial presentation at the emergency department (ED) to predict deterioration to one of three clinical endpoints in the remainder of the hospital stay: admission to intensive care, need for invasive mechanical ventilation and in-hospital mortality. Based on the trained models, we extracted the most informative clinical features in determining these patient trajectories. Considering our inclusion criteria, we have identified 129 of 879 (15%) patients that required intensive care, 62 of 878 (7%) patients needing mechanical ventilation, and 193 of 619 (31%) cases of in-hospital mortality. Our models learned successfully from early clinical data and predicted clinical endpoints with high accuracy, the best model achieving area under the receiver operating characteristic (AUC-ROC) scores of 0.76 to 0.87 (F1 scores of 0.42–0.60). Younger patient age was associated with an increased risk of receiving intensive care and ventilation, but lower risk of mortality. Clinical indicators of a patient’s oxygen supply and selected laboratory results, such as blood lactate and creatinine levels, were most predictive of COVID-19 patient trajectories. Among COVID-19 patients machine learning can aid in the early identification of those with a poor prognosis, using EHR data collected during a patient’s first presentation at ED. Patient age and measures of oxygenation status during ED stay are primary indicators of poor patient outcomes.
The preparation and application of calcium phosphate biomedical composites in filling of weight-bearing bone defects
Authors: Cheng Lijia , Lin Tianchang , Khalaf Ahmad Taha , Zhang Yamei , He Hongyan , Yang Liming , Yan Shuo , Zhu Jiang , Shi Zheng
Published: February 2021

Nowadays, artificial bone materials have been widely applied in the filling of non-weight bearing bone defects, but scarcely ever in weight-bearing bone defects. This study aims to develop an artificial bone with excellent mechanical properties and good osteogenic capability. Firstly, the collagen-thermosensitive hydrogel-calcium phosphate (CTC) composites were prepared as follows: dissolving thermosensitive hydrogel at 4 °C, then mixing with type I collagen as well as tricalcium phosphate (CaP) powder, and moulding the composites at 37 °C. Next, the CTC composites were subjected to evaluate for their chemical composition, micro morphology, pore size, Shore durometer, porosity and water absorption ability. Following this, the CTC composites were implanted into the muscle of mice while the 70% hydroxyapatite/30% β-tricalcium phosphate (HA/TCP) biomaterials were set as the control group; 8 weeks later, the osteoinductive abilities of biomaterials were detected by histological staining. Finally, the CTC and HA/TCP biomaterials were used to fill the large segments of tibia defects in mice. The bone repairing and load-bearing abilities of materials were evaluated by histological staining, X-ray and micro-CT at week 8. Both the CTC and HA/TCP biomaterials could induce ectopic bone formation in mice; however, the CTC composites tended to produce larger areas of bone and bone marrow tissues than HA/TCP. Simultaneously, bone-repairing experiments showed that HA/TCP biomaterials were easily crushed or pushed out by new bone growth as the material has a poor hardness. In comparison, the CTC composites could be replaced gradually by newly formed bone and repair larger segments of bone defects. The CTC composites trialled in this study have better mechanical properties, osteoinductivity and weight-bearing capacity than HA/TCP. The CTC composites provide an experimental foundation for the synthesis of artificial bone and a new option for orthopedic patients.
Cyanoalkylation/alkynylation of allylic alcohol through intramolecular radical 1,2-alkynyl migration
Authors: Jin Shengnan , Chen Fan , Qian Pengcheng , Cheng Jiang
Published: February 2021

A di-tert-butyl peroxide (DTBP)-promoted difunctionalization of α-aryl α-alkynyl allylic alcohols with alkyl nitriles was developed, affording a series of α-alkynyl γ-cyano functionalized ketones in moderate yields.
Designing heterostructured core@satellite Prussian Blue Analogue@Au–Ag nanoparticles: Effect on the magnetic properties and catalytic activity
Authors: Mamontova Ekaterina , Rodríguez-Castillo Maria , Oliviero Erwan , Guari Yannick , Larionova Joulia , Monge Miguel , Long Jérôme
Published: February 2021

Prussian Blue Analogue@Au–Ag nanoparticles: Effect on the magnetic properties and catalytic activity.
Local contrast measure with iterative error for infrared small target detection
Authors: Yan Zujing , Xin Yunhong , Zhang Yixuan
Published: February 2021

Local contrast measure (LCM) has been proved to be an effective method for infrared small target detection. However, the detection performance of LCM decreases dramatically when the background contains strong edges and pixel‐sized noises with high brightness (PNHB). Based on the analysis of the inherent causes of the poor performance of LCM in extremely complex backgrounds, this study presents an effective LCM with an iterative error. The contribution is as follows: first, the two‐dimensional least mean square (TDLMS) filter with an adaptive parameter is applied to suppress the background clutters roughly in each multiscale window. Then, the partial maximum pixel mean is applied to the LCM to optimise the sub‐block statistical parameters, which achieves excellent strong edges suppression performance. Finally, the iteration error generated by TDLMS and the sub‐block weight matrix is updated alternately to further optimise the statistical parameters of the contrast measure to make it more effective in suppressing PNHB. Experimental results demonstrate that the proposed approach is not only superior to the contrast methods in terms of high detection efficiency and low false alarm rate but also has satisfactory adaptability under extremely complex backgrounds.
ANN design of multiple open‐switch fault diagnosis for three‐phase PWM converters
Authors: Kim Won‐Jae , Kim Sang‐Hoon
Published: February 2021

In this paper, Artificial Neural Networks (ANNs) for diagnosing multiple open‐switch faults in three‐phase PWM (Pulse Width Modulation) converters are designed. For single and double open‐switch faults in the converters, there are 21 types of fault modes, causing distorted phase currents. Since these abnormal currents can induce secondary faults in peripherals, the open‐fault diagnosis is essentially required. In this paper, a two‐step technique based on ANNs is utilized for the diagnosis of the multiple open‐switch fault. First, dc and harmonic components of the currents are extracted by using an ADALINE (Adaptive Linear Neuron). In the first step, the ANN categorizes fault modes into six sectors by using dc components in the three‐phase plane. In the second step, the ANN localizes fault modes by using dc components and the ratio of d–q axes currents THDs (Total Harmonics Distortions) in each sector. Especially, both switches open‐faults in the same legs are localised by counting the sampled zero current of the fault currents. The proposed two‐step technique allows a simple design of the ANNs for the diagnosis, and a short execution time about 22 s. Simulations and experiments for a 3.7 kW three‐phase PWM converter confirmed the validity of the proposed diagnostic method.
Signalised intersection control in a connected vehicle environment: User throughput maximisation strategy
Authors: Mohammadi Roozbeh , Roncoli Claudio , Mladenović Miloš N.
Published: February 2021

Connected vehicle (CV) technology is expected to bring additional opportunities to share, collect, and exploit various information on vehicles and their occupants. Assuming that CVs are able to transmit on‐board users and vehicle data, a user‐based signal timing optimisation (UBSTO) strategy is proposed, designed to optimise user throughput for signalised intersections. In the CV environment, the inputs of the proposed algorithm consist of position and speed of CVs, as well as the number of passengers travelling in each vehicle, while the output is the optimum green time duration for each signal phase. In addition, authors' proposed strategy is able to adapt the cycle length to the traffic volume condition. In case of missing users data, the same strategy can also operate in vehicle‐based mode, where the objective is vehicle‐throughput maximization. The performance of the proposed strategy is compared with a fully actuated controller (FAC) in microscopic simulation, for several scenarios, including different CV penetration rates. Authors' findings show that UBSTO can effectively increase user throughput and decrease average user delay in comparison with FAC, while also prioritising vehicles with higher number of users on‐board. These findings have implications for further development of prioritization strategies for public transport and ride‐sharing vehicles.