bluuebunny/crossref_metadata_2025 huggingface dataset:
Safe option-critic: learning safety in the option-critic architecture
Authors: Jain Arushi , Khetarpal Khimya , Precup Doina
Published: April 2021

Designing hierarchical reinforcement learning algorithms that exhibit safe behaviour is not only vital for practical applications but also facilitates a better understanding of an agent’s decisions. We tackle this problem in the options framework (Sutton, Precup & Singh, 1999), a particular way to specify temporally abstract actions which allow an agent to use sub-policies with start and end conditions. We consider a behaviour assafethat avoids regions of state space with high uncertainty in the outcomes of actions. We propose an optimization objective that learnssafeoptions by encouraging the agent to visit states with higher behavioural consistency. The proposed objective results in a trade-off between maximizing the standard expected return and minimizing the effect of model uncertainty in the return. We propose a policy gradient algorithm to optimize the constrained objective function. We examine the quantitative and qualitative behaviours of the proposed approach in a tabular grid world, continuous-state puddle world, and three games from the Arcade Learning Environment: Ms. Pacman, Amidar, and Q*Bert. Our approach achieves a reduction in the variance of return, boosts performance in environments with intrinsic variability in the reward structure, and compares favourably both with primitive actions and with risk-neutral options.
150 Karten für das Konflikt-Coaching
Authors: ten Hoedt Francine , Lingsma Marijke
Published: April 2021

Wie kann aus einem Streit eine wertvolle Lernsituation werden? Wann kann ein Konflikt dazu beitragen, Beziehungen zu stärken? Mit welchen Eigenschaften kann man in Konfliktsituationen punkten? Sich richtig und produktiv zu streiten, kann Klarheit in Konflikte bringen. Mithilfe der 150 Karten in diesem Kartenset kann die Konfliktkompetenz spielerisch verbessert werden. Die 50 Eskalationskarten „Rote Linie“ beschreiben Verhaltensweisen, die Streit auslösen oder einen bestehenden Streit verschlimmern. Die 50 Deeskalationskarten „Mehr Respekt bitte!“ verweisen auf Verhaltensweisen, die einen Konflikt entschärfen. Die 50 Karten „Wenn es zum Streit kommt“ geben Hinweise auf Verhaltensweisen, die dazu geeignet sind, einen Konflikt zu lösen. Die Karten eignen sich zur Selbstreflexion, können aber vor allem auch als spielerisches Tool im Coaching und Training, in der Team- und Personalentwicklung und in der Mediation eingesetzt werden. Die Karten ermöglichen es, sich des eigenen typischen Verhaltens in Konfliktsituationen bewusstzuwerden und das persönliche Eskalations- bzw. Deeskalationsverhalten zu erkennen. Weiterhin geben sie Anregungen für alternative Herangehensweisen in Konfliktsituationen und ermöglichen es so, die Kunst des friedlichen und produktiven Streitens zu erlernen. Eine Checkliste zur Erfassung der Konfliktfähigkeit kann nach erfolgter Registrierung zusätzlich von der Hogrefe Website heruntergeladen werden.
Modulation of Land Photosynthesis by the Indian Ocean Dipole: Satellite‐Based Observations and CMIP6 Future Projections
Authors: Wang Jun , Wang Meirong , Kim Jin‐Soo , Joiner Joanna , Zeng Ning , Jiang Fei , Wang Hengmao , He Wei , Wu Mousong , Chen Tiexi , Ju Weimin , Chen Jing M.
Published: April 2021

Indian Ocean Dipole (IOD), a major climate variability in the tropics which drives the abiotic stress associated with heavy rainfalls and severe droughts, is not much understood in terms of its role in the carbon cycle, while El Niño‐Southern Oscillation (ENSO)‐related terrestrial carbon cycle variation has been intensively studied. Here, we investigate IOD's impact on land photosynthesis over the Indian ocean rim countries during austral spring using satellite‐based gross primary productivity (GPP) and Earth System Model simulations produced in the Coupled Model Intercomparison Project Phase 6 (CMIP6). IOD independently affects GPP with significant positive partial correlation coefficients () over most of Africa and India, and negative over southern China, Indo‐China peninsula, maritime continent, and Australia, mostly driven by precipitation variations; this obviously differs from the widespread significant negative pattern induced by ENSO. The recent extremely positive IOD in 2019 caused the canonical IOD‐affected GPP patterns, however, with its extreme impacts. Furthermore, though large inter‐model spreads exist, the CMIP6 multimodel median can basically capture the main characteristics of IOD‐affected precipitation and GPP patterns. Importantly, IOD is predicted to occur more frequently in future warming scenarios. Model future projections suggest that it will exert larger impacts on GPP variations over central and eastern Africa, Sumatra, western and southeastern Australia with stronger and enhanced explained variance, but less impacts over southern Africa, east India, Indo‐China peninsula, and northeastern Australia. Therefore, besides ENSO, understanding the IOD impacts can provide us new insights into regional and global carbon cycle interannual variability.
The Effect of Basal Melting of the Shirase Glacier Tongue on the CO2 System in Lützow‐Holm Bay, East Antarctica
Authors: Kiuchi Masaaki , Nomura Daiki , Hirano Daisuke , Tamura Takeshi , Hashida Gen , Ushio Shuki , Simizu Daisuke , Ono Kazuya , Aoki Shigeru
Published: April 2021

To clarify the effect of basal melting of ice tongues/ice shelf on the CO2 system in the Antarctic continental margin, seawater samples were collected for analysis of dissolved inorganic carbon (DIC), total alkalinity (TA), nutrients, chlorophyll a (chl.a), and oxygen isotopic ratios at the ice front of the Shirase Glacier Tongue (SGT) in Lützow‐Holm Bay (LHB), East Antarctica during the summers of 2017 and 2018. At depths greater than ∼20 dbar in LHB, CO2 system parameters were strongly influenced by the dilution effect of SGT basal melting and the inflow of modified Circumpolar Deep Water (mCDW). The distributions of DIC and TA agreed well with an offshore origin of mCDW that flowed beneath the SGT and mixing of basal meltwater and mCDW beneath the SGT. The fraction of SGT meltwater was highest at the station near the ice front. Dilution by SGT basal meltwater reduced the partial pressure of CO2 in the mCDW from 431 to 387 μatm. The water then became a sink rather than source of atmospheric CO2. In the sea surface, DIC and TA were strongly influenced by biological processes. Salinity‐normalized DIC decreased with the increase of salinity‐normalized TA in accord with 106:16 C:N molar stoichiometry; the chl.a concentration at the sea surface was as high as 31 μg L−1.
Dynamical machine learning volumetric reconstruction of objects’ interiors from limited angular views
Authors: Kang Iksung , Goy Alexandre , Barbastathis George
Published: April 2021

Limited-angle tomography of an interior volume is a challenging, highly ill-posed problem with practical implications in medical and biological imaging, manufacturing, automation, and environmental and food security. Regularizing priors are necessary to reduce artifacts by improving the condition of such problems. Recently, it was shown that one effective way to learn the priors for strongly scattering yet highly structured 3D objects, e.g. layered and Manhattan, is by a static neural network [Goy et al. Proc. Natl. Acad. Sci. 116, 19848–19856 (2019)]. Here, we present a radically different approach where the collection of raw images from multiple angles is viewed analogously to a dynamical system driven by the object-dependent forward scattering operator. The sequence index in the angle of illumination plays the role of discrete time in the dynamical system analogy. Thus, the imaging problem turns into a problem of nonlinear system identification, which also suggests dynamical learning as a better fit to regularize the reconstructions. We devised a Recurrent Neural Network (RNN) architecture with a novel Separable-Convolution Gated Recurrent Unit (SC-GRU) as the fundamental building block. Through a comprehensive comparison of several quantitative metrics, we show that the dynamic method is suitable for a generic interior-volumetric reconstruction under a limited-angle scheme. We show that this approach accurately reconstructs volume interiors under two conditions: weak scattering, when the Radon transform approximation is applicable and the forward operator well defined; and strong scattering, which is nonlinear with respect to the 3D refractive index distribution and includes uncertainty in the forward operator.
Author Correction: Non-Abelian generalizations of the Hofstadter model: spin–orbit-coupled butterfly pairs
Authors: Yang Yi , Zhen Bo , Joannopoulos John D. , Soljačić Marin
Published: April 2021

A Correction to this paper has been published: https://doi.org/10.1038/s41377-021-00519-4
Knockdown of MCM8 functions as a strategy to inhibit the development and progression of osteosarcoma through regulating CTGF
Authors: Ren Zhinan , Li Jun , Zhao Shanwen , Qiao Qi , Li Runguang
Published: April 2021

Osteosarcoma is the most common primary malignant tumor of bone derived from osteoblasts, which is a noteworthy threat to the health of children and adolescents. In this study, we found that MCM8 has significantly higher expression level in osteosarcoma tissues in comparison with normal tissues, which was also correlated with more advanced tumor grade and pathological stage. In agreement with the role of MCM proteins as indicators of cell proliferation, knockdown/overexpression of MCM8 inhibited/promoted osteosarcoma cell proliferation in vitro and tumor growth in vivo. Also, MCM8 knockdown/overexpression was also significantly associated with the promotion/inhibition of cell apoptosis and suppression/promotion of cell migration. More importantly, mechanistic study identified CTGF as a potential downstream target of MCM8, silencing of which could enhance the regulatory effects of MCM8 knockdown and alleviate the effects of MCM8 overexpression on osteosarcoma development. In summary, MCM8/CTGF axis was revealed as critical participant in the development and progression of osteosarcoma and MCM8 may be a promising therapeutic target for osteosarcoma treatment.
Orthogonal photochemistry-assisted printing of 3D tough and stretchable conductive hydrogels
Authors: Wei Hongqiu , Lei Ming , Zhang Ping , Leng Jinsong , Zheng Zijian , Yu You
Published: April 2021

3D-printing tough conductive hydrogels (TCHs) with complex structures is still a challenging task in related fields due to their inherent contrasting multinetworks, uncontrollable and slow polymerization of conductive components. Here we report an orthogonal photochemistry-assisted printing (OPAP) strategy to make 3D TCHs in one-pot via the combination of rational visible-light-chemistry design and reliable extrusion printing technique. This orthogonal chemistry is rapid, controllable, and simultaneously achieve the photopolymerization of EDOT and phenol-coupling reaction, leading to the construction of tough hydrogels in a short time (tgel ~30 s). As-prepared TCHs are tough, conductive, stretchable, and anti-freezing. This template-free 3D printing can process TCHs to arbitrary structures during the fabrication process. To further demonstrate the merits of this simple OPAP strategy and TCHs, 3D-printed TCHs hydrogel arrays and helical lines, as proofs-of-concept, are made to assemble high-performance pressure sensors and a temperature-responsive actuator. It is anticipated that this one-pot rapid, controllable OPAP strategy opens new horizons to tough hydrogels.
Metabolic capabilities mute positive response to direct and indirect impacts of warming throughout the soil profile
Authors: Dove Nicholas C. , Torn Margaret S. , Hart Stephen C. , Taş Neslihan
Published: April 2021

Increasing global temperatures are predicted to stimulate soil microbial respiration. The direct and indirect impacts of warming on soil microbes, nevertheless, remain unclear. This is particularly true for understudied subsoil microbes. Here, we show that 4.5 years of whole-profile soil warming in a temperate mixed forest results in altered microbial community composition and metabolism in surface soils, partly due to carbon limitation. However, microbial communities in the subsoil responded differently to warming than in the surface. Throughout the soil profile—but to a greater extent in the subsoil—physiologic and genomic measurements show that phylogenetically different microbes could utilize complex organic compounds, dampening the effect of altered resource availability induced by warming. We find subsoil microbes had 20% lower carbon use efficiencies and 47% lower growth rates compared to surface soils, which constrain microbial communities. Collectively, our results show that unlike in surface soils, elevated microbial respiration in subsoils may continue without microbial community change in the near-term.
Co-variation of silicate, carbonate and sulfide weathering drives CO2 release with erosion
Authors: Bufe Aaron , Hovius Niels , Emberson Robert , Rugenstein Jeremy K. C. , Galy Albert , Hassenruck-Gudipati Hima J. , Chang Jui-Ming
Published: April 2021

Global climate is thought to be modulated by the supply of minerals to Earth’s surface. Whereas silicate weathering removes carbon dioxide (CO2) from the atmosphere, weathering of accessory carbonate and sulfide minerals is a geologically relevant source of CO2. Although these weathering pathways commonly operate side by side, we lack quantitative constraints on their co-variation across erosion rate gradients. Here we use stream-water chemistry across an erosion rate gradient of three orders of magnitude in shales and sandstones of southern Taiwan, and find that sulfide and carbonate weathering rates rise with increasing erosion, while silicate weathering rates remain steady. As a result, on timescales shorter than marine sulfide compensation (approximately 106–107 years), weathering in rapidly eroding terrain leads to net CO2 emission rates that are about twice as fast as CO2 sequestration rates in slow-eroding terrain. We propose that these weathering reactions are linked and that sulfuric acid generated from sulfide oxidation boosts carbonate solubility, whereas silicate weathering kinetics remain unaffected, possibly due to efficient buffering of the pH. We expect that these patterns are broadly applicable to many Cenozoic mountain ranges that expose marine metasediments.
Kinetics of plasma cfDNA predicts clinical response in non-small cell lung cancer patients
Authors: Zhou Xiaorong , Li Chenchen , Zhang Zhao , Li Daniel Y. , Du Jinwei , Ding Ping , Meng Haiyan , Xu Hui , Li Ronglei , Ho Effie , Zhang Aiguo , Okunieff Paul , Lu Jianwei , Sha Michael Y.
Published: April 2021

Tyrosine kinase inhibitors (TKIs), VEGF/VEGF receptor inhibitors (VEGFIs) and immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced cancers including non-small-cell lung cancer (NSCLC). This study aims to evaluate the utility of plasma cell-free DNA (cfDNA) as a prognostic biomarker and efficacy predictor of chemotherapy (CT) with or without these precision therapies in NSCLC patients. Peripheral cfDNA levels in 154 NSCLC patients were quantified before and after the first target cycle of chemotherapy. The correlations of cfDNA with tumor burden, clinical characteristics, progression-free survival (PFS)/disease-free survival (DFS), objective response ratio (ORR), and therapy regimens were analyzed respectively. Baseline cfDNA, but not post-chemotherapeutic cfDNA, positively correlates with tumor burden. Notably, cfDNA kinetics (cfDNA Ratio, the ratio of post-chemotherapeutic cfDNA to baseline cfDNA) well distinguished responsive individuals (CR/PR) from the non-responsive (PD/SD). Additionally, cfDNA Ratio was found negatively correlated with PFS in lung adenocarcinoma (LUAD), but not lung squamous-cell carcinoma (LUSC) which may be due to a limited number of LUSC patients in this cohort. LUAD patients with low cfDNA Ratio have prolonged PFS and improved ORR, compared to those with high cfDNA Ratio. When stratified by therapy regimen, the predictive value of cfDNA Ratio is significant in patients with chemotherapy plus VEGFIs, while more patients need be included to validate the value of cfDNA Ratio in other regimens. Thus, the kinetics of plasma cfDNA during chemotherapy may function as a prognostic biomarker and efficacy predictor for NSCLC patients.
New insights into microstructure of neutron-irradiated tungsten
Authors: Dürrschnabel M. , Klimenkov M. , Jäntsch U. , Rieth M. , Schneider H. C. , Terentyev D.
Published: April 2021

The development of appropriate materials for fusion reactors that can sustain high neutron fluence at elevated temperatures remains a great challenge. Tungsten is one of the promising candidate materials for plasma-facing components of future fusion reactors, due to several favorable properties as for example a high melting point, a high sputtering resistivity, and a low coefficient of thermal expansion. The microstructural details of a tungsten sample with a 1.25 dpa (displacements per atom) damage dose after neutron irradiation at 800 °C were examined by transmission electron microscopy. Three types of radiation-induced defects were observed, analyzed and characterized: (1) voids with sizes ranging from 10 to 65 nm, (2) dislocation loops with a size of up to 10 nm and (3) W–Re–Os containing σ- and χ-type precipitates. The distribution of voids as well as the nature of the occurring dislocation loops were studied in detail. In addition, nano-chemical analyses revealed that the σ- and χ-type precipitates, which are sometimes attached to voids, are surrounded by a solid solution cloud enriched with Re. For the first time the crystallographic orientation relationship of the σ- and χ-phases to the W-matrix was specified. Furthermore, electron energy-loss spectroscopy could not unambiguously verify the presence of He within individual voids.
Large scale synthesis of copper nickel alloy nanoparticles with reduced compressibility using arc thermal plasma process
Authors: Das Subrat Kumar , Das Arkaprava , Gaboardi Mattia , Pollastri Simone , Dhamale G. D. , Balasubramanian C. , Joseph Boby
Published: April 2021

Among the various methods employed in the synthesis of nanostructures, those involving high operating temperature and sharp thermal gradients often lead to the establishment of new exotic properties. Herein, we report on the formation of Cu-Ni metallic alloy nanoparticles with greatly enhanced stiffness achieved through direct-current transferred arc-thermal plasma assisted vapour-phase condensation. High pressure synchrotron X-ray powder diffraction (XRPD) at ambient temperature as well as XRPD in the temperature range 180 to 920 K, show that the thermal arc-plasma route resulted in alloy nanoparticles with much enhanced bulk modulus compared to their bulk counterparts. Such a behaviour may find an explanation in the sudden quenching assisted by the retention of a large amount of local strain due to alloying, combined with the perfect miscibility of the elemental components during the thermal plasma synthesis process.
Accuracy of cup position following robot-assisted total hip arthroplasty may be associated with surgical approach and pelvic tilt
Authors: Hayashi Shinya , Hashimoto Shingo , Kuroda Yuichi , Nakano Naoki , Matsumoto Tomoyuki , Ishida Kazunari , Shibanuma Nao , Kamenaga Tomoyuki , Kuroda Ryosuke
Published: April 2021

This study aimed to investigate the accuracy of cup placement and determine the predictive risk factors for inaccurate cup positioning in robot-assisted total hip arthroplasty (THA). We retrospectively analyzed 115 patients who underwent robot-assisted THA between August 2018 and November 2019. Acetabular cup alignment and three-dimensional (3D) position were measured using pre- or postoperative computed tomography (CT) data. Absolute differences in cup inclination, anteversion, and 3D position were assessed, and their relation to preoperative factors was evaluated. The average measurement of the absolute differences was 1.8° ± 2.0° (inclination) and 1.9° ± 2.3° (anteversion). The average absolute difference in the 3D cup position was 1.1 ± 1.2 mm (coronal plane) and 0.9 ± 1.0 mm (axial plane). Multivariate analysis revealed that a posterior pelvic tilt [odds ratio (OR, 1.1; 95% confidence interval (CI), 1.00–1.23] and anterior surgical approach (OR, 5.1; 95% CI, 1.69–15.38) were predictive factors for inaccurate cup positioning with robot-assisted THA. This is the first study to demonstrate the predictive risk factors (posterior pelvic tilt and anterior surgical approach) for inaccurate cup position in robot-assisted THA.
Prognostic and therapeutic implications of extracellular matrix associated gene signature in renal clear cell carcinoma
Authors: Ahluwalia Pankaj , Ahluwalia Meenakshi , Mondal Ashis K. , Sahajpal Nikhil , Kota Vamsi , Rojiani Mumtaz V. , Rojiani Amyn M. , Kolhe Ravindra
Published: April 2021

Complex interactions in tumor microenvironment between ECM (extra-cellular matrix) and cancer cell plays a central role in the generation of tumor supportive microenvironment. In this study, the expression of ECM-related genes was explored for prognostic and immunological implication in clear cell renal clear cell carcinoma (ccRCC). Out of 964 ECM genes, higher expression (z-score > 2) of 35 genes showed significant association with overall survival (OS), progression-free survival (PFS) and disease-specific survival (DSS). On comparison to normal tissue, 12 genes (NUDT1, SIGLEC1, LRP1, LOXL2, SERPINE1, PLOD3, ZP3, RARRES2, TGM2, COL3A1, ANXA4, and POSTN) showed elevated expression in kidney tumor (n = 523) compared to normal (n = 100). Further, Cox proportional hazard model was utilized to develop 12 genes ECM signature that showed significant association with overall survival in TCGA dataset (HR = 2.45; 95% CI [1.78–3.38]; p < 0.01). This gene signature was further validated in 3 independent datasets from GEO database. Kaplan–Meier log-rank test significantly associated patients with elevated expression of this gene signature with a higher risk of mortality. Further, differential gene expression analysis using DESeq2 and principal component analysis (PCA) identified genes with the highest fold change forming distinct clusters between ECM-rich high-risk and ECM-poor low-risk patients. Geneset enrichment analysis (GSEA) identified significant perturbations in homeostatic kidney functions in the high-risk group. Further, higher infiltration of immunosuppressive T-reg and M2 macrophages was observed in high-risk group patients. The present study has identified a prognostic signature with associated tumor-promoting immune niche with clinical utility in ccRCC. Further exploration of ECM dynamics and validation of this gene signature can assist in design and application of novel therapeutic approaches.
Fluorescence based rapid optical volume screening system (OVSS) for interrogating multicellular organisms
Authors: Basumatary Jigmi , Ara Tarannum , Mukherjee Amartya , Dutta Debanjan , Nongthomba Upendra , Mondal Partha Pratim
Published: April 2021

Continuous monitoring of large specimens for long durations requires fast volume imaging. This is essential for understanding the processes occurring during the developmental stages of multicellular organisms. One of the key obstacles of fluorescence based prolonged monitoring and data collection is photobleaching. To capture the biological processes and simultaneously overcome the effect of bleaching, we developed single- and multi-color lightsheet based OVSS imaging technique that enables rapid screening of multiple tissues in an organism. Our approach based on OVSS imaging employs quantized step rotation of the specimen to record 2D angular data that reduces data acquisition time when compared to the existing light sheet imaging system (SPIM). A co-planar multicolor light sheet PSF is introduced to illuminate the tissues labelled with spectrally-separated fluorescent probes. The detection is carried out using a dual-channel sub-system that can simultaneously record spectrally separate volume stacks of the target organ. Arduino-based control systems were employed to automatize and control the volume data acquisition process. To illustrate the advantages of our approach, we have noninvasively imaged the Drosophila larvae and Zebrafish embryo. Dynamic studies of multiple organs (muscle and yolk-sac) in Zebrafish for a prolonged duration (5 days) were carried out to understand muscle structuring (Dystrophin, microfibers), primitive Macrophages (in yolk-sac) and inter-dependent lipid and protein-based metabolism. The volume-based study, intensity line-plots and inter-dependence ratio analysis allowed us to understand the transition from lipid-based metabolism to protein-based metabolism during early development (Pharyngula period with a critical transition time, $$\tau _c = 50$$

τ
c

=
50

h post-fertilization) in Zebrafish. The advantage of multicolor lightsheet illumination, fast volume scanning, simultaneous visualization of multiple organs and an order-less photobleaching makes OVSS imaging the system of choice for rapid monitoring and real-time assessment of macroscopic biological organisms with microscopic resolution.
Cytotoxic T-lymphocyte elicited vaccine against SARS-CoV-2 employing immunoinformatics framework
Authors: Kumar Neeraj , Admane Nikita , Kumari Anchala , Sood Damini , Grover Sonam , Prajapati Vijay Kumar , Chandra Ramesh , Grover Abhinav
Published: April 2021

Development of effective counteragents against the novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains, requires clear insights and information for understanding the immune responses associated with it. This global pandemic has pushed the healthcare system and restricted the movement of people and succumbing of the available therapeutics utterly warrants the development of a potential vaccine to contest the deadly situation. In the present study, highly efficacious, immunodominant cytotoxic T-lymphocyte (CTL) epitopes were predicted by advanced immunoinformatics assays using the spike glycoprotein of SARS-CoV2, generating a robust and specific immune response with convincing immunological parameters (Antigenicity, TAP affinity, MHC binder) engendering an efficient viral vaccine. The molecular docking studies show strong binding of the CTL construct with MHC-1 and host membrane specific TLR2 receptors. The molecular dynamics simulation in an explicit system confirmed the stable and robust binding of CTL epitope with TLR2. Steep magnitude RMSD variation and compelling residual fluctuations existed in terminal residues and various loops of the β linker segments of TLR2-epitope (residues 105-156 and 239-254) to about 0.4 nm. The reduced Rgvalue (3.3 nm) and stagnant SASA analysis (275 nm/S2/N after 8 ns and 5 ns) for protein surface and its orientation in the exposed and buried regions suggests more compactness due to the strong binding interaction of the epitope. The CTL vaccine candidate establishes a high capability to elicit the critical immune regulators, like T-cells and memory cells as proven by the in silico immunization assays and can be further corroborated through in vitro and in vivo assays.
A virtual reality interface for the immersive manipulation of live microscopic systems
Authors: Ferretti Stefano , Bianchi Silvio , Frangipane Giacomo , Di Leonardo Roberto
Published: April 2021

For more than three centuries we have been watching and studying microscopic phenomena behind a microscope. We discovered that cells live in a physical environment whose predominant factors are no longer those of our scale and for which we lack a direct experience and consequently a deep intuition. Here we demonstrate a new instrument which, by integrating holographic and virtual reality technologies, allows the user to be completely immersed in a dynamic virtual world which is a simultaneous replica of a real system under the microscope. We use holographic microscopy for fast 3D imaging and real-time rendering on a virtual reality headset. At the same time, hand tracking data is used to dynamically generate holographic optical traps that can be used as virtual projections of the user hands to interactively grab and manipulate ensembles of microparticles or living motile cells.
A strain of Phoma species improves drought tolerance of Pinus tabulaeformis
Authors: Zhou Xiu Ren , Dai Lei , Xu Gui Fang , Wang Hong Sheng
Published: April 2021

Global warming has led to frequent droughts, posing challenges for afforestation in arid and semiarid regions. In search of labor-saving and money-saving methods to improve the survival and growth rates of trees in these regions, we isolated and identified fungal endophytes that can potentially enhance the drought-resistance abilities of seedlings. We isolated 93 endophytic strains from the roots of Pinus tabulaeformis trees grown on an arid cliff. Three isolates increased the drought resistance of the tree seedlings. Using morphological, molecular, and physiological-biochemical methods, we identified three isolates as different clones of a strain of Phoma spp. and studied the strain’s effect on stress resistance-related substances in the seedlings. The results showed that the strain improved drought tolerance and increased the seedlings’ proline levels and antioxidant enzyme activities. The strain also secreted abundant extracellular abscisic acid, which likely triggered the seedlings’ protective mechanisms. This endophytic strain may provide a cheaper labor-saving, sustainable alternative to traditional methods of enhancing drought resistance.
Different Zn loading in Urea–Formaldehyde influences the N controlled release by structure modification
Authors: Giroto Amanda S. , do Valle Stella F. , Guimarães Gelton G. F. , Jablonowski Nicolai D. , Ribeiro Caue , Mattoso Luiz Henrique C.
Published: April 2021

Nitrogen fertilization has been a critical factor for high crop productivity, where urea is currently the most used N source due to its high concentration and affordability. Nevertheless, urea fast solubilization leads to frequent losses and lower agronomic efficiency. The modification of urea structure by condensation with formaldehyde has been proposed to improve nutrient uptake by plants and to reduce environmental losses. Herein we show that the co-formulation with Zn strongly modifies the N release (in lab conditions) and, more important, the Zn source—ZnSO4 or ZnO—has a critical role. Urea–formaldehyde (UF) served as a matrix for the zinc sources, and chemical characterizations revealed that Zn particles influenced the length of the polymeric chain formation. Release tests in an aqueous medium showed that the UF matrix favors ZnO release and, on the other hand, delays ZnSO4 delivery. Soil incubation with the fertilizer composites proved the slow-release of N from UF, is ideal for optimizing nutritional efficiency. Our results indicated that the ZnO-UF system has beneficial effects for both nutrients, i.e., reduces N volatilization and increases Zn release.
Reduction of dopant ions and enhancement of magnetic properties by UV irradiation in Ce-doped TiO2
Authors: Wu Tai-Sing , Syu Leng-You , Lin Bi-Hsuan , Weng Shih-Chang , Jeng Horng-Tay , Huang Yu-Shan , Soo Yun-Liang
Published: April 2021

We report the experimental observation of and theoretical explanation for the reduction of dopant ions and enhancement of magnetic properties in Ce-doped TiO2 diluted magnetic semiconductors from UV-light irradiation. Substantial increase in Ce3+ concentration and creation of oxygen vacancy defects in the sample due to UV-light irradiation was observed by X-ray and optical methods. Magnetic measurements demonstrate a combination of paramagnetism and ferromagnetism up to room temperatures in all samples. The magnetization of both paramagnetic and ferromagnetic components was observed to be dramatically enhanced in the irradiated sample. First-principle theoretical calculations show that valence holes created by UV irradiation can substantially lower the formation energy of oxygen vacancies. While the electron spin densities for defect states near oxygen vacancies in pure TiO2 are in antiferromagnetic orientation, they are in ferromagnetic orientations in Ce-doped TiO2. Therefore, the ferromagnetically-oriented spin densities near oxygen vacancies created by UV irradiation are the most probable cause for the experimentally observed enhancement of magnetism in the irradiated Ce-doped TiO2.
Discovery of uncompetitive inhibitors of SapM that compromise intracellular survival of Mycobacterium tuberculosis
Authors: Fernández-Soto Paulina , Casulli Joshua , Solano-Castro Danilo , Rodríguez-Fernández Pablo , Jowitt Thomas A. , Travis Mark A. , Cavet Jennifer S. , Tabernero Lydia
Published: April 2021

SapM is a secreted virulence factor from Mycobacterium tuberculosis critical for pathogen survival and persistence inside the host. Its full potential as a target for tuberculosis treatment has not yet been exploited because of the lack of potent inhibitors available. By screening over 1500 small molecules, we have identified new potent and selective inhibitors of SapM with an uncompetitive mechanism of inhibition. The best inhibitors share a trihydroxy-benzene moiety essential for activity. Importantly, the inhibitors significantly reduce mycobacterial burden in infected human macrophages at 1 µM, and they are selective with respect to other mycobacterial and human phosphatases. The best inhibitor also reduces intracellular burden of Francisella tularensis, which secretes the virulence factor AcpA, a homologue of SapM, with the same mechanism of catalysis and inhibition. Our findings demonstrate that inhibition of SapM with small molecule inhibitors is efficient in reducing intracellular mycobacterial survival in host macrophages and confirm SapM as a potential therapeutic target. These initial compounds have favourable physico-chemical properties and provide a basis for exploration towards the development of new tuberculosis treatments. The efficacy of a SapM inhibitor in reducing Francisella tularensis intracellular burden suggests the potential for developing broad-spectrum antivirulence agents to treat microbial infections.
Past climate variations recorded in needle-like aragonites correlate with organic carbon burial efficiency as revealed by lake sediments in Croatia
Authors: Razum Ivan , Bajo Petra , Brunović Dea , Ilijanić Nikolina , Hasan Ozren , Röhl Ursula , Miko Martina Šparica , Miko Slobodan
Published: April 2021

The drivers of organic carbon (OC) burial efficiency are still poorly understood despite their key role in reliable projections of future climate trends. Here, we provide insights on this issue by presenting a paleoclimate time series of sediments, including the OC contents, from Lake Veliko jezero, Croatia. The Sr/Ca ratios of the bulk sediment are mainly derived from the strontium (Sr) and calcium (Ca) concentrations of needle-like aragonite in Core M1-A and used as paleotemperature and paleohydrology indicators. Four major and six minor cold and dry events were detected in the interval from 8.3 to 2.6 calibrated kilo anno before present (cal ka BP). The combined assessment of Sr/Ca ratios, OC content, carbon/nitrogen (C/N) ratios, stable carbon isotope (δ13C) ratios, and modeled geochemical proxies for paleoredox conditions and aeolian input revealed that cold and dry climate states promoted anoxic conditions in the lake, thereby enhancing organic matter preservation and increasing the OC burial efficiency. Our study shows that the projected future increase in temperature might play an important role in the OC burial efficiency of meromictic lakes.
Magnetoelastic interactions and magnetic damping in Co2Fe0.4Mn0.6Si and Co2FeGa0.5Ge0.5 Heusler alloys thin films for spintronic applications
Authors: Chumak O. M. , Pacewicz A. , Lynnyk A. , Salski B. , Yamamoto T. , Seki T. , Domagala J. Z. , Głowiński H. , Takanashi K. , Baczewski L. T. , Szymczak H. , Nabiałek A.
Published: April 2021

Co2Fe0.4Mn0.6Si (CFMS) and Co2FeGa0.5Ge0.5 (CFGG) Heusler alloys are among the most promising thin film materials for spintronic devices due to a high spin polarization, low magnetic damping and giant/tunneling magnetoresistance ratios. Despite numerous investigations of Heusler alloys magnetic properties performed up to now, magnetoelastic effects in these materials remain not fully understood; due to quite rare studies of correlations between magnetoelastic and other magnetic properties, such as magnetic dissipation or magnetic anisotropy. In this research we have investigated epitaxial CFMS and CFGG Heusler alloys thin films of thickness in the range of 15–50 nm. We have determined the magnetoelastic tensor components and magnetic damping parameters as a function of the magnetic layer thickness. Magnetic damping measurements revealed the existence of non-Gilbert dissipation related contributions, including two-magnon scattering and spin pumping phenomena. Magnetoelastic constant B11 values and the effective magnetic damping parameter αeff values were found to be in the range of − 6 to 30 × 106 erg/cm3 and between 1 and 12 × 10–3, respectively. The values of saturation magnetostriction λS for CFMS Heusler alloy thin films were also obtained using the strain modulated ferromagnetic resonance technique. The correlation between αeff and B11, depending on magnetic layer thickness was determined based on the performed investigations of the above mentioned magnetic properties.
Structural transformation and phase change properties of Se substituted GeTe
Authors: Shekhawat Roopali , Pamuluri Haritha , Erkkara Madhavan Vinod , Ramesh K.
Published: April 2021

GeTe1−xSex (0 ≤ x ≤ 1.0) alloys have been prepared both in bulk and thin film forms to study the effect of selenium (Se) substitution for tellurium (Te) on the phase change properties. It is observed that with increasing Se substitution in GeTe, the structure transforms from rhombohdral structure to orthorhombic structure. Rietveld Refinement analysis support the phase transformation and show that the short and long bond lengths in crystalline GeTe decrease with increasing Se substitution but the rate of reduction of shorter bond length is more than the longer bond length. The GeTe1−xSex thin films undergo amorphous to crystalline phase change when annealed at high temperatures. The transition temperature shows an increasing trend with the Se substitution. The contrast in electrical resistivity between the amorphous and crystalline states is 104 for GeTe, and with the Se substitution, the contrast increases considerably to 106 for GeTe0.5Se0.5. Devices fabricated with thin films show that the threshold current decreases with the Se substitution indicating a reduction in the power required for WRITE operation. The present study shows that the crystalline structure, resistance, bandgap, transition temperature and threshold voltage of GeTe can be effectively controlled and tuned by the substitution of Te by Se, which is conducive for phase change memory applications.
Effect of selection bias on two sample summary data based Mendelian randomization
Authors: Wang Kai , Han Shizhong
Published: April 2021

Mendelian randomization (MR) is becoming more and more popular for inferring causal relationship between an exposure and a trait. Typically, instrument SNPs are selected from an exposure GWAS based on their summary statistics and the same summary statistics on the selected SNPs are used for subsequent analyses. However, this practice suffers from selection bias and can invalidate MR methods, as showcased via two popular methods: the summary data-based MR (SMR) method and the two-sample MR Steiger method. The SMR method is conservative while the MR Steiger method can be either conservative or liberal. A simple and yet more powerful alternative to SMR is proposed.
New cladotherian mammal from southern Chile and the evolution of mesungulatid meridiolestidans at the dusk of the Mesozoic era
Authors: Martinelli Agustín G. , Soto-Acuña Sergio , Goin Francisco J. , Kaluza Jonatan , Bostelmann J. Enrique , Fonseca Pedro H. M. , Reguero Marcelo A. , Leppe Marcelo , Vargas Alexander O.
Published: April 2021

In the last decades, several discoveries have uncovered the complexity of mammalian evolution during the Mesozoic Era, including important Gondwanan lineages: the australosphenidans, gondwanatherians, and meridiolestidans (Dryolestoidea). Most often, their presence and diversity is documented by isolated teeth and jaws. Here, we describe a new meridiolestidan mammal,Orretherium tzengen. et sp. nov., from the Late Cretaceous of southern Chile, based on a partial jaw with five cheek teethin locisand an isolated upper premolar. Phylogenetic analysis placesOrretheriumas the earliest divergence within Mesungulatidae, before other forms such as the Late CretaceousMesungulatumandColoniatherium, and the early PaleocenePeligrotherium. Thein locotooth sequence (last two premolars and three molars) is the first recovered for a Cretaceous taxon in this family and suggests that reconstructed tooth sequences for other Mesozoic mesungulatids may include more than one species. Tooth eruption and replacement show that molar eruption in mesungulatids is heterochronically delayed with regard to basal dryolestoids, with therian-like simultaneous eruption of the last premolar and last molar. Meridiolestidans seem endemic to Patagonia, but given their diversity and abundance, and the similarity of vertebrate faunas in other regions of Gondwana, they may yet be discovered in other continents.
A lower maximum bite force is a risk factor for developing cardiovascular disease: the Suita study
Authors: Hashimoto Sakae , Kosaka Takayuki , Nakai Michikazu , Kida Momoyo , Fushida Shuri , Kokubo Yoshihiro , Watanabe Makoto , Higashiyama Aya , Ikebe Kazunori , Ono Takahiro , Miyamoto Yoshihiro
Published: April 2021

Decreases in masticatory function are believed to be related to the development of cardiovascular disease (CVD) through inappropriate nutritional intake. This study focused on maximum bite force (MBF), which is an objective, quantitative index of masticatory function, and its association with the development of CVD (stroke and coronary heart disease) was investigated. The subjects were 1547 participants of the Suita study with no history of CVD who underwent medical and dental health examinations between June 2008 and June 2013. In addition to undergoing a basic physical examination at baseline, their MBF was measured. They subsequently underwent follow-up surveys for the development of CVD (mean follow-up, 3.5 years). The association between baseline MBF and the development of CVD was investigated by multivariate adjustment using a Cox proportional hazards model. CVD developed in 32 subjects during follow-up. The trend test showed a significant association between baseline MBF and CVD in a model that combined men and women. When analysed by sex, the trend test found a significant association between baseline MBF and CVD in women. Low MBF, which is an objective and quantitative index of masticatory function, may be a risk factor for the development of CVD.
The beneficial role of Asian-based RecurIndex test in the prognostic prediction in Chinese male breast cancer patients
Authors: Zhang Shuo , Liu Beichen , Zhou Mengli , Wang Jintian , Liu Jinzhao , Wang Li , Yang Chao , Liu Yueping , Niu Shuyao , Du Furong , Du Xiaohua , Wang Ning , Tang Jiyu , Song Chao , Liu Yunjiang
Published: April 2021

RecurIndex, a multigene profiling assay, can predict the risk of local recurrence and distant metastasis in female breast cancer (FBC), but its role in male breast cancer (MBC) remains unclear. In this study, the clinicopathological data of 43 consecutive MBC patients undergoing surgeries between 2009 and 2018 were retrospectively analysed. Their paraffin-embedded tissue sections were examined by RecurIndex test which comprised 2 models: recurrence index for local recurrence (RI-LR) and recurrence index for distant recurrence (RI-DR). Of 43 patients, there were 26 low-risk and 17 high-risk patients assessed by RI-LR, while 17 low-risk and 26 high-risk patients by RI-DR. For RI-LR, tumor N stage showed statistically significant (P < 0.001) between low- and high-risk patients; for RI-DR, differences were pronounced in tumor grade (P = 0.033), T stage (P = 0.043) and N stage (P = 0.003). In terms of clinical outcomes, the overall survival (OS) of low- and high-risk patients stratified by RI-LR showed no statistically significant differences (P = 0.460), while high-risk patients identified by RI-DR had a significantly worse distant recurrence-free survival (DRFS) (P = 0.035), progression-free survival (PFS) (P = 0.019) and OS (P = 0.044) than low-risk patients. Overall, RI-DR can effectively predict the DRFS, PFS and OS of MBC patients and identify those at low risk of recurrence, which may serve as a potential prognostic tool for MBC.
Nicotinamide mononucleotide production by fructophilic lactic acid bacteria
Authors: Sugiyama Kazane , Iijima Kana , Yoshino Miyako , Dohra Hideo , Tokimoto Yuji , Nishikawa Koji , Idogaki Hideaki , Yoshida Nobuyuki
Published: April 2021

Nicotinamide mononucleotide (NMN), an intermediate in nicotinamide adenine dinucleotide biosynthesis, is recently attracting much attention for its pharmacological and anti-aging efficacies. However, current commercial products containing NMN are very high-priced because efficient and facile methods for industrial NMN production are limited. In this study, aiming for its nutraceutical application, we attempted to screen lactic acid bacteria for intracellular and/or extracellular NMN production. Using a bioassay system with an auxotrophic yeast that requires nicotinamide riboside (NR; dephosphorylated NMN), three candidates were obtained from a library of 174 strains of facultative anaerobic lactic acid bacteria. All three candidates belonged to the genus Fructobacillus and produced NR in the culture media (0.8–1.5 mg/l). Lactic acid bacteria of the genus Fructobacillus are known to use d-fructose as an electron acceptor in anaerobic lactic acid fermentation; addition of d-fructose to the medium caused intracellular accumulation of NMN and NR, but no extracellular production of these compounds was observed. Draft genome sequencing for one of the candidates suggested that nicotinamide phosphoribosyltransferase, which exists commonly in mammals but is less reported in microorganisms, is a key enzyme for NMN and NR production in the fructophilic bacteria.
Flexible ferroelasticity in monolayer PdS2: a DFT study
Authors: Zhang Wei , Cui Yang , Zhu Chuanhui , Huang Biyi , Yan Shubin
Published: April 2021

The PdS2 monolayer with various allotropes highlights the variety and flexibility of ferroelastic switching in two-dimensional materials.
Uniform nickel–cobalt nanoparticles embedded in nitrogen-doped carbon nanofibers for highly active and durable oxygen reduction electrocatalysts
Authors: Song JingYu , Xie Xuan , Sun Kanjun , Zhang Mingxin , Lei HaiKuo , Peng Hui , Ma Guofu
Published: April 2021

Novel nickel–cobalt bimetallic nanoparticles uniformly embedded in nitrogen-doped carbon nanofibers (NiCo@NCNFs) have been fabricated via a facile electrospinning and subsequent carbonization process, which exhibits a high half-wave potential and excellent long-term stability.
On-demand lactate monitoring towards assessing physiological responses in sedentary populations
Authors: Bhide Ashlesha , Lin Kai-Chun , Muthukumar Sriram , Prasad Shalini
Published: April 2021

This work demonstrates the development of passive label-free sweat sensing capability to enable on-demand lactate monitoring in sedentary populations. Reporting of the electrochemical outputs representing lactate measures occurs in real-time.
A self-immolated fluorogenic agent triggered by H2S exhibiting potential anti-glioblastoma activity
Authors: Ge Chao , Li Ji , Liu Lu , Liu Hong-Ke , Qian Yong
Published: April 2021

We have developed a novel H2S-triggered fluorogenic agent SNF that released the active amonafide with fluorescence via a self-immolative process, which escaped from the lysosome to the nucleus and mainly caused autophagic cell death of glioma cells.