bluuebunny/crossref_metadata_2025 huggingface dataset:
A Methodology for Estimation of Hourly‐Monthly Stochastic Trend Characteristics of Midlatitude Ionosphere
Authors: Arikan F. , Koroglu O.
Published: October 2020

Spatiotemporal variability of ionosphere poses a major challenge in characterization of observable parameters, critical frequency of F2 layer (foF2), maximum ionization height (hmF2), total electron content (TEC), and slab thickness. The nature of the multiscale space‐time variability of ionosphere can be modeled as a random field. In this study, as a first step in random field modeling of the trend, hourly‐monthly parametric probability density functions (PPDF) of foF2, hmF2, slab thickness, and TEC are obtained using IONOLAB‐PDF method for three midlatitude stations (namely, Juliusruh, Pruhonice, and Rome) for low, moderate, and high solar activity years of 2009, 2012, and 2014, respectively. foF2 and hmF2 are obtained from ionosondes. TEC is estimated from dual‐frequency Global Positioning System (GPS) receivers. It is observed that hourly‐monthly PPDFs of all ionospheric parameters at the three midlatitude stations can best be represented by lognormal and Weibull distributions. The estimates of mean and standard deviations of hourly‐monthly PPDFs indicate that the spatiotemporal stochastic trend variation of the midlatitude ionosphere differs in terms of foF2 and GPS‐TEC. The hourly‐monthly PPDF of foF2 represents all major anomalies as well as seasonal and hourly trends, whereas those of GPS‐TEC is highly dependent on solar activity level and latitude. The general statistical trend of hmF2 is anticorrelated with foF2 as expected. The mean of hourly‐monthly PPDF of slab thickness is around 400 km in 2012 and 2014 for all stations between 0200 UT and 1600 UT.
Using Deep Learning to Improve Ensemble Smoother: Applications to Subsurface Characterization
Authors: Zhang Jiangjiang , Zheng Qiang , Wu Laosheng , Zeng Lingzao
Published: October 2020

Ensemble smoother (ES) has been widely used in various research fields to reduce the uncertainty of the system‐of‐interest. However, the commonly adopted ES method that employs the Kalman formula, that is, ES(K), does not perform well when the probability distributions involved are non‐Gaussian. To address this issue, we suggest to use deep learning (DL) to derive an alternative analysis scheme for ES in non‐Gaussian data assimilation problems. Here we show that the DL‐based ES method, that is, ES(DL), is more general and flexible. In this new scheme, a high volume of training data is generated from a relatively small‐sized ensemble of model parameters and simulation outputs, and possible non‐Gaussian features can be preserved in the training data and captured by an adequate DL model. This new variant of ES is tested in two subsurface characterization problems with or without the Gaussian assumption. Results indicate that ES(DL) can produce similar (in the Gaussian case) or even better (in the non‐Gaussian case) results compared to those from ES(K). The success of ES(DL) comes from the power of DL in extracting complex (including non‐Gaussian) features and learning nonlinear relationships from massive amounts of training data. Although in this work we only apply the ES(DL) method in parameter estimation problems, the proposed idea can be conveniently extended to analysis of model structural uncertainty and state estimation in real‐time forecasting problems.
Wnt5a enhances proliferation of chronic lymphocytic leukemia and ERK1/2 phosphorylation via a ROR1/DOCK2-dependent mechanism
Authors: Hasan Md Kamrul , Ghia Emanuela M. , Rassenti Laura Z. , Widhopf George F. , Kipps Thomas J.
Published: October 2020

Patients with chronic lymphocytic leukemia (CLL) have high plasma-levels of Wnt5a, which can induce phosphorylation of ERK1/2 and enhance CLL-cell proliferation. Such effects could be inhibited by treatment with an ERK1/2 inhibitor, ERK1/2-specific siRNA, or cirmtuzumab, an anti-ROR1 mAb. The CLL-derived line, MEC1, expresses Wnt5a, but not ROR1. MEC1 cells transfected to express ROR1 (MEC1-ROR1) had higher levels of phosphorylated ERK1/2 than parental MEC1, or MEC1 transfected with ROR1ΔPRD, a truncated ROR1 lacking the cytoplasmic proline-rich domain (PRD), or ROR1P808A a mutant ROR1 with a P→A substitution at 808, which is required for complexing with the Rac-specific-guanine-nucleotide-exchange factor DOCK2 upon stimulation with Wnt5a. We silenced DOCK2 with siRNA and found this repressed the capacity of Wnt5a to induce ERK1/2 phosphorylation in MEC1-ROR1 or CLL cells. CLL cells that expressed ROR1 had higher levels of phosphorylated ERK1/2 or DOCK2 than CLL cells lacking ROR1. Although we found ibrutinib could inhibit the phosphorylation of ERK1/2 and DOCK2 induced by B-cell-receptor ligation, we found that this drug was unable to inhibit Wnt5a-induced, ROR1-dependent phosphorylation of ERK1/2 or DOCK2. This study demonstrates that Wnt5a can induce activation of ERK1/2 and enhance CLL-cell proliferation via a ROR1/DOCK2-dependent pathway independent of BTK.
Irreversible electroporation plus allogenic Vγ9Vδ2 T cells enhances antitumor effect for locally advanced pancreatic cancer patients
Authors: Lin Mao , Zhang Xiaoyan , Liang Shuzhen , Luo Haihua , Alnaggar Mohammed , Liu Aihua , Yin Zhinan , Chen Jibing , Niu Lizhi , Jiang Yong
Published: October 2020

Immunotherapy has limited efficacy against locally advanced pancreatic cancer (LAPC) due to the presence of an immunosuppressive microenvironment (ISM). Irreversible electroporation (IRE) can not only induce immunogenic cell death, but also alleviate immunosuppression. This study aimed to investigate the antitumor efficacy of IRE plus allogeneic γδ T cells in LAPC patients. A total of 62 patients who met the eligibility criteria were enrolled in this trial, then randomized into two groups (A: n = 30 and B: n = 32). All patients received IRE therapy and after receiving IRE, the group A patients received at least two cycles of γδ T-cell infusion as one course continuously. Group A patients had better survival than group B patients (median OS: 14.5 months vs. 11 months; median PFS: 11 months vs. 8.5 months). Moreover, the group A patients treated with multiple courses of γδ T-cell infusion had longer OS (17 months) than those who received a single course (13.5 months). IRE combined with allogeneic γδ T-cell infusion is a promising strategy to enhance the antitumor efficacy in LAPC patients, yielding extended survival benefits.

ClinicalTrials.gov ID: NCT03180437.
Single-agent belantamab mafodotin for relapsed/refractory multiple myeloma: analysis of the lyophilised presentation cohort from the pivotal DREAMM-2 study
Authors: Richardson Paul G. , Lee Hans C. , Abdallah Al-Ola , Cohen Adam D. , Kapoor Prashant , Voorhees Peter M. , Hoos Axel , Wang Karrie , Baron January , Piontek Trisha , Byrne Julie , Richmond Scott , Jewell Roxanne C. , Opalinska Joanna , Gupta Ira , Lonial Sagar
Published: October 2020

DREAMM-2 (NCT03525678) is an ongoing global, open-label, phase 2 study of single-agent belantamab mafodotin (belamaf; GSK2857916), a B-cell maturation antigen-targeting antibody-drug conjugate, in a frozen-liquid presentation in patients with relapsed/refractory multiple myeloma (RRMM). Alongside the main study, following identical inclusion/exclusion criteria, a separate patient cohort was enrolled to receive belamaf in a lyophilised presentation (3.4 mg/kg, every 3 weeks) until disease progression/unacceptable toxicity. Primary outcome was independent review committee-assessed overall response rate (ORR). Twenty-five patients were enrolled; 24 received ≥1 dose of belamaf. As of 31 January 2020, ORR was 52% (95% CI: 31.3–72.2); 24% of patients achieved very good partial response. Median duration of response was 9.0 months (2.8–not reached [NR]); median progression-free survival was 5.7 months (2.2–9.7); median overall survival was not reached (8.7 months–NR). Most common grade 3/4 adverse events were keratopathy (microcyst-like corneal epithelial changes, a pathological finding seen on eye examination [75%]), thrombocytopenia (21%), anaemia (17%), hypercalcaemia and hypophosphatemia (both 13%), neutropenia and blurred vision (both 8%). Pharmacokinetics supported comparability of frozen-liquid and lyophilised presentations. Single-agent belamaf in a lyophilised presentation (intended for future use) showed a deep and durable clinical response and acceptable safety profile in patients with heavily pre-treated RRMM.
Recent progress in biodiversity research on the Xylariales and their secondary metabolism
Authors: Becker Kevin , Stadler Marc
Published: October 2020

The families Xylariaceae and Hypoxylaceae (Xylariales, Ascomycota) represent one of the most prolific lineages of secondary metabolite producers. Like many other fungal taxa, they exhibit their highest diversity in the tropics. The stromata as well as the mycelial cultures of these fungi (the latter of which are frequently being isolated as endophytes of seed plants) have given rise to the discovery of many unprecedented secondary metabolites. Some of those served as lead compounds for development of pharmaceuticals and agrochemicals. Recently, the endophytic Xylariales have also come in the focus of biological control, since some of their species show strong antagonistic effects against fungal and other pathogens. New compounds, including volatiles as well as nonvolatiles, are steadily being discovered from these ascomycetes, and polythetic taxonomy now allows for elucidation of the life cycle of the endophytes for the first time. Moreover, recently high-quality genome sequences of some strains have become available, which facilitates phylogenomic studies as well as the elucidation of the biosynthetic gene clusters (BGC) as a starting point for synthetic biotechnology approaches. In this review, we summarize recent findings, focusing on the publications of the past 3 years.
Quantum clocks observe classical and quantum time dilation
Authors: Smith Alexander R. H. , Ahmadi Mehdi
Published: October 2020

At the intersection of quantum theory and relativity lies the possibility of a clock experiencing a superposition of proper times. We consider quantum clocks constructed from the internal degrees of relativistic particles that move through curved spacetime. The probability that one clock reads a given proper time conditioned on another clock reading a different proper time is derived. From this conditional probability distribution, it is shown that when the center-of-mass of these clocks move in localized momentum wave packets they observe classical time dilation. We then illustrate a quantum correction to the time dilation observed by a clock moving in a superposition of localized momentum wave packets that has the potential to be observed in experiment. The Helstrom-Holevo lower bound is used to derive a proper time-energy/mass uncertainty relation.
Emergence of orbital angular moment at van Hove singularity in graphene/h-BN moiré superlattice
Authors: Moriya Rai , Kinoshita Kei , Crosse J. A. , Watanabe Kenji , Taniguchi Takashi , Masubuchi Satoru , Moon Pilkyung , Koshino Mikito , Machida Tomoki
Published: October 2020

Bloch electrons lacking inversion symmetry exhibit orbital magnetic moments owing to the rotation around their center of mass; this moment induces a valley splitting in a magnetic field. For the graphene/h-BN moiré superlattice, inversion symmetry is broken by the h-BN. The superlattice potential generates a series of Dirac points (DPs) and van Hove singularities (vHSs) within an experimentally accessible low energy state, providing a platform to study orbital moments with respect to band structure. In this work, theoretical calculations and magnetothermoelectric measurements are combined to reveal the emergence of an orbital magnetic moment at vHSs in graphene/h-BN moiré superlattices. The thermoelectric signal for the vHS at the low energy side of the hole-side secondary DP exhibited significant magnetic field-induced valley splitting with an effective g-factor of approximately 130; splitting for other vHSs was negligible. This was attributed to the emergence of an orbital magnetic moment at the second vHS at the hole-side.
Triboelectric nanogenerator sensors for soft robotics aiming at digital twin applications
Authors: Jin Tao , Sun Zhongda , Li Long , Zhang Quan , Zhu Minglu , Zhang Zixuan , Yuan Guangjie , Chen Tao , Tian Yingzhong , Hou Xuyan , Lee Chengkuo
Published: October 2020

Designing efficient sensors for soft robotics aiming at human machine interaction remains a challenge. Here, we report a smart soft-robotic gripper system based on triboelectric nanogenerator sensors to capture the continuous motion and tactile information for soft gripper. With the special distributed electrodes, the tactile sensor can perceive the contact position and area of external stimuli. The gear-based length sensor with a stretchable strip allows the continuous detection of elongation via the sequential contact of each tooth. The triboelectric sensory information collected during the operation of soft gripper is further trained by support vector machine algorithm to identify diverse objects with an accuracy of 98.1%. Demonstration of digital twin applications, which show the object identification and duplicate robotic manipulation in virtual environment according to the real-time operation of the soft-robotic gripper system, is successfully created for virtual assembly lines and unmanned warehouse applications.
Synergistic photoredox and copper catalysis by diode-like coordination polymer with twisted and polar copper–dye conjugation
Authors: Shi Yusheng , Zhang Tiexin , Jiang Xiao-Ming , Xu Gang , He Cheng , Duan Chunying
Published: October 2020

Synergistic photoredox and copper catalysis confers new synthetic possibilities in the pharmaceutical field, but is seriously affected by the consumptive fluorescence quenching of Cu(II). By decorating bulky auxiliaries into a photoreductive triphenylamine-based ligand to twist the conjugation between the triphenylamine-based ligand and the polar Cu(II)–carboxylate node in the coordination polymer, we report a heterogeneous approach to directly confront this inherent problem. The twisted and polar Cu(II)–dye conjunction endows the coordination polymer with diode-like photoelectronic behaviours, which hampers the inter- and intramolecular photoinduced electron transfer from the triphenylamine-moiety to the Cu(II) site and permits reversed-directional ground-state electronic conductivity, rectifying the productive loop circuit for synergising photoredox and copper catalysis in pharmaceutically valuable decarboxylative C(sp3)–heteroatom couplings. The well-retained Cu(II) sites during photoirradiation exhibit unique inner-spheric modulation effects, which endow the couplings with adaptability to different types of nucleophiles and radical precursors under concise reaction conditions, and distinguish the multi-olefinic moieties of biointeresting steride derivatives in their late-stage trifluoromethylation-chloration difunctionalisation.
CTF-based soft touch actuator for playing electronic piano
Authors: Mahato Manmatha , Tabassian Rassoul , Nguyen Van Hiep , Oh Saewoong , Nam Sanghee , Hwang Won-Jun , Oh Il-Kwon
Published: October 2020

In the field of bioinspired soft robotics, to accomplish sophisticated tasks in human fingers, electroactive artificial muscles are under development. However, most existing actuators show a lack of high bending displacement and irregular response characteristics under low input voltages. Here, based on metal free covalent triazine frameworks (CTFs), we report an electro-ionic soft actuator that shows high bending deformation under ultralow input voltages that can be implemented as a soft robotic touch finger on fragile displays. The as-synthesized CTFs, derived from a polymer of intrinsic microporosity (PIM-1), were combined with poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT-PSS) to make a flexible electrode for a high-performance electro-ionic soft actuator. The proposed soft touch finger showed high peak-to-peak displacement of 17.0 mm under ultralow square voltage of ±0.5 V, with 0.1 Hz frequency and 4 times reduced phase delay in harmonic response compared with that of a pure PEDOT-PSS-based actuator. The significant actuation performance is mainly due to the unique physical and chemical configurations of CTFs electrode with highly porous and electrically conjugated networks. On a fragile display, the developed soft robotic touch finger array was successfully used to perform soft touching, similar to that of a real human finger; device was used to accomplish a precise task, playing electronic piano.
Blue emission at atomically sharp 1D heterojunctions between graphene and h-BN
Authors: Kim Gwangwoo , Ma Kyung Yeol , Park Minsu , Kim Minsu , Jeon Jonghyuk , Song Jinouk , Barrios-Vargas José Eduardo , Sato Yuta , Lin Yung-Chang , Suenaga Kazu , Roche Stephan , Yoo Seunghyup , Sohn Byeong-Hyeok , Jeon Seokwoo , Shin Hyeon Suk
Published: October 2020

Atomically sharp heterojunctions in lateral two-dimensional heterostructures can provide the narrowest one-dimensional functionalities driven by unusual interfacial electronic states. For instance, the highly controlled growth of patchworks of graphene and hexagonal boron nitride (h-BN) would be a potential platform to explore unknown electronic, thermal, spin or optoelectronic property. However, to date, the possible emergence of physical properties and functionalities monitored by the interfaces between metallic graphene and insulating h-BN remains largely unexplored. Here, we demonstrate a blue emitting atomic-resolved heterojunction between graphene and h-BN. Such emission is tentatively attributed to localized energy states formed at the disordered boundaries of h-BN and graphene. The weak blue emission at the heterojunctions in simple in-plane heterostructures of h-BN and graphene can be enhanced by increasing the density of the interface in graphene quantum dots array embedded in the h-BN monolayer. This work suggests that the narrowest, atomically resolved heterojunctions of in-plane two-dimensional heterostructures provides a future playground for optoelectronics.
Diastereodivergent chiral aldehyde catalysis for asymmetric 1,6-conjugated addition and Mannich reactions
Authors: Wen Wei , Luo Ming-Jing , Yuan Yi , Liu Jian-Hua , Wu Zhu-Lian , Cai Tian , Wu Zhao-Wei , Ouyang Qin , Guo Qi-Xiang
Published: October 2020

Chiral aldehyde catalysis is a burgeoning strategy for the catalytic asymmetric α-functionalization of aminomethyl compounds. However, the reaction types are limited and to date include no examples of stereodivergent catalysis. In this work, we disclose two chiral aldehyde-catalysed diastereodivergent reactions: a 1,6-conjugate addition of amino acids topara-quinone methides and a bio-inspired Mannich reaction of pyridinylmethanamines and imines. Both thesyn- andanti-products of these two reactions can be obtained in moderate to high yields, diastereo- and enantioselectivities. Four potential reaction models produced by DFT calculations are proposed to explain the observed stereoselective control. Our work shows that chiral aldehyde catalysis based on a reversible imine formation principle is applicable for the α-functionalization of both amino acids and aryl methylamines, and holds potential to promote a range of asymmetric transformations diastereoselectively.
A hybrid and scalable brain-inspired robotic platform
Authors: Zou Zhe , Zhao Rong , Wu Yujie , Yang Zheyu , Tian Lei , Wu Shuang , Wang Guanrui , Yu Yongchao , Zhao Qi , Chen Mingwang , Pei Jing , Chen Feng , Zhang Youhui , Song Sen , Zhao Mingguo , Shi Luping
Published: October 2020

Recent years have witnessed tremendous progress of intelligent robots brought about by mimicking human intelligence. However, current robots are still far from being able to handle multiple tasks in a dynamic environment as efficiently as humans. To cope with complexity and variability, further progress toward scalability and adaptability are essential for intelligent robots. Here, we report a brain-inspired robotic platform implemented by an unmanned bicycle that exhibits scalability of network scale, quantity and diversity to handle the changing needs of different scenarios. The platform adopts rich coding schemes and a trainable and scalable neural state machine, enabling flexible cooperation of hybrid networks. In addition, an embedded system is developed using a cross-paradigm neuromorphic chip to facilitate the implementation of diverse neural networks in spike or non-spike form. The platform achieved various real-time tasks concurrently in different real-world scenarios, providing a new pathway to enhance robots’ intelligence.
Design of metacontinua in the aeroacoustic spacetime
Authors: Iemma Umberto , Palma Giorgio
Published: October 2020

The effect of background flows on the response of acoustic metamaterials is a key aspect that prevented the full disclosure of their potential in those applications where an aerodynamic velocity field strongly influences the propagation of acoustic disturbances. Indeed, the classic approaches for metamaterial design do not consider the aeroacoustic interaction, and the resulting metamaterials cannot preserve their response when operating in flows. So far, only few authors have addressed the problem, mostly focusing on understanding the phenomenon or identifying corrective techniques with limited usability in practical applications. The present study proposes a general method for the modification of the mechanical properties of acoustic metacontinua to preserve their response in presence of a background flow. The method is based on the application of spacetime coordinate transformations exploiting the spacetime formal invariance of the generalised d’Alembertian. This methodology applies to the equation governing the propagation of acoustic disturbances in a metamaterial having arbitrary constitutive equations independently on the method used for its original design. The approach is validated through numerical simulations, using as a benchmark the problem of the acoustic cloaking of a cylinder impinged by a perturbation generated by an isotropic point source within a flowing medium. Numerical results are obtained for an asymptotic Mach number $$M_\infty \le 0.35$$

M
∞

≤
0.35

.
Stable distribution of reciprocity motives in a population
Authors: van Baar Jeroen M. , Klaassen Felix H. , Ricci Filippo , Chang Luke J. , Sanfey Alan G.
Published: October 2020

Evolutionary models show that human cooperation can arise through direct reciprocity relationships. However, it remains unclear which psychological mechanisms proximally motivate individuals to reciprocate. Recent evidence suggests that the psychological motives for choosing to reciprocate trust differ between individuals, which raises the question whether these differences have a stable distribution in a population or are rather an artifact of the experimental task. Here, we combine data from three independent trust game studies to find that the relative prevalence of different reciprocity motives is highly stable across participant samples. Furthermore, the distribution of motives is relatively unaffected by changes to the salient features of the experimental paradigm. Finally, the motive classification assigned by our computational modeling analysis corresponds to the participants’ own subjective experience of their psychological decision process, and no existing models of social preference can account for the observed individual differences in reciprocity motives. These findings support the view that reciprocal decision-making is not just regulated by individual differences in 'pro-social’ versus ‘pro-self’ tendencies, but also by trait-like differences across several alternative pro-social motives, whose distribution in a population is stable.
La Palma island (Spain) geothermal system revealed by 3D magnetotelluric data inversion
Authors: Di Paolo Federico , Ledo Juanjo , Ślęzak Katarzyna , Martínez van Dorth David , Cabrera-Pérez Iván , Pérez Nemesio M.
Published: October 2020

The study of geothermal systems is nowadays a topic of great importance because of the huge amount of energy that could be converted in electricity for human consumption from such sources. Among the various geophysical methods employed to study geothermal reservoirs, the magnetotelluric (MT) method is capable to reveal the internal structures of the subsurface and interpret the geological structures from the electrical resistivity. We present the first 3D resistivity model of La Palma (Canary archipelago, Spain) obtained from a dataset of 44 broadband magnetotelluric soundings distributed around the island. Our results highlight the presence of resistivity anomalies, spatially coinciding with density anomalies present in literature. In the north of the island, a high resistivity anomaly can be interpreted as the signature of an old intrusive body beneath the Taburiente caldera. In the south, a complex resistivity structure around the Cumbre Vieja volcanic ridge could be indicative of presence of an active geothermal system. In particular, low-resistivity anomalies, located in a high-fractured zone, have values compatible with clay alteration caps (illite and illite–smectite). Such a result suggests the presence of hot rocks, or a dike system, heating fluids in the interior of Cumbre Vieja volcanic system.
Transcriptomic profile of Pea3 family members reveal regulatory codes for axon outgrowth and neuronal connection specificity
Authors: Kandemir Başak , Gulfidan Gizem , Arga Kazim Yalcin , Yilmaz Bayram , Kurnaz Isil Aksan
Published: October 2020

PEA3 transcription factor subfamily is present in a variety of tissues with branching morphogenesis, and play a particularly significant role in neural circuit formation and specificity. Many target genes in axon guidance and cell–cell adhesion pathways have been identified for Pea3 transcription factor (but not for Erm or Er81); however it was not so far clear whether all Pea3 subfamily members regulate same target genes, or whether there are unique targets for each subfamily member that help explain the exclusivity and specificity of these proteins in neuronal circuit formation. In this study, using transcriptomics and qPCR analyses in SH-SY5Y neuroblastoma cells, hypothalamic and hippocampal cell line, we have identified cell type-specific and subfamily member-specific targets for PEA3 transcription factor subfamily. While Pea3 upregulates transcription of Sema3D and represses Sema5B, for example, Erm and Er81 upregulate Sema5A and Er81 regulates Unc5C and Sema4G while repressing EFNB3 in SH-SY5Y neuroblastoma cells. We furthermore present a molecular model of how unique sites within the ETS domain of each family member can help recognize specific target motifs. Such cell-context and member-specific combinatorial expression profiles help identify cell–cell and cell-extracellular matrix communication networks and how they establish specific connections.
Carbon isotope evidence for large methane emissions to the Proterozoic atmosphere
Authors: Cadeau Pierre , Jézéquel Didier , Leboulanger Christophe , Fouilland Eric , Le Floc’h Emilie , Chaduteau Carine , Milesi Vincent , Guélard Julia , Sarazin Gérard , Katz Amandine , d’Amore Sophie , Bernard Cécile , Ader Magali
Published: October 2020

The Proterozoic Era records two periods of abundant positive carbon isotope excursions (CIEs), conventionally interpreted as resulting from increased organic carbon burial and leading to Earth’s surface oxygenation. As strong spatial variations in the amplitude and duration of these excursions are uncovered, this interpretation is challenged. Here, by studying the carbon cycle in the Dziani Dzaha Lake, we propose that they could be due to regionally variable methane emissions to the atmosphere. This lake presents carbon isotope signatures deviated by ~  + 12‰ compared to the modern ocean and shares a unique combination of analogies with putative Proterozoic lakes, interior seas or restricted epireic seas. A simple box model of its Carbon cycle demonstrates that its current isotopic signatures are due to high primary productivity, efficiently mineralized by methanogenesis, and to subsequent methane emissions to the atmosphere. By analogy, these results might allow the reinterpretation of some positive CIEs as at least partly due to regionally large methane emissions. This supports the view that methane may have been a major greenhouse gas during the Proterozoic Era, keeping the Earth from major glaciations, especially during periods of positive CIEs, when increased organic carbon burial would have drowned down atmospheric CO2.
Toxicological evaluation of the ultrasonic extract from Dichroae radix in mice and wistar rats
Authors: Wang Ling , Guo Zhiting , Cui Dongan , Ul Haq Shahbaz , Guo Wenzhu , Yang Feng , Zhang Hang
Published: October 2020

This study was aimed at evaluating the acute and subchronic toxicity of ultrasonic extract of Dichroae radix (UEDR) in mice and rats. High performance liquid chromatography (HPLC) and thin layer chromatogrephy (TLC) were used to detect β-dichroine and α-dichroine in UEDR for quality control. The levels of β-dichroine and α-dichroine in UEDR were 1.46 and 1.53 mg/g, respectively. An oral LD50 of 2.43 g/kg BW was observed in acute toxicity test. After 28-day repeated oral administration, compared with the control group, treatment-related changes in body weight (BW) and body weight gain (BWG), lymphocyte counts and ratios, as well as in the relative organ weights (ROWs) of liver, kidney, lung, and heart, were detected in the middle- and high-dose groups (P < 0.05, P < 0.01), no differences were noted in the serum biochemical parameters and necropsy examinations in both sexes at all doses. Histopathological examinations exhibited UEDR-associated signs of toxicity or abnormalities. After 14 days withdrawal, no statistically significant or toxicologically relevant differences were observed in any of the UEDR-treated groups, and the hispathological lesions in the high-dose group were alleviated. Findings showed that long-course and high-dose of UEDR administration was toxic, and showed dose-dependence, the toxic damage was reversible.
Security evaluation of quantum key distribution with weak basis-choice flaws
Authors: Sun Shi-Hai , Tian Zhi-Yu , Zhao Mei-Sheng , Ma Yan
Published: October 2020

Quantum key distribution (QKD) can share an unconditional secure key between two remote parties, but the deviation between theory and practice will break the security of the generated key. In this paper, we evaluate the security of QKD with weak basis-choice flaws, in which the random bits used by Alice and Bob are weakly controlled by Eve. Based on the definition of Li et al. (Sci Rep 5:16200, 2015) and GLLP’s analysis, we obtain a tight and analytical bound to estimate the phase error and key rate for both the single photon source and the weak coherent source. Our approach largely increases the key rate from that of the original approach. Finally, we investigate and confirm the security of BB84-QKD with a practical commercial devices.
Direct signaling of TL1A-DR3 on fibroblasts induces intestinal fibrosis in vivo
Authors: Jacob Noam , Kumagai Kotaro , Abraham Jay P. , Shimodaira Yosuke , Ye Yuefang , Luu Justin , Blackwood Anna Y. , Castanon Sofi L. , Stamps Dalton T. , Thomas Lisa S. , Gonsky Rivkah , Shih David Q. , Michelsen Kathrin S. , Targan Stephan R.
Published: October 2020

Tumor necrosis factor-like cytokine 1A (TL1A, TNFSF15) is implicated in inflammatory bowel disease, modulating the location and severity of inflammation and fibrosis. TL1A expression is increased in inflamed mucosa and associated with fibrostenosing Crohn’s disease. Tl1a-overexpression in mice causes spontaneous ileitis, and exacerbates induced proximal colitis and fibrosis. Intestinal fibroblasts express Death-receptor 3 (DR3; the only know receptor for TL1A) and stimulation with TL1A induces activation in vitro. However, the contribution of direct TL1A-DR3 activation on fibroblasts to fibrosis in vivo remains unknown. TL1A overexpressing naïve T cells were transferred into Rag−/− , Rag−/− mice lacking DR3 in all cell types (Rag−/−Dr3−/−), or Rag−/− mice lacking DR3 only on fibroblasts (Rag−/−Dr3∆Col1a2) to induce colitis and fibrosis, assessed by clinical disease activity index, intestinal inflammation, and collagen deposition. Rag−/− mice developed overt colitis with intestinal fibrostenosis. In contrast, Rag−/−Dr3−/− demonstrated decreased inflammation and fibrosis. Despite similar clinical disease and inflammation as Rag−/−, Rag−/−Dr3∆Col1a2 exhibited reduced intestinal fibrosis and attenuated fibroblast activation and migration. RNA-Sequencing of TL1A-stimulated fibroblasts identified Rho signal transduction as a major pathway activated by TL1A and inhibition of this pathway modulated TL1A-mediated fibroblast functions. Thus, direct TL1A signaling on fibroblasts promotes intestinal fibrosis in vivo. These results provide novel insight into profibrotic pathways mediated by TL1A paralleling its pro-inflammatory effects.
Logarithmic encoding of ensemble time intervals
Authors: Ren Yue , Allenmark Fredrik , Müller Hermann J. , Shi Zhuanghua
Published: October 2020

Although time perception is based on the internal representation of time, whether the subjective timeline is scaled linearly or logarithmically remains an open issue. Evidence from previous research is mixed: while the classical internal-clock model assumes a linear scale with scalar variability, there is evidence that logarithmic timing provides a better fit to behavioral data. A major challenge for investigating the nature of the internal scale is that the retrieval process required for time judgments may involve a remapping of the subjective time back to the objective scale, complicating any direct interpretation of behavioral findings. Here, we used a novel approach, requiring rapid intuitive ‘ensemble’ averaging of a whole set of time intervals, to probe the subjective timeline. Specifically, observers’ task was to average a series of successively presented, auditory or visual, intervals in the time range 300–1300 ms. Importantly, the intervals were taken from three sets of durations, which were distributed such that the arithmetic mean (from the linear scale) and the geometric mean (from the logarithmic scale) were clearly distinguishable. Consistently across the three sets and the two presentation modalities, our results revealed subjective averaging to be close to the geometric mean, indicative of a logarithmic timeline underlying time perception.
Development of a protein microarray-based diagnostic chip mimicking the skin prick test for allergy diagnosis
Authors: Kalli Marina , Blok Andrew , Jiang Long , Starr Nichola , Alcocer Marcos J. C. , Falcone Franco H.
Published: October 2020

Protein microarrays have been successfully used for detection of allergen-specific IgE in patient sera. Here, we demonstrate proof-of-concept of a solid-phase technique coupling the high-throughput potential of protein microarrays with the biologically relevant readout provided by IgE reporter cells, creating a novel allergic sensitization detection system. Three proteins (κ-casein, timothy grass pollen extract, polyclonal anti-human IgE) were printed onto three different polymer-coated surfaces (aldehyde-, epoxy- and NHS ester-coated). ToF–SIMs analysis was performed to assess printed protein stability and retention during washing steps. NFAT-DsRed rat basophil leukemia cell attachment and retention during washing steps was assessed after treatment with various extracellular matrix proteins. NFAT-DsRed IgE reporter cells were sensitized with serum of an allergic donor, incubated on the printed slides, and cell activation determined using a microarray laser scanner. NFAT DsRed IgE reporter cell binding was significantly increased on all polymer surfaces after incubation with fibronectin and vitronectin, but not collagen or laminin. All surfaces supported printed protein stability during washing procedure, with epoxy- and NHS ester-coated surfaces showing best protein retention. Cell activation was significantly higher in NHS ester-coated slides after timothy grass pollen extract stimulation appearing a suitable substrate for further development of an automated allergy diagnosis system.
Sampling of the conformational landscape of small proteins with Monte Carlo methods
Authors: Heilmann Nana , Wolf Moritz , Kozlowska Mariana , Sedghamiz Elaheh , Setzler Julia , Brieg Martin , Wenzel Wolfgang
Published: October 2020

Computer simulation provides an increasingly realistic picture of large-scale conformational change of proteins, but investigations remain fundamentally constrained by the femtosecond timestep of molecular dynamics simulations. For this reason, many biologically interesting questions cannot be addressed using accessible state-of-the-art computational resources. Here, we report the development of an all-atom Monte Carlo approach that permits the modelling of the large-scale conformational change of proteins using standard off-the-shelf computational hardware and standard all-atom force fields. We demonstrate extensive thermodynamic characterization of the folding process of the α-helical Trp-cage, the Villin headpiece and the β-sheet WW-domain. We fully characterize the free energy landscape, transition states, energy barriers between different states, and the per-residue stability of individual amino acids over a wide temperature range. We demonstrate that a state-of-the-art intramolecular force field can be combined with an implicit solvent model to obtain a high quality of the folded structures and also discuss limitations that still remain.
A novel bioassay for quantification of surface Cannabinoid receptor 1 expression
Authors: Rodríguez-Rodríguez Ismael , Kalafut Joanna , Czerwonka Arkadiusz , Rivero-Müller Adolfo
Published: October 2020

The cannabinoid receptor type 1 (CB1) plays critical roles in multiple physiological processes such as pain perception, brain development and body temperature regulation. Mutations on this gene (CNR1), results in altered functionality and/or biosynthesis such as reduced membrane expression, changes in mRNA stability or changes in downstream signaling that act as triggers for diseases such as obesity, Parkinson’s, Huntington’s, among others; thus, it is considered as a potential pharmacological target. To date, multiple quantification methods have been employed to determine how these mutations affect receptor expression and localization; however, they present serious disadvantages that may arise quantifying errors. Here, we describe a sensitive bioassay to quantify receptor surface expression; in this bioassay the Gaussia Luciferase (GLuc) was fused to the extracellular portion of the CB1. The GLuc activity was assessed by coelenterazine addition to the medium followed by immediate readout. Based on GLuc activity assay, we show that the GLuc signals corelate with CB1 localization, besides, we showed the assay’s functionality and reliability by comparing its results with those generated by previously reported mutations on the CNR1 gene and by using flow cytometry to determine the cell surface receptor expression. Detection of membrane-bound CB1, and potentially other GPCRs, is able to quickly screen for receptor levels and help to understand the effect of clinically relevant mutations or polymorphisms.
Acoustic preadaptation to transmit vocal individuality of savanna nightjars in noisy urban environments
Authors: Liang Shih-Hsiung , Walther Bruno Andreas , Jen Chia-Hung , Chen Chao-Chieh , Chen Yi-Chih , Shieh Bao-Sen
Published: October 2020

As urbanization has expanded dramatically, the impacts of urban noise on wildlife have drawn increasing attention. However, previous studies have focused primarily on diurnal songbirds and much less on nocturnal nonpasserines such as nightjars. The savanna nightjar has recently successfully colonized urban areas in Taiwan. Using 1925 calls recorded from 67 individuals, we first investigated the individual differences of the acoustic structures; and, for those acoustic variables with significant individual differences, we examined the correlation between the acoustic structures and the ambient noise levels. We then compared the transmission efficacy of vocal individuality among three sets of acoustic variables: all acoustic variables, noise-related variables, and noise-unrelated variables. Using seven artificial frequency-shifted calls to represent seven different individuals in playback-recording experiments, we also investigated the transmission efficacy of vocal individuality and variable accuracy in three different urban noise levels (high, medium, low). We found that all 30 acoustic variables derived from the acoustic structures demonstrated significant individual differences, and 14 frequency-based variables were negatively correlated with ambient noise levels. Although transmission efficacy was significantly affected by urban noise, individuality information was still transmitted with high accuracy. Furthermore, the noise-unrelated structures (which included the maximum frequency, the maximum amplitude frequency, and the mean frequency of the call) had a significantly higher transmission efficacy of vocal individuality than the noise-related variables (which included the minimum frequency, the frequency at the start and the end of the call) in both field observation and playback-recording experiments. We conclude that these noise-unrelated acoustic features may be one of the key preadaptations for this nocturnal nonpasserine to thrive so successfully in its newly adopted urban environment.
Cytotoxic lanthanum oxide nanoparticles sensitize glioblastoma cells to radiation therapy and temozolomide: an in vitro rationale for translational studies
Authors: Lu Victor M. , Jue Toni Rose , McDonald Kerrie L.
Published: October 2020

Glioblastoma (GBM) is a malignant brain tumour with a dismal prognosis, despite best treatment by surgical resection, radiation therapy (RT) and chemotherapy with temozolomide (TMZ). Nanoparticle (NP) therapy is an emerging consideration due to the ability of NPs to be formulated and cross the blood brain barrier. Lanthanum oxide (La2O3) NPs are therapeutically advantageous due to the unique chemical properties of lanthanum making it cytotoxic to cancers, and able to enhance existing anti-cancer treatments. However, La2O3 NPs have yet to be thoroughly investigated in brain tumors. We show that these NPs can reach the brain after venous injection, penetrate into GBM cells via endocytosis, dissociate to be cytotoxic, and enhance the therapeutic effects of RT and TMZ. The mechanisms of cell death by La2O3 NPs were found to be multifaceted. Increasing NP concentration was correlated to increased intrinsic and extrinsic apoptosis pathway markers in a radical oxygen species (ROS)-dependent manner, as well as involving direct DNA damage and autophagic pathways within GBM patient-derived cell lines. NP interactions to sensitize GBM to RT and TMZ were shown to involve these pathways by enhancing ROS and apoptotic mechanisms. We therefore demonstrate the therapeutic potential of La2O3 NPs to treat GBM cells in vitro, and encourage translational exploration in the future.
Single molecule, near full-length genome sequencing of dengue virus
Authors: Adikari Thiruni N. , Riaz Nasir , Sigera Chathurani , Leung Preston , Valencia Braulio M. , Barton Kirston , Smith Martin A. , Bull Rowena A. , Li Hui , Luciani Fabio , Weeratunga Praveen , Thein Tun-Linn , Lim Vanessa W. X. , Leo Yee-Sin , Rajapakse Senaka , Fink Katja , Lloyd Andrew R. , Fernando Deepika , Rodrigo Chaturaka
Published: October 2020

Current methods for dengue virus (DENV) genome amplification, amplify parts of the genome in at least 5 overlapping segments and then combine the output to characterize a full genome. This process is laborious, costly and requires at least 10 primers per serotype, thus increasing the likelihood of PCR bias. We introduce an assay to amplify near full-length dengue virus genomes as intact molecules, sequence these amplicons with third generation “nanopore” technology without fragmenting and use the sequence data to differentiate within-host viral variants with a bioinformatics tool (Nano-Q). The new assay successfully generated near full-length amplicons from DENV serotypes 1, 2 and 3 samples which were sequenced with nanopore technology. Consensus DENV sequences generated by nanopore sequencing had over 99.5% pairwise sequence similarity to Illumina generated counterparts provided the coverage was > 100 with both platforms. Maximum likelihood phylogenetic trees generated from nanopore consensus sequences were able to reproduce the exact trees made from Illumina sequencing with a conservative 99% bootstrapping threshold (after 1000 replicates and 10% burn-in). Pairwise genetic distances of within host variants identified from the Nano-Q tool were less than that of between host variants, thus enabling the phylogenetic segregation of variants from the same host.
Wide temporal horns are associated with cognitive dysfunction, as well as impaired gait and incontinence
Authors: Lilja-Lund Otto , Kockum Karin , Hellström Per , Söderström Lars , Nyberg Lars , Laurell Katarina
Published: October 2020

The association between morphology of the brain and symptoms of suspected idiopathic normal pressure hydrocephalus (iNPH) is largely unknown. We investigated how ventricular expansion (width of the temporal horns [TH], callosal angle [CA], and Evans’ index [EI]) related to symptom severity in suspected iNPH. Participants (n = 168; 74.9 years ± SD 6.7; 55% females) from the general population underwent neurological examination, computed tomography, and neuropsychological testing. Multiple linear regression analysis revealed that wide TH was independently associated with all examined iNPH symptoms (p < 0.01) except for fine-motor performance, whereas a narrow CA only was associated to specific motor and cognitive functions (p < 0.05). TH and EI correlated significantly with incontinence (rs0.17 and rs0.16;p < 0.05). In conclusion, wide TH was significantly associated with most iNPH-symptoms. This finding potentially reflects the complex nature of the hippocampus, however further studies are needed to demonstrate functional connectivity.
Nanofibrous asymmetric collagen/curcumin membrane containing aspirin-loaded PLGA nanoparticles for guided bone regeneration
Authors: Ghavimi Mohammad Ali , Bani Shahabadi Amirhossein , Jarolmasjed Seyedhosein , Memar Mohammad Yousef , Maleki Dizaj Solmaz , Sharifi Simin
Published: October 2020

The goal of the current study was to develop an asymmetric guided bone regeneration (GBR) membrane benefiting from curcumin and aspirin. The membrane was prepared using electrospinning technique and then was physic-chemically characterized by the conventional methods. The release profile of aspirin from the prepared membrane was also measured by ultraviolet spectrophotometry. Also, the antibacterial activities of the membrane was evaluated. We also assessed the in vitro effects of the prepared membrane on the biocompatibility and osteogenic differentiation of dental pulp stem cells (DPSCs), and evaluated in vivo bone regeneration using the prepared membrane in the defects created in both sides of the dog’s jaw by histology. The results from the characterization specified that the membrane was successfully prepared with monodispersed nanosized fibers, uniform network shaped morphology, negative surface charge and sustained release platform for aspirin. The membrane also showed antimicrobial effects against all tested bacteria. The presence of curcumin and aspirin in the asymmetric membrane enhanced osteogenic potential at both transcriptional and translational levels. The results of the animal test showed that the test area was completely filled with new bone after just 28 days, while the commercial membrane area remained empty. There was also a soft tissue layer above the new bone area in the test side. We suggested that the prepared membrane in this work could be used as a GBR membrane to keep soft tissue from occupying bone defects in GBR surgeries. Besides, the surgeries can be benefited from antibacterial activities and bone healing effects of this novel GBR membrane while, simultaneously, promoting bone regeneration.