bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multilevel Monte Carlo Predictions of First Passage Times in Three‐Dimensional Discrete Fracture Networks: A Graph‐Based Approach
Authors: Berrone S. , Hyman J. D. , Pieraccini S. 
Published: May 2020

AbstractWe present a method combining multilevel Monte Carlo (MLMC) and a graph‐based primary subnetwork identification algorithm to provide estimates of the mean and variance of the distribution of first passage times in fracture media at significantly lower computational cost than standard Monte Carlo (MC) methods. Simulations of solute transport are performed using a discrete fracture network (DFN), and instead of using various grid resolutions for levels in the MLMC, which is standard practice in MLMC, we identify a hierarchy of subnetworks in the DFN based on the shortest topological paths through the network using a graph‐based method. While the mean of these ensembles is of critical importance, the variance is also essential in fractured media where uncertainty is an overarching theme, and understanding variability across an ensemble is a requirement for safety assessments. The method provides good estimates of the mean and variance at two orders of magnitude lower computational cost than MC.
Severe Magnetic Fluctuations in the Near‐Earth Magnetotail: Spectral Analysis and Dependence on Solar Activity
Authors: Xu Heqiucen , Shiokawa Kazuo 
Published: May 2020

AbstractMagnetic fluctuations in the near‐Earth magnetotail are an important signature of substorm onset. In a previous statistical study, we reported their occurrence rates, spatial distributions, and relationship with plasma flows. In the present study, we investigated their spectral properties using 11 years of measurements from the Time History of Events and Macroscale Interactions during Substorms mission for 2008–2018. We found 10,848 severe magnetic fluctuation events with
, where σB and
are the standard deviation and average, respectively, of the magnetic field intensity for the local proton gyroperiod. The occurrence rates of severe magnetic fluctuations show no clear dependence on the F10.7 index in one solar cycle. We extracted 36 dipolarization events with severe magnetic fluctuations. In the power spectral density (PSD) of the magnetic fluctuations during dipolarizations, the steepness of the spectral slope increased with increasing frequency in almost all the events. The average PSDs are shown sorted by (a) distance to the neutral sheet and (b) ambient magnetic field intensity. In all groups, the slopes of the average PSDs increased abruptly from below ∼10−1.3 Hz (0.05 Hz) to above ∼10−1.3 Hz, which is close to the gyrofrequency of O+ ions. It is the first time that a change of slope near the proton gyrofrequency (frequency range: 0.05–1 Hz) was found in cases of larger ambient magnetic field intensity, implying that the magnetic fluctuations were relatively strong near the proton gyrofrequency. These results suggest that the magnetic fluctuations contribute to the nonmagnetohydrodynamic effect in the ion motion.
A dose-finding Phase 2 study of single agent isatuximab (anti-CD38 mAb) in relapsed/refractory multiple myeloma
Authors: Mikhael Joseph , Richter Joshua , Vij Ravi , Cole Craig , Zonder Jeffrey , Kaufman Jonathan L. , Bensinger William , Dimopoulos Meletios , Lendvai Nikoletta , Hari Parameswaran , Ocio Enrique M. , Gasparetto Cristina , Kumar Shaji , Oprea Corina , Chiron Marielle , Brillac Claire , Charpentier Eric , San-Miguel Jesús , Martin Thomas 
Published: May 2020

AbstractA Phase 2 dose-finding study evaluated isatuximab, an anti-CD38 monoclonal antibody, in relapsed/refractory multiple myeloma (RRMM; NCT01084252). Patients with ≥3 prior lines or refractory to both immunomodulatory drugs and proteasome inhibitors (dual refractory) were randomized to isatuximab 3 mg/kg every 2 weeks (Q2W), 10 mg/kg Q2W(2 cycles)/Q4W, or 10 mg/kg Q2W. A fourth arm evaluated 20 mg/kg QW(1 cycle)/Q2W. Patients (N = 97) had a median (range) age of 62 years (38–85), 5 (2–14) prior therapy lines, and 85% were double refractory. The overall response rate (ORR) was 4.3, 20.0, 29.2, and 24.0% with isatuximab 3 mg/kg Q2W, 10 mg/kg Q2W/Q4W, 10 mg/kg Q2W, and 20 mg/kg QW/Q2W, respectively. At doses ≥10 mg/kg, median progression-free survival and overall survival were 4.6 and 18.7 months, respectively, and the ORR was 40.9% (9/22) in patients with high-risk cytogenetics. CD38 receptor density was similar in responders and non-responders. The most common non-hematologic adverse events (typically grade ≤2) were nausea (34.0%), fatigue (32.0%), and upper respiratory tract infections (28.9%). Infusion reactions (typically with first infusion and grade ≤2) occurred in 51.5% of patients. In conclusion, isatuximab is active and generally well tolerated in heavily pretreated RRMM, with greatest efficacy at doses ≥10 mg/kg.
Cuprous oxide nanoparticles trigger reactive oxygen species-induced apoptosis through activation of erk-dependent autophagy in bladder cancer
Authors: Xiong Qiao , Liu Anwei , Ren Qian , Xue Yongping , Yu Xiaowen , Ying Yidie , Gao Hongliang , Tan Haoyuan , Zhang Zhensheng , Li Wei , Zeng Shuxiong , Xu Chuanliang 
Published: May 2020

AbstractCisplatin-based chemotherapy is the first-line treatment for patients with advanced bladder cancer. However, as more than 50% of patients are ineligible for cisplatin-based chemotherapy, there is an urgent need to develop new drugs. Cuprous oxide nanoparticles (CONPs), as a new nano-therapeutic agent, have been proved to be effective in many kinds of tumors. In the present study, CONPs showed dose-dependent and time-dependent inhibitory effects on various bladder cancer cell lines (T24, J82, 5637, and UMUC3) and weak inhibitory effects on non-cancerous epithelial cells (SVHUCs). We found that CONPs induced cell cycle arrest and apoptosis in bladder cancer cells. We further demonstrated that the potential mechanisms of CONP-induced cytotoxicity were apoptosis, which was triggered by reactive oxygen species through activation of ERK signaling pathway, and autophagy. Moreover, the cytotoxic effect of CONPs on bladder cancer was confirmed both in orthotopic xenografts and subcutaneous nude mouse models, indicating that CONPs could significantly suppress the growth of bladder cancer in vivo. In further drug combination experiments, we showed that CONPs had a synergistic drug–drug interaction with cisplatin and gemcitabine in vitro, both of which are commonly used chemotherapy agents for bladder cancer. We further proved that CONPs potentiated the antitumor activity of gemcitabine in vivo without exacerbating the adverse effects, suggesting that CONPs and gemcitabine can be used for combination intravesical chemotherapy. In conclusion, our preclinical data demonstrate that CONPs are a promising nanomedicine against bladder cancer and provide good insights into the application of CONPs and gemcitabine in combination for intravesical bladder cancer treatment.
Stimuli-responsive hydrogels as a model of the dynamic cellular microenvironment
Authors: Tanaka Motomu , Nakahata Masaki , Linke Philipp , Kaufmann Stefan 
Published: May 2020

AbstractAmple evidence has demonstrated that biological cells not only react to biochemical cues from the surrounding microenvironments but also sensitively detect the mechanical properties of the extracellular matrix and neighboring cells to adapt their shape, function, and fate. Mechanical aspects in biology, called mechanobiology, have been attracting biologists, chemists, physicists, and mechanical engineers. However, most in vitro studies to date have heavily relied on covalently cross-linked hydrogels with prefixed and hence unchangeable mechanical properties, although the mechanical properties of the cellular microenvironment are never uniform or static. From this context, stimuli-responsive hydrogels are highly attractive as surrogate materials that can simulate dynamic physical microenvironments in vivo. This review tries to provide a comprehensive overview of previous achievements, present pitfalls and challenges, and future perspectives on the recent development of stimuli-responsive hydrogel materials for the dynamic control of cell behavior.
Heteronuclear soliton molecules in optical microresonators
Authors: Weng Wenle , Bouchand Romain , Lucas Erwan , Obrzud Ewelina , Herr Tobias , Kippenberg Tobias J. 
Published: May 2020

AbstractOptical soliton molecules are bound states of solitons that arise from the balance between attractive and repulsive effects. Having been observed in systems ranging from optical fibres to mode-locked lasers, they provide insights into the fundamental interactions between solitons and the underlying dynamics of the nonlinear systems. Here, we enter the multistability regime of a Kerr microresonator to generate superpositions of distinct soliton states that are pumped at the same optical resonance, and report the discovery of heteronuclear dissipative Kerr soliton molecules. Ultrafast electrooptical sampling reveals the tightly short-range bound nature of such soliton molecules, despite comprising cavity solitons of dissimilar amplitudes, durations and carrier frequencies. Besides the significance they hold in resolving soliton dynamics in complex nonlinear systems, such heteronuclear soliton molecules yield coherent frequency combs whose unusual mode structure may find applications in metrology and spectroscopy.
Room-temperature coherent control of implanted defect spins in silicon carbide
Authors: Yan Fei-Fei , Yi Ai-Lun , Wang Jun-Feng , Li Qiang , Yu Pei , Zhang Jia-Xiang , Gali Adam , Wang Ya , Xu Jin-Shi , Ou Xin , Li Chuan-Feng , Guo Guang-Can 
Published: May 2020

AbstractRecently, vacancy-related spin defects in silicon carbide (SiC) have been demonstrated to be potentially suitable for versatile quantum interface building and scalable quantum network construction. Significant efforts have been undertaken to identify spin systems in SiC and to extend their quantum capabilities using large-scale growth and advanced nanofabrication methods. Here we demonstrated a type of spin defect in the 4H polytype of SiC generated via hydrogen ion implantation with high-temperature post-annealing, which is different from any known defects. These spin defects can be optically addressed and coherently controlled even at room temperature, and their fluorescence spectrum and optically detected magnetic resonance spectra are different from those of any previously discovered defects. Moreover, the generation of these defects can be well controlled by optimizing the annealing temperature after implantation. These defects demonstrate high thermal stability with coherently controlled electron spins, facilitating their application in quantum sensing and masers under harsh conditions.
Evaluation of heterologous prime-boost vaccination strategies using chimpanzee adenovirus and modified vaccinia virus for TB subunit vaccination in rhesus macaques
Authors: Vierboom Michel P. M. , Chenine Agnes L. , Darrah Patricia A. , Vervenne Richard A. W. , Boot Charelle , Hofman Sam O. , Sombroek Claudia C. , Dijkman Karin , Khayum Mohamed A. , Stammes Marieke A. , Haanstra Krista G. , Hoffmann Chantal , Schmitt Doris , Silvestre Nathalie , White Alexander G. , Borish H. Jacob , Seder Robert A. , Ouaked Nadia , Leung-Theung-Long Stephane , Inchauspé Geneviève , Anantha Ravi , Limbach Mary , Evans Thomas G. , Casimiro Danilo , Lempicki Maria , Laddy Dominick J. , Bonavia Aurelio , Verreck Frank A. W. 
Published: May 2020

AbstractTuberculosis (TB) still is the principal cause of death from infectious disease and improved vaccination strategies are required to reduce the disease burden and break TB transmission. Here, we investigated different routes of administration of vectored subunit vaccines based on chimpanzee-derived adenovirus serotype-3 (ChAd3) for homologous prime-boosting and modified vaccinia virus Ankara (MVA) for heterologous boosting with both vaccine vectors expressing the same antigens from Mycobacterium tuberculosis (Ag85B, ESAT6, Rv2626, Rv1733, RpfD). Prime-boost strategies were evaluated for immunogenicity and protective efficacy in highly susceptible rhesus macaques. A fully parenteral administration regimen was compared to exclusive respiratory mucosal administration, while parenteral ChAd3-5Ag prime-boosting and mucosal MVA-5Ag boosting were applied as a push-and-pull strategy from the periphery to the lung. Immune analyses corroborated compartmentalized responses induced by parenteral versus mucosal vaccination. Despite eliciting TB-specific immune responses, none of the investigational regimes conferred a protective effect by standard readouts of TB compared to non-vaccinated controls, while lack of protection by BCG underpinned the stringency of this non-human primate test modality. Yet, TB manifestation after full parenteral vaccination was significantly less compared to exclusive mucosal vaccination.
Bioprocess development for L-asparaginase production by Streptomyces rochei, purification and in-vitro efficacy against various human carcinoma cell lines
Authors: El-Naggar Noura El-Ahmady , El-Shweihy Nancy M. 
Published: May 2020

AbstractIn the near future, the demand for L-asparaginase is expected to rise several times due to an increase in its clinical and industrial applications in various industrial sectors, such as food processing. Streptomyces sp. strain NEAE-K is potent L-asparaginase producer, isolated and identified as new subsp. Streptomyces rochei subsp. chromatogenes NEAE-K and the sequence data has been deposited under accession number KJ200343 at the GenBank database. Sixteen different independent factors were examined for their effects on L-asparaginase production by Streptomyces rochei subsp. chromatogenes NEAE-K under solid state fermentation conditions using Plackett–Burman design. pH, dextrose and yeast extract were the most significant factors affecting L-asparaginase production. Thus, using central composite design, the optimum levels of these variables were determined. L-asparaginase purification was carried out by ammonium sulfate followed by DEAE-Sepharose CL-6B ion exchange column with a final purification fold of 16.18. The monomeric molecular weight of the purified L-asparaginase was 64 kD as determined by SDS-PAGE method. The in vitro effects of L-asparaginase were evaluated on five human tumor cell lines and found to have a strong anti-proliferative effects. The results showed that the strongest cytotoxic effect of L-asparaginase was exerted on the HeLa and HepG-2 cell lines (IC50 = 2.16 ± 0.2 and 2.54 ± 0.3 U/mL; respectively). In addition, the selectivity index of L-asparaginase against HeLa and HepG-2 cell lines was 3.94 and 3.35; respectively.
Reinforcement Quantum Annealing: A Hybrid Quantum Learning Automata
Authors: Ayanzadeh Ramin , Halem Milton , Finin Tim 
Published: May 2020

AbstractWe introduce the notion of reinforcement quantum annealing (RQA) scheme in which an intelligent agent searches in the space of Hamiltonians and interacts with a quantum annealer that plays the stochastic environment role of learning automata. At each iteration of RQA, after analyzing results (samples) from the previous iteration, the agent adjusts the penalty of unsatisfied constraints and re-casts the given problem to a new Ising Hamiltonian. As a proof-of-concept, we propose a novel approach for casting the problem of Boolean satisfiability (SAT) to Ising Hamiltonians and show how to apply the RQA for increasing the probability of finding the global optimum. Our experimental results on two different benchmark SAT problems (namely factoring pseudo-prime numbers and random SAT with phase transitions), using a D-Wave 2000Q quantum processor, demonstrated that RQA finds notably better solutions with fewer samples, compared to the best-known techniques in the realm of quantum annealing.
Probabilistic risk assessment of dietary exposure to aflatoxin B1 in Guangzhou, China
Authors: Zhang Weiwei , Liu Yufei , Liang Boheng , Zhang Yuhua , Zhong Xianwu , Luo Xiaoyan , Huang Jie , Wang Yanyan , Cheng Weibin , Chen Kuncai 
Published: May 2020

AbstractAflatoxin B1 (AFB1) contamination in foods is an important health challenge for low-and middle-income countries in subtropical regions. AFB1 has been detected in a variety of foodsin Guangzhou, while the risk of dietary exposure is unknown. This study aimed to assess the probabilistic risk of dietary exposure to AFB1 contamination in food stuffs in Guangzhou by using margin of exposure (MOE) and quantitative liver cancer risk approaches. A total of1854 AFB1-contaminated foodstuffs were sampled in supermarkets, agricultural markets, retail shops, and family workshops from 11 districts of Guangzhou, and AFB1 content was determined by HPLC-fluorescence detector. In total, 9.9% (184/1854) of the test samples had AFB1 concentrations above the limit of detection. Home-made peanut oil had the highest AFB1 concentration, with a mean value of 38.74 ± 47.45 μg kg−1. The average MOE levels of Guangzhou residents ranged from 100 to 1000. The risk of liver cancer was 0.0264 cancers (100,000 population year)−1. The health risks of suburban people were higher than those of urban people, and home-made peanut oil was the main contributorto dietary exposure to AFB1 among suburban residents in Guangzhou. The production of home-made peanut oil should be supervised to reduce the risk of AFB1 exposure.
Ultra Wideband Radar Cross Section Reduction by using non-Resonant Unit Cells
Authors: Nadi Morteza , Sedighy Seyed Hassan , Khalaj-Amirhosseini Mohamad 
Published: May 2020

AbstractA general approach is proposed to design ultra-wideband radar cross section reduction (RCSR) metasurface by using non-resonant unit cells in chessboard arrangement. The proposed miniaturized artificial magnetic conductor unit cell is composed of two stacked non-resonant patches separated from one another by thin dielectric substrates. The genetic optimization algorithm is used to optimize the unit cell design parameters and obtain wide 10-dB RCSR bandwidth. The proposed approach is performed to design three different RCSR metasurfaces, ideal, ROGERS and low cost. The low cost RCSR metasurface composed of low cost commercially available FR-4 substrate is fabricated and tested which reduces RCS more than 10-dB from 5.22 GHz to 30.85 GHz, 142% fractional bandwidth. This metasurface has significantly wider RCSR bandwidth rather than the state of the art references as well as low cost, simple and light weight structure which facilities its practical applications.
Serum neurofilament light chain levels as a biomarker of neuroaxonal injury and severity of oxaliplatin-induced peripheral neuropathy
Authors: Kim Su-Hyun , Choi Moon Ki , Park Na Young , Hyun Jae-Won , Lee Min Young , Kim Ho Jin , Jung Su Kyung , Cha Yongjun 
Published: May 2020

AbstractWe set out to determine the usability of serum neurofilament light chain (sNfL), serum glial fibrillary acidic protein (sGFAP), and retinal parameters by using optical coherence tomography (OCT) as reliable biomarkers of the progression of oxaliplatin-induced peripheral neuropathy (OIPN). Forty-three patients scheduled to undergo oxaliplatin-based chemotherapy at the National Cancer Center of Korea between June 2018 and October 2019 were prospectively assessed at baseline, 3 months, and 6 months of chemotherapy. Patients were assessed on clinical scales and underwent OCT, sNfL, and sGFAP level measurement at each follow-up visit. By applying the National Cancer Institute-Common Toxicity Criteria (NCI-CTC), OIPN was classified as grade 1 in 12 (28%) patients, grade 2 in 25 (58%), and grade 3 in 5 (12%) at 6 months of chemotherapy. sNfL levels increased during oxaliplatin administration, while serial sGFAP levels or retinal parameters did not change. Patients with grade-3 OIPN showed significantly higher mean sNfL levels than patients with grade 0–2 OIPN at 6 months of treatment. At 4–6 months after completion of chemotherapy, sNfL levels were significantly reduced compared to the levels at 6 months of chemotherapy. Monitoring of sNfL during chemotherapy can indicate ongoing neuroaxonal injury and the severity of OIPN.
Machine Learning (ML) based-method applied in recurrent pregnancy loss (RPL) patients diagnostic work-up: a potential innovation in common clinical practice
Authors: Bruno V. , D’Orazio M. , Ticconi C. , Abundo P. , Riccio S. , Martinelli E. , Rosato N. , Piccione E. , Zupi E. , Pietropolli A. 
Published: May 2020

AbstractRPL is a very debated condition, in which many issues concerning definition, etiological factors to investigate or therapies to apply are still controversial. ML could help clinicians to reach an objectiveness in RPL classification and access to care. Our aim was to stratify RPL patients in different risk classes by applying an ML algorithm, through a diagnostic work-up to validate it for the appropriate prognosis and potential therapeutic approach. 734 patients were enrolled and divided into 4 risk classes, according to the numbers of miscarriages. ML method, called Support Vector Machine (SVM), was used to analyze data. Using the whole set of 43 features and the set of the most informative 18 features we obtained comparable results: respectively 81.86 ± 0.35% and 81.71 ± 0.37% Unbalanced Accuracy. Applying the same method, introducing the only features recommended by ESHRE, a correct classification was obtained only in 58.52 ± 0.58%. ML approach could provide a Support Decision System tool to stratify RPL patients and address them objectively to the proper clinical management.
Differential responses to kinase inhibition in FGFR2-addicted triple negative breast cancer cells: a quantitative phosphoproteomics study
Authors: Cunningham Debbie L. , Sarhan Adil R. , Creese Andrew J. , Larkins Katherine P. B. , Zhao Hongyan , Ferguson Harriet R. , Brookes Katie , Marusiak Anna A. , Cooper Helen J. , Heath John K. 
Published: May 2020

AbstractFibroblast Growth Factor (FGF) dependent signalling is frequently activated in cancer by a variety of different mechanisms. However, the downstream signal transduction pathways involved are poorly characterised. Here a quantitative differential phosphoproteomics approach, SILAC, is applied to identify FGF-regulated phosphorylation events in two triple- negative breast tumour cell lines, MFM223 and SUM52, that exhibit amplified expression of FGF receptor 2 (FGFR2) and are dependent on continued FGFR2 signalling for cell viability. Comparative Gene Ontology proteome analysis revealed that SUM52 cells were enriched in proteins associated with cell metabolism and MFM223 cells enriched in proteins associated with cell adhesion and migration. FGFR2 inhibition by SU5402 impacts a significant fraction of the observed phosphoproteome of these cells. This study expands the known landscape of FGF signalling and identifies many new targets for functional investigation. FGF signalling pathways are found to be flexible in architecture as both shared, and divergent, responses to inhibition of FGFR2 kinase activity in the canonical RAF/MAPK/ERK/RSK and PI3K/AKT/PDK/mTOR/S6K pathways are identified. Inhibition of phosphorylation-dependent negative-feedback pathways is observed, defining mechanisms of intrinsic resistance to FGFR2 inhibition. These findings have implications for the therapeutic application of FGFR inhibitors as they identify both common and divergent responses in cells harbouring the same genetic lesion and pathways of drug resistance.