bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of fracture parameters and roughness on heat‐flow coupling in rock masses with two‐dimensional fracture networks
Authors: Huang Fan , Yao Chi , Zhang Xiaobo , Wu Ligong , Shao Yulong , Zhou Chuangbing 
Published: March 2021

AbstractDiscrete fracture network (DFN) is an effective means of describing the coupling of heat flow in an underground fractured rock mass. In this paper, an improved DFN is proposed by introducing the correlation function of fracture trace length and aperture, which is more consistent with the real fracture data. Next, based on the improved model, the influence of fracture roughness on the fluid flow and heat transmission was evaluated, and the relationship between the fracture aperture and the joint roughness coefficient (JRC) is established. Finally, based on the exponential function between confining pressure and aperture, the influence of confining pressure on the heat‐flow coupling process is considered in the improved model. Besides, the reliability of the model was verified by comparing with the analytical solution of the two‐dimensional single‐fracture heat‐flow coupling problem. The results show that under the same conditions, considering the correlation between the geometric parameters of the fracture, the seepage and heat transfer rates of the model increased, the outlet boundary flow reached the maximum value, and the average outlet temperature dropped rapidly. However, the fracture roughness reduces the outlet flow rate and the decline rate of average temperature. The confining pressure will lead to a decrease of about 3.5% in the outlet flow of the model, which is consistent with the seepage law in practical engineering. The model presented in this paper is an effective supplement to the two‐dimensional fracture network heat‐flow coupling model and can provide a theoretical basis and a numerical calculation tool for related underground rock mass engineering.
Outcomes on anti‐VEGFR‐2/paclitaxel treatment after progression on immune checkpoint inhibition in patients with metastatic gastroesophageal adenocarcinoma
Authors: Kankeu Fonkoua Lionel A. , Chakrabarti Sakti , Sonbol Mohamad B. , Kasi Pashtoon M. , Starr Jason S. , Liu Alex J. , Nevala Wendy K. , Maus Rachel L. , Bois Melanie C. , Pitot Henry C. , Chandrasekharan Chandrikha , Ross Helen J. , Wu Tsung‐Teh , Graham Rondell P. , Villasboas Jose C. , Weiss Matthias , Foster Nathan R. , Markovic Svetomir N. , Dong Haidong , Yoon Harry H. 
Published: March 2021

AbstractThrough our involvement in KEYNOTE‐059, we unexpectedly observed durable responses in two patients with metastatic gastroesophageal adenocarcinoma (mGEA) who received ramucirumab (anti‐VEGFR‐2)/paclitaxel after immune checkpoint inhibition (ICI). To assess the reproducibility of this observation, we piloted an approach to administer ramucirumab/paclitaxel after ICI in more patients, and explored changes in the immune microenvironment. Nineteen consecutive patients with mGEA received ICI followed by ramucirumab/paclitaxel. Most (95%) did not respond to ICI, yet after irRECIST‐defined progression on ICI, all patients experienced tumor size reduction on ramucirumab/paclitaxel. The objective response rate (ORR) and progression‐free survival (PFS) on ramucirumab/paclitaxel after ICI were higher than on the last chemotherapy before ICI in the same group of patients (ORR, 58.8% vs 11.8%; PFS 12.2 vs 3.0 months; respectively). Paired tumor biopsies examined by imaging mass cytometry showed a median 5.5‐fold (range 4‐121) lower frequency of immunosuppressive forkhead box P3+ regulatory T cells with relatively preserved CD8+ T cells, post‐treatment versus pre‐treatment (n = 5 pairs). We then compared the outcomes of these 19 patients with a separate group who received ramucirumab/paclitaxel without preceding ICI (n = 68). Median overall survival on ramucirumab/paclitaxel was longer with (vs without) immediately preceding ICI (14.8 vs 7.4 months) including after multivariate analysis, as was PFS. In our small clinical series, outcomes appeared improved on anti‐VEGFR‐2/paclitaxel treatment when preceded by ICI, in association with alterations in the immune microenvironment. However, further investigation is needed to determine the generalizability of these data. Prospective clinical trials to evaluate sequential treatment with ICI followed by anti‐VEGF(R)/taxane are underway.
Compressive Strength of Iliac Bone ECM Is Not Reduced in Osteogenesis Imperfecta and Increases With Mineralization
Authors: Indermaur Michael , Casari Daniele , Kochetkova Tatiana , Peruzzi Cinzia , Zimmermann Elizabeth , Rauch Frank , Willie Bettina , Michler Johann , Schwiedrzik Jakob , Zysset Philippe 
Published: March 2021

ABSTRACT
Osteogenesis imperfecta (OI) is an inheritable, genetic, and collagen-related disorder leading to an increase in bone fragility, but the origin of its “brittle behavior” is unclear. Because of its complex hierarchical structure, bone behaves differently at various length scales. This study aims to compare mechanical properties of human OI bone with healthy control bone at the extracellular matrix (ECM) level and to quantify the influence of the degree of mineralization. Degree of mineralization and mechanical properties were analyzed under dry conditions in 12 fixed and embedded transiliac crest biopsies (control n = 6, OI type I n = 3, OI type IV n = 2, and OI type III n = 1). Mean degree of mineralization was measured by microcomputed tomography at the biopsy level and the mineral-to-matrix ratio was assessed by Raman spectroscopy at the ECM level. Both methods revealed that the degree of mineralization is higher for OI bone compared with healthy control. Micropillar compression is a novel technique for quantifying post-yield properties of bone at the ECM level. Micropillars (d = 5 μm, h = 10 μm) were fabricated using focused ion beam milling and quasi-statically compressed to capture key post-yield properties such as ultimate strength. The qualitative inspection of the stress–strain curves showed that both OI and healthy control bone have a ductile response at the ECM level. The quantitative results showed that compressive strength is not reduced in OI bone and is increasing with OI severity. Nanoindentation measurements revealed that OI bone tends to have a higher Young's modulus, hardness, and dissipated energy compared with healthy bone. Micropillar strength and indentation modulus increased linearly and significantly (p &lt; .0001) with mineral-to-matrix ratio. In conclusion, this study indicates that compressive mechanical properties of dry OI bone at the iliac crest are not inferior to healthy control at the ECM level and increase with mineralization. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Saikosaponin‐d improved the stemness of mouse neural stem cells and increased their thermotolerance potential
Authors: Xu Panpan , Ma Xiaofang , Xiao Xiaolin , Shi Wanchao , Xue Na , Liu Xiaozhi , Zuo Guoxing , Hu Sheng , Du Xinping , Zheng Jun 
Published: March 2021

AbstractPurposeTo investigate the effect of saikosaponin‐d (Ssd) on proliferation, differentiation, and stemness of neural stem cells (NSCs), and to observe whether Ssd has a protective effect on NSCs at medium‐high and high temperature.Materials and methodsNSCs were extracted from 15‐day fetal mice. After subculture, Ssd treatment was performed. Cell cycle and apoptosis rate were detected by flow cytometry. Western Blot and immunofluorescence assay were used to detect the expression and spatial distribution of Nestin, NSE, GFAP, Oct4, and SOX2. Cell growth morphology was observed under a microscope; the concentration of extracellular lactate dehydrogenase (LDH) was determined by ELISA.ResultsCompared with the control group, the proportion of NSCs in the G0/G1 phase increased in the Ssd treatment group; on the contrary, the proportion in the G2/M phase significantly decreased. Microscopically, our results also suggested the sphere‐formation rate increased significantly. Besides, the percentage of dead cells in the Ssd group at 38.5, 40°C were reduced, and the level of LDH release was dropped.ConclusionSsd improved the stemness of NSCs, inhibited their differentiation into neural cells, and reduced cell damage under high temperature. Therefore, we speculate that Ssd can improve the thermotolerance of NSCs and protect the nervous system of children with fever.
Enhanced synaptic properties of the prefrontal cortex and hippocampus after learning a spatial working memory task in adult male mice
Authors: Stavroulaki Vasiliki , Ioakeimidis Vasileios , Konstantoudaki Xanthippi , Sidiropoulou Kyriaki 
Published: March 2021

AbstractWorking memory (WM) is the ability to hold on‐line and manipulate information. The prefrontal cortex (PFC) is a key brain region involved in WM, while the hippocampus is also involved, particularly, in spatial WM. Although several studies have investigated the neuronal substrates of WM in trained animals, the effects and the mechanisms underlying learning WM tasks have not been explored. In our study, we investigated the effects of learning WM tasks in mice on the function of PFC and hippocampus, by training mice in the delayed alternation task for 9 days (adaptive group). This group was compared to naïve mice (which stayed in their homecage) and mice trained in the alternation procedure only (non‐adaptive). Following training, a cohort of mice (Experiment A) was tested in the left–right discrimination task and the reversal learning task, while another cohort (Experiment B) was tested in the attention set‐shifting task (AST). The adaptive group performed significantly better in the reversal learning task (Experiment A) and AST (Experiment B), compared to non‐adaptive and naïve groups. At the end of the behavioral experiments in Experiment A, field excitatory post‐synaptic potential (fEPSP) recordings were performed in PFC and hippocampal brain slices. The adaptive group had enhanced the long‐term potentiation (LTP) in the PFC, compared to the other groups. In the hippocampus, both the adaptive and the non‐adaptive groups exhibited increased fEPSP compared to the naïve group, but no differences in LTP. In Experiment B, the dendritic spine density was measured, which, in the PFC, was found increased in the adaptive group, compared to the non‐adaptive and naïve groups. In the hippocampus, there was an increase in mature dendritic spine density in the adaptive group, compared to the other two groups. Our results indicate a role for LTP and dendritic spine density in learning WM tasks.
Controlled Cell Alignment Using Two‐Photon Direct Laser Writing‐Patterned Hydrogels in 2D and 3D
Authors: Song Jiaxi , Michas Christos , Chen Christopher S. , White Alice E. , Grinstaff Mark W. 
Published: March 2021

AbstractDirect laser writing (DLW) via two‐photon polymerization is an emerging highly precise technique for the fabrication of intricate cellular scaffolds. Despite recent progress in using two‐photon‐polymerized scaffolds to probe fundamental cell behaviors, new methods to direct and modulate microscale cell alignment and selective cell adhesion using two‐photon‐polymerized microstructures are of keen interest. Here, a DLW‐fabricated 2D and 3D hydrogel microstructures, with alternating soft and stiff regions, for precisely controlled cell alignment are reported. The use of both cell‐adhesive and cell‐repellent hydrogels allows selective adhesion and alignment of human mesenchymal stem cells within the printed structure. Importantly, DLW patterning enables cell alignment on flat surfaces as well as irregular and curved 3D microstructures, which are otherwise challenging to pattern with cells.
The Phenomenon of Exquisite Motor Control in Tic Disorders and its Pathophysiological Implications
Authors: Ganos Christos , Neumann Wolf‐Julian , Müller‐Vahl Kirsten R. , Bhatia Kailash P. , Hallett Mark , Haggard Patrick , Rothwell John 
Published: March 2021

ABSTRACTThe unifying characteristic of movement disorders is the phenotypic presentation of abnormal motor outputs, either as isolated phenomena or in association with further clinical, often neuropsychiatric, features. However, the possibility of a movement disorder also characterized by supranormal or enhanced volitional motor control has not received attention. Based on clinical observations and cases collected over a number of years, we here describe the intriguing clinical phenomenon that people with tic disorders are often able to control specific muscle contractions as part of their tic behaviors to a degree that most humans typically cannot. Examples are given in accompanying video documentation. We explore medical literature on this topic and draw analogies with early research of fine motor control physiology in healthy humans. By systematically analyzing the probable sources of this unusual capacity, and focusing on neuroscientific accounts of voluntary motor control, sensory feedback, and the role of motor learning in tic disorders, we provide a novel pathophysiological account explaining both the presence of exquisite control over motor output and that of overall tic behaviors. We finally comment on key questions for future research on the topic and provide concluding remarks on the complex movement disorder of tic behaviors. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
Climate‐adaptive design approach for embedded footing under extreme climate event
Authors: Mahmoudabadi Vahidreza , Ravichandran Nadarajah 
Published: March 2021

AbstractRecent records indicate that extreme climate events adversely affect the performance of earthen structures and superstructures supported on them by varying the strength and deformation properties of subsurface soil. To better design such structures, the effects of climate events must be well understood, and the conventional design procedures must be improved by incorporating the knowledge of climatology in geotechnical engineering. In this study, a new climate‐adaptive design method is developed to investigate the impact of extreme climate events on the safety and serviceability performances of embedded footing through incorporating the site‐specific hydrological loads such as precipitation, evapotranspiration, and water table depth to geotechnical parameters. The proposed method was applied to two arid climate sites in the United States, Austin, TX, and Albuquerque, NM. The site‐specific extreme hydrological cycle was determined based on historical records. The mathematical model was solved for temporal and spatial variations of the degree of saturation and matric suction considering the hydrological loads as the upper and lower boundary conditions, respectively. The results showed that the worst performance (higher elastic settlement and lower ultimate bearing capacity) was observed during the period when the degree of saturation in the influence zone was the highest. The critical design parameters including ultimate bearing capacity and settlement obtained from the proposed method increased by 28% and 35%, respectively, in Austin, compared to those calculated from conventional approaches where the soil is assumed to be fully saturated. In Albuquerque, the increase in ultimate bearing capacity and settlement were 61% and 45%, respectively.
An efficient positive‐definite block‐preconditioned finite volume solver for two‐sided fractional diffusion equations on composite mesh
Authors: Dai Pingfei , Jia Jinhong , Wang Hong , Wu Qingbiao , Zheng Xiangcheng 
Published: March 2021

AbstractIt is known that the solutions to space‐fractional diffusion equations exhibit singularities near the boundary. Therefore, numerical methods discretized on the composite mesh, in which the mesh size is refined near the boundary, provide more precise approximations to the solutions. However, the coefficient matrices of the corresponding linear systems usually lose the diagonal dominance and are ill‐conditioned, which in turn affect the convergence behavior of the iteration methods.In this work we study a finite volume method for two‐sided fractional diffusion equations, in which a locally refined composite mesh is applied to capture the boundary singularities of the solutions. The diagonal blocks of the resulting three‐by‐three block linear system are proved to be positive‐definite, based on which we propose an efficient block Gauss–Seidel method by decomposing the whole system into three subsystems with those diagonal blocks as the coefficient matrices. To further accelerate the convergence speed of the iteration, we use T. Chan's circulant preconditioner31 as the corresponding preconditioners and analyze the preconditioned matrices' spectra. Numerical experiments are presented to demonstrate the effectiveness and the efficiency of the proposed method and its strong potential in dealing with ill‐conditioned problems. While we have not proved the convergence of the method in theory, the numerical experiments show that the proposed method is convergent.
Effects of modified carbon nanotubes with different sizes on properties of epoxy shape memory polymers
Authors: Tang Longhao , Wang Yanling , Li Yongfei , Li Qiang 
Published: March 2021

AbstractShape memory polymers (SMPs) have occupied an important role in material application, in which the contribution of various fillers on the enhancement of their low mechanical and thermal properties is indispensable. Lots of excellent researches on carbon nanotubes improving comprehensive performance have been accomplished, while few comparative studies about carbon nanotubes with different sizes. In the present study, epoxy shape memory composites of multi‐walled carbon nanotubes/epoxy matrix (MWCNTs/epoxy) were prepared, in which MWCNTs with different sizes modified through epoxidation act as enhancement filler. The results indicated that MWCNTs with smaller size possess an efficient effect on improving mechanical properties, and MWCNTs with larger size achieve higher enhancement on increasing heat resistance as the filler content is low (0.1%, 0.2%). Furthermore, the effect of MWCNTs on shape recovery ratio and shape recovery speed of composites has also been systematically investigated.
Modeling the temperature‐dependent viscoelastic behavior of glass fabric with binder in the compaction process
Authors: Mei Ming , He Yujia , Wei Kai , Duan Shuyong , Li Maojun , Yang Xujing 
Published: March 2021

AbstractThe strain response and influence of elevated temperature on the viscoelastic behavior of fabric in the compaction process cannot be described and predicted by current viscoelastic models. Here, a viscoelastic model, verified by compaction experiments, is originally proposed to depict the stress and strain responses in different stages of the compaction, especially considering the effects of added binder and elevated temperature. The model effectively captures that with the rising temperature, the interaction among fibers is enhanced due to the fiber volume expansion. Accordingly, the elastic modulus is enlarged in the compression stage. In the relaxation stage, the interaction suppresses the fiber realignment, leading to the reduction of stress relaxation. In the creep stage, the elevated temperature increases the deformation stiffness, indicating the strain is declined. In the relaxation stage, the adhesive effect of added binder facilitates the stress relaxation, and then the increasing stress relaxation promotes the increment of strain in the creep stage.
Dereplication of phenolic derivatives of three Erythroxylum species using liquid chromatography coupled with ESI‐MSn and HRESIMS
Authors: Dantas César Augusto Gonçalves , Abreu Lucas Silva , da Cunha Hidna Nascimento , Veloso Carlos Arthur Gouveia , Souto Augusto Lopes , de Fátima Agra Maria , de Oliveira Costa Vicente Carlos , da Silva Marcelo Sobral , Tavares Josean Fechine 
Published: March 2021

AbstractIntroductionGiven the diversity of secondary metabolites produced by species of the genus Erythroxylum, in addition to the many methods that have already been described in the literature, modern screening and identification methodologies, such as dereplication, represent an efficient and quick strategy compared to the classic techniques linked to natural product research.ObjectiveThe objective of the present study was to determine the phenolic profiles obtained from three species of Erythroxylum (Erythroxylum pauferrense Plowman, Erythroxylum pulchrum A.St.‐Hil. and Erythroxylum simonis Plowman) by dereplication using liquid chromatography coupled with ESI‐MSn and HRESIMS.Material and MethodsEthyl acetate and n‐butanolic fractions from crude ethanolic extract of Erythroxylum species were analyzed by HPLC‐ESI‐MSn and HPLC‐HRESIMS, in order to identify its corresponding compounds. Experiments were performed in negative ionization mode, and the metabolites were provisionally identified based on deprotonated molecules, molecular formulas, fragmentation patterns and literature data. The corresponding isolated compounds were characterized by 1H and 13C NMR spectroscopy.ResultsAccording to the dereplication method, it was possible to establish and compare the phenolic profile of the corresponding species by the assignment of 55 compounds, most of which were first described in these species and among which some were also new to the Erytroxylum genus. Additionally, nine compounds were isolated, including biphenyl‐3,3′,4,4′‐tetraol, where the mass spectral data were not sufficient for their identification, and reported for the first time in the Erythroxylaceae family.ConclusionThis research contributes to the phytochemical knowledge of the Erythroxylum genus and demonstrates the importance of the dereplication method regarding the investigation of natural products, enabling accurate identification of the metabolites while avoiding the efforts and material expenses involved in the isolation of known compounds.
Ultrasmall Red Fluorescent Gold Nanoclusters for Highly Biocompatible and Long‐Time Nerve Imaging
Authors: Yang Zhe , Zhao Yueqi , Hao Yulei , Li Xingchen , Zvyagin Andrei V. , Whittaker Andrew K. , Cui Yong , Yang Bai , Lin Quan , Li Yang 
Published: March 2021

AbstractA rapidly growing area of neuroscience demands next‐generation neurofluorescent probes are fulfilling several stringent criteria, including water solubility, distinct signal‐to‐background ratio, anti‐photobleaching, and low toxicity. Herein, a novel neurofluorescent probe based on gold nanoclusters capped with glutathione (Au‐GSH) is introduced and characterized by advanced fluorescence photophysical properties composed of comparative high quantum yield (8.9%), negligible blinking, and bright fluorescence in the red spectral range (Em = 650 nm) with sub‐millisecond‐scale lifetime (0.62 ms). Fluorescent performance is tested and demonstrated negligible photobleaching under exposure to ultraviolet light (365 nm, 30 W) over 4 h, immunity to variation of the microenvironment characterized by pH range of 4–10, and colloidal stability in serum over 24 h during the blood circulation. Coupled with 2.4 ± 0.9 nm ultrasmall size and good water solubility, they are superior to fluorescent proteins, quantum dots, and organic fluorescent dyes. Au‐GSH are further confirmed that they can be used as a fluorescent label for in vivo nerve and brain imaging, and even after injecting Au‐GSH into the rat sciatic nerve for 21 d, the red fluorescence is still preserved. This combination of favorable properties makes Au‐GSH a promising candidate for neurofluorescent probes.