Search

Background: Inhibitor of DNA Binding 2 (ID2) plays a crucial role in tumor cell proliferation, invasion, metastasis, and stemness. Aberrant ID2 expression is associated with poor prognosis in various cancers. However, the specific function of ID2 in thyroid cancer remain unclear. Method: The TCGA database were utilized to explore the clinical relevance of ID2 in cancer. GO, KEGG, and TIMER were employed to predict the potential roles of ID2 in cancer. Functional analysis, including CCK-8, colony formation, transwell, wound healing, and sphere formation experiments, were conducted to determine the biological functions of ID2 in human cancers. Western blot (WB), RT-qPCR, and immunohistochemical (IHC) analyses were used to investigate the relationship between ID2 and downstream targets. Results: Our study revealed significant overexpression of ID2 in various malignant tumor cells. Knocking ID2 significantly inhibited cancer cell proliferation and invasion, while overexpressing ID2 enhanced these capabilities. Additionally, ID2 mediates resistance of cancer cells to protein kinase B (or Akt) inhibitions. Further WB and IHC experiments indicated that ID2 promotes the phosphorylation activation of phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway, thereby upregulating the expression of downstream proliferation, epithelial-mesenchymal transition (EMT), and stemness-related markers. Conclusion: We found that ID2 significantly promotes thyroid cancer cell proliferation, migration, EMT, and stemness through the PI3K/Akt pathway. Moreover, ID2 plays a crucial role in regulating cancer immune responses. It may serve as a potential biomarker for enhancing the efficacy of chemotherapy, targeted therapy, and immunotherapy against cancer.

The effect of yttrium on the 475 °C brittleness and microstructure stability of Fe–13Cr–6Al–2Mo-0.5Nb-0.15Zr alloy after long-term aging at 475 °C has been investigated. At the early stage of aging, the nanoscale metastable transition phase precipitates in large quantities. After aging for 10,000 h, the nanophase in the Y-free alloy has completely disappeared, and only a great deal of granular Laves phases are left, while a large number of nanoscale phases still exist in the grain of Y-containing alloys. This is because the addition of yttrium combines with vacancies, hinders the diffusion of Laves phase-forming elements, and has the result that the transformation of nanoscale phases Fe2(Mo0.3Nb0.7)Al to Laves phase is inhibited during the aging process of the Y-containing alloys. During aging, precipitation-free zones (PFZ) are formed in the surrounding area where the Laves phase and grain boundaries exist. The elongation of Y-containing alloys decreases with yttrium content, but it is still higher than that of Y-free alloy. The addition of yttrium improves the aging plasticity and weakens the degree of 475 °C brittleness of the alloy, and the effectiveness is diminished with the yttrium. This plays a key role in the further study of Fe–Cr–Al alloys for fuel cladding materials.

In large group decision-making, participators with different knowledge structures, backgrounds, and other characteristics are unlikely to accurately evaluate alternatives. For this, it is necessary to decompose alternatives into several elements, and consider the participators’ preferences for elements of alternatives and the multiple classifications for participators according to their characteristics. However, related studies are still scarce. The objective of this paper is to propose a multi-elemental large group decision-making method, in which the desirable alternative(s) are selected from a set of feasible alternatives according to the preference information on multiple elements of alternatives provided by participators from multiple subgroups, and multiple classifications for participators are considered. In the method, according to the strict preference ordering of elements provided by participators, the percentage distributions on preferences of each subgroup concerning each element are firstly presented under each classification for participators. Secondly, the decision weight of each subgroup is determined by three factors, i.e., the consensus of preferences provided by each subgroup, the organizer’s preference for each subgroup, and the number of participators in each subgroup. Then, the comprehensive preference concerning each element is determined by combing the preference information from multiple subgroups and the decision weights of multiple subgroups, the overall preference vector can be obtained under each classification, and the virtual alternatives are determined by normalizing the overall preference vector. Further, considering multiple classifications for participators, the overall dominant degrees of alternatives can be obtained by calculating the similarity degrees between each virtual alternative and each alternative, thus the ranking order of alternatives can be obtained based on the overall dominant degrees of alternatives. Finally, an example is given to confirm the feasibility of the proposed method. The results of the sensitivity and comparative analyses show that the proposed method is applicable and effective. The proposed method can further enrich and improve the theory and approach of large group decision-making with multiple elements considering multiple classifications for participators.

ABSTRACT In this paper, an innovative method to replace steel reinforcement cage by steel fiber to form a steel shape and steel fiber reinforced concrete has been proposed to solve [...]

Water immersion significantly influences the mechanical characteristics of rock materials, with the degradation of these properties often leading to engineering hazards. Understanding the micro mechanism of rock-water interaction is crucial when evaluating the mechanical behavior of a rock mass. A series of multiscale tests were conducted to investigate the micro and macro behaviors of Plagioclase amphibolite, sourced from Gansu, China, under water immersion conditions. The results indicated that the micro particles transitioned from a flake-dispersed structure in a dry state to floc clusters after 20 days of immersion. The surface micro morphology was analyzed using a laser scanning machine, revealing a transformation from a smooth state to roughness, attributed to the emergence and swelling of numerous micro humps. The evolution of parameters such as the standard deviation of the height distribution (Sq), profile area ratio(Sdr), and the root mean square of the first derivative of surface (Sdq) demonstrated that the rock expanded uniformly, with the micro grains swelling to varying degrees. NMR-based porosity testing suggested an exponential increase in damage, leading to the interconnectedness of newly formed micro-pores with neighboring ones due to water immersion. Ultimately, the water-induced porosity doubled compared to the original porosity. Additionally, the axial swelling rate exhibited a corresponding increase in tandem with the growth in porosity, with an average value of 0.141 %. Finally, linear functions were established between uniaxial compressive strength, elastic modulus, and axial swelling rate. These findings offer a comprehensive understanding of the multiscale evolution characteristics of Plagioclase amphibolite under water intrusion.

Neutron-sensitive microchannel plates (nMCPs) have applications in neutron detection, including energy spectrum measurements, neutron-induced cross sections, and neutron imaging. 10B-doped MCPs (B-MCPs) have attracted significant attention owing to their potential for exhibiting a high neutron detection efficiency over a large neutron energy range. Good spatial and temporal resolutions are useful for neutron energy-resolved imaging. However, their practical applications still face many technical challenges. In this study, a B-MCP with 10 mol% 10B was tested for its response to wide-energy neutrons from eV to MeV at the Back-n white neutron source at the China Spallation Neutron Source. The neutron detection efficiency was calibrated at 1 eV, which is approximately 300 times that of an ordinary MCP and indicates the success of 10B doping. The factors that caused the reduction in the detection efficiency were simulated and discussed. The neutron energy spectrum obtained using B-MCP was compared with that obtained by other measurement methods, and showed very good consistency for neutron energies below tens of keV. The response is more complicated at higher neutron energy, at which point the elastic and nonelastic reactions of all nuclides of B-MCP gradually become dominant. This is beneficial for the detection of neutrons, as it compensates for the detection efficiency of B-MCP for high-energy neutrons.

Multiciliated cells (MCCs) in the brain reside in the ependyma and the choroid plexus (CP) epithelia. The CP secretes cerebrospinal fluid that circulates within the ventricular system, driven by ependymal cilia movement. Tumors of the CP are rare primary brain neoplasms mostly found in children. CP tumors exist in three forms: CP papilloma (CPP), atypical CPP, and CP carcinoma (CPC). Though CPP and atypical CPP are generally benign and can be resolved by surgery, CPC is a particularly aggressive and little understood cancer with a poor survival rate and a tendency for recurrence and metastasis. In contrast to MCCs in the CP epithelia, CPCs in humans are characterized by solitary cilia, frequent TP53mutations, and disturbances to multiciliogenesis program directed by the GMNC-MCIDAS transcriptional network. GMNC and MCIDAS are early transcriptional regulators of MCC fate differentiation in diverse tissues. Consistently, components of the GMNC-MCIDAS transcriptional program are expressed during CP development and required for multiciliation in the CP, while CPC driven by deletion of Trp53and Rb1in mice exhibits multiciliation defects consequent to deficiencies in the GMNC-MCIDAS program. Previous studies revealed that abnormal NOTCH pathway activation leads to CPP. Here we show that combined defects in NOTCH and Sonic Hedgehog signaling in mice generates tumors that are similar to CPC in humans. NOTCH-driven CP tumors are monociliated, and disruption of the NOTCH complex restores multiciliation and decreases tumor growth. NOTCH suppresses multiciliation in tumor cells by inhibiting the expression of GMNC and MCIDAS, while Gmnc-Mcidasoverexpression rescues multiciliation defects and suppresses tumor cell proliferation. Taken together, these findings indicate that reactivation of the GMNC-MCIDAS multiciliogenesis program is critical for inhibiting tumorigenesis in the CP, and it may have therapeutic implications for the treatment of CPC.

A new measurement method for the spatial distribution of neutron beam flux in boron neutron capture therapy (BNCT) is being developed based on the two-dimensional Micromegas detector. To address the issue of long processing times in traditional offline position reconstruction methods, this paper proposes a field programmable gate array based online position reconstruction method utilizing the micro-time projection chamber principle. This method encapsulates key technical aspects: a self-adaptive serial link technique built upon the dynamical adjustment of the delay chain length, fast sorting, a coordinate-matching technique based on the mapping between signal timestamps and random access memory (RAM) addresses, and a precise start point-merging technique utilizing a circular combined RAM. The performance test of the self-adaptive serial link shows that the bit error rate of the link is better than 10−12at a confidence level of 99%, ensuring reliable data transmission. The experiment utilizing the readout electronics and Micromegas detector shows a spatial resolution of approximately 1.4 mm, surpassing the current method’s resolution level of 5 mm. The beam experiment confirms that the readout electronics system can obtain the flux spatial distribution of neutron beams online, thus validating the feasibility of the position reconstruction method. The online position reconstruction method avoids traditional methods, such as bubble sorting and traversal searching, simplifies the design of the logic firmware, and reduces the time complexity from O(n2) to O(n). This study contributes to the advancement in measuring neutron beam flux for BNCT.

Objective: The ataxia telangiectasia mutated (ATM) gene is a master regulator in cellular DNA damage response. The dysregulation of ATMexpression is frequent in breast cancer, and is known to be involved in the carcinogenesis and prognosis of cancer. However, the underlying mechanism remains unclear. The bioinformatic analysis predicted a potential antisense transcript ATM-antisense (AS) from the opposite strand of the ATMgene. The purpose of this study was to identify ATM-AS and investigate the possible effect of ATM-AS on the ATMgene regulation. Methods: Single strand-specific RT-PCR was performed to verify the predicted antisense transcript ATM-AS within the ATMgene locus. qRT-PCR and Western blotting were used to detect the expression levels of ATM-AS and ATM in normal and breast cancer cell lines as well as in tissue samples. Luciferase reporter gene assays, biological mass spectrometry, ChIP-qPCR and RIP were used to explore the function of ATM-AS in regulating the ATM expression. Immunofluorescence and host-cell reactivation (HCR) assay were performed to evaluate the biological significance of ATM-AS in ATM-mediated DNA damage repair. Breast cancer tissue samples were used for evaluating the correlation of the ATM-AS level with the ATM expression as well as prognosis of the patients. Results: The ATM-AS significantly upregulated the ATM gene activity by recruiting KAT5 histone acetyltransferase to the gene promoter. The reduced ATM-AS level led to the abnormal downregulation of ATM expression, and impaired the ATM-mediated DNA damage repair in normal breast cells in vitro.The ATM-AS level was positively correlated with the ATM expression in the examined breast cancer tissue samples, and the patient prognosis. Conclusion: The present study demonstrated that ATM-AS, an antisense transcript located within the ATMgene body, is an essential positive regulator of ATM expression, and functions by mediating the binding of KAT5 to the ATMpromoter. These findings uncover the novel mechanism underlying the dysregulation of the ATMgene in breast cancer, and enrich our understanding of how an antisense transcript regulates its host gene.

To evaluate the safety of stent malapposition of corrodible nitride iron stent as biodegradable cardiovascular implants, a total of 108 stents were implanted into the abdominal aortas, iliac arteries, and iliac artery bifurcations of 36 New Zealand white rabbits separately. Each rabbit was implanted with three stents. After a follow-up period of 3 months, no thrombus and embolism were found in local and downstream vessels. And no other adverse events occurred either. Stent strut covered by endothelial layer started to show signs of degradation, while struts exposed to bifurcated blood flow covered by a layer of tissue and no rust particle was found on the surface. Also, there were no traces of thrombosis and traces of excess inflammation. The authors conclude that the risk brought by stent malapposition in less than 9 months is acceptable.

The arc ignition based on charring conductive polymers has advantages of simple structure, low ignition power consumption and restart capacity, which bringing it broadly application prospect in hybrid propulsion system of micro/nano satellite. In order to optimize the performance of arc ignition system, it is essential to have a deeper understanding of the ignition processes and ignition characteristics of charring conductive polymers. In this paper, the thermal decomposition, electrical conductivity and thermal conductivity characteristics of charring conductive polymers with different conductive additives and matrix materials were comprehensively evaluated. An experimental investigation was conducted to determine the ignition behaviors and characteristics of different charring conductive polymers in a visual ignition combustor. The experiment result showed that the ignition delay and external energy required for ignition are negatively correlated with voltage and initial temperature of the ignition grain, but positively correlated with oxidizer flow velocity. Compared with charring conductive polymers containing multi-walled carbon nanotube, the ignition delay of charring conductive polymers with carbon black is significantly higher and the pyrolysis time is relatively longer. However, the ignition and initial flame propagation of charring conductive polymers with carbon black is more violent and more inclined to carbon particle ignition. Finally, the restart characteristic of different charring conductive polymers was studied. The ignition delay and external energy required for ignition of different charring conductive polymers all reduced with the increasing of the number of ignitions. However, the ignition characteristics would not change a lot after repeated ignition.

In the process of engineering construction such as tunnels and slopes, rock mass is frequently subjected to multiple levels of loading and unloading, while previous research ignores the impact of unloading rate on the stability of rock mass. A number of uniaxial multi-level cyclic loading-unloading experiments were conducted to better understand the effect of unloading rate on the deformation behavior, energy evolution, and damage properties of rock-like material. The experimental results demonstrated that the unloading rate and relative cyclic number clearly influence the deformation behavior and energy evolution of rock-like samples. In particular, as the relative cyclic number rises, the total strain and reversible strain both increase linearly, while the total energy density, elastic energy density, and dissipated energy density all rise nonlinearly. In contrast, the irreversible strain first decreases quickly, then stabilizes, and finally rises slowly. As the unloading rate increases, the total strain and reversible strain both increase, while the irreversible strain decreases. The dissipated energy damage was examined in light of the aforementioned experimental findings. The accuracy of the proposed damage model, which takes into account the impact of the unloading rate and relative cyclic number, is then confirmed by examining the consistency between the model predicted and the experimental results. The proposed damage model will make it easier to foresee how the multi-level loading-unloading cycles will affect the rock-like materials.

Nondestructive and noninvasive neutron assays are essential applications of neutron techniques. Neutron resonance transmission analysis (NRTA) is a powerful nondestructive method for investigating the elemental composition of an object. The back-streaming neutron line (Back-n) is a newly built time-of-flight facility at the China Spallation Neutron Source (CSNS) that provides neutrons in the eV to 300 MeV range. A feasibility study of the NRTA method for nuclide identification was conducted at the CSNS Back-n via two test experiments. The results demonstrate that it is feasible to identify different elements and isotopes in samples using the NRTA method at Back-n. This study reveals its potential future applications.

Abnormal activation of the fibroblast growth factor 19 (FGF19)/fibroblast growth factor receptor 4 (FGFR4) signaling pathway has been shown to drive the proliferation of a significant portion of hepatocellular carcinoma (HCC). Resistance and toxicity are serious drawbacks that have been observed upon use of the current first- and second-line treatment options for HCC, therefore warranting the investigation of alternative therapeutic approaches. We report the development and biological characterization of a covalent inhibitor that is highly potent and exquisitely specific to FGFR4. The crystal structure of this inhibitor in complex with FGFR4 was solved, confirming its covalent binding and revealing its binding mode. We also describe the first clickable probe for FGFR4 that can be used to directly measure target engagement in cells. Our compound exhibited great antitumor activity in HCC cell lines and tumor xenograft models. These results provide evidence of a promising therapeutic lead for the treatment of a subset of HCC patients.

ABSTRACTInteraction between humans and the gut microbiota is important for human physiology. Here, the gut microbiota was analyzed via metagenomic sequencing, and the fluctuations in the gut microbiota under the conditions of spaceflight were characterized. The composition and function of the gut microbiota were substantially affected by spaceflight; however, individual specificity was uncompromised. We further confirmed the species fluctuations and functional genes from both missions. Resistance and virulence genes in the gut microbiota were affected by spaceflight, but the species attributions remained stable. Spaceflight markedly affected the composition and function of the human gut microbiota, implying that the human gut microbiota is sensitive to spaceflight.

A generalized nonlinear Baker failure criterion is employed with the upper bound limit analysis to study the surrounding rock stability of underground cavities. A three-dimensional (3D) failure mode is established by extending the two-dimensional (2D) failure mode, which offers an upper bound expression of the surrounding rock pressure. This method is validated with a series of examples before the influence of four parameters of scale parameter, curvature parameter, shift parameter and lateral pressure coefficient, on the surrounding rock pressure is analyzed. According to these results, failure ranges of the underground cavities are determined. The following conclusions are reached: (1) the proposed approach is more accurate to predict surrounding rock pressure than the Mohr−Coulomb failure criterion; (2) the surrounding rock with large scale parameter, curvature parameter, shift parameter, and lateral pressure coefficient can lead to a more stable underground cavity; (3) the failure range in 3D mode can be predicted according to the upper bound solutions.

Hydrogen peroxide degrades into water and oxygen, and it is generally recognized as a safe and nonaggressive disinfectant without residues or toxic chemicals, a feature especially important for its implementation in manned spacecraft. It has been extensively and safely used as a food preservative, and the use of hydrogen peroxide as a biocide in water in long-duration space missions to complement the use of iodine and silver, and in the sanitation of vegetable crops harvested in controlled ecological life support systems prior to consumption, are both proposed. Traditional detection methods for hydrogen peroxide concentrations include the iodine method or titanium salt colorimetric method, which use a variety of reagents and need cumbersome operating steps and are thus not suitable for quantitative detection applications under the microgravity environment in manned spacecraft. In order to further realize the detection of hydrogen peroxide under a microgravity environment, vacuum-introduced liquid-core waveguide Raman (LCWR) apparatus is designed and combined with a uniform design scheme. The results showed that the developed quantitative approach for hydrogen peroxide has advantages, including a standard error of calibration of 0.22, a coefficient of determination (R2) of 0.9986, and a standard error of prediction of 0.42. This study demonstrates the great potential of the apparatus for the quantitative analysis of hydrogen peroxide in water under a microgravity environment.

In this paper, we consider a manufacturer with limited production capacity producing multiple kinds of independent products, such that each kind of product is sold by a distinct retailer who is offered a commission production contract with revenue sharing by the manufacturer. We study the contract in the centralised and decentralised systems respectively. Under certain conditions of price elasticities and cost fractions, we show the uniqueness of optimal revenue share for all products. Moreover, by comparing both systems with same capacity constraint, we find that at least one retailer's price in the centralised system is higher than that of the decentralised system, and the order quantity for that retailer is lower under some conditions. As a consequence, the decentralised system's profit is always higher than the centralised system's profit under that condition. Also, the retailers' optimal prices (resp. order quantities) are increasing (resp. decreasing) in production capacity of the manufacturer, whereas the manufacturer's expected profit is increasing in its production capacity in both systems. Finally, we conduct numerical study to justify our theoretical results, and examine the effect of processing cost on both systems' profits, and the effect of demand uncertainty on the optimal prices and order quantities. [Received 22 May 2018; Accepted 28 October 2019]

The neutron capture cross sections are very important in the field of nuclear device design and basic physics research. Hydrogen-free liquid scintillator such as C6D6detectors are widely used in the neutron capture cross-sectional measurements for the low neutron sensitivity and fast time response. The Back-n white neutron source at China Spallation Neutron Source is the first spallation white neutron source in China, and it is suitable for neutron capture cross-sectional measurement. A C6D6detector system was built in the Back-n experimental station. The pulse height weighting technique was used to determine the system’s detection efficiency. The response to gamma rays of the C6D6detector was measured, and the energy resolution function was determined. Monte Carlo simulation with Geant4 code was carried out to get the weighting function of this C6D6detector system. Additionally, the systematic uncertainty of the weighting function was also determined. According to the experimental and simulation results, this C6D6detector system can be used to measure neutron capture cross section.

To verify the performance of the neutron total cross-sectional spectrometer, the neutron total cross section of carbon is initially measured in the energy range of 1 eV to 20 MeV using the time-of-flight method. The measurement is performed at the Back-n white neutron source with a 76-m time-of-flight path using the China Spallation Neutron Source. A multilayer fast fission chamber with 235U and 238U is employed as the neutron detector. The diameter and thickness of the natural graphite sample are 70 mm and 40 mm, respectively. Signal waveforms are collected using a data acquisition system. Off-line data processing was used to obtain the neutron time-of-flight spectra and transmissions. The uncertainty of the counting statistics is generally approximately 3% for each bin in the energy range of 1–20 MeV. It is determined that the results for the neutron total cross section of carbon obtained using 235U cells are in good agreement with the results obtained using 238U cells within limits of statistical uncertainty. Moreover, the measured total cross sections show good agreement with the broadening evaluated data.

Introduction: Class III receptor tyrosine kinases include FLT3, KIT, PDGFRA/B and CSF1R. Activating mutations in FLT3 represent the most common genetic anomalies in AML (30%). While there are numerous examples of KIT TKIs that do not inhibit FLT3 (imatinib, avapritinib, dasatinib), to date, all clinically active FLT3 TKIs (quizartinib, gilteritinib, midostaurin, sorafenib) fail to spare KIT inhibition. Preclinical studies suggest that coinhibition of FLT3 and KIT can result in non-specific myelosuppression, which can limit dose intensification and the ability to safely achieve maintenance dosing. A potent FLT3 TKI that is non-myelosuppressive may enable prolonged treatment in conjunction with chemotherapy and thereby substantially improve clinical outcomes, similar to BCR::ABL1 TKIs in Ph+ ALL (Slayton et al, JCO 2018). FF-10101 is a recently described covalent inhibitor to irreversibly bind FLT3. In vitroand in vivostudies have revealed that FF-10101 exhibits substantial activity against FLT3 and resistant mutants F691L and D835V/Y. However, it does not effectively discriminate against KIT inhibition (Yamara et al, Blood 2018). In clinical experience, a majority of responses were associated with persistent myelosuppression (Levis et al, JCO 2021 39:15_suppl, 7008). Further clinical development of FF-10101 has been abandoned. Here we describe a novel covalent inhibitor (BGS-2456) that potently targets FLT3 with outstanding selectivity against KIT.

The 232Th(n,f) cross section is very important in basic nuclear physics and applications based on the Th/U fuel cycle. Using the time-of-flight method and a multi-cell fast-fission ionization chamber, a novel measurement of the 232Th(n,f) cross section relative to 235U in the 1–200 MeV range was performed at the China Spallation Neutron Source Back-n white neutron source (Back-n). The fission event-neutron energy spectra of 232Th and 235U fission cells were measured in the single-bunch mode. Corrected 232Th/235U fission cross-sectional ratios were obtained, and the measurement uncertainties were 2.5–3.7% for energies in the 2–20 MeV range and 3.6–6.2% for energies in the 20–200 MeV range. The 232Th(n,f) cross section was obtained by introducing the standard cross section of 235U(n,f). The results were compared with those of previous theoretical calculations, measurements, and evaluations. The measured 232Th fission cross section agreed with the main evaluation results in terms of the experimental uncertainty, and 232Th fission resonances were observed in the 1–3 MeV range. The present results provide 232Th(n,f) cross-sectional data for the evaluation and design of Th/U cycle nuclear systems.

We study a continuous-review inventory system with dual sourcing modes and Brownian motion demand. The regular order is from one supplier at some constant rate with a low unit cost while the expedite order is from the other one with a fixed setup cost and an expensive unit cost. With usual holding/shortage cost, the system's objective is to choose a regular constant order rate and an expedite replenishment policy such that the long-run average cost is minimized. We show that the regular ordering rate must be strictly less than the expected demand rate and an optimal expedite ordering policy is the well-known $(s, S)$ policy. In particular, based on the theoretical analysis, we give a computational algorithm to demonstrate how to find the optimal regular ordering rate $\lambda ^*$ and expedite policy parameters $s^*$ and $S^*$. Finally, using the algorithm, we investigate the effects of system's parameters on the optimal policy parameters and value of dual sourcing by numerical studies. [ABSTRACT FROM AUTHOR]

The highway base layers performance is significantly affected by its component of particles. A particle flow code numerical simulation study was conducted to determine particle size distribution (PSD) effects on deformation properties of highway base layers under cyclic loading. Nine kinds of graded aggregate were chosen. A series of analysis, the stress–strain response, deformation characteristics, and dynamic elastic modulus of the graded aggregate were performed through dynamic biaxial numerical simulation. Under vibratory loading, the fine particles filled the interspace of the coarse particles, and with re-orientation of the fine particles account for plastic strain. After the compaction of granular material, the interaction between fine particles and coarse particles contributes to the increase in dynamic elastic modulus. And there exists an optimum PSD of fine particles to yield maximum dynamic elastic modulus.

Using the hybrid received signal strength (RSS) and angle of arrival (AOA) measurements, a position estimation model is proposed for sensor localisation in three-dimensional plane. Then the unconstraint linear least square (ULLS) and constraint linear least square (CLLS) estimators are designed to obtain the closed-form solutions to the positions of source nodes by considering the known transmit power. When the transmit power is unavailable, a global linear least square (GLLS) estimator is also put forward to estimate the positions of source nodes along with the transmit power. The simulations show that the computational complexity of the proposed linear estimators is greatly lower than that of the convex semidefinite programming (SDP) method. When the measurement noises are small, the linear ULLS, CLLS and GLLS estimators perform better than that of the SDP method. Due to the exploiting of constraint condition, the accuracy performance of the CLLS estimator can approach the Cramér-Rao lower bound (CRLB) of position estimation.

Chronic rhinosinusitis (CRS) is a heterogeneous disorder with distinct pathophysiologic mechanisms. Based on transcription factor expression and cytokine production patterns in different innate lymphoid cell (ILC) types, in parallel with those of adaptive CD4+T-helper (TH) cells and CD8+cytotoxic T (Tc) cells, new perspectives on endotypes of patients are emerging for the immune response deviation into type 1 (orchestrated by ILC1s and Tc1, and TH1 cells), type 2 (characterized by ILC2s and Tc2 and TH2 cells), and type 3 (mediated by ILC3s and Tc17 and TH17 cells). In addition, cluster analysis has been applied to endotyping of CRS in recent years, which has provided additional novel insights into CRS pathogenesis. This review assessed pathologic mechanisms of CRS based on type 1, 2, and 3 immune responses and how they inform us to begin to understand CRS endotypes. This review also assessed recent cluster analysis studies of CRS endotypes. The impact of endotype on therapeutic management of CRS also is summarized.

The relationship between thyroid dysfunction and gallstone disease (GSD) has been examined by some observational studies. However, evidence about the relationship between thyroid function and GSD among euthyroid subjects was scarce. The aim of this study was to investigate the association between thyroid function and the presence of GSD in a large-sample euthyroid subjects. A total of 5476 euthyroid subjects who underwent health checkup were included. GSD was diagnosed by hepatic ultrasonography. Conventional risk factors for GSD were assessed as well as serum levels of TSH, TT3, TT4 and Log-transformed TT3/TT4 ratio. A total of 4958 subjects were finally included. Levels of TSH, TT3, TT4, and ln (TT3/TT4) were comparable between GSD and non-GSD group (TSH: 1.73 ± 1.07 vs 1.74 ± 1.07 mIU/L, P = .931; TT3: 1.55 ± 0.40 vs 1.54 ± 0.39 ng/mL, P = .797; TT4: 9.37 ± 2.07 vs 9.49 ± 2.06 ug/dL, P = .245, ln (TT3/TT4): −1.80 ± 0.23 vs −1.83 ± 0.23, P = .130, respectively). Multivariate logistic regression analysis among all subjects revealed that the thyroid function parameters did not reach significant difference. Subgroup analyses showed that the relationship between thyroid function and GSD was different according to gender, with negative association for ln (TT3/TT4) and (odds ratio:0.551, 95% CI: 0.306–0.992, P = .047) and positive association for TT4 (odds ratio:1.077, 1 95% CI: .001–1.158, P = .046) in men. None of the thyroid function parameters was significantly associated with GSD in women. Our findings indicated that low levels of TT3-to-TT4 ratio and high levels of TT4 were significantly and independently associated with GSD among euthyroid male subjects, but not female subjects.

The strength and failure characteristics of most natural rock mass are influenced by discontinues such as fissures, joints, and weak surfaces. In the present study, the strength and failure behavior of ubiquitous-joint rock-like specimens under uniaxial loading have been investigated by DIC (digital image correlation) and discrete element numerical method (PFC2D). The results are obtained. Firstly, the UCSJof specimens with γ = 15° or 30° shows similar tendency while αgoes from 0° to 75°. With γ = 45° or 60°, the UCSJof specimens increases when αgoes from 0° to 30° and decreases after αgoes beyond 30°. With γ = 75°, the peak UCSJvalue is reached when α = 0°. The UCSJvalue shows an increasing trend when αgoes from 60° to 75°. Secondly, the ubiquitous-joint specimens present different failure modes for various levels of αand γ(β-α). Based on the experimental results, the failure mode of ubiquitous-joint specimens can be classified into three categories: stepped path failure, failure through parallel plane, and failure through cross plane.

In order to improve the charged particle identification capability, end-cap time-of-flight (ETOF) detector of the Beijing Spectrometer (BESIII) has been upgraded with multi-gap resistive plate chamber (MRPC) technology, aiming at an overall time resolution of 80 ps for minimum-ionization particles to extend the K/$$\pi $$ π separation (2$$\sigma $$ σ ) momentum range to 1.4 GeV/c. The previous version of ETOF in BESIII consisted of plastic scintillators. The multi-hit events distort both shape and amplitude of the output signals. MRPC technique was chosen for the BESIII ETOF upgrade as it provides high time resolution and high detection efficiency, is of relatively low cost and is insensitive to neutral particles. Most importantly, the fine segmentation of the MRPC readout stripes can suppress multi-hit events effectively. The final design of MRPC module for ETOF is characterized by double-stack (2$$\times $$ × 6) structure, dual-end readout mode and precision electronics. To batch-produce and test these MRPC modules, a series of tools and production procedures as well as related performance simulation and test methods were developed. Results showed that each MRPC module’s intrinsic time resolution (including the electronics contribution) is around 50 ps and the efficiency is better than 97%. The overall performance of the upgraded ETOF is better than the designed index. The new ETOF has been successfully installed at BESIII and run in 2016.

Because of the chemical corrosion of underground water on rock bolts that persistently present in complicated geological conditions, the mechanical properties and integrity of bolts may be affected, even bolt failure may occur. In the present article, first, the effect of the chemical reaction and the corrosion expansion on bond strength has been analyzed. Second, a coupled creep model of anchor structures and soil has been proposed based on the stress condition and deformation characteristics of the anchor segment. In this model, the Mohr–Coulomb (M–C) plastic element was used to simulate the complete creep deformation, and the constitutive equation of the coupled creep and the loss of the anchor force were obtained. A comparison between previous studies and the present model indicates that the results of this model agree well with previous results. The coupled creep of the anchor segment and soil is properly reflected in this model. Thus, this model can accurately predict the variation of the anchorage force.

When subjected to shear loading condition, a steel rock bolt will become bent in the field close to the loading point in situ. The bolt is deformed as the joint displacement increases, which can mobilize a normal load and a shear load on the bolt accordingly. In this work, the relationship analysis between the displacing angle and loading angle is carried out. By considering elastic and plastic states of rock bolt during shearing, the rotation of bolt extremity can be calculated analytically. Thus, the loading angle is obtained from displacing angle. The verification of analytical results and laboratory results from reference research implies that the analytical method is correct and working. In terms of in-situ condition, the direction of the load acting on steel bolt can be predicted well according to the direction of the deformed rock bolt with respect to original bolt axis.

In this study, we developed a new generation of metal chelating polymer (MCP) reagents that carry multiple polyethylene glycol (PEG) pendant groups to provide stealth to MCP-based radioimmunoconjugates (RICs). We describe the MCP synthesis for covalent attachment to panitumumab F(ab′)2fragments (pmabF(ab′)2) in which different numbers of pendant methoxy-PEG chains [M = 2000, ∼45 ethylene glycol (EG) repeat units, referred to as PEG2K] are incorporated into the polymer backbone. The pendant PEG2Kchains were designed to provide a protein-repellant corona so that metal chelators attached closer to the polymer backbone will be less apparent to the physiological environment. DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) groups to chelate 64Cu were installed on these conjugates to be employed for PET imaging. The conjugation of MCPs to pmabF(ab′)2was based on a UV quantifiable bis-aromatic hydrazone formation under mild conditions (pH 5–6) between an aromatic aldehyde introduced on ε-NH2groups of lysines in the F(ab′)2fragments and a hydrazinonicotinamide (HyNic) group installed on the initiating end of the MCP. Three MCPs with 17 polyglutamide (PGlu) repeat units, DOTA chelators and with an average of 2, 4, and 8 pendant PEG2Kchains were studied to examine their in vitroand in vivocharacteristics, as well as their potential for PET/CT imaging. A pmabF(ab′)2-MCP conjugate carrying 2 PEG2Kand one carrying 8 PEG2Kpendant chains in the polymer were selected for microPET/CT imaging and biodistribution studies in tumor-bearing mice. Orthotopic pancreatic patient-derived xenografts tumors were visualized by PET/CT imaging. These RICs showed low levels of liver and spleen uptake along with even lower levels of kidney uptake. These encouraging results confirm the stealth properties of the MCPs with pendant PEG2Kchains.

One of the key obstacles in preparing high-performance supercapacitors is designing advanced structures with excellent electrochemical capacitance properties. This paper proposes a simple and fast hydrothermal synthesis method for synthesizing high-performance flower-shaped NiCoZn layered hydroxides (NiCoZn-LDH) on a foam nickel substrate with a heterostructure of NiMoO4(NMO) nanoneedles, and further forming a heterostructure with NiCoZn-LDH nanoflowers. The electrode material synthesized by this method has significantly improved electrochemical performance. Its specific capacitance reached 3030 mF/cm2(863C/g) at 4 mA/cm2and 2317 mF/cm2(662C/g) at 10 mA/cm2. In addition, an asymmetric supercapacitor (ASC) constructs with NiCoZn-LDH@NMO@NF as the positive electrode material and activated carbon as the negative electrode material achieves an energy density of 0.222 mWh/cm2at a power density of 0.08 W/cm2. Experimental studies shown that the heterostructure of NiCoZn-LDH@NMO plays a crucial role in improving the electrochemical performance of asymmetric supercapacitors. This provides new insights for the design of next-generation ASC active materials and is beneficial for the development of new energy storage devices.

In this study, we consider a stochastic inventory system in which the objective of the manufacturer is to maximize the long-run average profit by dynamically offering the selling price and switching the production on or off. The demand process is non-homogeneous Poisson with a price-dependent arrival rate. System costs consist of switching costs, inventory holding and backlogging costs. We show that an (s,S,\mathbf p) policy is optimal. Moreover, we characterize the structural properties of the optimal profit function and pricing strategy, and show that the optimal price is a quasiconcave function of the inventory level when the production is off and is a quasiconvex function when the production is on. [ABSTRACT FROM AUTHOR]

Previous studies on slope stability mainly focused on conditions under gravity load in which the slope tends to slide down along the potential slip surface. However, the existence of a horizontal load on the slope surface can restrain the slope-slipping trend and improve the stability of the slope, similar to the effect of a retaining wall. The slope failure mode can be altered by a sufficiently large horizontal surface load. In this case, the slope stability problem will be converted to a rock foundation stability problem. However, the reciprocal transformation of slope stability and rock foundation stability has been rarely studied. This study considers the Ice and Snow World project in Changsha, China, as the engineering background. This project is located at an abandoned mine pit, the structural load of which mainly acts on the top of the pit. To study the three-dimensional (3D) slope stability under the slope surface load, a 3D slope model is established using the numerical commercial code. The mechanical parameters of the rock mass, as well as the value and the distribution areas of the surface load, are changed to identify the corresponding safety factor of rock mass, deformation and failure mode.

Roadway instability has been a major concern in the fields of mining engineering. This paper aims to provide practical and efficient strategy to support the roadways under high in-situ stress. A case study on the stability of deep roadways was carried out in an underground mine in Gansu province, China. Currently, the surrounding rock strata is extremely fractured, which results in a series of engineering disasters, such as side wall collapse and severe floor heave in the past decades. Aiming to solve these problems, an improved support method was proposed, which includes optimal bolt parameters and arrangement, floor beam layout by grooving, and full length grouting. Based on the modeling results by FLAC3D, the new support method is much better than the current one in terms of preventing the large deformation of surrounding rock and restricting the development of plastic zones. For implementation and verification, field experiments, along with deformation monitoring, were conducted in the 958 level roadway of Mining II areas. The results show that the improved support can significantly reduce surrounding rock deformation, avoid frequent repair, and maintain the long-term stability of the roadway. Compared to the original support, the new support method can greatly save investment of mines, and has good application value and popularization value.

Based on fracture mechanics and previous study, theoretical, laboratory and numerical studies are conducted to investigate the influence of confining stress on rock fracture characteristics and cutting efficiency of TBM cutters. Both theoretical and numerical studies show directly that the increasing confining stress will restrain the initiation and propagation of median cracks, while the fracture angle of lateral cracks will be increased. The fracture characteristics of the specimens in laboratory tests affirm the conclusions made by theoretical and numerical studies in further. Based on relevant assumptions, both favorable and adverse effects on cutting efficiency are observed as the confining stress increases. Combined with theoretical results, the conclusions proposed about the cutting efficiency are affirmed.

The uniaxial compression tests are conducted for the specimens with single pre-existing flaw. Numerical simulations using PFC (Particle Flow Code) are carried out to investigate the localization phenomenon. The formation and evolution of deformation localization are studied with PFC models, including the one of intact and different flaw inclination. The dips change from 0 ̊ to 75 ̊. Based on the simulation results, the effects of pre-existing flaw on the macro shear zone are analyzed. Compared with the intact specimen, the deformation localization is more likely to occur in the pre-flawed specimen, because the flaws accelerate the development of localization phenomenon. The flaw advances the micro-crack emergence and accelerates their increase. It is also found that the flaw inclination has an effect on the formation and evolution of the shear zone. By affecting the distribution of micro-cracks, the flaw changes the macro shear zone of specimens.

In practical engineering, the joints or fissures with similar characteristics are commonly found in natural rocks, they decrease the mechanics properties of the rock mass and also can be seen as a source of initiation of new discontinuities. The previous studies (experimental or numerical) has promoted the understanding of coalescence patterns or failure process obtained from brittle specimens which contain single, two or three fissures. However, the failure characteristics of multi-fissure specimens has not been studied comprehensively. In this paper, the crack coalescence pattern and failure mode of the rock-like materials with multi-fissures have been explored. Based on the experiment results, under unaxial compression, we found that the coalescence modes between fissures can be generally classified into three categories: T/S/M pattern. Moreover, due to the difference of inclination angle and fissure numbers, the specimens present different failure mode. Careful examination all of specimens, the failure mode can be classified into 4 categories: Mix failure model(shear+splitting), Shear failure, Stepped path, Intact failure.

The derating control strategy for motor stator temperature is a very effective protection measures. It not only can make better use of motor ability but also can satisfy the requirement of the vehicle. This paper presents a derating control strategy based on the temperature of stator winding ends since it is the highest temperature point from the simulation results. The motor stator temperature is divided into several regions applied with the various derating control rules. To limit the peak phase current instead of the torque is proposed to inhibit the temperature rise especially in the field weakening region because a large extra demagnetizing current is required in this region.

Al doped ZnO thin film have been prepared by a sol-gel method. The structural, and optical properties of the sample were investigated. X-ray diffraction and X-ray absorption spectroscopy analyses and UV absorption spectroscopy analyses indicate that Al3+ substitute for Zn2+ without changing the wurtzite structure. With the Al doping, the visible emission increased and the UV emission decreased, which is attributed to the increase of O vacancies and Zn interstitials.

This paper presents a method for determining the rotor temperature of an electric motor by observing the dq-axis flux linkage. A reference dq-axis flux linkage is obtained at a defined rotor temperature. The difference between calculated and reference flux in the d-axis is supposed to be caused by temperature, therefore the temperature can be back-calculated according to the permanent magnet temperature characteristic. The proposed method was confirmed to be correct and effective by the test results.

As the mining operation of Chenmen Mountain copper mine gradually extents to a deeper stage, the stability of open pit slopes should be revaluated and new reasonable gradient is to be designed. Because of the big amount of calculation workload that should be applied to all the slopes, this paper proposed a method which is based on Newton Interpolation theory to reduce some numerous and repetitive job. Base on differential notes calculated by FLAC3D, a function precisely expressing the relation between the safety factor and slope angle was established, through which the safety factor of any slope of different gradients could be obtained directly. By comparative study of traditional methods such as the finite difference technique, it is indicated that the results from the new method that proposed in this study have a good agreement with results calculated by program FLAC3D.

Unixial compression tests have been conducted to investigate the influence of bridge length between two collinear cracks on the specimen strength and fracture patterns. Based on the local connectivity rate of cracks, the evolution of the fracture patterns of the bridge is illustrated. It can be concluded that the sensitivity of the strength to the bridge length is reduced as the connectivity rate, L, is higher than 0.8. The fracture pattern composed of tensile and shear fracture will be induced in rock bridges when the bridges are short. Wing cracks develop well as the distance between prefabricated cracks increases, however, the fracture events caused by the conjunction of the secondary cracks are restrained.

Geotechnical engineering in large scale is endangered by the karst areas which are close to the engineering. The stability of the tunnels is greatly affected by the sizes and locations of the karst caves. Based on a engineering example, a study of the effects of karst area beneath the tunnel on the stability of surrounding rock is conducted. It can be concluded that the displacement release of surrounding rocks and the distribution of the vertical stress in surrounding rocks are greatly affected by the sizes of the karst caves and the distance between the tunnel floor and the karst cave.

Mechanical behavior and failure mode of jointed rock is one of the significant researches in rock mechanics field. In this work, combined with similar material testing and discrete element numerical method(PFC) to investigate the mechanical behavior and failure mode of the rock-like materials with multi-fissures. The numerical analyses agree well with physical experimentation. It is found that, fissures will weaken the strength of the rock-like material, and when the angle of the fissures is about 25°, the strength of the material reaches a minimum value. The weakening effect of fissure on specimen strength would decrease gradually along with the increase of fissure angle. Compared with the effects of fissure angle, the influence of cracks number to the strength is relatively small. The fissure inclination angle was the main factor of the failure modes. With the different fissure inclination angles, the crack tip of Micro-cracks presents different developmental pattern. However, the influence of fissure distribution density on the failure mode mainly reflects at the fracture penetration mode.

To study the effect of rock joint parameters, the joint orientation, the filling situation of joint and the distance between the center of joint and the position of penetration on rock fragmentation mechanism by tunnel boring machines (TBM) cutters, a series of penetration tests were conducted on rock-like specimens using the modified triaxial testing machine. Data of indentation load and penetration depth during the loading process were recorded and analyzed. Results show that the filling situation of joint can significantly influence the resistance of rock to penetration. The joint interface closer to the position of penetration plays a more positive role in rock fragmentation than that farther to the position of penetration. The joint orientation can greatly affect the peak indentation load, the anti-invasive factor, the crushing work as well as modes of rock fragmentation. With the increase of joint orientation, the peak indentation load, anti-invasive factor and crushing work decrease firstly, and then increase. When joint orientation equals to 60° and 90°, they reach the minimum and maximum values, respectively.

Effects of additives WEC on strength properties of second fiber were investigated in this study. For single use of WEC02A, the improvement of ring crush index was most remarkable, which increased by 21% for bottom pulp and 31% for surface pulp. Significant increase was also achieved in burst index while the improvement of tightness and folding endurance was not obvious. Besides, combined use of 0.2% WEC02 and 0.3% WEC03S improved folding endurance, burst index and ring crush index of pulp by remarkable 105%, 23% and 52%, respectively, showing a great performance for pulp strength enhancement, being beneficial to broadening the utilization of second fiber.