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At present, the production of micro parts and components with characteristic sizes ranging from micron to millimeter mainly relies on micro machining technology, but the dimensional size of micro tools (including micro cutting tools, micro grinding tools, and microelectrodes) involved in micro machining is ultra small and made of super hard material like cemented carbide and polycrystalline diamond, which makes the preparation of ultra small micro tools have become the main bottleneck restricting the development of micro machining technology. The non-contact nature of electrical discharge machining (EDM) process makes it more competent in fabricating micro tools with relatively high efficiency and low cost; especially the wire electrical discharge grinding (WEDG) invented in 1985 provides a new approach and direction to fabricate micro tools; following this trend, numerous new design requirements and theoretical concepts of EDM-based processes utilized in fabricating micro tools have been proposed and studied successively, but, very few studies have been proceed from an integrated perspective. To address the gap, this study provides a comprehensive and well-arranged literature survey of the advancements made in the fabrication of micro tools using various EDM-based methods to date along with an insightful discussion on the science and application of EDM process. The critical factors influencing process performance, different numerical models, limitations, as well as possible future research direction and development in the field of micro tools fabricated by various EDM-based methods are identified and reviewed. This article is expected to help the researchers in identifying the existing gaps and contributing towards making EDM-based processes more competent in catering the trend of parameterized and non-standardized fabrication of ultra small micro tools.

At present, the design and optimization of the linear explosive separation device mainly depends on experiment, which is not only costly but also low efficient. The introduction of finite element analysis prior to experiment may reduce the cost to design a linear explosive separation device. Herein, arbitrary Lagrangian–Eulerian (ALE) numerical method is utilized to investigate the functioning of an axisymmetric explosive separation device. Firstly, several ALE models are validated via explosive separation experiments and photonic Doppler velocimetry (PDV) measurements, and found to have reasonable accuracy. Then, a series of ALE models are developed to study the transient separation process of an axisymmetric explosive separation device. Multiple factors which may influence the process are identified through parametric study. Especially, it is found that the linear density of the explosive core in the detonating cord and the bottom radius of the v-notch on the separation plate are critical for the accumulation of effective plastic strain at the v-notch. In addition, the material of the protection plate and the angle of the v-notch have a certain influence on the effective plastic strain at the v-notch. The material strength of the protection plate almost has little influence on the effective plastic strain at the v-notch. The study may facilitate the optimal design of the axisymmetric explosive separation device.

In consideration of recycling solid waste to achieve high value-added products, glass-ceramics have been fabricated from municipal solid waste incineration (MSWI) fly ash, pickling sludge (PS), and waste glass (WG) by melting at 1450 °C firstly to achieve parent glass and then crystallizing at 850 °C. Results demonstrated that heavy metals have been well solidified in the prepared glass-ceramics, and relatively/extremely low leaching concentrations of heavy metals have been detected. The synthetic toxicity index of heavy metals has been greatly reduced from 7-18 to

Background Osteosarcoma was the most common primary bone malignancy in children and adolescents. It was imperative to identify effective prognostic biomarkers for this cancer. This study was aimed to identify potential crucial genes of osteosarcoma by integrated bioinformatics analysis. Methods Identification of differentially expressed genes from public data gene expression profiles (GSE42352), functional and pathway enrichment analysis, protein–protein interaction (PPI) network construction and module analysis, Cox regression and survival analysis was conducted. Results Totally 17 co-differential genes were found to be differentially expressed. These genes were enriched in biological processes, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA) pathway of inflammatory immune response. PPI network was constructed with 63 differentially expressed genes that co-existed between the test set and the validation set. The area under the receiver operating characteristic curve (AUC value) was 0.855, which indicated that the expression of PODN had a good diagnostic value for osteosarcoma. Furthermore, Cox regression and survival analysis revealed 5 genes were statistically significant. Conclusions PODN was regarded as a potential biomarker for the diagnosis and prognosis of osteosarcoma, ACTA2, COL6A1, FAP, OLFML2B and COL6A3, can be used as potential prognostic indicators for osteosarcoma.

Studies showed that the increase of myeloid‐derived suppressor cells (MDSCs) in tumour microenvironment is closely related to the resistant treatment and poor prognosis of metastatic breast cancer. However, the effect of tumour‐derived exosomes on MDSCs and its mechanism are not clear. Here, we reported that breast cancer cells (4T1)‐secreted exosomes (BCC‐Ex) were able to differentiate bone marrow cells into MDSCs and significantly inhibited the proliferation of T lymphocytes to provide an immunosuppressive microenvironment for cancer cells in vivo and in vitro. The number of MDSCs in bone marrow and spleen of 4T1 tumour‐bearing mice and BCC‐Ex infused mice was significantly higher than that of normal mice, whereas the number of T lymphocytes in spleen was significantly decreased. In addition, BCC‐Ex markedly promoted the differentiation of MDSCs from bone marrow cells or bone marrow cells derived macrophages, seen as the increased expressions of MDSCs‐related functional proteins Arginase‐1 (Arg‐1) and inducible nitric oxide synthase (iNOS). Furthermore, BCC‐Ex significantly down‐regulated the expressions of chemokine receptor CXCR4 and markedly up‐regulated the levels of inflammatory cytokines IL‐6 and IL‐10 in bone marrow cells and macrophages and remarkably inhibited the division and proliferation of T cells. Importantly, CXCR4 agonist, CXCL12, could reverse the function of BCC‐Ex, indicating that BCC‐Ex‐induced MDSCs might be dependent on the down‐regulation of CXCR4. Western blot showed that BCC‐Ex significantly promoted the phosphorylation of STAT3 in bone marrow cells, resulting in the inhibitions of the proliferation and apoptosis of bone marrow cells, and the aggravation of the differentiation of bone marrow cells into MDSCs.

We provide evidence regarding mutual funds’ motivation to hold lottery stocks. Funds with higher managerial ownership invest less in lottery stocks, suggesting that managers themselves do not prefer such stocks. The evidence instead supports that managers cater to fund investors’ preference for such stocks. In particular, funds with more lottery holdings attract larger flows after portfolio disclosure compared with their peers, and poorly performing funds tend to engage in risk shifting by increasing their lottery holdings toward year-ends. Funds’ aggregate holdings of lottery stocks contribute to their overpricing.

The butt welds of 4-mm thick 5A06 aluminum alloy plates were produced by adjustable-gap bobbin-tool friction stir travel with travel speeds of 200, 300, and 400 mm/min in this study. The microstructure was studied using optical microscopy and electron backscatter diffraction (EBSD). Tensile tests and microhardness measurements were performed to identify the effect of the travel speed on the joint mechanical properties. Sound joints were obtained at 200 mm/min while voids were present at different positions of the joints as the travel speed increased. The EBSD results show that the grain size, high angle grain boundaries, and density of geometrically necessary dislocations in different regions of the joint vary depending on the recovery and recrystallization behavior. Specific attention was given to the relationship between the local microstructure and mechanical properties. Microhardness measurements show that the average hardness of the stir zone (SZ) was greater than that of the base material, which was only affected slightly by the travel speed. The tensile strength of the joint decreased with increasing travel speed and the maximal strength efficiency reached 99%.

As a surveillance mechanism, the activated spindle assembly checkpoint (SAC) potently inhibits the E3 ubiquitin ligase APC/C (anaphase-promoting complex/cyclosome) to ensure accurate chromosome segregation. Although the protein phosphatase 2A (PP2A) has been proposed to be both, directly and indirectly, involved in spindle assembly checkpoint inactivation in mammalian cells, whether it is similarly operating in the fission yeast Schizosaccharomycer pombe has never been demonstrated. Here, we investigated whether fission yeast PP2A is involved in SAC silencing by following the rate of cyclin B (Cdc13) destruction at SPBs during the recovery phase in nda3-KM311 cells released from the inhibition of APC/C by the activated spindle checkpoint. The timing of the SAC inactivation is only slightly delayed when two B56 regulatory subunits (Par1 and Par2) of fission yeast PP2A are absent. Overproduction of individual PP2A subunits either globally in the nda3-KM311 arrest-and-release system or locally in the synthetic spindle checkpoint activation system only slightly suppresses the SAC silencing defects in PP1 deletion (dis2Δ) cells. Our study thus demonstrates that the fission yeast PP2A is not a key regulator actively involved in SAC inactivation.

Considering the influence of non-equibiaxial stress state and initial residual strain on the compressive buckling of the ceramic layer, a quantitative characterization method of the damage generated at the interface between the top coat and bond coat in thermal barrier coating based on uniaxial compression was developed. It was verified by the axial compression tests of the single crystal specimens with EB-PVD thermal barrier coating after undergoing various isothermal oxidation times and thermal cycles. On this basis, the correlations between the measured interfacial damage and the thermal loads experienced as well as the thickness of thermally grown oxide (TGO) were analyzed. The results show that the critical compressive strain inducing the spallation of thermal barrier coating at room temperature can effectively characterize the accumulation of interfacial damage caused by isothermal oxidation and thermal fatigue. Under the same TGO thickness, the damage caused by thermal fatigue is greater than that caused by isothermal oxidation. The total damage generated in thermal barrier coating can be divided into three parts: oxidatively driven damage related to TGO thickness, mechanically driven damage related to stress–strain cycles in the coating, and their interaction, where the interaction term is negative.

Although many studies have reported toxic effects of cadmium (Cd) and lead (Pb) in the central nervous system, few studies have investigated the combined toxicity of Cd and Pb. The mechanisms by which these combined heavy metals induce toxicity, as well as effective means to exert neuroprotection from these agents, remain poorly understood. To investigate the protective effects of alpha-lipoic acid (α-LA) on Cd- and/or Pb-induced cortical damage in rats, 48 Sprague-Dawley rats were exposed to drinking water containing 50 mg/L of Cd and/or 300 mg/L of Pb for 12 weeks, in the presence or absence of α-LA co-treatment (50 mg/kg) via gavage. We observed that exposure to Cd and/or Pb decreased the brain weight/body weight ratio and increased Cd and/or Pb contents as well as ultrastructural damage to the cerebral cortex. Cd and/or Pb also induced endoplasmic-reticulum (ER) stress and activated Fas (CD95/APO-1)/Fas ligand (FasL) and mitochondrial apoptotic pathways. Furthermore, co-treatment of Cd and Pb further exacerbated part of these phenotypes than treatment of Cd or Pb alone. However, simultaneous supplementation with α-LA attenuated Cd and/or Pb-induced neurotoxicity by increasing the brain weight/body weight ratio, reducing Cd and/or Pb contents, ameliorating both nuclear/mitochondrial damage and ER stress, and attenuating activation of Fas/FasL and mitochondrial apoptotic pathways. Collectively, our results indicate that the accumulation of Cd and/or Pb causes cortical damage and that α-LA exerts protection against Cd- and/or Pb-induced neurotoxicity. These findings highlight that α-LA may be exploited for the treatment and prevention of Cd- and/or Pb-induced neurotoxicity.

Background The treatment for displaced Salter-Harris II (S-H II) distal tibia fractures remains controversial. The purpose of this study was to review S-H II distal tibia fractures and evaluate the rate of premature physeal closure (PPC) treated by open reduction and internal fixation (ORIF). Methods We reviewed the charts and radiographs of S-H II fractures of the distal tibia with displacement > 3 mm between 2012 and 2019 treated by ORIF. Patients were followed up for a minimum of 6 months. CT scans of injured side or contralateral ankle radiograph were obtained if there was any evidence of PPC. Any angular deformity or shortening of the involved leg was documented. Multivariable logistic regression was performed to identify risk factors for the occurrence of PPC. Results A total of 65 patients with a mean age of 11.8 years were included in this study. The mean initial displacement was 8.0 mm. All patients but one were treated within 7 days after injury and the mean interval was 3.7 days. Supination-external rotation injuries occurred in 50 patients, pronation-eversion external rotation in 13, and supination-plantar flexion in two. The residual gap was less than 1 mm in all patients following ORIF and all fractures healed within 4–6 weeks. Superficial skin infection developed in one patient. Ten patients complained of the cosmetic scar. The rate of PPC was 29.2% and two patients with PPC developed a varus deformity of the ankle. Patients with associated fibular fracture had 7 times greater odds of developing PPC. Age, gender, injured side, mechanism of injury, amount of initial displacement, interval from injury to surgery, or energy of injury did not significantly affect the rate of PPC. Conclusions ORIF was an effective choice of treatment for S-H II distal tibia fractures with displacement > 3 mm to obtain a satisfactory reduction. PPC is a common complication following ORIF. The presence of concomitant fibula fracture was associated with PPC.

In this paper, we study the impacts and effects of the number of countries and green technology on climate agreements. In a repeated climate game framework, we focus on the symmetric and self-enforcing weakly renegotiation-proof equilibrium. The set of every country’s feasible abatements is bounded and independent of the number of signatory countries. We derive the maximal number of signatory countries that can reach a fully cooperative (most efficient) climate agreement. We also analyze the maximal equilibrium abatement level when there are too many countries to sustain the fully cooperative agreement. The maximal equilibrium abatement level changes non-monotonically in the number of the countries; it first increases and then decreases in the number of countries involved. Our findings demonstrate a trade-off between the breadth and the depth for international climate agreements.

Long-term reversals in corporate bonds are economically and statistically significant in a comprehensive sample spanning the period 1977 to 2017. Such reversals are stronger for bonds with high credit risk and more binding regulatory, capital, and funding liquidity constraints. Bond long-term reversal is not a manifestation of the equity counterpart and is mainly driven by long-term losers. A long-term reversal factor carries a sizable premium and is not explained by long-established equity and bond market factors. Thus, past returns capture investors’ ex-ante risk assessment and the degree of institutional constraints they face, so losing bonds command higher expected returns. (JEL classification: G11, G12, C13)

Optoelectronic devices, especially III-nitride quantum-structure devices, are suffering from a series of material problems, such as polarization induced quantum efficiency drop and the lack of a suitable p-type dopant. Herein, dopant-free polarization-induced doping by deposition of a linearly graded AlGaN was utilized to achieve the p-type layer. Benefiting from the polarization doping, p-down structure p–i–n photodiodes based on InGaN/GaN multiple quantum wells (MQWs), in which the polarization field in the InGaN QWs is aligned with the built-in electric field, were fabricated to promote the quantum efficiency. As a result, high responsivity, high speed, and bandpass response were realized via polarization engineering. The photodiodes exhibited a turn-on voltage of ∼2.5 V and a very low dark current below 3.0 × 10−13 A at 0 to −3 V. Bandpass responses of 420 to 365 nm were observed with a peak responsivity of 0.56 A W−1 at 395 nm, an EQE of 145%, and a light to dark current ratio of ∼104 at 26 μW cm−2 illumination. In addition to the enhanced field in the QWs, the pure photoconductive gain originating from the polarization-induced energy band incline and carrier escape mechanism in the MQWs also contributes to the improved responsivity. The gain mechanism without involving trap states is supported by the high-speed response with a rising time of ∼41 ns.

Two novel photochromic complexes [Zn2(bpdc)2(m-DPNDI)2]·H2O (1) and [Cd(bpdc)(m-DPNDI)]·H2O (2) (H2bpdc = 4,4′-diphenic acid, m-DPNDI = N,N′-bis(3-pyridyl)-1,4,5,8-naphthalenetetracarboxydiimide) were prepared through a solvothermal method. In complexes 1 and 2, the selection of electron-deficient ligand m-DPNDI and electron-rich ligand bpdc2− is aimed at forming a complete donor–acceptor pair and establishing a suitable electron transfer pathway to realize photoinduced electron transfer. Both complexes exhibited interesting photochromic and photoresponsive luminescence behaviours, which was verified by EPR, XRD and IR measurements. Furthermore, the existence of interpenetrating networks and abundant π⋯π interactions in 1 makes the framework intact at below 460 °C.

Octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) is extensively employed in military weapons as the main constituent of HMX-based polymer-bonded explosives (PBXs). It is known that the safety of PBXs is closely related to their microstructures. Discontinuities in PBXs, such as micron-sized pores, air bubbles, and interfaces between the explosive crystal and polymer bonds, may transform into hot spots when subjected to impact. Herein, a three-dimensional mechanical–thermal–chemical coupled mesoscopic model is proposed to study the collapse of an air bubble in an HMX crystal under impact. A viscoplastic constitutive model and the Birch–Murnaghan equation of state are employed for the HMX crystal to predict its mechanical response. Thermal decomposition of HMX is taken into account by using multistep thermal decomposition equations. The viscoplastic model yields results that reasonably agree with data obtained in the plane shock experiment. The influence of the edge length of the mesh elements on simulation results is analyzed. Then more simulations are conducted for studying the feasibility of using the viscoplastic model for different orientations of the HMX lattice. Afterwards, the coupled model is applied to study the collapse of an air-bubble/pore in the HMX crystal for different impact velocities.

Acidic leucine-rich nuclear phosphoprotein-32A (ANP32A) has been reported to play an essential role in the development and progression of various human cancers. However, its expression pattern and possible mechanism in human hepatocellular carcinoma (HCC) remain to be elucidated. In this study, we used western blot and immunohistochemical staining to detect protein expression. The effects of ANP32A on the proliferation, migration and invasion of HCC cells were examined using 5-ethynyl-20-deoxyuridine (EdU), colony formation, CCK-8, and transwell assays. RT-qPCR was performed to detect mRNA expression. The interaction between ANP32A and the high mobility group A1 (HMGA1) mRNA was assessed using RNA immunoprecipitation (RIP). The tumorigenicity of ANP32A was assessed by establishing a xenograft tumor model in Balb/c nude mice. We found that the ANP32A protein was expressed at high levels in patients with HCC, which was associated with a poor prognosis. Functional experiments revealed that the silencing of ANP32A inhibited the proliferation, migration, and invasion of HCC cells, whereas overexpression of ANP32A promoted these processes. Further investigations indicated that ANP32A bound the HMGA1 mRNA and maintained its stability to promote the expression of HMGA1, thereby increasing the expression and activation of STAT3. Finally, a xenograft tumor model of Balb/c nude mice confirmed the tumorigenicity of ANP32A. This study found that ANP32A is up-regulated in patients with HCC and may accelerate the proliferation, migration and invasion of HCC cells by modulating the HMGA1/STAT3 pathway.