Resistance to cytotoxic chemotherapy drugs remains as the major cause of treatment failure in acute myeloid leukemia. Histone deacetylases (HDAC) are important regulators to maintain chromatin ...structure and control DNA damage; nevertheless, how each HDAC regulates genome stability remains unclear, especially under genome stress conditions. Here, we identified a mechanism by which HDAC3 regulates DNA damage repair and mediates resistance to chemotherapy drugs. In addition to inducing DNA damage, chemotherapy drugs trigger upregulation of HDAC3 expression in leukemia cells. Using genetic and pharmacological approaches, we show that HDAC3 contributes to chemotherapy resistance by regulating the activation of AKT, a well-documented factor in drug resistance development. HDAC3 binds to AKT and deacetylates it at the site Lys20, thereby promoting the phosphorylation of AKT. Chemotherapy drug exposure enhances the interaction between HDAC3 and AKT, resulting in decrease in AKT acetylation and increase in AKT phosphorylation. Whereas HDAC3 depletion or inhibition abrogates these responses and meanwhile sensitizes leukemia cells to chemotoxicity-induced apoptosis. Importantly, in vivo HDAC3 suppression reduces leukemia progression and sensitizes MLL-AF9
leukemia to chemotherapy. Our findings suggest that combination therapy with HDAC3 inhibitor and genotoxic agents may constitute a successful strategy for overcoming chemotherapy resistance.
The Rare-RI Ring (R3) is a recently commissioned cyclotronlike storage ring mass spectrometer dedicated to mass measurements of exotic nuclei far from stability at Radioactive Isotope Beam Factory ...(RIBF) in RIKEN. The first application of mass measurement using the R3 mass spectrometer at RIBF is reported. Rare isotopes produced at RIBF-^{127}Sn, ^{126}In, ^{125}Cd, ^{124}Ag, ^{123}Pd-were injected in R3. Masses of ^{126}In, ^{125}Cd, and ^{123}Pd were measured whereby the mass uncertainty of ^{123}Pd was improved. This is the first reported measurement with a new storage ring mass spectrometry technique realized at a heavy-ion cyclotron and employing individual injection of the preidentified rare nuclei. The latter is essential for the future mass measurements of the rarest isotopes produced at RIBF. The impact of the new ^{123}Pd result on the solar r-process abundances in a neutron star merger event is investigated by performing reaction network calculations of 20 trajectories with varying electron fraction Y_{e}. It is found that the neutron capture cross section on ^{123}Pd increases by a factor of 2.2 and β-delayed neutron emission probability, P_{1 n}, of ^{123}Rh increases by 14%. The neutron capture cross section on ^{122}Pd decreases by a factor of 2.6 leading to pileup of material at A=122, thus reproducing the trend of the solar r-process abundances. The trend of the two-neutron separation energies (S_{2n}) was investigated for the Pd isotopic chain. The new mass measurement with improved uncertainty excludes large changes of the S_{2n} value at N=77. Such large increase of the S_{2n} values before N=82 was proposed as an alternative to the quenching of the N=82 shell gap to reproduce r-process abundances in the mass region of A=112-124.
In this paper, the preparation, microstructures and mechanical properties of in-situ (TiB2 + ZrB2)/AlSi9Cu3 composites are investigated by X-Ray diffraction (XRD), optical microscope (OM), scanning ...electronic microscopy (SEM), energy dispersive spectrometer (EDS), transmission electron microscope (TEM) and tensile testing. The composites are fabricated from Al–K2TiF6–K2ZrF6–KBF4 system via melt in-situ reaction technology. The results reveal that the morphology of TiB2 and ZrB2 particles is presented in rectangular and nearly hexagonal, and the size of 20–100 nm in the synthesized composites. In addition, the particles are agglomerated as many of “Reinforced Group”, which are distributed along the crystal boundary of the matrix. The silicon phase and secondary dendrite arm spacing of AlSi9Cu3 alloy are obviously changed by the introduction of in-situ particles. The morphology of the silicon phase is presented in rod-shape or needle-shape with the size of about 3–10 μm. The particles affect the formation of dendrites and the size of the secondary dendrite arm spacing is 9.8–20 μm, while it seems to not affect the morphology of the CuAl2 phase. Tensile testing results show that the tensile strength and elongation clearly increase with the introduction of in-situ particles. Moreover, the tensile strength and elongation reach 265 MPa and 14.8% respectively, with the best reaction time (30 min) and mass fraction of reactants (20wt.%). The mechanical stirring also significantly affected the particles dispersion in the composites.
•The (TiB2 + ZrB2)/AlSi9Cu3 matrix composite is successfully fabricated.•Effect of reaction time and reactants mass fraction on the composites is studied.•Effect of mechanical stirring on the in situ composites is studied.•The reinforcing mechanism of the in situ composites is discussed.
3D modeling and DEM results have played an important role in economic construction, national defense construction, social development, and ecological protection. And the regional network adjustment ...is the basic work of DEM, and 3D modeling. In order to ensure the quality of the following results, this paper selects the regional network adjustment results of the ZY3 stereo satellite image and puts forward the test method of the regional network adjustment results from the inspection content. Meanwhile, the northwest of Africa is selected as the test area, and the inspection contents and methods proposed in this paper are verified. The inspection results show that the quality problems existing in the adjustment results of the regional network can be effectively checked. It has a certain reference function to the quality problem of the production process.
Abstract Poly(aspartic acid) (PAsp) has been employed as the potential backbone for the preparation of efficient gene carriers, due to its low cytotoxicity, good biodegradability and excellent ...biocompatibility. In this work, the degradable linear or star-shaped PBLA was first prepared via ring-opining polymerization of β -benzyl- l -aspartate N -carboxy anhydride (BLA-NCA) initiated by ethylenediamine (ED) or ED-functionalized cyclodextrin cores. Then, PBLA was functionalized via aminolysis reaction with low-molecular-weight poly(2-(dimethylamino)ethyl methacrylate) with one terminal primary amine group (PDMAEMA-NH2 ), followed by addition of excess ED or ethanolamine (EA) to complete the aminolysis process. The obtained different types of cationic PAsp-based vectors including linear or star PAsp-PDM-NH2 and PAsp-PDM-OH exhibited good condensation capability and degradability, benefiting gene delivery process. In comparison with gold standard polyethylenimine (PEI, ∼25 kDa), the cationic PAsp-based vectors, particularly star-shaped ones, exhibited much better transfection performances.
Full understanding of the thermomechanical behaviors of materials at high strain rates and high temperatures are of great importance from not only scientific meaning but also practical value in ...engineering structure design and safety assessment. Great efforts have been made for abilities of operation the split Hopkinson bars, the most popular technique for experimental determination of mechanical behaviors of materials over the strain rates from 10
2
to 10
4
s
−1
over the past 70 years, at high temperatures since 1960s. A review of experiment work is presented in this paper to give an overview of the development of experimental techniques at high temperatures based on Hopkinson bar systems. The principles of the split Hopkinson bar requires the loading bars avoiding temperature gradient or keeping relatively low temperature when performing high temperature testing. Techniques such as performing temperature gradient corrections, rapid heating or using special designed automatically assembled systems were proposed by researchers to enable the operation of the split Hopkinson bars at temperature as high as possible. Moreover, to the application of high speed photographic technique for capturing the dynamic deformation process of the specimen in high temperature Hopkinson bar testing, some key issues of eliminating the strong thermal radiation induced lights oversaturation and de-blurring of images due to insufficient exposure at high temperature and high strain rate condition, as well as fabrication of high contrast speckle pattern for high temperature digital image correlation measurement were also proposed. The technique can now enable the split Hopkinson bar testing to be performed at high temperature up to 1873 K under the loading conditions of compression or tension with the in situ observation and full field measurement of deformation as well. The paper concludes with summaries of the most important achievements and highlighting of the prospects, trends and remaining challenges for future research.
Graphic abstract
To enhance the understanding of Takayasu's arteritis with pulmonary vascular involvement through the analyses on clinical features, imaging findings, misdiagnoses and treatments.
A retrospective ...study was conducted to analyze the clinical records of patients diagnosed as Takayasu's arteritis with pulmonary vascular involvement admitted to Beijing Chaoyang Hospital from January 2004 to December 2014.
In recent 10 years, there were 90 patients diagnosed as Takayasu's arteritis in Beijing Chaoyang Hospital, 33 of them were involved with pulmonary arterial, which account for 36.7%, while 12 cases were involved with pulmonary arteries alone, which account for 13.3% of all. Among the 33 patients, dyspnea (23 cases, 69.7%) was the most common symptom, followed by hemoptysis (19 cases, 57.6%) and Vascular murmur (23 cases, 69.7%), pleural effusion (8 cases, 24.2%), unequal blood pressure of upper limbs (4 cases, 12.1%) were the main signs. The diagnostic time varied significantly, from 1 month to 10 years. 21 patient
The goal of this study was to examine the relationship between stearoyl-CoA desaturase 1 (SCD1) and osteogenesis in bone marrow mesenchymal stem cells (BM-MSCs).
SCD1 was overexpressed in BM-MSCs ...using lentiviral transduction. Then, osteogenesis was induced by low glucose DMEM (10% fetal bovine serum). Alkaline phosphatase (ALP) activity assays, Western blot analyses of SCD1 and osteocalcin, and stainings for ALP and alizarin red were done to assess the extent of osteogenesis in BM-MSCs.
ALP activity was markedly higher in the SCD1 overexpressing cells compared with cells transduced with empty vector or control (untransduced) cells at 1 and 2 weeks after osteogenic induction. By contrast, ALP activities were comparable between control cells and cells transduced with empty vector. Western blot analysis demonstrated that osteocalcin levels were higher in the SCD1 overexpressing cells, compared with cells transduced with empty vector or control cells, at 1 and 2 weeks after osteogenic induction. These findings were corroborated by stainings for ALP and alizarin red that demonstrated a more active osteogenesis in the SCD1 overexpressing cells 2 weeks after osteogenic induction.
Increased levels of SCD1 enhance osteogenesis in BM-MSCs.
An open resonator system is designed and constructed for the accurate measurement of complex permittivity at Ka band. It is solved successfully for the first time in how to achieve the consistency of ...cavity lengths corresponding to different resonant frequencies over a broad band and how to determine the proper permittivity from multiple transcendental equation roots of one sample. Many kinds of samples such as fused quartz, Teflon, quartz ceramic, MgF^sub 2^ and MgAl^sub 2^O^sub 4^ are measured, and the results are in good agreement with published data. The systematic error analysis shows that, the relative standard deviation of the measurement system is less than 0.172% for permittivity and 18.35% for loss tangent. The software developed to control the system improves the measurement efficiency greatly.
In this paper, we present an approach to study the electrical and spectral degradation properties of InxGa1-xAs (x = 0.2, 0.3, 0.53) solar cell under 150 keV proton irradiation based on numerical ...simulation. First, the structures of InxGa1-xAs solar cell were optimized by adjusting the doping concentration of base layer and modifying the thickness of base and emitter layer. The structural parameter related to providing higher conversion efficiency was figured out. Then, the degradation of electrical parameters such as short-circuit current density (Jsc), open-circuit voltage (Voc), maximum output power (Pmax), fill factor (FF), as well as the spectral response were obtained. The degradation correlation with radiation-induced defects was built to reveal the damage mechanism under 150 keV proton irradiation. This study provides constructive model of InxGa1-xAs to be applied in multi-junction solar cells, and the predicted degradation behavior could contribute to design the radiation-hardened space devices.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, GIS, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
PDF
