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Objectives Cancer patients with diabetes have an increasing risk of Doxorubicin (Dox)-induced cardiotoxicity. Despite previous studies reporting benefits of dapagliflozin on the cardiovascular system, it remains unknown whether dapagliflozin has a cardioprotective effect in cancer patients with diabetes receiving Dox therapy. The purpose of this study is to investigate the potentials of dapagliflozin in preventing Dox induced cardiotoxicity. Methods Using National Health Insurance Database, the incidence of heart failure of breast cancer patients with or without diabetes was investigated. Also, streptozotocin (STZ) induced diabetic rats were pretreated with oral dapagliflozin (10 mg/kg/day) for 6 weeks and received Dox (5 mg/kg/week) for 4 weeks via intraperitoneally injection. Sequential echocardiography was applied to assess the cardiac function. For in vitro analysis, H9C2 cardiomyocytes, cultured in high glucose (30 mM), were treated with dapagliflozin at 10 mM and subsequently exposed to Dox at 1 mM. The apoptosis and endoplasmic reticulum (ER) stress related protein expression were measured by immunohistochemistry and western blotting. Results Among the studied patients, those with diabetes have a higher risk of heart failure while patients prescribed with dapagliflozin lowered the risks. Correspondingly, dapagliflozin treatment effectively inhibited Dox-induced apoptosis and reactive oxygen species accumulation in cardiomyocytes. Also, the reduction of cardiac fibrosis as well as apoptosis in rats treated with dapagliflozin resulted in significantly improved cardiac function. Dapagliflozin also decreased the cardiac expression of Bax, cleaved caspase 3 and increased Bcl-2. Mechanistically, we showed that dapagliflozin significantly reduced ER stress-associated proteins including GRP78, PERK, eIF 2a, ATF-4, and CHOP. Conclusions Our study revealed for the first time that dapagliflozin mitigated Dox-induced cardiomyocyte apoptosis in diabetes via inhibiting ER stress. These results indicate that dapagliflozin could be useful in preventing cardiotoxicity in diabetic cancer patients receiving Dox treatment. Funding Acknowledgement Type of funding source: Private hospital(s). Main funding source(s): Chi-Mei Medical Center, Tainan, Taiwan

SUMMARY The implementation efficiencies of the Natural Forest Protection Program (NFPP) in ten provinces in Western China are evaluated by using Data Envelopment Analysis (DEA). Some findings are found that the average technical efficiency of technology is 0.910; the average growth rate of the total factor productivity among ten provinces is minus 13%. And the change in efficiency is predominantly due to technical progress. Some conclusions and recommendations are put forward to enhance the implementation efficiency based on the factor of input and output.

Structural and magnetic properties have been studied for polycrystalline Zn1 − xTMxO films where transition metal (TM) = Fe, Cr. The Zn1 − xTMxO films were prepared by the radio frequency magnetron sputtering technique on Al2O3 (001) substrates. The microstructures of the films are characterized by X-ray diffraction and X-ray photoelectron spectroscopy. TM in the films exists mainly in the form of TM2+, and the TM2+ ions have substituted for the Zn2+ ions bonded in TM–O in the ZnO lattice and do not change the wurtzite structure of ZnO. The result of magnetic measurement shows that the Zn1 − xTMxO films are ferromagnetic at 5 K and 300 K respectively. Subsequently, we discuss the origin of the ferromagnetism in the films.

The origin of mafic enclaves in intermediate and felsic granitoids has long been debated. In this paper, petrological and geochemical analyses (whole-rock geochemistry, Nd–Sr and zircon in-situ Hf isotopic compositions) are used to address this controversial issue. Mafic enclaves in the Taihang felsic plutons (north China craton) are fine-grained and show typical magmatic textures. They occur as rounded to ellipsoidal globules, and are sometimes highly elongated (without solid state deformation) due to stretching within the partially crystallized, convective felsic magma. Such occurrence suggests that the mafic enclaves and host rocks represent two co-existing, compositionally distinct magmas. The mafic enclaves contain abundant hydrous phases (hornblende and biotite) and show the reaction relationship of clinopyroxene being rimmed by hornblende. They also contain plagioclase xenocrysts showing compositional and textural disequilibrium. In terms of Nd–Hf isotopes, mafic enclaves have eNd(t) values of − 10 to − 15, and host rocks have lower values as a whole (− 13 to − 18). Zircons from a single enclave show a large variation in Hf isotopic compositions (eHf(t) = − 5 to − 20). A model is proposed whereby an evolved basaltic magma first mixed with a granitic magma of crustal origin at depth; and then the mixed magma broke up into discrete globules upon entering the felsic magma chamber, forming enclaves by convective motion, or forceful injection in the host felsic magma. This was followed by a double mechanical transfer of plagioclase crystals at the contact of the two magmas, and by the diffusion of mobile elements (e.g., Si, alkalis, P, Y, Yb, Pb) from felsic magma to enclave-forming magma.

The North China craton (NCC) was stabilized in Paleo-Proterozoic times, and the eastern part of it was remobilized in the Mesozoic, as is indicated by the presence of voluminous Mesozoic magmas in eastern NCC. In particular, the lithospheric mantle beneath eastern NCC was significantly thinned during the intense Mesozoic tectono-magmatic activity, which makes the NCC different from most other ancient cratons. The Mesozoic magmas may thus provide crucial evidence regarding the processes that transformed the NCC from craton to a tectonically active region. The South Taihang magmatic complex lies in the western part of the Mesozoic magmatic zone in the NCC. The complex falls into three main plutonic rocks: the Hongshan syenite, the Xishu gabbroic diorite–monzonite and the Wu'an monzonitic rocks. Zircon U–Pb dating reveals that the three plutonic rocks were emplaced contemporaneously at ∼ 132 Ma. In-situ Hf isotopic analyses for the dated zircons indicate that the Hongshan syenites show homogeneous ɛ Hf ( t ) values (− 10 to − 13) which are slightly lower than those (− 9.0) for the enriched subcontinental lithospheric mantle (SCLM), as revealed by zircons from mafic rocks that originated from melting of SCLM. This suggests that the parental magma to the syenites was likely derived from melting of the enriched SCLM and contaminated slightly by old lower continental crustal material during ascent. The Xishu and Wu'an gabbroic diorites to monzonitic rocks, however, show significantly varied Hf isotopic compositions, with ɛ Hf ( t ) = – 9.2 to – 16 and – 15.5 to − 24, respectively. The wide range of ɛ Hf ( t ) values for a single sample suggests that the Xishu and Wu'an plutons formed through a process of hybridization between enriched mantle-derived mafic magma and crustal components in variable proportions. This is supported by the textural and compositional disequilibrium of plagioclase phenocrysts from the two plutons. The Wu'an monzonitic rocks show lower ɛ Hf ( t ) values than the Xishu gabbroic diorite–monzonite, suggesting more incorporation of crustal components in the source. The sudden surge of magmatic activity in the South Taihang orogen took place as a result of lithospheric extension that caused partial fusion of the enriched portions of SCLM generating voluminous mafic magmas. Underplating of the mafic magmas in the lower crust consequently caused partial melting of the old basement rocks to produce granitic melts, which was followed by mixing between the mafic and granitic magmas.

Zn1−xFexO (x = 0, 0.052, 0.103, 0.157 and 0.212) films were prepared by the radio-frequency magnetron sputtering technique on Si (111) substrates and the microstructure of which was characterized by X-ray diffraction, X-ray photoelectron spectroscopy, and scanning electron microscopy. The samples had a preferential c-axis orientation and the position of (002) diffraction peak shifted to the lower degree side with increasing Fe component. In order to investigate the optical transmittance properties of Zn1−xFexO films, we prepared the films on Al2O3 (001) substrates simultaneity and the UV–VIS optical transmittance spectra showed that the band gap energy of Zn1−xFexO films decreased with increase of Fe concentration. Photoluminescence spectra of the samples were observed at room temperature.

For large structures in actual engineering practice such as shipbuilding, it is hard to realize the welding process simulation by thermal elastic plastic FEM owing to the calculation time and cost. Elastic FEM based on inherent strain theory was developed to investigate welding distortion of large scale and complex welded structures. Structural responses induced by welding were treated as initial strains in the local structure near weld lines. Deng & Murakawa (2007, 2008) used the elastic FEM to predict welding distortion of a large structures considering both local shrinkage and root gap and the accuracy were verified by experimental results. Based on the calculation results of small joints by thermal elastic plastic FEM, elastic FEM1 INTRODUCTIONAs an efficient and reliable joining method, welding technology is widely used in shipbuilding, with high productivity and flexibility during manufacture process of structural components fabrication, sections assembly and blocks closure (Zacke 2011). However, it is inevitable that residual distortion and stress exists in the welded structures due to the non-uniform expansion and shrinkage of material near weld line. Welding distortion not only affects the appearance of products but also degrades the structural performance due to the loss of structural integrity and dimensional accuracy. It is meaningful to predict welding induced distortion at the design stage itself, for the purpose of controlling such distortion in production (Tsai et al. 1999).

Using the RF-magnetron sputtering technique, we have fabricated ZnO film on Si(1 1 1) substrate with a SiC buffer layer chosen to reduce the lattice mismatch between ZnO and Si. The as-deposited films were annealed in the temperature range of 600–1000 °C under nitrogen ambient. Then the thin films have been characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and photoluminescence (PL). According to the measurement results, it was found that the ZnO/SiC/Si(1 1 1) films have better crystal quality than that of the ZnO/Si(1 1 1) films, which is more apparent with the increase of annealing temperature, and after annealed at 1000 °C, two new peak at 870 and 891 cm −1 in the FTIR spectra appear and are related to the Zn–C and Zn–Si bonds, respectively, indicating the interface between the ZnO and SiC becomes more impacted and complicated. We have also discussed the PL properties of ZnO/SiC in great detail. There are two PL peaks at 376 and 413 nm. The 376 nm band is related to the free-exciton recombination of ZnO and has a great relation to the crystal quality of the ZnO film. The origin of the 413 nm peak is associated with the interface traps existing in the depletion regions between the ZnO–ZnO grain boundaries, which bears on the condition of the interface between ZnO and SiC.

Today, sculptured parts are widely used in aeronautical, automotive, and many other industries. To make high-quality sculptured surfaces through efficient toolpaths in three-axis CNC machining is a major technical challenge. In this work, a new toolpath generation method for three-axis CNC milling, the Steepest-Directed and Iso-Cusped (SDIC) toolpath generation scheme, is introduced. The method integrates the steepest-directed and iso-cusped toolpaths in three-axis CNC programming. The steepest-directed toolpaths ensure the best geometry matching between cutter and surface for high cutting efficiency, and form a frame to control the trend in direction of the iso-cusped toolpaths. The iso-cusped toolpaths eliminate overmachining on the surface. Their combination ensures high sculptured part productivity, less redundant milling, and good surface quality. Machining examples of a half-cylinder part and a sculptured part are used to illustrate and to compare a range of SDIC toolpath patterns. The proposed SDIC toolpath scheme produces shorter toolpaths with higher machining efficiency. With the help of global optimization algorithms, this method of optimal toolpath generation can be applied to three-axis CNC machining of sculptured surfaces.

STGC3 is a potential tumor suppressor in nasopharyngeal carcinoma. We previously found that CNE2 cells that re-expressed STGC3 formed smaller tumors in female mice than in male mice. Here, we investigated the sexual dimorphism of STGC3 as a tumor-suppressor in female and male nude mice injected subcutaneously with pcDNA3.1(+)-STGC3/CNE2 cells. ER-α was positively expressed in vitro in the CNE2 cells. The pcDNA3.1(+)-STGC3/CNE2 cell growth rate decreased after treatment with β-estradiol in vitro. There were significant differences in tumor size or mass between pcDNA3.1(+)-STGC3/CNE2 and control cases (P < 0.05), but there were significant differences in tumor size between female and male nude mice in the STGC3 transfection groups, and the pcDNA3.1(+)-STGC3/CNE2 tumor growth rate in the female nude mice was the lowest in all cases (P < 0.05). There were no significant differences between female and male nude mice in control groups. Furthermore, a greater number of cells were blocked in the G(0)/G(1) phase in pcDNA3.1(+)-STGC3/ CNE2 tumor xenografts in the female mice. Protemic analysis found 9 differentially expressed proteins in the pcDNA3.1-STGC3/CNE2 xenograft tissues in females and males. A heat shock 70 protein 8 isoform 2 variant was identified as a down-regulated protein associated with cell cycle control and its downstream factor cyclin D1 was also decreased in STGC3-repressed xenografts in female mice. The data above suggest that STGC3 and its associated proteins play an important role in nasopharyngeal carcinoma gender differences.

Let Ω be a bounded domain in Rm with piecewise smooth boundary. We consider the upper bound of the (n+1)th eigenvalue λn+1 for the two problems [formula] and [formula] where l and r are positive integers with l>r, v is the unit outward normal to ∂Ω, and P(t)=al−rtl+al−r−1tl−1+ . . . +a1tr+1 with the constant coefficients al−r=1, ai≥0 for i=1, 2,..., l−r−1. The bounds of λn+1 are expressed in terms of the preceding eigenvalues. This generalizes the inequalities obtained by Payne, Polya, Weinberger, Protter, Hile, and Yeh.

The L X-rays of 71 Lu, 73 Ta and 79 Au were produced by 1.5–4.5 MeV alpha particle bombardment. The emitted L α , L γ1 and L γ2,3 lines were selected to convert X-ray production cross sections into ionisation cross sections. The ionisation cross sections obtained were compared with the predictions of the ECPSSR theory. A reasonable agreement of L 3 -subshell ionisation cross sections between the present experiment and the ECPSSR theory is found. The departures of the measured L 2 -subshell ionisation cross sections from the ECPSSR theory are discussed.

The single electron memory effect in TiO/sub x/ nanostructure (thickness 3nm, length 150 nm and width 150 nm) based on localized density of state (LDOS) in metallic oxides is observed. The potential of application in the single electron memory is discussed.

The M x-rays of Th and U have been produced by alpha particle bombardment in the energy range of 2.5-4.5 MeV. N6,7 → M5(Mα), N6 → M4(Mβ), N5 → M3(Mγ), N4 → M2 and N2 → M1 lines were selected to deduce M-subshell x-ray production cross sections. The radiative transition rates and the Coster-Kronig yields and M-subshell fluorescence yields were used to convert the x-ray production cross sections into M-subshell ionization cross sections. The deduced M-subshell ionization cross sections were compared with the ECPSSR predictions. The discrepancies of our experimental results from the theoretical calculations are discussed.

THE interaction between the natural anti-Gal antibody and the a-gal epitope (Gala1-3Galb1-4GlcNAc-R) on xenograft cells results in rejection of the xenograft. Moreover, activity of anti-Gal increases by manyfold in xenograft recipients as a result of immune response to a-gal epitopes on the graft. This elicited anti-Gal greatly exacerbates xenograft rejection. A potential method for prevention of anti-Gal production in xenograft recipients is the treatment of such patients with anti-idiotype antibodies for anti-Gal. Such antibodies may neutralize anti-Gal and destroy cells capable of producing this antibody. To determine the possible diversity of such anti-idiotypes, the anti-Gal Ig genes have to be analyzed. As a first step, we studied the diversity of the immunoglobulin genes coding for this antibody in a1,3galactosyltransferase (a1,3GT) knock-out (KO) mice. These mice lack a-gal epitopes and are capable of producing large amounts of anti-Gal, upon immunization with xenograft cell membranes that express a-gal epitopes. Anti-Gal hybridomas were produced by fusion of splenocytes from KO mice, immunized with rabbit red cell membranes, with the mouse myeloma fusion partner X63.Ag.653. Hybridomas from several mice were screened for secretion of anti-Gal in ELISA with synthetic a-gal epitopes linked to BSA, as solid-phase antigen, as previously described. The specificity of these monoclonal antibodies was confirmed by demonstrating their specific binding to glycoproteins that express the a-gal epitope, such as mouse laminin and bovine thyroglobulin. Three hybridomas producing anti-Gal IgM were isolated, each from a different mouse. The Ig genes in these hybridomas were cloned and sequenced. All three anti-Gal clones contained heavy chain (VH) genes derived from the germline Ig gene VH22.1 and light chain (VL) genes derived from the germline Ig gene K5.1 (Table 1). These anti-Gal coding genes contained various somatic mutations in CDR1 and CDR2 regions. Some mutations were also found in frame work (FR) 2 and 3 regions. In addition, the CDR 3 regions differed significantly from one clone to the other. Interestingly, the sequences of the VL genes were much more conserved than those of the VH genes. Analysis of replacement (R) versus silent (S) mutations demonstrated a much higher proportion of R mutations in the CDR regions than in the FR regions (Table 1). Overall, these findings indicated that the Ig gene repertoire for anti-Gal is highly restricted in KO mice, and it consists primarily of one light and one heavy chain Ig genes. This limited repertoire is likely to reflect the structural

This paper describes the configuration and performance of T/R module used for the small scale array of multifunction phased array radar. The transmitting channel, receiving channel, structure and cooling design of the T/R module are introduced. The technological problems such as the design, test process and tuning of the T/R modules for engineering application are analysed. The measures to reduce costs and improve reliability are also described.

Chitin, a linear β1–4-linked poly-N-acetylglucosamine, enhanced the in vivo immune response of normal mice to sheep red blood cells, but not that of mice with thymic aplasia (nude mice). The compound is mitogenic for murine B lymphocytes but not for thymocytes or splenic T lymphocytes. Similarly to well-known polyclonal B-lymphocyte activators; e.g. lipopolysaccharide, chitin induces differentiation of B lymphocytes into antibody-forming cells in vitro.