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Rationale: Cisplatin derivatives are first-line chemotherapeutic agents for epithelial ovarian cancer. However, chemoresistance remains a major hurdle for successful therapy and the underlying molecular mechanisms are poorly understood at present. Methods: RNA sequencing of organoids (PDO) established from cisplatin-sensitive and -resistant ovarian cancer tissue samples was performed. Glucose metabolism, cell senescence, and chemosensitivity properties were subsequently examined. Immunoprecipitation, mass spectrometry, Fӧrster resonance energy transfer-fluorescence lifetime imaging (FRET-FLIM), luciferase reporter assay, ChIP and animal experiments were conducted to gain insights into the specific functions and mechanisms of action of the serine/threonine kinase, Aurora-A, in ovarian cancer. Results: Aurora-A levels were significantly enhanced in cisplatin-resistant PDO. Furthermore, Aurora-A promoted chemoresistance through suppression of cell senescence and induction of glucose metabolism in ovarian cancer organoids and cells. Mechanistically, Aurora-A bound directly to the transcription factor sex determining region Y-box 8 (SOX8) and phosphorylated the Ser327 site, in turn, regulating genes related to cell senescence and glycolysis, including hTERT, P16, LDHA and HK2, through enhancement of forkhead-box k1 (FOXK1) expression. Conclusions: Aurora-A regulates cell senescence and glucose metabolism to induce cisplatin resistance by participating in the SOX8/FOXK1 signaling axis in ovarian cancer. Our collective findings highlight a novel mechanism of cisplatin resistance and present potential therapeutic targets to overcome chemoresistance in ovarian cancer.

The role of mitochondrial ROS production and signalling in muscle adaptations to exercise training has not been explored in detail. Here we investigated the effect of supplementation with the mitochondria-targeted antioxidant MitoQ on a) the skeletal muscle mitochondrial and antioxidant gene transcriptional response to acute high-intensity exercise and b) skeletal muscle mitochondrial content and function following exercise training. In a randomised, double-blind, placebo-controlled, parallel design study, 23 untrained men (age: 44 ± 7 years, VO2peak: 39.6 ± 7.9 ml/kg/min) were randomised to receive either MitoQ (20 mg/d) or a placebo for 10 days before completing a bout of high-intensity interval exercise (cycle ergometer, 10 × 60 s at VO2peak workload with 75 s rest). Blood samples and vastus lateralis muscle biopsies were collected before exercise and immediately and 3 hours after exercise. Participants then completed high-intensity interval training (HIIT; 3 sessions per week for 3 weeks) and another blood sample and muscle biopsy were collected. MitoQ supplementation augmented acute exercise-induced increases in skeletal muscle mRNA expression of the major regulator of proteins involved in mitochondrial biogenesis peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1-α). Despite this, training-induced increases in skeletal muscle mitochondrial content were unaffected by MitoQ supplementation. HIIT-induced increases in VO2peak and 20 km time trial performance were also unaffected by MitoQ while MitoQ augmented training-induced increases in peak power achieved during the VO2peak test. These data suggest that MitoQ supplementation enhances the effect of training on peak power, which may be related to the augmentation of skeletal muscle PGC1α expression following acute exercise. However, this effect does not appear to be related to an effect of MitoQ supplementation on HIIT-induced mitochondrial biogenesis in skeletal muscle and may therefore be the result of other adaptations mediated by PGC1α.

Accurate assessing CO2 exchange of tundra ecosystems is essential for better understanding and prediction of the CO2 responses of tundra ecosystems to climate change. In this study, the effects of warming on growing season CO2 exchange in an alpine tundra ecosystem were examined with closed transparent chamber attached to an infrared gas analyzer. Compared to ambient controls, open-top chambers (OTCs) increased growing season air (15 cm above ground surface) and soil (10 cm in depth) temperature by 1 and 0.2°C, respectively. Compared to the controls, OTCs tended to increase the plant height of Dryas octopetala and Vaccinium uliginosum by 15.1% (but P > 0.05) and 7.5% (P > 0.05), respectively. During the growing season, OTC-warming increased net ecosystem CO2 exchange by 136% and gross ecosystem exchange by 63%, whereas no significant difference in ecosystem respiration was found. Our results suggest that the predicted air warming will increase ecosystem carbon uptake of the Changbai Mountain alpine tundra during growing season. However, there is an uncertainty about the net CO2 exchange of that ecosystem at an annual scale, because, due to the inaccessibility, we did not study the winter respiration. Further studies are, therefore, needed to estimate the annual and long-term trade-off between CO2 uptake and emission in that region.

A compact photoneutron source (PNS), based on an electron LINAC was designed and constructed to provide required experimental nuclear data for Thorium Molten Salt Reactor (TMSR). All devices including the LINAC, the neutron production target and the detector systems were arranged in a shared hall, leading to a high background of neutron and γ-ray. The necessary shielding design was made to reduce the backgrounds. A series of preliminary measurements of total cross section in thermal neutron energy region for some key nuclides of TMSR, such as 232Th and 7Li, have been performed at this PNS. It was found, however, that additional shielding needs to be constructed to further reduce the neutron and γ-ray backgrounds. MCNP is a major tool for the background shielding design since it has the calculation capability for a coupled neutron-photon-electron transport problem. A two-step subsection simulation based on MCNP involving with variance reduction techniques (Sub-Var method) was performed to provide required flux and spectrum calculation for the new background shielding design. Based on the simulated results, a new local shielding was designed and constructed, which can reduce the thermal neutron background by three orders of magnitude and the γ-ray background by two orders of magnitude. The neutron flux and energy spectrum were measured under the new shielding condition and compared with the simulated ones, showing a good agreement with each other in the thermal energy region. Therefore, a significant improved shielding for the PNS is achieved, which is expected to provide a required assurance for the future measurements of neutron cross section at the PNS.

Measurement of skeletal muscle mitochondrial respiration requires invasive biopsy to obtain a muscle sample. Peripheral blood mononuclear cell (PBMC) mitochondrial protein content appears to reflect training status in young men; however, no studies have investigated whether there are training-induced changes in PBMC mitochondrial respiration. Therefore, we determined whether PBMC mitochondrial respiration could be used as a marker of skeletal muscle mitochondrial respiration in young healthy men and whether PBMC mitochondrial respiration responds to short-term training. Skeletal muscle and PBMC samples from 10 healthy young (18–35 yr) male participants were taken before and after a 2-wk high-intensity interval training protocol. High-resolution respirometry was used to determine mitochondrial respiration from muscle and PBMCs, and Western blotting and quantitative PCR were used to assess mitochondrial biogenesis in PBMCs. PBMC mitochondrial respiration was not correlated with muscle mitochondrial respiration at baseline ( R2 = 0.012–0.364, P > 0.05). While muscle mitochondrial respiration increased in response to training (32.1–61.5%, P < 0.05), PBMC respiration was not affected by training. Consequently, PBMCs did not predict training effect on muscle mitochondrial respiration ( R2 = 0.024–0.283, P > 0.05). Similarly, gene and protein markers of mitochondrial biogenesis did not increase in PBMCs following training. This suggests PBMC mitochondrial function does not reflect that of skeletal muscle and does not increase following short-term high-intensity training. PBMCs are therefore not a suitable biomarker for muscle mitochondrial function in young healthy men. It may be useful to study PBMC mitochondrial function as a biomarker of muscle mitochondrial function in pathological populations with different respiration capacities. NEW & NOTEWORTHY Research in primates has suggested that peripheral blood mononuclear cells (PBMCs) may provide a less-invasive alternative to a muscle biopsy for measuring muscle mitochondrial function. Furthermore, trained individuals appear to have greater mitochondrial content in PBMCs. Here we show that in healthy young men, PBMCs do not reflect skeletal muscle mitochondrial function and do not adapt in response to a training intervention that increases muscle mitochondrial function, suggesting PBMCs are a poor marker of muscle mitochondrial function in humans.

We present the latest development of measuring (γ, n) cross sections and giant dipole resonance (GDR) cross sections in the IAEA photonuclear data project. Photoneutron cross sections were measured for 21 isotopes below 2n threshold to construct the γ-ray strength function (γSF) with the γSF method; (γ, n) cross sections are used as experimental constraints on the model E1 and M1 γSFs from the Hartree–Fock–Bogolyubov plus quasi-particle random phase approximation based on the Gogny D1M interaction supplemented with the M1 upbend. GDR cross sections were measured for 11 nuclei from 9Be to 209Bi by direct neutron-multiplicity sorting with a flat-efficiency neutron detector toward a goal of resolving the long-standing discrepancy between the Livermore and Saclay data. We present γSFs for the Ni isotopic chain and GDR cross sections for 159Tb as well as those updated for 209Bi.

Proton radiography is a widely-fielded diagnostic used to measure magnetic structures in plasma. The deflection of protons with multi-MeV kinetic energy by the magnetic fields is used to infer their path-integrated field strength. Here, the use of tomographic methods is proposed for the first time to lift the degeneracy inherent in these path-integrated measurements, allowing full reconstruction of spatially resolved magnetic field structures in three dimensions. Two techniques are proposed which improve the performance of tomographic reconstruction algorithms in cases with severely limited numbers of available probe beams, as is the case in laser-plasma interaction experiments where the probes are created by short, high-power laser pulse irradiation of secondary foil targets. The methods are equally applicable to optical probes such as shadowgraphy and interferometry [M. Kasim et al. Phys. Rev. E 95, 023306 (2017)], thereby providing a disruptive new approach to three dimensional imaging across the physical sciences and engineering disciplines., Comment: 11 pages, 6 figures, companion article to arXiv:2103.11268

A European consortium of 15 laboratories across nine nations have worked together under the EUROFusion Enabling Research grants for the past decade with three principle objectives. These are: (a) investigating obstacles to ignition on megaJoule-class laser facilities; (b) investigating novel alternative approaches to ignition, including basic studies for fast ignition (both electron and ion-driven), auxiliary heating, shock ignition, etc.; and (c) developing technologies that will be required in the future for a fusion reactor. A brief overview of these activities, presented here, along with new calculations relates the concept of auxiliary heating of inertial fusion targets, and provides possible future directions of research and development for the updated European Roadmap that is due at the end of 2020. This article is part of a discussion meeting issue ‘Prospects for high gain inertial fusion energy (part 2)’.

Fast ignition inertial confinement fusion requires the production of a low-density channel in plasma with density scale-lengths of several hundred microns. The channel assists in the propagation of an ultra-intense laser pulse used to generate fast electrons which form a hot spot on the side of pre-compressed fusion fuel. We present a systematic characterization of an expanding laser-produced plasma using optical interferometry, benchmarked against three-dimensional hydrodynamic simulations. Magnetic fields associated with channel formation are probed using proton radiography, and compared to magnetic field structures generated in full-scale particle-in-cell simulations. We present observations of long-lived, straight channels produced by the Habara–Kodama–Tanaka whole-beam self-focusing mechanism, overcoming a critical barrier on the path to realizing fast ignition. This article is part of a discussion meeting issue ‘Prospects for high gain inertial fusion energy (part 2)’.

β-delayed one-proton emissions of ^{22}Si, the lightest nucleus with an isospin projection T_{z}=-3, are studied with a silicon array surrounded by high-purity germanium detectors. Properties of β-decay branches and the reduced transition probabilities for the transitions to the low-lying states of ^{22}Al are determined. Compared to the mirror β decay of ^{22}O, the largest value of mirror asymmetry in low-lying states by far, with δ=209(96), is found in the transition to the first 1^{+} excited state. Shell-model calculation with isospin-nonconserving forces, including the T=1, J=2, 3 interaction related to the s_{1/2} orbit that introduces explicitly the isospin-symmetry breaking force and describes the loosely bound nature of the wave functions of the s_{1/2} orbit, can reproduce the observed data well and consistently explain the observation that a large δ value occurs for the first but not for the second 1^{+} excited state of ^{22}Al. Our results, while supporting the proton-halo structure in ^{22}Al, might provide another means to identify halo nuclei.

Laser and beam driven wakefields promise orders of magnitude increases in electric field gradients for particle accelerators for future applications. Key areas to explore include the emittance properties of the generated beams and overcoming the dephasing limit in the plasma. In this paper, the first in-depth study of the self-injection mechanism into wakefield structures from non-homogeneous cluster plasmas is provided using high-resolution two dimensional particle-in-cell simulations. The clusters which are typical structures caused by ejection of gases from a high-pressure gas jet have a diameter much smaller than the laser wavelength. Conclusive evidence is provided for the underlying mechanism that leads to particle trapping, comparing uniform and cluster plasma cases. The accelerated electron beam properties are found to be tunable by changing the cluster parameters. The mechanism explains enhanced beam charge paired with large transverse momentum and energy which has implications for the betatron x-ray flux. Finally, the impact of clusters on the high-power laser propagation behavior is discussed.

In this article, we showcase the experimental results of methods to produce and characterize orbital angular momentum (OAM) carrying high-power lasers. The OAM pulses were produced on the ASTRA laser of the Central Laser Facility using a continuous spiral phase plate. Three different characterization methods were then used to measure the OAM content of the beam. The methods that were used were a cylindrical lens diagnostic, an interferometric diagnostic, and a projective diagnostic. We further discuss the relative advantages and disadvantages of each method in the context of high-power laser experiments.

Triple-negative breast cancers (TNBC) are a subtype of breast cancer lacking of estrogen receptor (ER), progesterone receptor (PR), and human EGF-like receptor 2 (HER2). MiR-193 always acted as an oncogene and promoted toxic aldehyde accumulation and tyrosine hydroxylase dysfunction. The purpose of this study is to explore the function of miR-193 in triple-negative breast cancer.Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was performed to examine the mRNA level of miR-193 expression in 50 cases of TNBC tissues and para-cancerous specimens. Also, the relation between miR-193 level and the overall survival of TNBC patient was analyzed. MiR-193 mimic and miR-193 inhibitor oligos, as well as the corresponding negative control, were synthesized from RiboBio (Guangzhou, China).MiR-193 expression was higher in triple-negative breast cancer tissues and cell lines than the corresponding adjacent non-tumor tissues and normal cell lines. Upregulation of miR-193 predicted poor prognosis of TNBC patients. Overexpression of miR-193 promoted cell proliferation and invasion, while that was suppressed by the knockdown of miR-193. MiR-193 binds to the 3'-UTR of an inhibitor of growth family member 5 (ING5) mRNA to mediate the expression of ING5 in TNBC cells. The knockdown of miR-193 inhibited cell invasion-mediated epithelial-mesenchymal transition (EMT). Furthermore, the knockdown of miR-193 suppressed cell proliferation through the ING5/phosphatidylinositol 3-hydroxy kinase/protein kinase B (PI3K/AKT) signal pathway.MiR-193 enhanced cell invasion-mediated EMT and improved cell proliferation through the ING5/PI3K/AKT signal pathway in triple-negative breast cancer. The newly identified miR-193/ING5/PI3K/AKT axis provides novel insight into the pathogenesis of triple-negative breast cancer.

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β-delayed one-proton emissions of ^{22}Si, the lightest nucleus with an isospin projection T_{z}=-3, are studied with a silicon array surrounded by high-purity germanium detectors. Properties of β-decay branches and the reduced transition probabilities for the transitions to the low-lying states of ^{22}Al are determined. Compared to the mirror β decay of ^{22}O, the largest value of mirror asymmetry in low-lying states by far, with δ=209(96), is found in the transition to the first 1^{+} excited state. Shell-model calculation with isospin-nonconserving forces, including the T=1, J=2, 3 interaction related to the s_{1/2} orbit that introduces explicitly the isospin-symmetry breaking force and describes the loosely bound nature of the wave functions of the s_{1/2} orbit, can reproduce the observed data well and consistently explain the observation that a large δ value occurs for the first but not for the second 1^{+} excited state of ^{22}Al. Our results, while supporting the proton-halo structure in ^{22}Al, might provide another means to identify halo nuclei.

The β-delayed two-proton emission from 22Al was investigated experimentally through the implantation-decay method. A β-delayed two-proton decay branch from 22Al were identified based on the coincidence of the charged particles and γ-ray signals. The relative momentum ( q p p ) and the opening angle ( θ p p ) distributions of the two β-delayed protons are measured and a strong peak at q p p ∼ 20 MeV/c , as well as a peak at θ p p ∼ 30 ∘ are observed clearly. The β-delayed 2He emission from 22Al with a probability of 29 (13)% by fitting the experimental data with the results of Monte Carlo simulations.

Resistive Plate Chambers have largely been used in High Energy Physics and Cosmic Ray research. In view of using this detector for calorimetry applications it is important to know the maximum measurable particle density, or its intrinsic linearity limit, which is tightly related to the dimension of the discharge region. In this paper we report the results of measurements performed at the Beam Test Facility (INFN National Laboratory of Frascati, Italy) where the intrinsic linearity of bakelite RPCs operated in streamer mode has been tested at different impinging particle densities.

To investigate the relationships of the severity of diabetic retinopathy with erythropoietin (EPO), Caspase-3 expression, and oxidative stress.A total of 20 patients with non-proliferative diabetic retinopathy hospitalized from January 2017 to January 2018 were enrolled as observation group 1, 20 patients with proliferative diabetic retinopathy were chosen as observation group 2, and 20 patients with idiopathic macular hole were selected as control group. After admission, patients received all necessary examinations and underwent vitrectomy during which vitreous and retinal tissues were taken, and venous blood was collected. Then, the content of EPO, Caspase-3, nitric oxide (NO), and malondialdehyde (MDA) was detected through enzyme-linked immunosorbent assay (ELISA), the messenger ribonucleic acid (mRNA) levels of EPO, Caspase-3, NO, and MDA were measured via quantitative Polymerase Chain Reaction (qPCR), and the severity of diabetic retinopathy was evaluated by diabetic retinopathy grading score.Observation group 1 and 2 had significantly decreased the content of EPO (p0.05) and overtly increased Caspase-3, NO, and MDA content (p0.05) in comparison with control group. Compared with those in observation group 1, the EPO content was clearly lowered in observation group 2 (p0.05), and the content of Caspase-3, NO, and MDA was evidently elevated (p0.05). The diabetic retinopathy grading score was remarkably lower in control group than that in both observation group 1 and observation group 2 (p p0.05), and it was significantly enhanced in observation group 2 compared with that in observation group 1 (p0.05). Correlation analysis showed that the EPO content was negatively correlated with the severity of diabetic retinopathy, while the content of Caspase-3, NO, and MDA was positively related to the severity of diabetic retinopathy.The severity of diabetic retinopathy has a negative association with EPO and positive correlations with Caspase-3, NO, and MDA content.

Shanghai laser electron gamma source (SLEGS) is an energy-variable gamma-ray source developed based on the inverse Compton scattering of 10640 nm photons from a 100 W CO 2 laser on 3.5 GeV electrons from the Shanghai Light Source. It produces gamma-rays in the energy range of 0.4–21.7 MeV with a flux of 10 5 –10 7 photons/s. A collimator system was designed to produce quasimonochromatic gamma-ray beams with a best possible bandwidth of 1.1%–4.4% and filter out the substandard gamma-rays. The collimator system composed of coarse and fine collimators, constitutes a critical component of the SLEGS. By Geant4 simulations, we show that the collimator system is effective in tuning beam bandwidths and regular dodecagonal beam spots at the target position.

Shanghai HIgh repetition rate XFEL aNd Extreme light facility (SHINE) is a quasi-continuous wave hard X-ray free electron laser facility, which is currently under construction. The data storage system holds large volumes of data generated instantaneously during the operation. A combination architecture of relational database, non-relational database and the distributed file system is designed as the centralized data storage system serving to multiple application demands for SHINE. The storage of high-speed stream data such as waveform and image data is studied and relevant storage schemas are tested and compared. The optimized schema is identified finally.

The energy levels and transition properties of In-like ions are investigated by using the multi-configuration Dirac–Hartree–Fock method. The results for the energy levels, transition probabilities, wavelengths, line strengths and lifetimes of In-like Cs VII—Pm XIII are reported. Relativistic effects and electron correlation are included. Our calculations agree well with the experimental and other theoretical values. The new data of energy levels and transition parameters are predicted. The level crossing happens between the configurations 5s 24f and 5s 25p with increasing nuclear charge. The transition frequencies are within the range of usual lasers because of the level crossing. In-like ions may be developed into atomic clock.

Discharge measurement is a critical task for gravel-bed channels. Under high-flow conditions, the elevation of the riverbed changes significantly by intensive torrential flow. The stage–discharge relations commonly used for stream discharge estimation may no longer be adequate. The contact-type velocity measuring is also subject to measurement errors and/or instrument failures by the high-flow velocities, driftwood, stumps, and debris. This study developed a new real-time method to estimate river discharge in gravel-bed channels. A systematic measuring technology combining ground-penetrating radar and surface-velocity radar was employed. The rating curves representing the relations of water surface velocity to the channel cross-sectional mean velocity and flow area were established. Stream discharge was then deduced from the resulting mean velocity and flow area. The proposed method was examined in a steep gravel-bed reach of the Cho-Shui River in central Taiwan. The estimated stream discharge during three flood events were compared to the prediction by using the stage–discharge relation and the index-velocity method. The proposed method of this study is capable of computing reasonable values of discharge for an entire flood hydrograph, whereas the other two methods tend to produce large extrapolation errors. Moreover, when the computed discharge is used in 2D flood flow simulation, the proposed method demonstrates better performance than the commonly used stage–discharge and index-velocity methods.

In 2011 ARGO-YBJ experiment has reported a work to study the absolute rigidity scale of the primary cosmic ray particles based on the Moon's shadow observation. Given the progress in high energy hadronic interaction models with LHC data, in cosmic ray chemical composition measurement and in experimental data accumulation, more updates can be researched. This paper aims to further disentangle the composition dependence in absolute-energy-scale calibration by using specific moon-shadow data which mainly is comprised of light component cosmic rays. Results show that, 17% energy scale error is estimated from 3 TeV to 50 TeV. To validate the performance of this technique, the light component cosmic ray spectrum in the same energy region is shown. (C) 2017 Elsevier B.V. All rights reserved.

Although high-resolution single-particle cryo-electron microscopy (cryo-EM) is now producing a rapid stream of breakthroughs in structural biology, it nevertheless remains the case that the preparation of suitable frozen-hydrated samples on electron microscopy grids is often quite challenging. Purified samples that are intact and structurally homogeneous - while still in the test tube - may not necessarily survive the standard methods of making extremely thin, aqueous films on grids. As a result, it is often necessary to try a variety of experimental conditions before finally finding an approach that is optimal for the specimen at hand. Here, we summarize some of our collective experiences to date in optimizing sample preparation, in the hope that doing so will be useful to others, especially those new to the field. We also hope that an open discussion of these common challenges will encourage the development of more generally applicable methodology. Our collective experiences span a diverse range of biochemical samples and most of the commonly used variations in how grids are currently prepared. Unfortunately, none of the currently used optimization methods can be said, in advance, to be the one that ultimately will work when a project first begins. Nevertheless, there are some preferred first steps to explore when facing specific problems that can be more generally recommended, based on our experience and that of many others in the cryo-EM field.

In this letter, we investigate the effect of orbital angular momentum (OAM) on elastic photon-photon scattering in vacuum for the first time. We define exact solutions to the vacuum electro-magnetic wave equation which carry OAM. Using those, the expected coupling between three initialwaves is derived in the framework of an effective field theory based on the Euler-Heisenberg La-grangian and shows that OAM adds a signature to the generated photons thereby greatly improvingthe signal-to-noise ratio. This forms the basis for a proposed high-power laser experiment utilizingquantum optics techniques to filter the generated photons based on their OAM state, Comment: 7 Pages, 3 Figures (color), added supplemental materials to elaborate on some arguments and added some relevant references