Nkx6.1 is essential for maintaining the functional state of pancreatic beta cells

Recently, loss of beta-cell-specific traits has been proposed as an early cause of beta cell failure in diabetes. However, the molecular mechanisms that underlie the loss of beta cell features remain unclear. Here, we identify an Nkx6.1-controlled gene regulatory network as essential for maintaining the functional and molecular traits of mature beta cells. Conditional Nkx6.1 inactivation in adult mice caused rapid-onset diabetes and hypoinsulinemia. Genome-wide analysis of Nkx6.1-regulated genes and functional assays further revealed a critical role for Nkx6.1 in the control of insulin biosynthesis, insulin secretion, and beta cell proliferation. Over time, Nkx6.1-deficient beta cells acquired molecular characteristics of delta cells, revealing a molecular link between impaired beta cell functional properties and loss of cell identity. Given that Nkx6.1 levels are reduced in human type 2 diabetic beta cells, our study lends support to the concept that loss of beta cell features could contribute to the pathogenesis of diabetes

Coupled superconducting qudit-resonator system: Energy spectrum, state population, and state transition under microwave drive

Superconducting quantum multilevel systems coupled to resonators have recently been considered in some applications such as microwave lasing and high-fidelity quantum logical gates. In this work, using an rf-SQUID type phase qudit coupled to a microwave coplanar waveguide resonator, we study both theoretically and experimentally the energy spectrum of the system when the qudit level spacings are varied around the resonator frequency by changing the magnetic flux applied to the qudit loop. We show that the experimental result can be well described by a theoretical model that extends from the usual two-level Jaynes-Cummings system to the present four-level system. It is also shown that due to the small anharmonicity of the phase device a simplified model capturing the leading state interactions fits the experimental spectra very well. Furthermore we use the Lindblad master equation containing various relaxation and dephasing processes to calculate the level populations in the simpler qutrit-resonator system, which allows a clear understanding of the dynamics of the system under the microwave drive. Our results help to better understand and perform the experiments of coupled multilevel and resonator systems and can be applied in the case of transmon or Xmon qudits having similar anharmonicity to the present phase device.This work was supported by the Ministry of Science and Technology of China (Grants No. 2014CB921202, No. 2015CB921104, and No. 2016YFA0300601),the National Natural Science Foundation of China (Grants No. 91321208 and No. 11674380)the Key Research Program of the Chinese Academy of Sciences (Grant No. XDPB08-3)S.H. acknowledges support by the US NSF (PHY-1314861)

Light Induced Surface Reactions at the Bismuth Vanadate Potassium Phosphate Interface

Bismuth vanadate has recently drawn significant research attention as a light absorbing photoanode due to its performance for photoelectrochemical water splitting. In this study, we use in situ ambient pressure X ray photoelectron spectroscopy with Tender X rays 4.0 keV to investigate a polycrystalline bismuth vanadate BiVO4 electrode in contact with an aqueous potassium phosphate KPi solution at open circuit potential under both dark and light conditions. This is facilitated by the creation of a 25 to 30 nanometers thick electrolyte layer using the dip and pull method. We observe that under illumination bismuth phosphate forms on the BiVO4 surface leading to an increase of the surface negative charge. The bismuth phosphate layer may act to passivate surface states observed in photoelectrochemical measurements. The repulsive interaction between the negatively charged surface under illumination and the phosphate ions in solution causes a shift in the distribution of ions in the thin aqueous electrolyte film, which is observed as an increase in their photoelectron signals. Interestingly, we find that such changes at the BiVO4 KPi electrolyte interface are reversible upon returning to dark conditions. By measuring the oxygen 1s photoelectron peak intensities from the phosphate ions and liquid water as a function of time under dark and light conditions, we determine the timescales for the forward and reverse reactions. Our results provide direct evidence for light induced chemical modification of the BiVO4 KPi electrolyte interfac

Recyclable and Robust Optical Nanoprobes with Engineered Enzymes for Sustainable Serodiagnostics

Recyclable fluorescence assays that can be stored at room temperature would greatly benefit biomedical diagnostics by bringing sustainability and cost-efficiency, especially for point-of-care serodiagnostics in developing regions. Here, a general strategy is proposed to generate recyclable fluorescent probes by using engineered enzymes with enhanced thermo-/chemo-stability, which maintains an outstanding serodiagnostic performance (accuracy >95%) after 10 times of recycling as well as after storage at elevated temperatures (37 °C for 10 days). With these three outstanding properties, recyclable fluorescent probes can be designed to detect various biomarkers of clinical importance by using different enzymes

Experiments and Simulation on Mannesmann Piercing Process in the Drill Steel Manufacture

Steel drill rods are employed in the mining industry to drill blast holes in rock, for them a high-quality metal surface and accurate geometrical parameters are essential. Drill steel is a special material exclusively designed for drill rods. To estimate the microstructure and dimensional stability of drill steel, a rigid plastic finite element method (FEM) was applied in examining the Mannesmann piercing in the drill steel manufacture. The three-dimensional thermal-force coupling FEM models were computer-generated with different plug positions.Стальные буровые штанги используются в горной промышленности для бурения взрывных скважин в породе, для них высокое качество металлической поверхности и точные геометрические параметры являются непременным условием. Буровая сталь особый материал, разработанный специально для буровых штанг. Для оценки микроструктуры и устойчивости размеров буровой стали был использован метод конечных элементов для жесткопластического анализа прошивки Маннесмана в производстве буровой стали. Трехмерные конечноэлементные модели термосилового взаимодействия разрабатывали на компьютере, используя различные положения оправки

Multi-Channel Lanthanide Nanocomposites for Customized Synergistic Treatment of Orthotopic Multi-Tumor Cases

<p>Simultaneous photothermal ablation of multiple tumors is limited by unpredictable photo-induced apoptosis, caused by individual intratumoral differences. Here, a multi-channel lanthanide nanocomposite was used to achieve tailored synergistic treatment of multiple subcutaneous orthotopic tumors under non-uniform whole-body infrared irradiation prescription. The nanocomposite reduces intratumoral glutathione by simultaneously activating the fluorescence and photothermal channels. The fluorescence provides individual information on different tumors, allowing customized prescriptions to be made. This enables optimal induction of hyperthermia and dosage of chemo drugs, to ensure treatment efficacy, while avoiding overtherapy. With an accessional therapeutic laser system, customized synergistic treatment of subcutaneous orthotopic cancer cases with multiple tumors is possible with both high efficacy and minimized side effects.</p&gt

Multi-Channel Lanthanide Nanocomposites for Customized Synergistic Treatment of Orthotopic Multi-Tumor Cases

Simultaneous photothermal ablation of multiple tumors is limited by unpredictable photo-induced apoptosis, caused by individual intratumoral differences. Here, a multi-channel lanthanide nanocomposite was used to achieve tailored synergistic treatment of multiple subcutaneous orthotopic tumors under non-uniform whole-body infrared irradiation prescription. The nanocomposite reduces intratumoral glutathione by simultaneously activating the fluorescence and photothermal channels. The fluorescence provides individual information on different tumors, allowing customized prescriptions to be made. This enables optimal induction of hyperthermia and dosage of chemo drugs, to ensure treatment efficacy, while avoiding overtherapy. With an accessional therapeutic laser system, customized synergistic treatment of subcutaneous orthotopic cancer cases with multiple tumors is possible with both high efficacy and minimized side effects.</p

Numerical approximation of the Euler-Poisson-Boltzmann model in the quasineutral limit

This paper analyzes various schemes for the Euler-Poisson-Boltzmann (EPB) model of plasma physics. This model consists of the pressureless gas dynamics equations coupled with the Poisson equation and where the Boltzmann relation relates the potential to the electron density. If the quasi-neutral assumption is made, the Poisson equation is replaced by the constraint of zero local charge and the model reduces to the Isothermal Compressible Euler (ICE) model. We compare a numerical strategy based on the EPB model to a strategy using a reformulation (called REPB formulation). The REPB scheme captures the quasi-neutral limit more accurately