The National Institute of Metrology (NIM, China) proposed a joule balance method to measure the Planck constant in 2006, and built the first prototype NIM-1 to verify its principle with a relative uncertainty of 8.9 × 10 -6 by 2013. Since 2013, a new joule balance NIM-2 has been designed, with a series of improvements to reduce the measurement uncertainty. By April 2017, NIM-2 has been constructed and can be employed to measure the Planck constant in vacuum. A first measurement on NIM-2 yields a determination of the Planck constant is 6.626 069 2(16) × 10 -34 Js with a relative uncertainty of 2.4 × 10 -7 . The determination differs in relative terms by −1.27 × 10 -7 from the CODATA 2014 value. Further improvement of NIM-2 is still in progress towards 10 -8 level uncertainty in the future.
The joule balance experiment has been carried out at the National Institute of Metrology, China (NIM) since 2007. By the end of 2013 the first generation of the joule balance (NIM-1) achieved a measurement uncertainty of 7.2 × 10 −6 (k = 1). To reduce the measurement uncertainty further, the next generation of the joule balance apparatus (NIM-2) system is under construction. A new coil system using ferromagnetic material is being adopted in NIM-2 to reduce self-heating in the coils. However, the effects on the measurement of the mutual inductance from the nonlinearity and hysteresis of the ferromagnetic material will bring a considerable measurement uncertainty. Inspired by the watt balance, the measurement of the mutual inductance is replaced by an equivalent measurement of the magnetic flux linkage difference. The nonlinearity and hysteresis will not be a problem in the measurement of the magnetic flux linkage difference. This technique comes from the watt balance method. It is called the generalized joule balance method, which is actually a modification of the watt balance method. However, it still represents a valid change that can reduce the difficulty of dynamic measurement experienced using the watt balance. Permanent magnets can also be adopted in the generalized joule balance. To check the feasibility of the generalized joule balance method, some preliminary experiments have been performed on NIM-1. A yokeless permanent magnet system has been designed and used to replace the exciting coils in NIM-1. In this paper, the structure of the yokeless permanent magnet system is introduced. Furthermore, a determination of the Planck constant with the permanent magnet system is presented. The value of the Planck constant h we obtained is 6.626 069(17) × 10 −34 J s with a relative standard uncertainty of 2.6 × 10 −6 .
Herein, we describe the design, synthesis, and structure−activity relationships of a series of unique 4-(1Hpyrazol-4-yl)-pyrimidin-2-amine derivatives that selectively inhibit Janus kinase 2 (JAK2) and FLT3 kinases. These screening cascades revealed that 18e was a preferred compound, with IC 50 values of 0.7 and 4 nM for JAK2 and FLT3, respectively. Moreover, 18e was a potent JAK2 inhibitor with 37-fold and 56-fold selectivity over JAK1 and JAK3, respectively, and possessed an excellent selectivity profile over the other 100 representative kinases. In a series of cytokine-stimulated cell-based assays, 18e exhibited a higher JAK2 selectivity over other JAK isoforms. The oral administration of 60 mg/kg of 18e could significantly inhibit tumor growth, with a tumor growth inhibition rate of 93 and 85% in MV4-11 and SET-2 xenograft models, respectively. Additionally, 18e showed an excellent bioavailability (F = 58%), a suitable half-life time (T 1/2 = 4.1 h), a satisfactory metabolic stability, and a weak CYP3A4 inhibitory activity, suggesting that 18e might be a potential drug candidate for JAK2-driven myeloproliferative neoplasms and FLT3-internal tandem duplication-driven acute myelogenous leukemia. ■ INTRODUCTIONJanus kinase 2 (JAK2) is an intracellular nonreceptor tyrosine kinase that belongs to the JAK family of kinases (JAK1, JAK2, JAK3, and TYK2). The JAK-signal transducer and activator of the transcription (JAK−STAT) pathway mediates signaling by cytokines, which controls the survival, proliferation, and differentiation of a variety of cells. 1−4 JAK2 phosphorylation, downstream STAT phosphorylation, and activation of gene transcription ultimately result in increased proliferation, differentiation, and survival of erythroid and myeloid cells. 5 Among the four JAK subtypes, JAK2 was proven to be critical for the growth and progression of hematologic malignancies, especially for myeloproliferative neoplasms (MPNs). 6 Activating JAK2 fusion proteins has been also described in chronic myelogenous leukemia, 7,8 acute myelocytic leukemia (AML), 9 and acute lymphoblastic leukemia. 10 Currently, a number of pan JAK and selective JAK inhibitors, such as ruxolitinib, a JAK1/2 inhibitor, used for myelofibrosis, 11,12 tofacitinib, a JAK1/JAK3 inhibitor used for rheumatoid arthritis, 13 and fedratinib, a JAK2/FLT3 inhibitor used for myelofibrosis in Aug 2019, 14 have been used clinically.FMS-like tyrosine kinase 3 (FLT3) is a receptor tyrosine kinase that plays a crucial role in the development of hematopoietic progenitor cells. 15 Up to 20−30% of patients with AML have been shown to have an activated FLT3 internal tandem duplication (ITD) mutation, which is a high-risk factor for disease relapse. 16−18 To date, several small-molecule inhibitors against FLT3, 19 such as midostaurin (PKC412, approved for AML by the FDA), 20,21 quizartinib (AC220, approved for AML in Japan in 2019), 22 and gilteritinib (ASP2215, approved for AML by the FDA in 2018) have been developed. 23 Although positive outcomes were obtained for thes...
Abstract-In the joule balance developed at National Institute of Metrology (NIM), the dynamic phase of a watt balance is replaced by the mutual inductance measurement in an attempt to provide an alternative method for the kg redefinition. But for this method a rather large current in the exciting coil, is needed to offer the necessary magnetic field in the force weighing phase, and the coil heating becomes an important uncertainty source. To reduce coil heating, a new coil system, in which a ferromagnetic material is used to increase the magnetic field was designed recently. But adopting the ferromagnetic material brings the difficulty from the nonlinear characteristic of material. This problem can be removed by measuring the magnetic flux linkage difference of the suspended coil at two vertical positions directly to replace the mutual inductance parameter. Some systematic effects of this magnet are discussed.
A simple differential capacitive sensor is provided in this paper to measure the absolute positions of length measuring systems. By utilizing a shield window inside the differential capacitor, the measurement range and linearity range of the sensor can reach several millimeters. What is more interesting is that this differential capacitive sensor is only sensitive to one translational degree of freedom (DOF) movement, and immune to the vibration along the other two translational DOFs. In the experiment, we used a novel circuit based on an AC capacitance bridge to directly measure the differential capacitance value. The experimental result shows that this differential capacitive sensor has a sensitivity of 2 × 10−4 pF/μm with 0.08 μm resolution. The measurement range of this differential capacitive sensor is 6 mm, and the linearity error are less than 0.01% over the whole absolute position measurement range.
This report describes the first CCM key comparison of realizations of the kilogram definition based on the fixed numerical value of the Planck constant, which came into force on 20 May 2019. The objectives were to determine the level of agreement between realizations of the kilogram using Kibble and joule balances and the X-ray crystal density (XRCD) method and to provide input for the calculation of the first "consensus value" of the kilogram. The consensus value will serve as the basis for an internationally coordinated dissemination of the kilogram which will continue until sufficient agreement between realization experiments has been achieved. The comparison was organized by the BIPM and had seven participants. The BIPM, KRISS, NIST and NRC operated Kibble balances, the NIM used a joule balance and the NMIJ and the PTB participated using 28Si spheres, the masses of which were determined with the XRCD method. These realization methods were used to calibrate 1 kg mass standards under vacuum. The standards were sent (in air) to the BIPM where they were compared under vacuum with each other and with BIPM Pt-Ir working standards. The latter were calibrated (in air) traceable to the International Prototype of the Kilogram (IPK), the mass of which served as the definition of the kilogram until 20 May 2019. The results of the weighings at the BIPM together with the measurement results communicated by the participants allowed comparison of the values attributed to mass standards of 1 kg using the participating realization experiments. The level of agreement between mass determinations with the realization experiments and the BIPM as-maintained mass unit, traceable to the Planck constant through the mass of the International Prototype of the Kilogram can also be deduced. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).
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