CODATA Recommended Values of the Fundamental Physical Constants: 2018.

We report the 2018 self-consistent values of constants and conversion factors of physics and chemistry recommended by the Committee on Data of the International Science Council. The recommended values can also be found at physics.nist.gov/constants. The values are based on a least-squares adjustment that takes into account all theoretical and experimental data available through 31 December 2018. A discussion of the major improvements as well as inconsistencies within the data is given. The former include a decrease in the uncertainty of the dimensionless fine-structure constant and a nearly two orders of magnitude improvement of particle masses expressed in units of kg due to the transition to the revised International System of Units (SI) with an exact value for the Planck constant. Further, because the elementary charge, Boltzmann constant, and Avogadro constant also have exact values in the revised SI, many other constants are either exact or have significantly reduced uncertainties. Inconsistencies remain for the gravitational constant and the muon magnetic-moment anomaly. The proton charge radius puzzle has been partially resolved by improved measurements of hydrogen energy levels.

CODATA recommended values of the fundamental physical constants: 2018.

We report the 2018 self-consistent values of constants and conversion factors of physics and chemistry recommended by the Committee on Data of the International Science Council (CODATA). The recommended values can also be found at physics.nist.gov/constants. The values are based on a least-squares adjustment that takes into account all theoretical and experimental data available through 31 December 2018. A discussion of the major improvements as well as inconsistencies within the data is given. The former include a decrease in the uncertainty of the dimensionless fine-structure constant and a nearly two orders of magnitude improvement of particle masses expressed in units of kg due to the transition to the revised International System of Units (SI) with an exact value for the Planck constant. Further, because the elementary charge, Boltzmann constant, and Avogadro constant also have exact values in the revised SI, many other constants are either exact or have significantly reduced uncertainties. Inconsistencies remain for the gravitational constant and the muon magnetic-moment anomaly. The proton charge radius puzzle has been partially resolved by improved measurements of hydrogen energy levels.

Clinical outcomes of endovascular treatment of TASC-II C and D femoropopliteal lesions with the Viabahn endoprosthesis.

OBJECTIVES: The objective of this study was to evaluate clinical outcomes and patency rates using the Viabahn endoprosthesis in complex (TASC-II C and D) femoropopliteal lesions. BACKGROUND: Traditional treatment of symptomatic TASC-II C and D femoropopliteal lesions has mainly centered on open surgical options in patients deemed appropriate candidates. Endovascular treatment of these lesions with balloon angioplasty has been historically hampered by aggressive restenosis and relatively early clinical failure. The Viabahn endoprosthesis was developed with the intent of reducing restenosis while improving overall flexibility in the femoropopliteal segment. METHODS: Between March 2009 and July 2011 a total of 51 limbs in 41 patients underwent implantation of one or more Viabahn endovascular stent grafts for the treatment of symptomatic TASC-II C or D lesions. Patients were followed clinically at regular intervals and also underwent routine surveillance duplex ultrasound at 1, 3, 6, and 12 months post-procedure. The average follow-up from the index procedure was 14.6 months (range 13-35.2 months). RESULTS: A total of 22 TASC-II C and 29 TASC-II D lesions were treated (51 limbs in 41 patients). The mean lesion length was 22.4 cm. The overall 1-year primary patency rate was 74.8% (95% CI: 61.2%-88.4%), assisted primary patency rate was 87.4% (95% CI: 70.9%-95.9%), and the secondary patency rate was 94.9% (95% CI: 88.0%-100.0%). CONCLUSIONS: The Viabahn endoprosthesis is a safe and effective option for the treatment of TASC-II C and D femoropopliteal lesions. Patency rates are favorable despite the complexity of these lesions, although multiple endovascular re-interventions may be necessary to achieve an acceptable long-term result.

C5-Alkyl-2-methylurea-Substituted Pyridines as a New Class of Glucokinase Activators.

Glucokinase (GK) activators represent a class of type 2 diabetes therapeutics actively pursued due to the central role that GK plays in regulating glucose homeostasis. Herein we report a novel C5-alkyl-2-methylurea-substituted pyridine series of GK activators derived from our previously reported thiazolylamino pyridine series. Our efforts in optimizing potency, enzyme kinetic properties, and metabolic stability led to the identification of compound 26 (AM-9514). This analogue showed a favorable combination of in vitro potency, enzyme kinetic properties, acceptable pharmacokinetic profiles in preclinical species, and robust efficacy in a rodent PD model.

Discovery of Disubstituted Imidazo[4,5-b]pyridines and Purines as Potent TrkA Inhibitors.

Trk receptor tyrosine kinases have been implicated in cancer and pain. A crystal structure of TrkA with AZ-23 (1a) was obtained, and scaffold hopping resulted in two 5/6-bicyclic series comprising either imidazo[4,5-b]pyridines or purines. Further optimization of these two fusion series led to compounds with subnanomolar potencies against TrkA kinase in cellular assays. Antitumor effects in a TrkA-driven mouse allograft model were demonstrated with compounds 2d and 3a.

Adapting the International System of Units to the twenty-first century.

We review the proposal of the International Committee for Weights and Measures (Comité International des Poids et Mesures, CIPM), currently being considered by the General Conference on Weights and Measures (Conférences Générales des Poids et Mesures, CGPM), to revise the International System of Units (Le Système International d'Unitès, SI). The proposal includes new definitions for four of the seven base units of the SI, and a new form of words to present the definitions of all the units. The objective of the proposed changes is to adopt definitions referenced to constants of nature, taken in the widest sense, so that the definitions may be based on what are believed to be true invariants. In particular, whereas in the current SI the kilogram, ampere, kelvin and mole are linked to exact numerical values of the mass of the international prototype of the kilogram, the magnetic constant (permeability of vacuum), the triple-point temperature of water and the molar mass of carbon-12, respectively, in the new SI these units are linked to exact numerical values of the Planck constant, the elementary charge, the Boltzmann constant and the Avogadro constant, respectively. The new wording used expresses the definitions in a simple and unambiguous manner without the need for the distinction between base and derived units. The importance of relations among the fundamental constants to the definitions, and the importance of establishing a mise en pratique for the realization of each definition, are also discussed.

Single-agent inhibition of Chk1 is antiproliferative in human cancer cell lines in vitro and inhibits tumor xenograft growth in vivo.

Chk1 is a serine/threonine kinase that plays several important roles in the cellular response to genotoxic stress. Since many current standard-of-care therapies for human cancer directly damage DNA or inhibit DNA synthesis, there is interest in using small molecule inhibitors of Chk1 to potentiate their clinical activity. Additionally, Chk1 is known to be critically involved in cell cycle progression of unperturbed cells. Therefore, it is plausible that treatment with a Chkl inhibitor alone could also be an efficacious cancer therapy. Here we report that Chk1-A, a potent and highly selective small molecule inhibitor of Chk1, is antiproliferative as a single agent in a variety of human cancer cell lines in vitro. The inhibition of proliferation is associated with collapse of DNA replication and apoptosis. Rapid decreases in inhibitory phosphorylation of CDKs and a concomitant increase in CDK kinase activity and chromatin loading of Cdc45 suggest that the antiproliferative and proapoptotic activity of Chk1-A is at least in part due to deregulation of DNA synthesis. We extend these in vitro studies by demonstrating that Chk1-A inhibits the growth of tumor xenografts in vivo in a treatment regimen that is well tolerated. Together, these results suggest that single-agent inhibition of Chk1 may be an effective treatment strategy for selected human malignancies.

Identification of 4-aminopyrazolylpyrimidines as potent inhibitors of Trk kinases.

The design, synthesis and biological evaluation of a series of 4-aminopyrazolylpyrimidines as potent Trk kinase inhibitors is reported. High-throughput screening identified a promising hit in the 4-aminopyrazolylpyrimidine chemotype. Initial optimization of the series led to more potent Trk inhibitors. Further optimization using two strategies resulted in significant improvement of physical properties and led to the discovery of 10z (AZ-23), a potent, orally bioavailable Trk A/B inhibitor. The compound offers the potential to test the hypothesis that modulation of Trk activity will be of benefit in the treatment of cancer and other indications in vivo.

Fundamental constants and tests of theory in Rydberg states of hydrogenlike ions.

A comparison of precision frequency measurements to quantum electrodynamics (QED) predictions for Rydberg states of hydrogenlike ions can yield information on values of fundamental constants and test theory. With the results of a calculation of a key QED contribution reported here, the uncertainty in the theory of the energy levels is reduced to a level where such a comparison can yield an improved value of the Rydberg constant.

Straight-edge diffraction of Planck radiation.

The irradiance diffraction profile of a straight edge is given as a Taylor series in powers of the distance from the geometrical shadow boundary to any point in the profile for monochromatic radiation. The coefficients of the series, which are obtained as simple analytic expressions, are proportional to the real part of a complex number whose phase cycles through a complete period every eight terms in the series. Integration of this series over a Planck distribution of radiation yields the power series for the Planck profile; this derived series has a finite radius of convergence. The asymptotic series for the Planck profile far from the shadow boundary and beyond the radius of convergence of its power series is obtained by analytic continuation of the power series with the aid of a Barnes type of integral representation.

Precise calculation of transition frequencies of hydrogen and deuterium based on a least-squares analysis.

We combine a limited number of accurately measured transition frequencies in hydrogen and deuterium, recent quantum electrodynamics (QED) calculations, and, as an essential additional ingredient, a generalized least-squares analysis, to obtain precise and optimal predictions for hydrogen and deuterium transition frequencies. Some of the predicted transition frequencies have relative uncertainties more than an order of magnitude smaller than that of the g factor of the electron, which was previously the most accurate prediction of QED.

The fundamental constants and theory.

The Committee on Data for Science and Technology has recently recommended a new self-consistent set of values of basic constants and conversion factors of physics and chemistry. These values are based on a least-squares analysis that takes into account all of the latest relevant experimental and theoretical information in a consistent framework. Theory plays a role, because the experimental data are compared to the corresponding theoretical predictions which are functions of the fundamental constants. The best values of the constants are taken to be those that give the best agreement between the data and these predictions, in the least-squares sense. An overview of the calculations that influence the recommended values of the constants will be given.

Asymptotic properties of self-energy coefficients.

We investigate the asymptotic properties of higher-order binding corrections to the one-loop self-energy of excited states in atomic hydrogen. We evaluate the historically problematic A60 coefficient for all P states with principal quantum numbers n

Total synthesis of (+)-phomactin a using a B-alkyl Suzuki macrocyclization.

A total synthesis of (+)-phomactin A is described using a B-alkyl Suzuki macrocyclization to incorporate the isolated trisubstituted olefin. This macrocyclization was accomplished with the sensitive hydrated furan ring in place. (R)-(+)-pulegone was used to establish the highly substituted cyclohexene core of the molecule.

Convergent enantioselective synthesis of the tricyclic core of phomactin A.

[reaction: see text] The tricyclic core of phomactin A was synthesized from 6,6-dimethyl-2-cyclohexen-1-one. Key reactions include the addition of a cyclohexenyllithium reagent to an epoxyaldehyde and a regioselective intramolecular epoxide opening to install the oxadecalin core.