A practical synthesis of SGLT2 inhibitor candidate ertugliflozin (1) has been developed for potential commercial application. The highly telescoped process involves only three intermediate isolations ...over a 12-step sequence. The dioxa-bicyclo3.2.1octane motif is prepared from commercially available 2,3,4,6-tetra-O-benzyl-d-glucose, with nucleophilic hydroxymethylation of a 5-ketogluconamide intermediate as a key step. The aglycone moiety is introduced via aryl anion addition to a methylpiperazine amide. High chemical purity of the API is assured through isolation of the crystalline penultimate intermediate, tetraacetate 39. A cocrystalline complex of the amorphous solid 1 with l-pyroglutamic acid has been prepared in order to improve the physical properties for manufacture and to ensure robust API quality.
In this Letter we report on the results of our search for photons from a U(1) gauge factor in the hidden sector of the full theory. With our experimental setup we observe the single spectrum in a ...HPGe detector arising as a result of the photoelectric-like absorption of hidden photons emitted from the Sun on germanium atoms inside the detector. The main ingredient of the theory used in our analysis, a severely constrained kinetic mixing from the two U(1) gauge factors and massive hidden photons, entails both photon into hidden state oscillations and a minuscule coupling of hidden photons to visible matter, of which the latter our experimental setup has been designed to observe. On a theoretical side, full account was taken of the effects of refraction and damping of photons while propagating in Sunʼs interior as well as in the detector. We exclude hidden photons with kinetic couplings χ>(2.2×10−13–3×10−7) in the mass region 0.2 eV≲mγ′≲30 keV. Our constraints on the mixing parameter χ in the mass region from 20 eV up to 15 keV prove even slightly better then those obtained recently by using data from the CAST experiment, albeit still somewhat weaker than those obtained from solar and HB stars lifetime arguments.
There is a paucity of data regarding respiratory health in restorers of cultural heritage or similar occupations, such as visual artists or museum workers, although they are exposed to a complex ...mixture of various respiratory hazards.
To evaluate atopy and respiratory health parameters, including bronchial and nasal non-specific reactivity, in restorers and conservators of cultural heritage (restorers).
Fifty-six restorers and 62 controls provided general data and data on ever experienced rhinitic or asthma-like symptoms, spirometry, non-specific bronchial and nasal responsiveness to histamine, skin prick testing to common inhalational allergens and serum total IgE levels.
Spirometry values were in the range of normal values in 55 of 56 restorers and did not differ significantly from those in control subjects. However, restorers had more than two times higher prevalence of nasal hyper-responsiveness (NHR), with 2.3 times higher risk of NHR compared to controls 95% confidence interval (CI): 1.4-3.6, P < 0.001. The risk of NHR was slightly reduced by increasing age (odds ratio 0.95, 95% CI: 0.91-0.99, P < 0.05). NHR was not associated with gender, smoking status, bronchial hyperresponsiveness (BHR), upper or lower respiratory symptoms or atopy status.
Compared with controls, the studied group of workers occupationally exposed to respiratory hazards during restoration/conservation activities had no deterioration of lung function but had an increased non-specific nasal responsiveness that was not correlated with upper and lower respiratory symptoms, BHR or atopy. The relationship of this finding to future clinical outcome should be investigated in a longitudinal study.
In the process of nuclear excitation in positron-electron annihilation (NEPEA) experimental results have been found to be larger than theoretical predictions. In our previous works we have analyzed ...the NEPEA experimental data for 1078 keV in In and for 1330 keV in Cd, respectively, by applying our model of indistinguishable quantum oscillators. In the present work we extend this model to estimate the cross section of nuclear excitation in positron-electron annihilation for Lu from the experimentally measured effective cross section of sigma = (2.6+/-0.9)*10 cm. The estimated NEPEA cross section of sigma=2.7*10 cm is in very good agreement with that of the theoretical prediction sigma =2.2*10 cm.
We made a search for hadronic axions which could be emitted from the Sun in M1 transitions between the first 14.4 keV thermally excited and the ground state in 57Fe, and absorbed in the HPGe detector ...by axioelectric effect. An upper limit on hadronic axion mass of 400 eV is obtained at the 95% confidence level.
Hypothetical low-mass particles, such as axions, provide a compelling explanation for the dark matter in the universe. Such particles are expected to emerge abundantly from the hot interior of stars. ...To test this prediction, the CERN Axion Solar Telescope (CAST) uses a 9 T refurbished Large Hadron Collider test magnet directed towards the Sun. In the strong magnetic field, solar axions can be converted to X-ray photons which can be recorded by X-ray detectors. In the 2013-2015 run, thanks to low-background detectors and a new X-ray telescope, the signal-to-noise ratio was increased by about a factor of three. Here, we report the best limit on the axion-photon coupling strength (0.66 × 10-10 GeV-1 at 95% confidence level) set by CAST, which now reaches similar levels to the most restrictive astrophysical bounds.
In this experiment we aim to look for keV-mass bosons emitted from the Sun, by looking at a process analogous to the photoelectric/Compton effect inside the HPGe detector. Their coupling to both ...electrons and nucleons is assumed. For masses above 25 keV, the mass dependence of our limit on the scalar-electron coupling reveals a constraint which proves stronger than that obtained recently and based on the very good agreement between the measured and predicted solar neutrino flux from the 8B reaction. On the other hand, the mass dependence of our limit on the scalar-proton/electron coupling together entails a limit on a possible Yukawa addition to the gravitational inverse square low. Such a constraint on the Yukawa interactions proves much stronger than that derived from the latest AFM Casimir force measurement.
We have searched for hadronic axions which may be produced in the Sun by a bremsstrahlung-like process, and observed in the HPGe detector by an axioelectric effect. A conservative upper limit on the ...hadronic axion mass of ma≲334 eV at 95% C.L. is obtained. Our experimental approach is based on the axion–electron coupling and it does not include the axion–nucleon coupling, which suffers from the large uncertainties related to the estimation of the flavor-singlet axial-vector matrix element.
A
bstract
The OPERA experiment has discovered the tau neutrino appearance in the CNGS muon neutrino beam, in agreement with the 3 neutrino flavour oscillation hypothesis. The OPERA neutrino ...interaction target, made of Emulsion Cloud Chambers, was particularly efficient in the reconstruction of electromagnetic showers. Moreover, thanks to the very high granularity of the emulsion films, showers induced by electrons can be distinguished from those induced by
π
0
s, thus allowing the detection of charged current interactions of electron neutrinos. In this paper the results of the search for electron neutrino events using the full dataset are reported. An improved method for the electron neutrino energy estimation is exploited. Data are compatible with the 3 neutrino flavour mixing model expectations and are used to set limits on the oscillation parameters of the 3+1 neutrino mixing model, in which an additional mass eigenstate
m
4
is introduced. At high Δ
m
41
2
(≳0.1 eV
2
), an upper limit on sin
2
2
θ
μe
is set to 0.021 at 90% C.L. and Δ
m
41
2
≳ 4 × 10
− 3
eV
2
is excluded for maximal mixing in appearance mode.
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