Synthesis and biological evaluation of benzodiazepines containing a pentafluorosulfanyl group

The widely used pentafluorosulfanyl group (SF5) was deployed as a bioisosteric replacement for a chloro-group in the benzodiazepine diazepam (Valium™). Reaction of 2-amino-5-pentafluorosulfanyl-benzophenone with chloroacetyl chloride followed by hexamethylenetetramine, in the presence of ammonia, led to 7-sulfurpentafluoro-5-phenyl-1H-benzo[1,4]diazepin-2(3H)-one (2c). The latter was able to undergo a Pd-catalysed ortho-arylation, demonstrating that these highly fluorinated benzodiazepines can be further modified to form more complicated scaffolds. The replacement of Cl by the SF5 group, led to a loss of potency for potentiating GABAA receptor activation, most likely because of a lost ligand interaction with His102 in the GABAA receptor α subunit. Dedicated to Professor Jonathan Williams, an inspirational and humble pioneer, a colleague and mentor in chemistry

Expectations of the Size Evolution of Massive Galaxies at 3 ≤ z ≤ 6 from the TNG50 Simulation: The CEERS/JWST View

Abstract We present a catalog of about 25,000 images of massive (M ⋆ ≥ 109 M ⊙) galaxies at redshifts 3 ≤ z ≤ 6 from the TNG50 cosmological simulation, tailored for observations at multiple wavelengths carried out with JWST. The synthetic images were created with the SKIRT radiative transfer code, including the effects of dust attenuation and scattering. The noiseless images were processed with the mirage simulator to mimic the Near Infrared Camera (NIRCam) observational strategy (e.g., noise, dithering pattern, etc.) of the Cosmic Evolution Early Release Science (CEERS) survey. In this paper, we analyse the predictions of the TNG50 simulation for the size evolution of galaxies at 3 ≤ z ≤ 6 and the expectations for CEERS to probe that evolution. In particular, we investigate how sizes depend on the wavelength, redshift, mass, and angular resolution of the images. We find that the effective radius accurately describes the three-dimensional half-mass–radius of the TNG50 galaxies. Sizes observed at 2 μm are consistent with those measured at 3.56 μm at all redshifts and masses. At all masses, the population of higher-z galaxies is more compact than their lower-z counterparts. However, the intrinsic sizes are smaller than the mock observed sizes for the most massive galaxies, especially at z ≲ 4. This discrepancy between the mass and light distributions may point to a transition in the galaxy morphology at z = 4–5, where massive compact systems start to develop more extended stellar structures. 22 22 Data publicly released at https://www.tng-project.org/costantin22. </jats:p

Identifying Galaxy Mergers in Simulated CEERS NIRCam Images Using Random Forests

Abstract Identifying merging galaxies is an important—but difficult—step in galaxy evolution studies. We present random forest (RF) classifications of galaxy mergers from simulated JWST images based on various standard morphological parameters. We describe (a) constructing the simulated images from IllustrisTNG and the Santa Cruz SAM and modifying them to mimic future CEERS observations and nearly noiseless observations, (b) measuring morphological parameters from these images, and (c) constructing and training the RFs using the merger history information for the simulated galaxies available from IllustrisTNG. The RFs correctly classify ∼60% of non-merging and merging galaxies across 0.5 &lt; z &lt; 4.0. Rest-frame asymmetry parameters appear more important for lower-redshift merger classifications, while rest-frame bulge and clump parameters appear more important for higher-redshift classifications. Adjusting the classification probability threshold does not improve the performance of the forests. Finally, the shape and slope of the resulting merger fraction and merger rate derived from the RF classifications match with theoretical Illustris predictions but are underestimated by a factor of ∼0.5.</jats:p

Identifying Galaxy Mergers in Simulated CEERS NIRCam Images Using Random Forests

Abstract Identifying merging galaxies is an important—but difficult—step in galaxy evolution studies. We present random forest (RF) classifications of galaxy mergers from simulated JWST images based on various standard morphological parameters. We describe (a) constructing the simulated images from IllustrisTNG and the Santa Cruz SAM and modifying them to mimic future CEERS observations and nearly noiseless observations, (b) measuring morphological parameters from these images, and (c) constructing and training the RFs using the merger history information for the simulated galaxies available from IllustrisTNG. The RFs correctly classify ∼60% of non-merging and merging galaxies across 0.5 &lt; z &lt; 4.0. Rest-frame asymmetry parameters appear more important for lower-redshift merger classifications, while rest-frame bulge and clump parameters appear more important for higher-redshift classifications. Adjusting the classification probability threshold does not improve the performance of the forests. Finally, the shape and slope of the resulting merger fraction and merger rate derived from the RF classifications match with theoretical Illustris predictions but are underestimated by a factor of ∼0.5.</jats:p

Do we have a moral responsibility to compensate for vulnerable groups? A discussion on the right to health for LGBT people

Vulnerability is a broad concept widely addressed in recent scholarly literature. Lesbian, gay, bisexual, and transgender (LGBT) people are among the vulnerable populations with significant disadvantages related to health and the social determinants of health. Medical ethics discourse tackles vulnerability from philosophical and political perspectives. LGBT people experience several disadvantages from both perspectives. This article aims to justify the right to health for LGBT people and their particular claims regarding healthcare because they belong to a vulnerable group. Rawls' theory of justice and Norman Daniels' normal functioning approach will be discussed in this context. Despite the fact that the right to health can be justified by Daniels' normal functioning approach, there is still a theoretical gap in justifying the right to health for particular vulnerable populations such as LGBT peopleand discussing society's duty to compensate for these disadvantages. In search of solid theoretical grounds for the justification of the right to health for LGBT people, the present author takes the opportunity to utilize Daniels' flexible definition of normal functioning to show that normal functioning not only varies by age but also by different states of human existence, including sexual orientation and gender identity, and to propose replacing the life span approach with normal states of human existence