Synthesis, Biological Activity, and NMR-Based Structural Studies of Deltorphin I Analogs Modified in Message Domain with a New a,a-Disubstituted Glycines

This article describes new deltorphin I analogs in which phenylalanine residues were replaced by the corresponding (R) or (S)-a-benzyl-b-azidoalanine, a-benzyl-b- (1-pyrrolidinyl)alanine, a-benzyl-b-(1-piperidinyl)alanine, and a-benzyl-b-(4-morpholinyl)-alanine residues. The potency and selectivity of the new analogs were evaluated by a competitive receptor binding assay in the rat brain using [3H]DAMGO (a l ligand) and [3H]DELT (a d ligand). The affinity of analogs containing (R) or (S)-abenzyl- b-azidoalanine in position 3 to d-receptors strongly depended on the chirality of the a,a-disubstituted residue. The conformational behavior of peptides modified with (R) or (S)-a-benzyl-b-(1-piperidinyl)Ala, which displays the opposite selectivity, was analyzed by 1H and 13C NMR. The l-selective Tyr-D-Ala-(R)- a-benzyl-b-(1-piperidinyl)Ala-Asp-Val-Val-Gly-NH2 lacks the helical conformation observed in the d-selective Tyr- D-Ala-(S)-a-benzyl-b-(1-piperidinyl)Ala-Asp-Val-Val-Gly- NH2. Our results support the proposal that differences between d- and l-selective opioid peptides are attributable to the presence or absence of a spatial overlap between the N-terminal message domain and the C-terminal address domain

Testing the gravitational phenomenology of compact objects: superradiance, scalarization and screening mechanisms

In the last decades, an interesting variety of extended models of gravity has been proposed with the goal of capturing cosmological effects such as the accelerated phases of expansion and/or the so-called "dark sector" of our universe. In parallel, the quest for a full-fledged theory of quantum gravity proceeds by investigating the low-energy limit of candidate models. Many of these modified gravity models might leave imprints in the physics of compact objects and with gravitational-wave astronomy we have the unprecedented opportunity to test them against data with improving accuracy. A popular class of models (scalar-tensor theories) extends the field content of general relativity with an additional scalar field. These theories provide multiple examples where black hole and neutron star physics deviates from general relativity and can be constrained with observations. In this sense, superradiance and spontaneous growth of scalar fields around black holes and neutron stars are potentially detectable signatures of new physics. Screening mechanisms can in principle hide scalar effects, but their effectiveness in the strong-field regime is still largely unmodeled. In this thesis I briefly review the traditional tests of gravity, from the weak-field observations to gravitational-wave tests, before moving to discuss in details a collection of personal contributions in modeling the aforementioned scalar effects

Taming Reversible Halftoning via Predictive Luminance

Traditional halftoning usually drops colors when dithering images with binary dots, which makes it difficult to recover the original color information. We proposed a novel halftoning technique that converts a color image into a binary halftone with full restorability to its original version. Our novel base halftoning technique consists of two convolutional neural networks (CNNs) to produce the reversible halftone patterns, and a noise incentive block (NIB) to mitigate the flatness degradation issue of CNNs. Furthermore, to tackle the conflicts between the blue-noise quality and restoration accuracy in our novel base method, we proposed a predictor-embedded approach to offload predictable information from the network, which in our case is the luminance information resembling from the halftone pattern. Such an approach allows the network to gain more flexibility to produce halftones with better blue-noise quality without compromising the restoration quality. Detailed studies on the multiple-stage training method and loss weightings have been conducted. We have compared our predictor-embedded method and our novel method regarding spectrum analysis on halftone, halftone accuracy, restoration accuracy, and the data embedding studies. Our entropy evaluation evidences our halftone contains less encoding information than our novel base method. The experiments show our predictor-embedded method gains more flexibility to improve the blue-noise quality of halftones and maintains a comparable restoration quality with a higher tolerance for disturbances.Comment: to be published in IEEE Transactions on Visualization and Computer Graphic

Arg206 of SNAP-25 is essential for neuroexocytosis at the Drosophila melanogaster neuromuscular junction

An analysis of SNAP-25 isoform sequences indicates that there is a highly conserved arginine residue (198 in vertebrates, 206 in the genus Drosophila ) within the C-terminal region, which is cleaved by botulinum neurotoxin A, with consequent blockade of neuroexocytosis. The possibility that it may play an important role in the function of the neuroexocytosis machinery was tested at neuromuscular junctions of Drosophila melanogaster larvae expressing SNAP-25 in which Arg206 had been replaced by alanine. Electrophysiological recordings of spontaneous and evoked neurotransmitter release under different conditions as well as testing for the assembly of the SNARE complex indicate that this residue, which is at the P 1 ′ position of the botulinum neurotoxin A cleavage site, plays an essential role in neuroexocytosis. Computer graphic modelling suggests that this arginine residue mediates protein–protein contacts within a rosette of SNARE complexes that assembles to mediate the fusion of synaptic vesicles with the presynaptic plasma membrane