Machine-designed biotherapeutics: opportunities, feasibility and advantages of deep learning in computational antibody discovery.

Antibodies are versatile molecular binders with an established and growing role as therapeutics. Computational approaches to developing and designing these molecules are being increasingly used to complement traditional lab-based processes. Nowadays, in silico methods fill multiple elements of the discovery stage, such as characterizing antibody-antigen interactions and identifying developability liabilities.

Mutually unbiased bases and symmetric informationally complete measurements in Bell experiments.

Mutually unbiased bases (MUBs) and symmetric informationally complete projectors (SICs) are crucial to many conceptual and practical aspects of quantum theory. Here, we develop their role in quantum nonlocality by (i) introducing families of Bell inequalities that are maximally violated by -dimensional MUBs and SICs, respectively, (ii) proving device-independent certification of natural operational notions of MUBs and SICs, and (iii) using MUBs and SICs to develop optimal-rate and nearly optimal-rate protocols for device-independent quantum key distribution and device-independent quantum random number generation, respectively. Moreover, we also present the first example of an extremal point of the quantum set of correlations that admits physically inequivalent quantum realizations.

Self-Testing Entangled Measurements in Quantum Networks.

Self-testing refers to the possibility of characterizing an unknown quantum device based only on the observed statistics. Here we develop methods for self-testing entangled quantum measurements, a key element for quantum networks. Our approach is based on the natural assumption that separated physical sources in a network should be considered independent.

A universal test for gravitational decoherence.

Quantum mechanics and the theory of gravity are presently not compatible. A particular question is whether gravity causes decoherence. Several models for gravitational decoherence have been proposed, not all of which can be described quantum mechanically.

Analytic and Nearly Optimal Self-Testing Bounds for the Clauser-Horne-Shimony-Holt and Mermin Inequalities.

Self-testing refers to the phenomenon that certain extremal quantum correlations (almost) uniquely identify the quantum system under consideration. For instance, observing the maximal violation of the Clauser-Horne-Shimony-Holt (CHSH) inequality certifies that the two parties share a singlet. While self-testing results are known for several classes of states, in many cases they are only applicable if the observed statistics are almost perfect, which makes them unsuitable for practical applications.

Practical Relativistic Bit Commitment.

Bit commitment is a fundamental cryptographic primitive in which Alice wishes to commit a secret bit to Bob. Perfectly secure bit commitment between two mistrustful parties is impossible through an asynchronous exchange of quantum information. Perfect security is, however, possible when Alice and Bob each split into several agents exchanging classical information at times and locations suitably chosen to satisfy specific relativistic constraints.

Equivalence of wave-particle duality to entropic uncertainty.

Interferometers capture a basic mystery of quantum mechanics: a single particle can exhibit wave behaviour, yet that wave behaviour disappears when one tries to determine the particle's path inside the interferometer. This idea has been formulated quantitatively as an inequality, for example, by Englert and Jaeger, Shimony and Vaidman, which upper bounds the sum of the interference visibility and the path distinguishability. Such wave-particle duality relations (WPDRs) are often thought to be conceptually inequivalent to Heisenberg's uncertainty principle, although this has been debated.

Experimental bit commitment based on quantum communication and special relativity.

Bit commitment is a fundamental cryptographic primitive in which Bob wishes to commit a secret bit to Alice. Perfectly secure bit commitment between two mistrustful parties is impossible through asynchronous exchange of quantum information. Perfect security is however possible when Alice and Bob split into several agents exchanging classical and quantum information at times and locations suitably chosen to satisfy specific relativistic constraints.

Dual oxidase2 is expressed all along the digestive tract.

The dual oxidase (Duox)2 flavoprotein is strongly expressed in the thyroid gland, where it plays a critical role in the synthesis of thyroid hormones by providing thyroperoxidase with H2O2. DUOX2 mRNA was recently detected by RT-PCR and in-situ hybridization experiments in other tissues, such as rat colon and rat and human epithelial cells from the salivary excretory ducts and rectal glands. We examined Duox2 expression at the protein level throughout the porcine digestive tract and in human colon.

Iodotyrosine dehalogenase 1 (DEHAL1) is a transmembrane protein involved in the recycling of iodide close to the thyroglobulin iodination site.

In the thyroid, iodotyrosine dehalogenase acts on the mono and diiodotyrosines released during the hydrolysis of thyroglobulin to liberate iodide, which can then reenter the hormone-producing pathways. It has been reported that the deiodination of iodotyrosines occurs predominantly in the microsomes and is mediated by NADPH. Recently, two cDNAs, 7401- and 7513-base pairs long that encode proteins with a conserved nitroreductase domain were published in GenBank as iodotyrosine dehalogenase 1 (DEHAL1) and iodotyrosine dehalogenase 1B (DEHAL1B), respectively.

Targeting of the dual oxidase 2 N-terminal region to the plasma membrane.

Dual oxidase 2 (Duox2) is a cell surface glycoprotein that probably provides thyroperoxidase with the H2O2 required to catalyze thyroid hormone synthesis. No functional H2O2-generating system has yet been obtained after transfecting Duox2 into non-thyroid cell lines, because it is retained in the endoplasmic reticulum (ER). We investigated the level of maturation of various Duox2 truncated proteins in an attempt to identify the region of Duox2 responsible for its remaining in the ER.

Identification of a truncated dual oxidase 2 (DUOX2) messenger ribonucleic acid (mRNA) in two rat thyroid cell lines. Insulin and forskolin regulation of DUOX2 mRNA levels in FRTL-5 cells and porcine thyrocytes.

The Duox2 flavoprotein is strongly expressed in the thyroid gland, where it plays a critical role in the synthesis of thyroid hormones likely by providing thyroperoxidase with H(2)O(2). A truncated DUOX2 mRNA was isolated from the rat thyroid cell line FRTL-5. The cDNA sequence predicted an open reading frame of 1458 bp, encoding a polypeptide of 486 amino acids corresponding to the carboxyl fragment of the Duox2 flavoprotein.

Solubilization and characterization of a thyroid Ca(2+)-dependent and NADPH-dependent K3Fe(CN)6 reductase. Relationship with the NADPH-dependent H2O2-generating system.

The thyroid plasma membrane contains a Ca(2+)-regulated NADPH-dependent H2O2-generating system which provides H2O2 for the thyroid-peroxidase-catalyzed biosynthesis of thyroid hormones. The molecular nature of the membrane-associated electron transport chain that generates H2O2 in the thyroid is unknown, but recent observations indicate that a flavoprotein containing a FAD prosthetic group is involved. Solubilization was reinvestigated using 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (Chaps), Triton X-100, and high salt concentrations.

Activation of the NADPH-dependent H2O2-generating system in pig thyroid particulate fraction by limited proteolysis and Zn2+ treatment.

The NADPH-dependent H2O2-generating system in a pig thyroid particulate fraction requires micromolar concentrations of Ca2+ for activity. The H2O2 generator could be Ca(2+)-desensitized (i.e.

Effect of N-glycan removal on the enzymatic activity of porcine thyroid peroxidase.

Active porcine thyroid peroxidase (pTPO) has been purified either by deoxycholate extraction followed by immunoaffinity purification (pTPO A) or by trypsin/digitonin extraction followed by ion-exchange and gelfiltration chromatography (pTPO B); pTPO A appeared as a full-length molecule, while pTPO B appeared as peptide fragments. Purified pTPO were deglycosylated either by peptide N-glycosidase F (PNGase F) or by endo-beta-N-acetylglucosaminidase H (endo H) treatment. Electrophoretic controls and affinity blotting with concanavalin A indicated that deglycosylation was not total and that pTPO was more efficiently deglycosylated by endo H than by PNGase F.

Mechanism of NADPH oxidation catalyzed by horse-radish peroxidase and 2,4-diacetyl-[2H]heme-substituted horse-radish peroxidase.

The mechanism of NADPH oxidation catalyzed by horse-radish peroxidase (HRP) and 2,4-diacetyl-[2H]heme-substituted horse-radish peroxidase (DHRP) was studied. The roles of the different H2O2/peroxidase compounds were examined by spectral studies. The oxidized NADPH species were identified using the superoxide dismutase effect and by measuring the stoichiometry between NADPH oxidized and H2O2 used.

Mechanism of hydrogen peroxide formation catalyzed by NADPH oxidase in thyroid plasma membrane.

The thyroid plasma membrane contains a Ca2(+)-regulated NADPH-dependent H2O2 generating system which provides H2O2 for the thyroid peroxidase-catalyzed biosynthesis of thyroid hormones. The plasma membrane fraction contains a Ca2(+)-independent cytochrome c reductase activity which is not inhibited by superoxide dismutase. But it is not known whether H2O2 is produced directly from molecular oxygen (O2) or formed via dismutation of super-oxide anion (O2-).

Nonenzymatic NADPH-dependent reduction of 2,6-dichlorophenol-indophenol.

The reduction of 2,6-dichloroindophenol (DCIP) by direct interaction with NADPH was studied. The results indicate that reduction proceeds via a direct electron transfer from NADPH to DCIP, with no oxygen consumption, and a rate constant of k = 4.69 M-1.

NADPH-dependent H2O2 generation catalyzed by thyroid plasma membranes. Studies with electron scavengers.

Hog thyroid plasma membrane preparations containing a Ca2+-regulated NADPH-dependent H2O2-generating system were studied. The Ca2+-dependent reductase activities of ferricytochrome c, 2,6-dichloroindophenol, nitroblue tetrazolium, and potassium ferricyanide were tested and the effect of these scavengers on H2O2 formation, NADPH oxidation and O2 consumption were measured, with the following results. 1.

Ca2+ regulation of thyroid NADPH-dependent H2O2 generation.

A thyroid particulate fraction contains an NADPH-dependent H2O2-generating enzyme which requires Ca2+ for activity. A Chaps solubilized extract of the thyroid particulate fraction partially purified by DEAE chromatography did not show a dependence on Ca2+ for activity. Preincubation of the particulate fraction with Ca2+ yielded a preparation insensitive to Ca2+.

Solubilization and characteristics of the thyroid NADPH-dependent H2O2 generating system.

Solubilization of the thyroid particulate-associated NADPH-dependent H2O2 generating system has been tested with different detergents; (3-(3-cholamidopropyl)-dimethylammonio)1-propane sulfonate (CHAPS) was found to be the best of the six detergents tested. The ratio of H2O2 generation to NADPH oxidation was similar for CHAPS extract and native particulate material. CHAPS was also the only detergent able to preserve the Ca++-sensitivity of the NADPH oxidase.

Spectral characteristics and catalytic properties of thyroid peroxidase-H2O2 compounds in the iodination and coupling reactions.

Hog thyroid peroxidase (TPO) was highly purified in order to study the spectral properties and catalytic specificities of its H2O2 compounds in iodothyronine biosynthesis. Purified TPO exhibited a Soret spectrum with an absorption maximum at 410 nm and had an A410/A280 value of 0.55.

NADPH-dependent H2O2 generation and peroxidase activity in thyroid particular fraction.

A NADPH-dependent H2O2 generating system associated with a thyroid particular fraction is described. H2O2 is measured by two different methods: iodination of NADPH itself when the system is supplemented with lactoperoxidase and [125I]iodide, and by the scopoletin method. It is shown that: H2O2 generation is inhibited by catalase and is dependent on NADPH or particulate protein concentration; radical scavengers of OH and of singlet oxygen have no effect while superoxide dismutase has only a marginal effect; disruption of the particular fraction by phospholipase A2 or digitonin treatment completely abolished H2O2 generation activity while thyroid peroxidase activity appears, suggesting different sites for the two activities in the membrane vesicles.