Bounded rationality

We study concentration operators associated with either the discrete or the continuous Fourier transform, that is, operators that incorporate a spatial cut-off and a subsequent frequency cut-off to the Fourier inversion formula. The spectral profiles of these operators describe the number of prominent degrees of freedom in problems where functions are assumed to be supported on a certain domain and their Fourier transforms are known or measured on a second domain. We derive eigenvalue estimates that quantify the extent to which Fourier concentration operators deviate from orthogonal projectors, by bounding the number of eigenvalues that are away from 0 and 1 in terms of the geometry of the spatial and frequency domains, and a factor that grows at most poly-logarithmically on the inverse of the spectral margin...

PURPOSE: Accurately locating and analysing surgical instruments in laparoscopic surgical videos can assist doctors in postoperative quality assessment. This can provide patients with more scientific and rational solutions for healing surgical complications. Therefore, we propose an end-to-end algorithm for the detection of surgical instruments. METHODS: Dual-Branched Head (DBH) and Overall Intersection over Union Loss (OIoU Loss) are introduced to solve the problem of inaccurate surgical instrument detection, both in terms of localization and classification...

INTRODUCTION: Patient satisfaction is a crucial metric to gauge the quality of medical services, but the psychological factors influencing patient satisfaction remain insufficiently explored. METHODS: This study examines these psychological factors by applying the theory of bounded rationality to 1,442 inpatients in Hangzhou, China, whose data were collected using a questionnaire. One-way ANOVA, correlation analysis, and hierarchical regression were used to analyze patient satisfaction and its associated factors...

Allostery is an essential biological phenomenon in which perturbation at one site in a biomolecule elicits a functional response at a distal location(s). It is integral to biological processes, such as cellular signaling, metabolism, and transcription regulation. Understanding allostery is also crucial for rational drug discovery. In this work, we focus on an allosteric S100B protein that belongs to the S100 class of EF-hand Ca2+ -binding proteins. The Ca2+ -binding affinity of S100B is modulated allosterically by TRTK-12 peptide binding 25 Å away from the Ca2+ -binding site...

Communities face the challenge of finding restoration strategies in the aftermath of disasters. In particular, independent and self-interested utility managers devise such strategies for infrastructure through a heuristic decentralized process. This paper takes a game-theoretic approach to model the decentralized and strategic restoration decision making with application to interdependent infrastructure. Particularly, we model the decision process using simultaneous games to investigate decision makers' conflicting preferences...

The next generation of anticancer agents are emerging from rationally designed nanostructured materials. This work involved the synthesis and characterization of novel hollow DNA-conjugated gold nanoparticles (DNA-AuNPs) for controlled drug delivery. Polyethyleneimine (PEI) was bound to AuNPs, forming polymer-shell nanoparticles. Dissolution of the gold core via iodine formed hollow core polymeric nanoparticles (HCPNPs) and a high density (85 molecules/particle) of DNA intercalated with daunorubicin was conjugated...

Previous mass spectrometric (MS) studies demonstrated that singly charged hydration clusters of manganese ions [Mn(H2 O) n ]+ were, on one hand, highly reactive toward intracluster water insertion but, on the other hand, inert toward nitrous oxide activation. This contrast in reactivity has been rationalized by our present theoretical investigation for the interconversion between the pristine Mn(I) monovalent form as a monatomic ion in [MnI (H2 O) n ]+ and the oxidized Mn(III) trivalent form as a hydride-hydroxide in [HMnIII OH(H2 O) n -1 ], as well as their reactivity toward nitrous oxide activation...

PI3Kα is a lipid kinase that phosphorylates PIP2 and generates PIP3. The hyperactive PI3Kα mutation, H1047R, accounts for about 14% of breast cancer, making it a highly attractive target for drug discovery. Here, we report the cryo-EM structures of PI3KαH1047R bound to two different allosteric inhibitors QR-7909 and QR-8557 at a global resolution of 2.7 Å and 3.0 Å, respectively. The structures reveal two distinct binding pockets on the opposite sides of the activation loop...

Fungal paracyclophane-decahydrofluorene-containing natural products are complex polycyclic metabolites derived from similar hybrid PKS-NRPS pathways. Herein we studied the biosynthesis of pyrrocidines, one representative of this family, by gene inactivation in the producer Sarocladium zeae coupled to thorough metabolic analysis and molecular modeling of key enzymes. We characterized nine pyrrocidines and analogues as well as in mutants a variety of accumulating metabolites with new structures including rare cis -decalin, cytochalasan, and fused 6/15/5 macrocycles...

The intramolecular Stetter reaction catalyzed by a carbene is investigated by density functional theory (DFT) calculations and kinetic simulations. Catalyst 1 first reacts with aldehyde 2 to give the primary adduct (PA). The PA undergoes the intramolecular oxa-Michael reaction to irreversibly generate enol ether intermediate 9. The conversion of the enol ether to the Breslow intermediate (BI) requires the assistance of a base such as the PA. The next step involves formation of a carbon-carbon bond through the Michael addition, and expulsion of the catalyst generates the Stetter product 7...

Despite the central role that antibodies play in modern medicine, there is currently no way to rationally design novel antibodies to bind a specific epitope on a target. Instead, antibody discovery currently involves time-consuming immunization of an animal or library screening approaches. Here we demonstrate that a fine-tuned RFdiffusion network is capable of designing de novo antibody variable heavy chains (VHH's) that bind user-specified epitopes. We experimentally confirm binders to four disease-relevant epitopes, and the cryo-EM structure of a designed VHH bound to influenza hemagglutinin is nearly identical to the design model both in the configuration of the CDR loops and the overall binding pose...

Following a comparison of nutrient total-tract digestibility estimates in lactating buffaloes using single-point undigestible NDF (uNDF) or acid-insoluble ash (AIA) as internal markers, the potential of fecal near-infrared spectroscopy (NIRS) to provide calibration equations for the assessment of the chemical composition of feces and nutrient total-tract digestibility estimated with internal markers was explored. Chemical analyses were performed on 147 fecal samples from lactating buffaloes reared in 5 farms in central Italy (Naples)...

Pharmacological modulation of RNA splicing by small molecules is an emerging facet of drug discovery. In this context, the SMN2 splicing modifier SMN-C5 was used as a prototype to understand the mode of action of small molecule splicing modifiers and propose the concept of 5'-splice site bulge repair. In this study, we combined in vitro binding assays and structure determination by NMR spectroscopy to identify the binding modes of four other small molecule splicing modifiers that switch the splicing of either the SMN2 or the HTT gene...

The synergistic regulation of the multi-functional sites on one receptor molecule with different cationic effectors for anion recognition is scarce to be well understood from the experiment and theory. In this work, a new anion receptor with three functional zones including ether hole, biurea and double bipyridine groups (EUPR) is designed expecting to enhance the chloride anion recognition together with a rational synthesis path being proposed based on four simple and mature organic reaction steps. The conformational structures of the designed receptor EUPR and the binding behaviors for three kinds of ions (Cl- , Na+ , and Ag+ ) are deeply investigated by using density functional theoretical calculations...

While pancreatic ductal adenocarcinomas (PDACs) are addicted to KRAS-activating mutations, inhibitors of downstream KRAS effectors, such as the MEK1/2 kinase inhibitor trametinib, are devoid of therapeutic effects. However, the extensive rewiring of regulatory circuits driven by the attenuation of the KRAS pathway may induce vulnerabilities of therapeutic relevance. An in-depth molecular analysis of the transcriptional and epigenomic alterations occurring in PDAC cells in the initial hours after MEK1/2 inhibition by trametinib unveiled the induction of endogenous retroviruses (ERVs) escaping epigenetic silencing, leading to the production of double-stranded RNAs and the increased expression of interferon (IFN) genes...

Mastering selective molecule trafficking across human cell membranes poses a formidable challenge in healthcare biotechnology while offering the prospect of breakthroughs in drug delivery, gene therapy, and diagnostic imaging. The cholera toxin B-subunit (CTB) has the potential to be a useful cargo transporter for these applications. CTB is a robust protein that is amenable to reengineering for diverse applications; however, protein redesign has mostly focused on modifications of the N- and C-termini of the protein...

Life-threatening systemic fungal infections occur in immunocompromised patients at an alarming rate. Current antifungal therapies face challenges like drug resistance and patient toxicity, emphasizing the need for new treatments. Membrane-bound enzymes account for a large proportion of current and potential antifungal targets, especially ones that contribute to cell wall and cell membrane biosynthesis. Moreover, structural biology has led to a better understanding of the mechanisms by which these enzymes synthesize their products, as well as the mechanism of action for some antifungals...

Over the past two decades, there has been growing interest in developing catalysts to enable Haber-Bosch ammonia synthesis under milder conditions than currently pertain. Rational catalyst design requires theoretical guidance and clear mechanistic understanding. Recently, a spin-mediated promotion mechanism was proposed to activate traditionally unreactive magnetic materials such as cobalt (Co) for ammonia synthesis by introducing hetero metal atoms bound to the active site of the catalyst surface. We combined theory and experiment to validate this promotion mechanism on a lanthanum (La)/Co system...

The histamine H4 receptor (H4 R) plays key role in immune cell function and is a highly valued target for treating allergic and inflammatory diseases. However, structural information of H4 R remains elusive. Here, we report four cryo-EM structures of H4 R/Gi complexes, with either histamine or synthetic agonists clobenpropit, VUF6884 and clozapine bound. Combined with mutagenesis, ligand binding and functional assays, the structural data reveal a distinct ligand binding mode where D943.32 and a π-π network determine the orientation of the positively charged group of ligands, while E1825...

Cellular entry of the hepatitis B and D viruses (HBV/HDV) requires binding of the viral surface polypeptide preS1 to the hepatobiliary transporter Na+ -taurocholate co-transporting polypeptide (NTCP). This interaction can be blocked by bulevirtide (BLV, formerly Myrcludex B), a preS1 derivative and approved drug for treating HDV infection. Here, to elucidate the basis of this inhibitory function, we determined a cryo-EM structure of BLV-bound human NTCP. BLV forms two domains, a plug lodged in the bile salt transport tunnel of NTCP and a string that covers the receptor's extracellular surface...