Learning Ordinal Preferences on Multiattribute Domains: the Case of CP-nets

International audienceA recurrent issue in decision making is to extract a preference structure by observing the user's behavior in different situations. In this paper, we investigate the problem of learning ordinal preference orderings over discrete multi-attribute, or combinatorial, domains. Specifically, we focus on the learnability issue of conditional preference networks, or CP- nets, that have recently emerged as a popular graphical language for representing ordinal preferences in a concise and intuitive manner. This paper provides results in both passive and active learning. In the passive setting, the learner aims at finding a CP-net compatible with a supplied set of examples, while in the active setting the learner searches for the cheapest interaction policy with the user for acquiring the target CP-net

Preference-based Search using Example-Critiquing with Suggestions

We consider interactive tools that help users search for their most preferred item in a large collection of options. In particular, we examine example-critiquing, a technique for enabling users to incrementally construct preference models by critiquing example options that are presented to them. We present novel techniques for improving the example-critiquing technology by adding suggestions to its displayed options. Such suggestions are calculated based on an analysis of users current preference model and their potential hidden preferences. We evaluate the performance of our model-based suggestion techniques with both synthetic and real users. Results show that such suggestions are highly attractive to users and can stimulate them to express more preferences to improve the chance of identifying their most preferred item by up to 78%

Design and implementation of an active load test rig for high-precision evaluation of servomechanisms in industrial applications

Position-controlled servomechanisms are the core elements of flexible manufacturing plants, primarily utilized to actuate robotic systems and automated machines. To match specific torque and costs requirements, typical servomechanism arrangements comprise precision reducers, which introduce motion errors that heavily limit the final performance achievable. Such errors are complex to model and depend from speed, dynamic loading conditions and temperature. Accurate characterization is fundamental to develop digital twins and advanced control strategies aimed at their active prediction and compensation. To properly assess the servomechanisms behavior and elaborate high-fidelity virtual models, instrumented test rigs have been proposed which can replicate the time-varying working conditions encountered in real industrial environments. In this context, the present paper reports about a novel engineering method for developing an active loading apparatus, namely a programmable mechatronic device that can deliver custom loads in a highly dynamic manner. The proposed system, consisting of a secondary servomotor and related rotating vector reducer, is integrated and synchronized within an existing instrumented test rig and is controlled in torque mode via a programmable logic controller. The paper mainly focuses on the description of the implemented closed-loop control and on the related tuning and calibration processes, demonstrating that the proposed solutions avoid important measurement errors that could compromise the final effectiveness of the system. The study finally explores the potential benefits of introducing a filter to further enhance system performance. At last, to prove the importance of stabilizing the rig and demonstrate the influence of the control parameters on its measurements, a standard test aimed at assessing the reducer transmission error is conducted adopting different parameter settings

Targeted photoimmunotherapy for cancer

Photodynamic therapy (PDT) is a clinically approved procedure that can exert a curative action against malignant cells. The treatment implies the administration of a photoactive molecular species that, upon absorption of visible or near infrared light, sensitizes the formation of reactive oxygen species. These species are cytotoxic and lead to tumor cell death, damage vasculature, and induce inflammation. Clinical investigations demonstrated that PDT is curative and does not compromise other treatment options. One of the major limitations of the original method was the low selectivity of the photoactive compounds for malignant over healthy tissues. The development of conjugates with antibodies has endowed photosensitizing molecules with targeting capability, so that the compounds are delivered with unprecedented precision to the site of action. Given their fluorescence emission capability, these supramolecular species are intrinsically theranostic agents

A Double Payload Complex between Hypericin and All-trans Retinoic Acid in the β-Lactoglobulin Protein

Combined therapies are usually used to treat acne vulgaris since this approach can tackle various foci simultaneously. Using a combination of spectroscopic, computational, and microbiological techniques and methods, herein we report on the use of β-lactoglobulin as a double payload carrier of hypericin (an antimicrobial photodynamic agent) and all-trans retinoic acid (an anti-inflammatory drug) for S. aureus in vitro photodynamic inactivation. The addition of all-trans retinoic acid to hypericinβ-lactoglobulin complex renders a photochemically safe vehicle due to the photophysical quenching of hypericin, which recovers its photodynamic activity when in contact with bacteria. The ability of hypericin to photoinactivate S. aureus was not affected by retinoic acid. β-Lactoglobulin is a novel biocompatible and photochemically safe nanovehicle with strong potential for the treatment of acne

A photosensitizing fusion protein with targeting capabilities

The photodynamic treatment for antimicrobial applications or anticancer therapy relies on reactive oxygen species generated by photosensitizing molecules after absorption of visible or near-infrared light. If the photosensitizing molecule is in close vicinity of the microorganism or the malignant cell, a photocytotoxic action is exerted. Therefore, the effectiveness of photosensitizing compounds strongly depends on their capability to target microbial or cancer-specific proteins. In this study, we report on the preparation and preliminary characterization of human recombinant myoglobin fused to the vasoactive intestinal peptide to target vasoactive intestinal peptide receptor (VPAC) receptors. Fe-protoporphyrin IX was replaced by the photosensitizing compound Zn-protoporphyrin IX. Taking advantage of the fluorescence emission by Zn-protoporphyrin IX, we show that the construct can bind prostate cancer cells where the VPAC receptors are expressed

The Interaction of Hypericin with SARS-CoV-2 Reveals a Multimodal Antiviral Activity

Hypericin is a photosensitizing drug that is active against membrane-enveloped viruses and therefore constitutes a promising candidate for the treatment of SARS-CoV-2 infections. The antiviral efficacy of hypericin is largely determined by its affinity toward viral components and by the number of active molecules loaded on single viruses. Here we use an experimental approach to follow the interaction of hypericin with SARS-CoV-2, and we evaluate its antiviral efficacy, both in the dark and upon photoactivation. Binding to viral particles is directly visualized with fluorescence microscopy, and a strong affinity for the viral particles, most likely for the viral envelope, is measured spectroscopically. The loading of a maximum of approximately 30 molecules per viral particle is estimated, despite with marked heterogeneity among particles. Because of this interaction, nanomolar concentrations of photoactivated hypericin substantially reduce virus infectivity on Vero E6 cells, but a partial effect is also observed in dark conditions, suggesting multiple mechanisms of action for this drug

Structural bases for the regulation of CO binding in the archaeal protoglobin from Methanosarcina acetivorans

Studies of CO ligand binding revealed that two protein states with different ligand affinities exist in the protoglobin from Methanosarcina acetivorans (in MaPgb∗, residue Cys(E20)101 was mutated to Ser). The switch between the two states occurs upon the ligation of MaPgb∗. In this work, site-directed mutagenesis was used to explore the role of selected amino acids in ligand sensing and stabilization and in affecting the equilibrium between the "more reactive" and "less reactive" conformational states of MaPgb∗. A combination of experimental data obtained from electronic and resonance Raman absorption spectra, CO ligand-binding kinetics, and X-ray crystallography was employed. Three amino acids were assigned a critical role: Trp(60)B9, Tyr(61)B10, and Phe(93)E11. Trp(60)B9 and Tyr(61) B10 are involved in ligand stabilization in the distal heme pocket; the strength of their interaction was reflected by the spectra of the CO-ligated MaPgb∗and by the CO dissociation rate constants. In contrast, Phe(93)E11 is a key player in sensing the heme-bound ligand and promotes the rotation of the Trp(60)B9 side chain, thus favoring ligand stabilization. Although the structural bases of the fast CO binding rate constant of MaPgb∗are still unclear, Trp(60)B9, Tyr(61)B10, and Phe(93)E11 play a role in regulating heme/ligand affinity

Role of sortase-dependent pili of Bifidobacterium bifidum PRL2010 in modulating bacterium-host interactions

Bifidobacteria represent one of the dominant groups of microorganisms colonizing the human infant intestine. Commensal bacteria that interact with a eukaryotic host are believed to express adhesive molecules on their cell surface that bind to specific host cell receptors or soluble macromolecules. Whole-genome transcription profiling of Bifidobacterium bifidum PRL2010, a strain isolated from infant stool, revealed a small number of commonly expressed extracellular proteins, among which were genes that specify sortase-dependent pili. Expression of the coding sequences of these B. bifidum PRL2010 appendages in nonpiliated Lactococcus lactis enhanced adherence to human enterocytes through extracellular matrix protein and bacterial aggregation. Furthermore, such piliated L. lactis cells evoked a higher TNF-α response during murine colonization compared with their nonpiliated parent, suggesting that bifidobacterial sortase-dependent pili not only contribute to adherence but also display immunomodulatory activity