Talk to us about your skin: The relationship between spoken language and haptic exploratory procedures.

OBJECTIVE: To enhance satisfaction, the cosmetics industry needs to clearly understand consumers' descriptions of their key tactile preferences. It is difficult for researchers to understand verbal descriptions from people whose native language is different from their own. Previous research has implied that some sensory words with the same lexical meanings have been observed in different haptic exploratory procedures (HEPs). Therefore, our study aims to investigate and understand the key tactile perceptions of people from five different countries based on their descriptions and their HEPs. METHODS: In Experiment 1, 1545 participants living in the US, Japan, China, Italy, and Thailand described their major tactile perceptions as efficacy in skincare, and we analysed the frequency of each word used in their answers. In Experiment 2, we confirmed the task to observe HEPs for Chinese, Italian, and Thai participants. A total of 24 participants in China, 33 participants in Italy, and 30 participants in Thailand freely explored their faces with their hands and answered which side more closely matched the major tactile adjectives. Experts classified the observed HEPs into six classifications within two categories and three contact area sizes and investigated the cultural differences. RESULTS: More than 2% of the Chinese, Italian, Thai, US, and Japanese participants described 33, 20, 29, 22, and 18 words, respectively, as efficacy in skincare. Verified words that described the major tactile perceptions in each native language had the same meanings as moistness, firmness, softness, smoothness, and so on. We could confirm the HEPs of these major feelings for the participants from each culture. Chinese and Thai participants' HEPs for moistness or softness were observed with a pressing movement. Conversely, Italian participants' HEPs for moistness or softness were observed with a rubbing movement. CONCLUSION: This study showed that words with the same lexical meanings evoked different HEPs. The results imply that different HEPs can provide different physical stimuli on the skin. Therefore, it is important to survey both objects and HEPs to better understand the tactile experience.

OBJECTIF: Pour améliorer la satisfaction, l'industrie cosmétique doit bien comprendre les descriptions que font les consommateurs de leurs principales préférences tactiles. Il est difficile pour les chercheurs de comprendre les descriptions verbales des personnes dont la langue maternelle est différente de la leur. Des recherches antérieures ont suggéré que certains mots sensoriels ayant les mêmes significations lexicales ont été observés dans différentes procédures exploratoires haptiques (PEH). Par conséquent, notre étude vise à étudier et à comprendre les perceptions tactiles clés des personnes de cinq pays différents en fonction de leurs descriptions et de leurs PEH. MÉTHODES: Dans l'expérience 1 545 participantes vivant aux États­Unis, au Japon, en Chine, en Italie et en Thaïlande ont décrit leurs principales perceptions tactiles comme l'efficacité dans les soins de la peau, et nous avons analysé la fréquence de chaque mot utilisé dans leurs réponses. Dans l'expérience 2, nous l'avons confirmé en observant les PEH pour les participantes chinoises, italiennes et thaïs. 24 participantes en Chine, 33 participantes en Italie et 30 participantes en Thaïlande ont librement exploré leur visage avec leurs mains et ont répondu à la question de savoir quel côté correspondait le mieux aux principaux adjectifs tactiles. Les experts ont classé les PEH observées en six classifications dans deux catégories et trois tailles de surface de contact, et ont étudié les différences culturelles. RÉSULTAT: Plus de deux pour cent des participantes chinoises, italiennes, thaïs, américaines et japonaises ont décrit 33, 20, 29, 22 et 18 mots, respectivement, comme une efficacité dans les soins de la peau. Les mots vérifiés qui décrivaient les principales perceptions tactiles dans chaque langue maternelle ayant les mêmes significations sont l'humidité, la fermeté, la douceur, la texture lisse, etc. Nous avons pu confirmer les PEH de ces sensations majeures pour les participants de chaque culture. Les PEH des participantes chinoises et thaïs pour l'humidité ou la douceur ont été observées avec un mouvement de pression. A l'inverse, les PEH pour l'humidité ou la douceur des participantes italiennes ont été observées avec un mouvement de frottement. CONCLUSION: Cette étude a montré que les mots ayant les mêmes significations lexicales évoquaient différentes PEH. Les résultats impliquent que différentes PEH peuvent fournir différents stimuli physiques sur la peau. Par conséquent, il est important d'étudier les objets et les PEH pour mieux comprendre l'expérience tactile.

SAR study of small molecule inhibitors of the programmed cell death-1/programmed cell death-ligand 1 interaction.

The development of small molecule inhibitors of programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) has drawn research interest for the treatment of cancer. Recently, we reported the discovery of a novel dimeric core small molecule PD-1/PD-L1 inhibitor. In an effort to discover more potent inhibitors, we further explored the dimeric core scaffold. Our investigations of the structure-activity-relationship revealed that introduction of lipophilic substituents onto one of the di-alkoxylated phenyl rings improved binding affinities to PD-L1, and inhibitory activities of PD-1/PD-L1 in cellular assays. Furthermore, conversion of the ether linker part to an olefin linker not only improved binding affinity but also led to slow dissociation binding kinetics. We also explored more potent, as well as downsized, scaffolds. Compounds bearing a linear chain in place of one of the di-alkoxylated phenyl rings exhibited good binding affinity with improved ligand efficiency (LE). Representative compounds demonstrated potent inhibitory activities of PD-1/PD-L1 in the submicromolar range in cellular assays as well as cellular function in the mixed lymphocyte reaction (MLR) assay with efficacy comparable to anti-PD-1 antibody. Our results provide applicable information for the design of more potent inhibitors targeting PD-1/PD-L1 pathway.

Sensory words may facilitate certain haptic exploratory procedures in facial cosmetics.

OBJECTIVE: Many people want to have healthy facial skin. They tend to check their skin's condition by touching their face with their hands. In the cosmetic industry, we need to understand what consumers are perceiving in a tactile sense when touching their own facial skin. The purpose of this study was to investigate these observation methods in order to systematically understand people's haptic exploratory procedures (HEPs). METHODS: Thirty-four participants living in the United States and twenty-two participants living in Japan freely explored their faces and answered which side felt more closely related to the six tactile adjectives. A new analysis was applied to classify the observed HEPs into six classifications within two categories and three sizes of contact area by experts. RESULT: It was confirmed that the new task was useful to observe the HEPs for participants from United States and Japan. The US participants' HEPs for 'moisturized' were mainly a middle-sized contact area using a stroking motion. On the other hand, Japanese participants' HEPs for 'moisturized' ('shittori' in Japanese) mainly used a pushing movement. Moreover, the US participants' HEPs for 'soft' included both pushing and stroking, but Japanese participants HEPs for 'soft' ('yawarakai' in Japanese) were again mainly pushing. CONCLUSION: This study suggests that the proposed analysis method enables the systematic understanding of HEPs when checking the skin, along with the cross-cultural differences affecting those procedures. These systematic findings could allow cosmetic formulators to have a better understanding of the tactile sensations consumers themselves are feeling in a variety of different global markets.

OBJECTIF: de nombreuses personnes veulent avoir une peau du visage en bonne santé. Elles ont tendance à examiner l'état de leur peau en se touchant le visage avec les mains. Dans l'industrie cosmétique, nous devons comprendre ce que les consommateurs perçoivent d'un point de vue tactile lorsqu'ils se touchent la peau du visage. L'objectif de cette étude était d'évaluer ces méthodes d'observation afin de comprendre de manière systématique les procédures exploratoires haptiques (PEH) des individus. MÉTHODES: trente-quatre participants vivant aux États-Unis et vingt-deux vivant au Japon ont librement examiné leur visage en le touchant et indiqué quel côté semblait le plus proche des six adjectifs tactiles. Une nouvelle analyse a été appliquée pour classer les PEH observées en six groupes de classification au sein de deux catégories et trois tailles de zone de contact par des experts. RÉSULTAT: il a été confirmé que cette nouvelle étude était utile pour observer les PEH chez les participants provenant des États-Unis et du Japon. Les PEH des participants américains pour l'adjectif « hydratée ¼ correspondaient principalement à des mouvements de caresse sur une zone de contact de taille moyenne. En revanche, les PEH des participants japonais pour « hydratée ¼ (« shittori ¼ en japonais) correspondaient principalement à des mouvements de pression. De plus, les PEH des participants américains pour l'adjectif « douce ¼ comprenaient à la fois des mouvements de caresse et de pression, mais celles des participants japonais pour « douce ¼ (« yawarakai ¼ en japonais) correspondaient de nouveau principalement à des mouvements de pression. CONCLUSION: cette étude suggère que la méthode d'analyse proposée permet une compréhension systématique des PEH lors de l'examen de la peau, ainsi que des différences interculturelles influençant ces procédures. Ces résultats systématiques pourraient permettre aux formulateurs de cosmétiques de mieux comprendre les sensations tactiles des consommateurs eux-mêmes pour un ensemble de marchés mondiaux différents.

Symmetry-based ligand design and evaluation of small molecule inhibitors of programmed cell death-1/programmed death-ligand 1 interaction.

The development of small molecule inhibitors of PD-1/PD-L1 is eagerly anticipated for treatment of cancer. We focused on the symmetry of the ternary complex structure of reported small molecule ligands and hPD-L1 homodimers, and designed partially- or fully-symmetric compounds for more potent inhibitors. The design of the new compounds was guided by our hypothesis that the designed symmetric compound would induce a flip of sidechain of ATyr56 protein residue to form a new cavity. The designed compound 4 exhibited substantially increased binding affinity to hPD-L1, as well as PD-1/PD-L1 inhibitory activity in physiological conditions. Compound 4 also showed a dose-dependent increase in IFN-γ secretion levels in a mixed lymphocyte reaction assay. These results not only indicate the feasibility of targeting the PD-1/PD-L1 pathway with small molecules, but illustrate the applicability of the symmetry-based ligand design as an attractive methodology for targeting protein-protein interaction stabilizers.

Concise SAR Exploration Based on the "Head-to-Tail" Approach: Discovery of PI4KIIIα Inhibitors Bearing Diverse Scaffolds.

In typical kinase inhibitor programs, a hinge binder showing best potency with preferential specificity is initially selected, followed by fine-tuning of the accompanying substituents on its core module. A shortcoming of this approach is that the exclusive focus on a single chemotype can endanger all the analogues in the series if a critical shortcoming is revealed. Thus, an early evaluation of structure-activity relationships (SARs) can mitigate unforeseen outcomes within a series of multiple compounds, although there have been very few examples to follow such a policy. PI4KIIIα is one of four mammalian phosphatidylinositol-4 kinases and has recently drawn significant attention as an emerging target for hepatitis C virus (HCV) treatment. In this letter, a novel "head-to-tail" approach to discover a diverse set of PI4KIIIα inhibitors is reported. We believe this method will generate distinct core scaffolds, a rational strategy to circumvent potential risks in general kinase programs.

Quantitative comparison of a corona-charged aerosol detector and an evaporative light-scattering detector for the analysis of a synthetic polymer by supercritical fluid chromatography.

A corona-charged aerosol detector (CAD) was developed to improve the sensitivity, reproducibility and quantitativeness of detection as compared to evaporative light-scattering detector (ELSD) for liquid chromatography. Our laboratory used the corona CAD as a detector for supercritical fluid chromatography (SFC) and evaluated its performance compared to the ELSD by using a certified reference material of poly(ethylene glycol) (PEG) and a well-defined equimass mixture of uniform PEG oligomers. The corona CAD was able to detect a 10 times more dilute solution of uniform oligomers compared to the ELSD. Although the original data of molecular mass by ELSD was 4.6% smaller than the certified value of PEG 1000, molecular mass distribution obtained by corona CAD was virtually almost the same as the certified value without any calibrations.