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1.
Phys Rev E ; 108(3-1): 034213, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37849115

ABSTRACT

We develop a data-driven characterization of the pilot-wave hydrodynamic system in which a bouncing droplet self-propels along the surface of a vibrating bath. We consider drop motion in a confined one-dimensional geometry and apply the dynamic mode decomposition (DMD) in order to characterize the evolution of the wave field as the bath's vibrational acceleration is increased progressively. Dynamic mode decomposition provides a regression framework for adaptively learning a best-fit linear dynamics model over snapshots of spatiotemporal data. Thus, DMD reduces the complex nonlinear interactions between pilot waves and droplet to a low-dimensional linear superposition of DMD modes characterizing the wave field. In particular, it provides a low-dimensional characterization of the bifurcation structure of the pilot-wave physics, wherein the excitation and recruitment of additional modes in the linear superposition models the bifurcation sequence. This DMD characterization yields a fresh perspective on the bouncing-droplet problem that forges valuable new links with the mathematical machinery of quantum mechanics. Specifically, the analysis shows that as the vibrational acceleration is increased, the pilot-wave field undergoes a series of Hopf bifurcations that ultimately lead to a chaotic wave field. The established relation between the mean pilot-wave field and the droplet statistics allows us to characterize the evolution of the emergent statistics with increased vibrational forcing from the evolution of the pilot-wave field. We thus develop a numerical framework with the same basic structure as quantum mechanics, specifically a wave theory that predicts particle statistics.

2.
J Appl Psychol ; 108(10): 1619-1639, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37289524

ABSTRACT

The literature on abusive supervision largely presumes that employees respond to abuse in a relatively straightforward way: When abuse is present, outcomes are unfavorable, and when abuse is absent, outcomes are favorable (or, at least less unfavorable). Yet despite the recognition that abusive supervision can vary over time, little consideration has been given to how past experiences of abuse may impact the ways employees react to it (or, its absence) in the present. This is a notable oversight, as it is widely acknowledged that past experiences create a context against which experiences in the present are compared. By applying a temporal lens to the experience of abusive supervision, we identify abusive supervision inconsistency as a phenomenon that may have different outcomes than would otherwise be predicted by the current consensus in this literature. We draw from theories on time and stress appraisal to develop a model that explains when, why, and for which employees, inconsistent abusive supervision may have negative outcomes (specifically, identifying anxiety as a proximal outcome of abusive supervision inconsistency that has downstream effects on turnover intentions). Moreover, the aforementioned theoretical perspectives dovetail in identifying employee workplace status as a moderator that may buffer employees from the stressful consequences of inconsistent abusive supervision. We test our model using two experience sampling studies with polynomial regression and response surface analyses. Our research makes important theoretical and practical contributions to the abusive supervision literature, as well as the literature on time. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

3.
Viruses ; 15(2)2023 02 04.
Article in English | MEDLINE | ID: mdl-36851646

ABSTRACT

Adjuvants are essential components of subunit vaccines added to enhance immune responses to antigens through immunomodulation. Very few adjuvants have been approved for human use by regulatory agencies due to safety concerns. Current subunit vaccine adjuvants approved for human use are very effective in promoting humoral immune responses but are less effective at promoting T-cell immunity. In this study, we evaluated a novel pure enantio-specific cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (R-DOTAP) as an immunomodulator for subunit vaccines capable of inducing both humoral- and cellular-mediated immunity. Using recombinant protein antigens derived from SARS-CoV2 spike or novel computationally optimized broadly reactive influenza antigen (COBRA) proteins, we demonstrated that R-DOTAP nanoparticles promoted strong cellular- and antibody-mediated immune responses in both monovalent and bivalent vaccines. R-DOTAP-based vaccines induced antigen-specific and polyfunctional CD8+ and CD4+ effector T cells and memory T cells, respectively. Antibody responses induced by R-DOTAP showed a balanced Th1/Th2 type immunity, neutralizing activity and protection of mice from challenge with live SARS-CoV2 or influenza viruses. R-DOTAP also facilitated significant dose sparing of the vaccine antigens. These studies demonstrate that R-DOTAP is an excellent immune stimulator for the production of next-generation subunit vaccines containing multiple recombinant proteins.


Subject(s)
COVID-19 , RNA, Viral , Animals , Humans , Mice , Adjuvants, Immunologic , Cations , COVID-19/prevention & control , Fatty Acids, Monounsaturated , Immunity , Lipids , SARS-CoV-2 , Vaccines, Synthetic/genetics , Antibodies, Viral/immunology
4.
Phys Rev Lett ; 130(6): 064002, 2023 Feb 10.
Article in English | MEDLINE | ID: mdl-36827574

ABSTRACT

Superradiance occurs when a collection of atoms exhibits a cooperative, spontaneous emission of photons at a rate that exceeds that of its component parts. Here, we reveal a similar phenomenon in a hydrodynamic system consisting of a pair of vibrationally excited cavities, coupled through their common wave field, that spontaneously emit droplets via interfacial fracture. We show that the droplet emission rate of two coupled cavities is higher than the emission rate of two isolated cavities. Moreover, the amplified emission rate varies sinusoidally with distance between the cavities, as is characteristic of superradiance. We thus present a hydrodynamic phenomenon that captures several essential features of superradiance in optical systems.

5.
Am J Ophthalmol ; 237: 267-277, 2022 05.
Article in English | MEDLINE | ID: mdl-34788595

ABSTRACT

PURPOSE: To investigate the safety and efficacy of cultured human corneal endothelial cell (hCEC) injection therapy with mature differentiated (mature) cell subpopulations (SPs) for corneal endothelial failure (CEF). DESIGN: Comparative, interventional case series. METHODS: This study involved 18 eyes with CEF that underwent cultured hCEC injection therapy, categorized into 2 groups: (1) 11 eyes administered a relatively lower proportion (0.1 to 76.3%) of mature cell SPs (group 1 [Gr1]), and (2) 7 eyes administered a relatively higher proportion (>90%) of mature cell SPs (group 2 [Gr2]). From 1 week to 3 years postoperation, corneal endothelial cell (CEC) density (CECD), central corneal thickness (CCT), and best-corrected visual acuity (BCVA) were recorded, and the CEC parameter's "spring constant" was calculated. The proportion of mature SPs was evaluated by fluorescence-activated cell sorting analysis based on cell-surface markers. RESULTS: At 3 years postoperation, corneal restoration with improved BCVA was attained in 10 of the 11 Gr1 eyes and all Gr2 eyes, the median CECD in Gr2 (3083 cells/mm2; range, 2182-4417 cells/mm2) was higher than that in Gr1 (1349 cells/mm2; range, 746-2104 cells/mm2) (P < .001), and the spring constant verified the superiority of the mature cultured hCECs. From 24 weeks through 3 years postoperation, the median percentage of CECD decrease was 3.2% in Gr2 and 23.6% in Gr1 (P < .005). CCT recovery was prompt and constant in Gr2, while diverse in Gr1. No adverse events were observed. CONCLUSION: Our findings showed that mature cell SPs for hCEC injection therapy provide rapid recovery of CCT, better CECD, and low CECD attrition over 3 years postsurgery.


Subject(s)
Cornea , Endothelium, Corneal , Cell Count , Cell Differentiation , Cells, Cultured , Endothelial Cells , Humans
6.
PLoS One ; 16(12): e0260730, 2021.
Article in English | MEDLINE | ID: mdl-34941887

ABSTRACT

This study aimed to clarify the etiologic factors predicting acute ocular progression in SJS/TEN, and identify patients who require immediate and intensive ophthalmological treatment. We previously conducted two Japanese Surveys of SJS/TEN (i.e., cases arising between 2005-2007 and between 2008-2010), and obtained the medical records, including detailed dermatological and ophthalmological findings, of 230 patients. Acute ocular severity was evaluated as none, mild, severe, and very severe. A multi-state model assuming the Markov process based on the Cox proportional hazards model was used to elucidate the specific factors affecting the acute ocular progression. Our findings revealed that of the total 230 patients, 23 (24%) of 97 cases that were mild at initial presentation worsened to severe/very severe. Acute ocular progression developed within 3 weeks from disease onset. Exposure to nonsteroidal anti-inflammatory drugs (NSAIDs) and younger patient age were found to be statistically significant for the progression of ocular severity from mild to severe/very severe [hazard ratio (HR) 3.83; 95% confidence interval (CI) 1.48 to 9.91] and none to severe/very severe [HR 0.98; 95% CI 0.97 to 0.99], respectively. The acute ocular severity score at worst-condition was found to be significantly correlated with ocular sequelae. Thus, our detailed findings on acute ocular progression revealed that in 24% of SJS/TEN cases with ocular involvement, ocular severity progresses even after initiating intensive treatment, and that in younger-age patients with a history of exposure to NSAIDs, very strict attention must be given to their ophthalmological appearances.


Subject(s)
Eye Diseases/pathology , Stevens-Johnson Syndrome/pathology , Vision, Ocular , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Disease Progression , Eye Diseases/etiology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Models, Statistical , Prognosis , Retrospective Studies , Severity of Illness Index , Young Adult
7.
Nature ; 596(7870): 58-62, 2021 08.
Article in English | MEDLINE | ID: mdl-34349289

ABSTRACT

Macroscale analogues1-3 of microscopic spin systems offer direct insights into fundamental physical principles, thereby advancing our understanding of synchronization phenomena4 and informing the design of novel classes of chiral metamaterials5-7. Here we introduce hydrodynamic spin lattices (HSLs) of 'walking' droplets as a class of active spin systems with particle-wave coupling. HSLs reveal various non-equilibrium symmetry-breaking phenomena, including transitions from antiferromagnetic to ferromagnetic order that can be controlled by varying the lattice geometry and system rotation8. Theoretical predictions based on a generalized Kuramoto model4 derived from first principles rationalize our experimental observations, establishing HSLs as a versatile platform for exploring active phase oscillator dynamics. The tunability of HSLs suggests exciting directions for future research, from active spin-wave dynamics to hydrodynamic analogue computation and droplet-based topological insulators.

8.
Proc Natl Acad Sci U S A ; 118(17)2021 04 27.
Article in English | MEDLINE | ID: mdl-33858987

ABSTRACT

The current revival of the American economy is being predicated on social distancing, specifically the Six-Foot Rule, a guideline that offers little protection from pathogen-bearing aerosol droplets sufficiently small to be continuously mixed through an indoor space. The importance of airborne transmission of COVID-19 is now widely recognized. While tools for risk assessment have recently been developed, no safety guideline has been proposed to protect against it. We here build on models of airborne disease transmission in order to derive an indoor safety guideline that would impose an upper bound on the "cumulative exposure time," the product of the number of occupants and their time in an enclosed space. We demonstrate how this bound depends on the rates of ventilation and air filtration, dimensions of the room, breathing rate, respiratory activity and face mask use of its occupants, and infectiousness of the respiratory aerosols. By synthesizing available data from the best-characterized indoor spreading events with respiratory drop size distributions, we estimate an infectious dose on the order of 10 aerosol-borne virions. The new virus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) is thus inferred to be an order of magnitude more infectious than its forerunner (SARS-CoV), consistent with the pandemic status achieved by COVID-19. Case studies are presented for classrooms and nursing homes, and a spreadsheet and online app are provided to facilitate use of our guideline. Implications for contact tracing and quarantining are considered, and appropriate caveats enumerated. Particular consideration is given to respiratory jets, which may substantially elevate risk when face masks are not worn.


Subject(s)
Air Microbiology , COVID-19/prevention & control , Guidelines as Topic , SARS-CoV-2 , Aerosols , Air Pollution, Indoor , COVID-19/transmission , Humans , Models, Theoretical , Safety
9.
Chaos ; 31(3): 033136, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33810713

ABSTRACT

We present the results of a theoretical investigation into the dynamics of a vibrating particle propelled by its self-induced wave field. Inspired by the hydrodynamic pilot-wave system discovered by Yves Couder and Emmanuel Fort, the idealized pilot-wave system considered here consists of a particle guided by the slope of its quasi-monochromatic "pilot" wave, which encodes the history of the particle motion. We characterize this idealized pilot-wave system in terms of two dimensionless groups that prescribe the relative importance of particle inertia, drag and wave forcing. Prior work has delineated regimes in which self-propulsion of the free particle leads to steady or oscillatory rectilinear motion; it has further revealed parameter regimes in which the particle executes a stable circular orbit, confined by its pilot wave. We here report a number of new dynamical states in which the free particle executes self-induced wobbling and precessing orbital motion. We also explore the statistics of the chaotic regime arising when the time scale of the wave decay is long relative to that of particle motion and characterize the diffusive and rotational nature of the resultant particle dynamics. We thus present a detailed characterization of free-particle motion in this rich two-parameter family of dynamical systems.

10.
Ophthalmology ; 128(4): 504-514, 2021 04.
Article in English | MEDLINE | ID: mdl-32898516

ABSTRACT

PURPOSE: To report the safety and efficacy of a novel cell injection therapy using cultured human corneal endothelial cells (hCECs) for endothelial failure conditions via the report of the long-term 5-year postoperative clinical data from a first-in-humans clinical trial group. DESIGN: Prospective observational study. PARTICIPANTS: This study involved 11 eyes of 11 patients with pseudophakic endothelial failure conditions who underwent hCEC injection therapy between December 2013 and December 2014. METHODS: All patients underwent follow-up examinations at 1 week, 4 weeks, 12 weeks, and 24 weeks and 1 year, 2 years, 3 years, 4 years, and 5 years after surgery. Specific corneal endothelial cell parameters (i.e., corneal endothelial cell density [ECD], coefficient of variation of area, and percentage of hexagonal cells) and central corneal thickness, best-corrected visual acuity (BCVA) on a Landolt C eye chart, and intraocular pressure (IOP) were recorded. MAIN OUTCOME MEASURES: The primary outcome was the change in central ECD after cell injection therapy, and the secondary outcome was corneal thickness, BCVA, and IOP during the 5-year-postoperative follow-up period. RESULTS: At 5 years after surgery, normal corneal endothelial function was restored in 10 of the 11 eyes, the mean ± standard deviation central corneal ECD was 1257 ± 467 cells/mm2 (range, 601-2067 cells/mm2), BCVA improved significantly in 10 treated eyes, the mean visual acuity changed from 0.876 logarithm of the minimum angle of resolution before surgery to 0.046 logarithm of the minimum angle of resolution after surgery, and no major adverse reactions directly related to the hCEC injection therapy were observed. CONCLUSIONS: The findings in this study confirmed the safety and efficacy of cultured hCEC injection therapy for up to 5 years after surgery.


Subject(s)
Amides/therapeutic use , Corneal Edema/therapy , Endothelium, Corneal/transplantation , Fuchs' Endothelial Dystrophy/therapy , Protein Kinase Inhibitors/therapeutic use , Pyridines/therapeutic use , rho-Associated Kinases/antagonists & inhibitors , Adult , Aged , Anterior Chamber , Cell Count , Cells, Cultured , Combined Modality Therapy , Corneal Edema/diagnosis , Corneal Edema/physiopathology , Endothelium, Corneal/cytology , Female , Follow-Up Studies , Fuchs' Endothelial Dystrophy/diagnosis , Fuchs' Endothelial Dystrophy/physiopathology , Graft Rejection/prevention & control , Humans , Injections, Intraocular , Intraocular Pressure/physiology , Male , Middle Aged , Prone Position , Prospective Studies , Regenerative Medicine , Slit Lamp Microscopy , Visual Acuity/physiology
11.
Rep Prog Phys ; 84(1)2020 Dec 21.
Article in English | MEDLINE | ID: mdl-33065567

ABSTRACT

The walking droplet system discovered by Yves Couder and Emmanuel Fort presents an example of a vibrating particle self-propelling through a resonant interaction with its own wave field. It provides a means of visualizing a particle as an excitation of a field, a common notion in quantum field theory. Moreover, it represents the first macroscopic realization of a form of dynamics proposed for quantum particles by Louis de Broglie in the 1920s. The fact that this hydrodynamic pilot-wave system exhibits many features typically associated with the microscopic, quantum realm raises a number of intriguing questions. At a minimum, it extends the range of classical systems to include quantum-like statistics in a number of settings. A more optimistic stance is that it suggests the manner in which quantum mechanics might be completed through a theoretical description of particle trajectories. We here review the experimental studies of the walker system, and the hierarchy of theoretical models developed to rationalize its behavior. Particular attention is given to enumerating the dynamical mechanisms responsible for the emergence of robust, structured statistical behavior. Another focus is demonstrating how the temporal nonlocality of the droplet dynamics, as results from the persistence of its pilot wave field, may give rise to behavior that appears to be spatially nonlocal. Finally, we describe recent explorations of a generalized theoretical framework that provides a mathematical bridge between the hydrodynamic pilot-wave system and various realist models of quantum dynamics.

12.
Science ; 369(6504): 685-688, 2020 08 07.
Article in English | MEDLINE | ID: mdl-32764069

ABSTRACT

Viscous bubbles are prevalent in both natural and industrial settings. Their rupture and collapse may be accompanied by features typically associated with elastic sheets, including the development of radial wrinkles. Previous investigators concluded that the film weight is responsible for both the film collapse and wrinkling instability. Conversely, we show here experimentally that gravity plays a negligible role: The same collapse and wrinkling arise independently of the bubble's orientation. We found that surface tension drives the collapse and initiates a dynamic buckling instability. Because the film weight is irrelevant, our results suggest that wrinkling may likewise accompany the breakup of relatively small-scale, curved viscous and viscoelastic films, including those in the respiratory tract responsible for aerosol production from exhalation events.

13.
Phys Rev E ; 102(1-1): 013104, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32795022

ABSTRACT

A walker is a macroscopic coupling of a droplet and a capillary wave field that exhibits several quantumlike properties. In 2009, Eddi et al. [Phys. Rev. Lett. 102, 240401 (2009)PRLTAO0031-900710.1103/PhysRevLett.102.240401] showed that walkers may cross a submerged barrier in an unpredictable manner and named this behavior "unpredictable walker tunneling." In quantum mechanics, tunneling is one of the simplest arrangements where similar unpredictability occurs. In this paper, we investigate how unpredictability can be unveiled for walkers through an experimental study of walker tunneling with precision. We refine both time and position measurements to take into account the fast bouncing dynamics of the system. Tunneling is shown to be unpredictable until a distance of 2.6 mm from the barrier center, where we observe the separation of reflected and transmitted trajectories in the position-velocity phase-space. The unpredictability is unlikely to be attributable to either uncertainty in the initial conditions or to the noise in the experiment. It is more likely due to changes in the drop's vertical dynamics arising when it interacts with the barrier. We compare this macroscopic system to a tunneling quantum particle that is subjected to repeated measurements of its position and momentum. We show that, despite the different theoretical treatments of these two disparate systems, similar patterns emerge in the position-velocity phase space.

14.
Proc Math Phys Eng Sci ; 476(2239): 20190884, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32831603

ABSTRACT

We present the results of a theoretical investigation of a dynamical system consisting of a particle self-propelling through a resonant interaction with its own quasi-monochromatic pilot-wave field. We rationalize two distinct mechanisms, arising in different regions of parameter space, that may lead to a wavelike statistical signature with the pilot-wavelength. First, resonant speed oscillations with the wavelength of the guiding wave may arise when the particle is perturbed from its steady self-propelling state. Second, a random-walk-like motion may set in when the decay rate of the pilot-wave field is sufficiently small. The implications for the emergent statistics in classical pilot-wave systems are discussed.

15.
Cornea ; 39(12): 1510-1515, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32482965

ABSTRACT

PURPOSE: To investigate the key factors associated with eyes with an endothelial cell density (ECD) of ≥2000 cells/mm at 5 years after corneal transplantation. METHODS: This retrospective cohort study included 174 eyes that underwent penetrating keratoplasty by 1 corneal specialist surgeon at the Baptist Eye Institute, Kyoto, Japan, from 1998 through 2011 and that were carefully followed for over 5 years postoperative. In all operated eyes, corneal ECD was measured at 1, 2, 3, 4, and 5 years postoperative. Multivariate analysis with adjustment for preoperative donor ECD was performed between eyes with an ECD of ≥2000 cells/mm and those with an ECD of <2000 cells/mm at 5 years postoperative. RESULTS: Of the 174 eligible eyes, 16 eyes (9.2%) had an ECD of ≥2000 cells/mm at 5 years postoperative, and the annual rate of endothelial cell loss (mean ± SD) was 2.3% ± 3.7%. Multivariate analysis findings revealed that the donor-associated and surgery-related factors were not significant factors. Only the recipient diagnosis of bullous keratopathy was significantly associated with an ECD of <2000 cells/mm at 5 years postoperative. Of those 16 eyes, 6 (37.5%) had a recipient diagnosis of bullous keratopathy. CONCLUSIONS: None of the donor- and surgery-related factors, previously recognized as associated with a lower endothelial cell loss after penetrating keratoplasty, were found to be significant in this study, thus suggesting that there are still unknown factors associated with maintaining a higher ECD over the long-term postoperative period.


Subject(s)
Corneal Diseases/surgery , Corneal Endothelial Cell Loss/diagnosis , Endothelium, Corneal/pathology , Keratoplasty, Penetrating , Adult , Aged , Aged, 80 and over , Cell Count , Corneal Diseases/physiopathology , Corneal Endothelial Cell Loss/physiopathology , Female , Follow-Up Studies , Graft Survival/physiology , Humans , Male , Middle Aged , Retrospective Studies , Tissue Donors , Transplant Recipients , Young Adult
16.
Sci Adv ; 6(20): eaay9234, 2020 May.
Article in English | MEDLINE | ID: mdl-32440541

ABSTRACT

We present a macroscopic analog of an open quantum system, achieved with a classical pilot-wave system. Friedel oscillations are the angstrom-scale statistical signature of an impurity on a metal surface, concentric circular modulations in the probability density function of the surrounding electron sea. We consider a millimetric drop, propelled by its own wave field along the surface of a vibrating liquid bath, interacting with a submerged circular well. An ensemble of drop trajectories displays a statistical signature in the vicinity of the well that is strikingly similar to Friedel oscillations. The droplet trajectories reveal the dynamical roots of the emergent statistics. Our study elucidates a new mechanism for emergent quantum-like statistics in pilot-wave hydrodynamics and so suggests new directions for the nascent field of hydrodynamic quantum analogs.

17.
Pharmacol Biochem Behav ; 195: 172949, 2020 08.
Article in English | MEDLINE | ID: mdl-32413436

ABSTRACT

AKB48 and its fluorinated derivative 5F-AKB48 are synthetic cannabinoids (SCs) which have caused hospitalizations and deaths in human users. Abuse of SCs is dangerous because users may mistake them for natural cannabis, which is generally considered to be unlikely to elicit adverse effects. The present studies were designed to investigate the in vitro oxidative metabolism of 5F-AKB48 by human microsomal fractions from different organs and sexes as well as recombinant human cytochrome P450s (P450s). Mass spectrometry data tentatively provides evidence for the existence of mono-, di-, and trihydroxylated metabolites in a successive metabolism. Experiments utilizing P450s revealed that the most active enzymes (CYP2D6, CYP2J2, CYP3A4, and CYP3A5) effectively produced mono- and dihydroxylated metabolites, while CYP3A4/5 also produced significant amounts of the trihydroxylated metabolite. Moreover, although the affinity and potency of Phase I metabolite 4OH-5F-AKB48 is reduced when compared to that of the parent drug, this metabolite nevertheless retains similar high affinity for CB1 receptors, and greater efficacy for G protein activation, when compared to THC. Finally, 5F-AKB48 produced time- and dose-dependent cannabimimetic effects in mice which were more potent, but shorter acting, than those of Δ9-THC, and were attenuated by prior treatment with the CB1 antagonist rimonabant. Based on our data, we hypothesize that while many cases of toxicity result from genetic mutations, which can lead to a decrease or even absence of activity for Phase I drug-metabolizing enzymes, other P450s could potentially increase their role in the metabolism of these SCs. Because many metabolites of SCs remain biologically active, they could contribute to the deleterious effects of these substances.


Subject(s)
Adamantane/analogs & derivatives , Indazoles/metabolism , Indazoles/toxicity , Receptor, Cannabinoid, CB1/agonists , Receptor, Cannabinoid, CB1/metabolism , Adamantane/metabolism , Adamantane/toxicity , Animals , Cannabinoid Receptor Antagonists/pharmacology , Cytochrome P-450 CYP2D6/genetics , Cytochrome P-450 CYP2D6/metabolism , Cytochrome P-450 CYP3A/genetics , Cytochrome P-450 CYP3A/metabolism , Female , Humans , Male , Mice , Mice, Inbred C57BL , Microsomes, Liver/drug effects , Microsomes, Liver/metabolism , Oxidation-Reduction/drug effects , Polymorphism, Genetic , Protein Binding , Recombinant Proteins/metabolism , Rimonabant/pharmacology , Sex Factors
18.
Invest Ophthalmol Vis Sci ; 61(5): 47, 2020 05 11.
Article in English | MEDLINE | ID: mdl-32455435

ABSTRACT

Purpose: To clarify the expression profiles of ion channels and transporters of metabolic substrates among heterogeneous cultured human corneal endothelial cells (cHCECs) distinct in their effectiveness in reconstituting the corneal endothelium. Methods: Integrated proteomics for cell lysates by liquid chromatography-tandem mass spectrometry was carried out from three aliquots of cHCECs enriched in either cluster of definition (CD)44-/+ (mature) cHCECs or CD44++/+++ cell-state transition (CST) cHCECs. The expression profiles of cations/anions, monocarboxylic acid transporters (MCTs), and solute carrier (SLC) family proteins, as well as carbonic anhydrases (CAs), were investigated. Results: The polarized expression of cations/anions, MCTs, and SLC family proteins, as well as CAs, was clarified for mature and CST cHCECs. Most SLC4 family members, including SLC4A11 and SLC4A4 (NBCe1), were upregulated in the CST cHCECs, whereas SLC9A1 (Na+/H+ exchanger isoform one [NHE1]) and CA5B were detected only in the mature cHCECs. In addition, SLC25A42, catalyzing the entry of coenzyme A into the mitochondria, and SLC25A18, functioning as a mitochondrial glutamate carrier 2 (both relevant for providing the substrates for mitochondrial bioenergetics), were selectively expressed in the mature cHCECs. Conclusions: Our findings may suggest the relevance of qualifying the polarized expression of these ion channels and transporter-like proteins to ensure not only the suitability but also the in vivo biological functionality of cHCECs selected for use in a cell-injection therapy.


Subject(s)
Endothelial Cells/metabolism , Endothelium, Corneal/cytology , Ion Channels/biosynthesis , Solute Carrier Proteins/biosynthesis , Cells, Cultured , Humans
19.
Pharmacol Res Perspect ; 8(1): e00561, 2020 02.
Article in English | MEDLINE | ID: mdl-32003945

ABSTRACT

Synthetic cannabinoids (SCBs), designer drugs marketed as legal alternatives to marijuana, act as ligands to cannabinoid receptors; however, they have increased binding affinity and potency, resulting in toxicity symptoms such as cardiovascular incidents, seizures, and potentially death. N-(adamantan-1-yl)-1-(5-fluoropentyl)-1H-indole-3-carboxamide (STS-135) is a third generation SCB. When incubated with hepatocytes, it undergoes oxidation, hydrolysis, and glucuronidation, resulting in 29 metabolites, with monohydroxy STS-135 (M25) and dihydroxy STS-135 (M21) being the predominant metabolites. The enzymes responsible for this oxidative metabolism were unknown. Thus, the aim of this study was to identify the cytochrome P450 (P450s or CYPs) enzymes involved in the oxidative metabolism of STS-135. In this study, STS-135 was incubated with liver, intestinal, and brain microsomes and recombinant P450s to determine the enzymes involved in its metabolism. Metabolite quantification was carried out using ultra-performance liquid chromatography. STS-135 was extensively metabolized in HLMs and HIMs. Screening assays indicated CYP3A4 and CYP3A5 could be responsible for STS-135's oxidation. Through incubations with genotyped HLMs, CYP3A4 was identified as the primary oxidative enzyme. Interestingly, CYP2J2, a P450 isoform expressed in cardiovascular tissues, showed high activity towards the formation of M25 with a Km value of 11.4 µmol/L. Thus, it was concluded that STS-135 was primarily metabolized by CYP3A4 but may have extrahepatic metabolic pathways as well. Upon exposure to STS-135, individuals with low CYP3A4 activity could retain elevated blood concentration, resulting in toxicity. Additionally, CYP2J2 may aid in protecting against STS-135-induced cardiovascular toxicity.


Subject(s)
Adamantane/analogs & derivatives , Cytochrome P-450 CYP3A/metabolism , Indoles/pharmacokinetics , Microsomes/metabolism , Adamantane/chemistry , Adamantane/pharmacokinetics , Brain/cytology , Chromatography, High Pressure Liquid , Humans , Indoles/chemistry , Intestines/cytology , Liver/cytology , Oxidation-Reduction
20.
J Appl Psychol ; 105(1): 1-18, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31204829

ABSTRACT

Engagement is widely viewed as a motivational state that captures the degree to which individuals apply their physical, cognitive, and emotional energies to their jobs, and ultimately improves job performance. However, this job-level view overlooks the possibility that engagement may vary across the different tasks within a job and that engagement in one task may influence engagement and performance in a subsequent task. In this article, we develop and test hypotheses based on a task-level view of engagement and the general notion that there is "residual engagement" from a task that carries forward to a subsequent task. We propose that although task engagement (engagement in a specific task that comprises a broader role) positively spills over to influence task engagement and performance in a subsequent task, in part because of the transmission of positive affect, task engagement simultaneously engenders attention residue, which in turn impedes subsequent task engagement and performance. These predictions were supported in a study of 477 task transitions made by 20 crew members aboard The National Aeronautics and Space Administration's Human Exploration Research Analog (Study 1) and in a laboratory study of 346 participants who transitioned between a firefighting task and an assembly task (Study 2). Our investigation explains how engagement flows across tasks, illuminates a negative implication of engagement that has been masked by the predominant job-level perspective, and identifies completeness as a task attribute that reduces this negative consequence of engagement. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Subject(s)
Attention/physiology , Motivation/physiology , Psychomotor Performance/physiology , Adult , Astronauts , Female , Humans , Male , Models, Theoretical , Work Performance , Young Adult
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