Exceptional cavity quantum electrodynamics

An open quantum system operated at the spectral singularities where dimensionality reduces, known as exceptional points (EPs), demonstrates distinguishing behavior from the Hermitian counterpart. Based on the recently proposed microcavity with exceptional surface (ES), we report and explain the peculiar quantum dynamics in atom-photon interaction associated with EPs: cavity transparency, decoherence suppression beyond the limitation of Jaynes-Cummings (JC) system, and the population trapping of lossy cavity. An analytical description of the local density of states (LDOS) for ES microcavity is derived from an equivalent cavity quantum electrodynamics (QED) model, which goes beyond the single-excitation approximation and allows exploring the quantum effects of EPs on multiphoton process by parametrizing the extended cascaded quantum master equation. It reveals that a square Lorentzian term in LDOS induced by second-order EPs interferes with the linear Lorentzian profile, giving rise to cavity transparency for atom with special transition frequency in the weak coupling regime. This additional contribution from EPs also breaks the limit on dissipation rate of JC system bounded by bare components, resulting in the decoherence suppression with anomalously small decay rate of the Rabi oscillation and the long-time dynamics. Remarkably, we find that the cavity population can be partially trapped at EPs, achieved by forming a bound dressed state in the limiting case of vanishing atom decay. Our work unveils the exotic phenomena unique to EPs in cavity QED systems, which opens the door for controlling light-matter interaction at the quantum level through non-Hermiticity, and holds great potential in building high-performance quantum-optics devices.Comment: 11 pages, 6 figure

CYTOCHROME P450 3A-MEDIATED PHARMACOKINETIC VARIATIONS FOR ANTI-INFECTIVE AGENTS

Two highly homologous enzymes, cytochrome P450 enzyme 3A4 (CYP3A4) and CYP3A5 play predominant roles in drug elimination by metabolizing more than half of the marketed drugs. This thesis focuses on pharmacokinetics of anti-infective drugs that are CYP3A4/5 substrates, inducers, or inhibitors in order to provide a mechanistic understanding of CYP3A4/5-related pharmacokinetic variations. In a dose-escalation study in healthy volunteers for daily doses of the anti-tuberculosis drug rifapentine, we developed and validated Ultra Performance Liquid Chromatrography-Mass Spectrometry (UPLC-MS)-based quantitation assays for measurement of plasma concentrations of rifapentine and the comparator drug, rifampin, and their desacetyl metabolites. We identified a less-than-proportional increase in rifapentine plasma peak concentration (Cmax) and area under the plasma concentration-time curve (AUC) as the rifapentine dose increased from 5 mg/kg to 20 mg/kg. Co-administration of rifapentine decreased AUC of a CYP3A4/5 substrate drug, midazolam, in a dose-independent manner and the reduction was bigger than that caused by the co-administration of rifampin. Ritonavir is a CYP3A4/5 inhibitor used in fixed combination with several anti-HIV drugs to prolong their half-lives by inhibiting CYP3A4/5-mediated metabolism of those drugs. We conducted a drug-drug interaction study to evaluate the effect of ritonavir-boosted anti-HIV drug lopinavir (LPV/r) on the anti-malarial drug quinine, which has a narrow therapeutic window. We developed a High Performance Liquid Chromatrography (HPLC) interfaced with fluorescence detector assay for simultaneous measurement of plasma concentrations of quinine and its major pharmacologically active metabolite, 3-hydroxyquinine. We found that LPV/r significantly decreased the exposure of quinine and 3-hydroxyquinine, in both total and protein-bound free forms. The finding highlights the complex nature of the influence exerted by LPV/r on CYP3A4/5 and other drug-metabolizing enzymes involved in quinine disposition including UDP-glucuronosyltransferase, and P-glycoprotein. Through studying metabolism of the anti-HIV drug maraviroc, we found CYP3A5 was the principal enzyme responsible for the formation of an abundant metabolite, namely, M1. The M1 formation capacity of CYP3A5 was 23 times higher than that of CYP3A4 in vitro. Further, human liver microsomes isolated from donors with two loss-of-function CYP3A5*3 alleles exhibited a 79% decrease in M1 formation as compared to those with two wild-type CYP3A5*1 alleles. These results indicate that maraviroc can be used as a chemical phenotyping probe to examine CYP3A5 activity in vitro. The excellent safety profile of maraviroc allowed us to further examine the utility of maraviroc to assess CYP3A5 activity in clinical settings with potential for use as a phenotyping probe. Following an oral dose of 300 mg maraviroc, people with two CYP3A5*1 alleles had 41% lower maraviroc AUC and 66% higher apparent clearance compared with those who do not have CYP3A5*1 allele. Subjects who do not have CYP3A5*1 allele had > 2 times the AUC ratio of maraviroc to its M1 metabolite compared with those who carry at least one CYP3A5*1 allele. Strong correlations between plasma concentration ratios and AUC ratios of maraviroc to M1 were observed from 4 to 10 h following the dose with R2 > 0.87. These results suggest that maraviroc has the potential to be used in clinical studies, possibly with single-point blood collections after the dose, to determine CYP3A5 activity. In conclusion, we characterized the changes in pharmacokinetics of CYP3A4/5 substrate drugs caused by anti-infective agents that are CYP3A4/5 inducers or inhibitors; and discovered a novel use of maraviroc to assess activity of the highly variable enzyme CYP3A5 in both in vitro and in clinical settings. The results from this thesis inform several anti-infective dosing regimens and provide a phenotyping tool for identification of CYP3A5 substrates, inducers, or inhibitors

Palladium-Catalyzed Enantioselective C_(sp)^3–C_(sp)^3 Cross-Coupling for the Synthesis of (Poly)fluorinated Chiral Building Blocks

A general method for the enantioselective synthesis of carbo- and heterocyclic carbonyl compounds bearing fluorinated α-tetrasubstituted stereocenters using palladium-catalyzed decarboxylative allylic alkylation is described. The stereoselective C_(sp)^3–C_(sp)^3 cross-coupling reaction delivers five- and six-membered ketone and lactam products bearing (poly)fluorinated tetrasubstituted chiral centers in high yields and enantioselectivities. These fluorinated, stereochemically rich building blocks hold potential value in medicinal chemistry and are prepared using an orthogonal and enantioselective approach into such chiral moieties compared to traditional approaches, often without the use of electrophilic fluorinating reagents

Boundary stabilization of quasilinear hyperbolic systems of balance laws: Exponential decay for small source terms

We investigate the long-time behavior of solutions of quasilinear hyperbolic systems with transparent boundary conditions when small source terms are incorporated in the system. Even if the finite-time stability of the system is not preserved, it is shown here that an exponential convergence towards the steady state still holds with a decay rate which is proportional to the logarithm of the amplitude of the source term. The result is stated for a system with dynamical boundary conditions in order to deal with initial data that are free of any compatibility condition

Effect of X-ray irradiation on the biological parameters of Xestia c-nigrum

The sterile insect technique (SIT) is widely used to control Lepidopteran pests by inducing inherited sterility. The noctuid moth Xestia c-nigrum is a polyphagous pest whose subterranean larvae severely injure cereals and some vegetables. The goals of this study were to assess the impact of X-ray irradiation on the development and survival of X. c-nigrum and use the data to select suitable sterilizing doses for potential future use in pest management. Batches of male pupae were exposed to 0 (control), 10, 30, 50, 100, 200, 300, or 400 Gy of X-rays, approximately 24 h before adult emergence. Exposure of late-stage pupae to 10–200 Gy of radiation had no significant effect on adult emergence, but all doses (10–400 Gy) reduced adult longevity, the number of spermatophores in mated females, and the number of eggs laid per female in the irradiated parental generation compared with the controls. Exposure to 10 and 30 Gy had no significant effects in the F1 generation on 1) the rate of egg hatch, 2) the duration of larval or pupal development, or 3) adult longevity. However, exposure to 50 Gy reduced the rate of egg hatch in the F1 generation, and when male pupae were exposed to 100 Gy only 1% of the F1 eggs hatched. Also at 100 Gy, the developmental durations of larvae and pupae were significantly prolonged, and longevity of adult moths was reduced. There were no significant differences between the control group and any treatments in 1) the sex ratio of the F1 adults, 2) the duration of F1 pre-oviposition or oviposition periods, or 3) the number of eggs laid per F1 female. Our findings indicate that a dose of 100 Gy can effectively slow pest development and reduce larval survival in the F1 generation. In addition, F1 adults from lines treated with 100 Gy were able to mate and lay eggs, but all F2 eggs failed to hatch. Our results suggest that use of X-ray irradiation has potential to control this polyphagous pest at the regional level

Conceptual Study of a Real-Time Hybrid Simulation Framework for Monopile Offshore Wind Turbines Under Wind and Wave Loads

As an attractive renewable energy source, offshore wind plants are becoming increasingly popular for energy production. However, the performance assessment of offshore wind turbine (OWT) structure is a challenging task due to the combined wind-wave loading and difficulties in reproducing such loading conditions in laboratory. Real-time hybrid simulation (RTHS), combining physical testing and numerical simulation in real-time, offers a new venue to study the structural behavior of OWTs. It overcomes the scaling incompatibilities in OWT scaled model testing by replacing the rotor components with an actuation system, driven by an aerodynamic simulation tool running in real-time. In this study, a RTHS framework for monopile OWTs is proposed. A set of sensitivity analyses is carried out to evaluate the feasibility of this RTHS framework and determine possible tolerances on its design. By simulating different scaling laws and possible error contributors (delays and noises) in the proposed framework, the sensitivity of the OWT responses to these parameters are quantified. An example using a National Renewable Energy Lab (NREL) 5-MW reference OWT system at 1:25 scale is simulated in this study to demonstrate the proposed RTHS framework and sensitivity analyses. Three different scaling laws are considered. The sensitivity results show that the delays in the RTHS framework significantly impact the performance on the response evaluation, higher than the impact of noises. The proposed framework and sensitivity analyses presented in this study provides important information for future implementation and further development of the RTHS technology for similar marine structures

Palladium-Catalyzed Enantioselective C_(sp)^3–C_(sp)^3 Cross-Coupling for the Synthesis of (Poly)fluorinated Chiral Building Blocks

A general method for the enantioselective synthesis of carbo- and heterocyclic carbonyl compounds bearing fluorinated α-tetrasubstituted stereocenters using palladium-catalyzed decarboxylative allylic alkylation is described. The stereoselective C_(sp)^3–C_(sp)^3 cross-coupling reaction delivers five- and six-membered ketone and lactam products bearing (poly)fluorinated tetrasubstituted chiral centers in high yields and enantioselectivities. These fluorinated, stereochemically rich building blocks hold potential value in medicinal chemistry and are prepared using an orthogonal and enantioselective approach into such chiral moieties compared to traditional approaches, often without the use of electrophilic fluorinating reagents

Competitive and/or cooperative interactions of graphene-family materials and benzo[a]pyrene with pulmonary surfactant: a computational and experimental study

Background Airborne nanoparticles can be inhaled and deposit in human alveoli, where pulmonary surfactant (PS) molecules lining at the alveolar air–water interface act as the first barrier against inhaled nanoparticles entering the body. Although considerable efforts have been devoted to elucidate the mechanisms underlying nanoparticle-PS interactions, our understanding on this important issue is limited due to the high complexity of the atmosphere, in which nanoparticles are believed to experience transformations that remarkably change the nanoparticles’ surface properties and states. By contrast with bare nanoparticles that have been extensively studied, relatively little is known about the interactions between PS and inhaled nanoparticles which already adsorb contaminants. In this combined experimental and computational effort, we investigate the joint interactions between PS and graphene-family materials (GFMs) with coexisting benzo[a]pyrene (BaP). Results Depending on the BaP concentration, molecular agglomeration, and graphene oxidation, different nanocomposite structures are formed via BaPs adsorption on GFMs. Upon deposition of GFMs carrying BaPs at the pulmonary surfactant (PS) layer, competition and cooperation of interactions between different components determines the interfacial processes including BaP solubilization, GFM translocation and PS perturbation. Importantly, BaPs adsorbed on GFMs are solubilized to increase BaP’s bioavailability. By contrast with graphene adhering on the PS layer to release part of adsorbed BaPs, more BaPs are released from graphene oxide, which induces a hydrophilic pore in the PS layer and shows adverse effect on the PS biophysical function. Translocation of graphene across the PS layer is facilitated by BaP adsorption through segregating it from contact with PS, while translocation of graphene oxide is suppressed by BaP adsorption due to the increase of surface hydrophobicity. Graphene extracts PS molecules from the layer, and the resultant PS depletion declines with graphene oxidation and BaP adsorption. Conclusion GFMs showed high adsorption capacity towards BaPs to form nanocomposites. Upon deposition of GFMs carrying BaPs at the alveolar air–water interface covered by a thin PS layer, the interactions of GFM-PS, GFM-BaP and BaP-PS determined the interfacial processes of BaP solubilization, GFM translocation and PS perturbation