Novel PI3K/Akt Inhibitors Screened by the Cytoprotective Function of Human Immunodeficiency Virus Type 1 Tat

The PI3K/Akt pathway regulates various stress-related cellular responses such as cell survival, cell proliferation, metabolism and protein synthesis. Many cancer cell types display the activation of this pathway, and compounds inhibiting this cell survival pathway have been extensively evaluated as anti-cancer agents. In addition to cancers, several human viruses, such as HTLV, HPV, HCV and HIV-1, also modulate this pathway, presumably in order to extend the life span of the infected target cells for productive viral replication. The expression of HIV-1 Tat protein exhibited the cytoprotective effect in macrophages and a human microglial cell line by inhibiting the negative regulator of this pathway, PTEN. This cytoprotective effect of HIV-1 appears to contribute to the long-term survival and persistent HIV-1 production in human macrophage reservoirs. In this study we exploited the PI3K/Akt dependent cytoprotective effect of Tat-expressing CHME5 cells. We screened a collection of compounds known to modulate inflammation, and identified three novel compounds: Lancemaside A, Compound K and Arctigenin that abolished the cytoprotective phenotype of Tat-expressing CHME5 cells. All three compounds antagonized the kinase activity of Akt. Further detailed signaling studies revealed that each of these three compounds targeted different steps of the PI3K/Akt pathway. Arctigenin regulates the upstream PI3K enzyme from converting PIP2 to PIP3. Lancemaside A1 inhibited the movement of Akt to the plasma membrane, a critical step for Akt activation. Compound K inhibited Akt phosphorylation. This study supports that Tat-expressing CHME5 cells are an effective model system for screening novel PI3K/Akt inhibitors

Qutrit Circuits and Algebraic Relations: A Pathway to Efficient Spin-1 Hamiltonian Simulation

Quantum information processing has witnessed significant advancements through the application of qubit-based techniques within universal gate sets. Recently, exploration beyond the qubit paradigm to $d$-dimensional quantum units or qudits has opened new avenues for improving computational efficiency. This paper delves into the qudit-based approach, particularly addressing the challenges presented in the high-fidelity implementation of qudit-based circuits due to increased complexity. As an innovative approach towards enhancing qudit circuit fidelity, we explore algebraic relations, such as the Yang-Baxter-like turnover equation, that may enable circuit compression and optimization. The paper introduces the turnover relation for the three-qutrit time propagator and its potential use in reducing circuit depth. We further investigate whether this relation can be generalized for higher-dimensional quantum circuits, including a focused study on the one-dimensional spin-1 Heisenberg model. Our work outlines both rigorous and numerically efficient approaches to potentially achieve this generalization, providing a foundation for further explorations in the field of qudit-based quantum computing

Advanced fiber in-coupling through nanoprinted axially symmetric structures

Here, we introduce and demonstrate nanoprinted all-dielectric nanostructures located on fiber end faces as a novel concept for the efficient coupling of light into optical fibers, especially at multiple incidence angles and across large angular intervals. Taking advantage of the unique properties of the nanoprinting technology, such as flexibly varying the width, height, and gap distance of each individual element, we realize different polymeric axial-symmetric structures, such as double-pitch gratings and aperiodic arrays, placed on the facet of commercial step-index fibers. Of particular note is the aperiodic geometry, enabling an unprecedentedly high average coupling efficiency across the entire angular range up to 80°, outperforming regular gratings and especially bare fibers by orders of magnitude. The excellent agreement between simulation and experiment clearly demonstrates the quality of the fabricated structures and the high accuracy of the nanoprinting process. Our approach enables realizing highly integrated and ready-to-use fiber devices, defining a new class of compact, flexible, and practically relevant all-fiber devices beyond the state-of-art. Applications can be found in a variety of cutting-edge fields that require highly efficient light collection over selected angular intervals, such as endoscopy or quantum technologies. Furthermore, fiber functionalization through nanoprinting represents a promising approach for interfacing highly complex functional photonic structures with optical fibers

Nernst-Ettingshausen effect in two-component electronic liquids

A simple model describing the Nernst-Ettingshausen effect (NEE) in two-component electronic liquids is formulated. The examples considered include graphite, where the normal and Dirac fermions coexist, superconductor in fluctuating regime, with coexisting Cooper pairs and normal electrons, and the inter-stellar plasma of electrons and protons. We give a general expression for the Nernst constant and show that the origin of a giant NEE is in the strong dependence of the chemical potential on temperature in all cases

Broadband optical gain via interference in the free electron laser: principles and proposed realizations

We propose experimentally simplified schemes of an optically dispersive interface region between two coupled free electron lasers (FELs), aimed at achieving a much broader gain bandwidth than in a conventional FEL or a conventional optical klystron composed of two separated FELs. The proposed schemes can {\it universally} enhance the gain of FELs, regardless of their design when operated in the short pulsed regime

Chiral electroluminescence from thin-film perovskite metacavities

Chiral light sources realized in ultracompact device platforms are highly desirable for various applications. Among active media employed for thin-film emission devices, lead-halide perovskites have been extensively studied for photoluminescence due to their exceptional properties. However, up to date, there have been no demonstrations of chiral electroluminescence with a substantial degree of circular polarization (DCP), being critical for the development of practical devices. Here, we propose a new concept of chiral light sources based on a thin-film perovskite metacavity and experimentally demonstrate chiral electroluminescence with DCP approaching 0.38. We design a metacavity created by a metal and a dielectric metasurface supporting photonic eigenstates with close-to-maximum chiral response. Chiral cavity modes facilitate asymmetric electroluminescence of pairs of left and right circularly polarized waves propagating in the opposite oblique directions. The proposed ultracompact light sources are especially advantageous for many applications requiring chiral light beams of both helicities.Comment: 20 pages, 4 figure

Dietary intake based on physical activity level in Korean elementary school students

Prevalence of childhood obesity is increasing significantly worldwide due to energy imbalance perhaps stemming from undesirable dietary behavior and physical activity level. The objective of the study was to examine the effects of physical activity level on nutritional status in elementary school students. The subjects were comprised of 287 elementary school students between 4th and 6th grades in Seoul, Korea. The level of physical activity was scored with a modified Godin leisure-time exercise questionnaire and was categorized as active, moderately active, and sedentary. Dietary intakes were obtained using a 24-hour food recall method. An analysis of variance (ANOVA) was conducted to test for global significant differences of nutrient intakes by physical activity level. Boys were more active than girls. Daily intakes of energy in moderately active boys were significantly higher than in the sedentary group, but intakes of calcium and iron in moderately active boys were lower than active boys. For girls, physical activity level did not affect nutrient density at all. Intakes of calcium, vitamin C, and folate for both boys and girls were below 50% of recommended intake. Physical activity did not affect nutrient density and our participants were exposed to nutritional imbalance. Therefore, the results suggest that nutrition education regarding balanced diet and optimum physical activity is required for children's health and growth

Effects of finite curvature on soliton dynamics in a chain of nonlinear oscillators

We consider a curved chain of nonlinear oscillators and show that the interplay of curvature and nonlinearity leads to a number of qualitative effects. In particular, the energy of nonlinear localized excitations centered on the bending decreases when curvature increases, i.e. bending manifests itself as a trap for excitations. Moreover, the potential of this trap is double-well, thus leading to a symmetry breaking phenomenon: a symmetric stationary state may become unstable and transform into an energetically favorable asymmetric stationary state. The essentials of symmetry breaking are examined analytically for a simplified model. We also demonstrate a threshold character of the scattering process, i.e. transmission, trapping, or reflection of the moving nonlinear excitation passing through the bending.Comment: 13 pages (LaTeX) with 10 figures (EPS

Bioactive Lipids and Circulating Progenitor Cells in Patients with Cardiovascular Disease

Bone marrow-derived progenitor cells are mobilized into the peripheral blood after acute myocardial injury and in chronic ischemic heart disease. However, the mechanisms responsible for this mobilization are poorly understood. We examined the relationship between plasma levels of bioactive lipids and number of circulating progenitor cells (CPCs) in patients (N = 437) undergoing elective or emergent cardiac catheterization. Plasma levels of sphingosine-1 phosphate (S1P) and ceramide-1 phosphate (C1P) were quantified using mass spectrometry. CPCs were assessed using flow cytometry. S1P levels correlated with the numbers of CD34+, CD34+/CD133+, and CD34+/CXCR4+ CPCs even after adjustment for potential confounding factors. However, no significant correlation was observed between C1P levels and CPC count. Plasma levels of S1P correlated with the number of CPCs in patients with coronary artery disease, suggesting an important mechanistic role for S1P in stem cell mobilization. The therapeutic effects of adjunctive S1P therapy to mobilize endogenous stem cells need to be investigated