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Lipid rafts are membrane microdomains specialized in the regulation of numerous cellular processes related to membrane organization, as diverse as signal transduction, protein sorting, membrane trafficking or pathogen invasion. It has been proposed that this functional diversity would require a heterogeneous population of raft domains with varying compositions. However, a mechanism for such diversification is not known. We recently discovered that bacterial membranes organize their signal transduction pathways in functional membrane microdomains (FMMs) that are structurally and functionally similar to the eukaryotic lipid rafts. In this report, we took advantage of the tractability of the prokaryotic model Bacillus subtilis to provide evidence for the coexistence of two distinct families of FMMs in bacterial membranes, displaying a distinctive distribution of proteins specialized in different biological processes. One family of microdomains harbors the scaffolding flotillin protein FloA that selectively tethers proteins specialized in regulating cell envelope turnover and primary metabolism. A second population of microdomains containing the two scaffolding flotillins, FloA and FloT, arises exclusively at later stages of cell growth and specializes in adaptation of cells to stationary phase. Importantly, the diversification of membrane microdomains does not occur arbitrarily. We discovered that bacterial cells control the spatio-temporal remodeling of microdomains by restricting the activation of FloT expression to stationary phase. This regulation ensures a sequential assembly of functionally specialized membrane microdomains to strategically organize signaling networks at the right time during the lifespan of a bacterium.
Objective: The assessment of response to lithium maintenance treatment in bipolar disorder (BD) is complicated by variable length of treatment, unpredictable clinical course, and often inconsistent compliance. Prospective and retrospective methods of assessment of lithium response have been proposed in the literature. In this study we report the key phenotypic measures of the "Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder" scale currently used in the Consortium on Lithium Genetics (ConLiGen) study.
Materials and Methods: Twenty-nine ConLiGen sites took part in a two-stage case-vignette rating procedure to examine inter-rater agreement [Kappa (\(\kappa\))] and reliability [intra-class correlation coefficient (ICC)] of lithium response. Annotated first-round vignettes and rating guidelines were circulated to expert research clinicians for training purposes between the two stages. Further, we analyzed the distributional properties of the treatment response scores available for 1,308 patients using mixture modeling.
Results: Substantial and moderate agreement was shown across sites in the first and second sets of vignettes (\(\kappa\) = 0.66 and \(\kappa\) = 0.54, respectively), without significant improvement from training. However, definition of response using the A score as a quantitative trait and selecting cases with B criteria of 4 or less showed an improvement between the two stages (\(ICC_1 = 0.71\) and \(ICC_2 = 0.75\), respectively). Mixture modeling of score distribution indicated three subpopulations (full responders, partial responders, non responders).
Conclusions: We identified two definitions of lithium response, one dichotomous and the other continuous, with moderate to substantial inter-rater agreement and reliability. Accurate phenotypic measurement of lithium response is crucial for the ongoing ConLiGen pharmacogenomic study.
In this letter we study the influence of temperature and excitation power on the emission linewidth from site-controlled InGaAs/GaAs quantum dots grown on nanoholes defined by electron beam lithography and wet chemical etching. We identify thermal electron activation as well as direct exciton loss as the dominant intensity quenching channels. Additionally, we carefully analyze the effects of optical and acoustic phonons as well as close-by defects on the emission linewidth by means of temperature and power dependent micro-photoluminescence on single quantum dots with large pitches. (C) 2014 Author(s).
46 Patienten mit affektiven Erkrankungen und pathologischem CT wurden untersucht (Infarkt: 22, Kontusion: 6, Leukoaraiose: 11, frühkindlicher Hirnschaden: 7). Monopolar Depressive (DSMIII- R; MD) zeigten oft Leukoaraiose, Infarkte waren mit MD, Kontusionen und frühkindliche Schäden mit bipolarer Erkrankung assoziiert (BP; ANCOV A, p< .1). Kortikale Läsionen waren bei BP häufiger, jedoch fehlten signifikante Effekte von Läsionsort oder -zeitpunkt auf die Polarität der Erkrankung (ANOV A). Bei einigen Infarktpatienten kam es zur Verlaufsänderung (Chronifizierung, Bipolarität) nach Infarkt, alle Post-Infarkt-Ersterkrankungen waren bipolar.
This paper describes the influence of neuroleptic therapy on facial action in drug-naive schizophrenics. In a comparative study of medicated and unmedicated schizophrenic patients, the coordinates of 12 small light-reflecting points, attached to subjects' faces, were computer-recorded and analyzed automatically during a semistandardized clinical interview. In addition, facial activity in videotaped interviews was coded using the Facial Action Coding System (FACS). Each sample group comprised of eight patients with the DSMIII- R diagnostic criteria "schizophrenia" or "schizophreniform disorder". Subjects were studied on two occasions, one shortly after admission to the hospital, the other three weeks later. Group I was unmedicated during the first session, whereas group2 was medicated throughout the study. Three weeks after the start of medication, at the second interview, both recording methods showed a reduction in facial activity and facial expression across all subjects in group 1. The facial action of patients in group2, however, remained unchanged.
Microcavity exciton polaritons are promising candidates to build a new generation of highly nonlinear and integrated optoelectronic devices. Such devices range from novel coherent light emitters to reconfigurable potential landscapes for electro-optical polariton-lattice based quantum simulators as well as building blocks of optical logic architectures. Especially for the latter, the strongly interacting nature of the light-matter hybrid particles has been used to facilitate fast and efficient switching of light by light, something which is very hard to achieve with weakly interacting photons. We demonstrate here that polariton transistor switches can be fully integrated in electro-optical schemes by implementing a one-dimensional polariton channel which is operated by an electrical gate rather than by a control laser beam. The operation of the device, which is the polariton equivalent to a field-effect transistor, relies on combining electro-optical potential landscape engineering with local exciton ionization to control the scattering dynamics underneath the gate. We furthermore demonstrate that our device has a region of negative differential resistance and features a completely new way to create bistable behavior.
Bloch oscillations are a phenomenon well known from quantum mechanics where electrons in a lattice experience an oscillatory motion in the presence of an electric field gradient. Here, the authors report on Bloch oscillations of hybrid light−matter particles, called exciton‐polaritons (polaritons), being confined in an array of coupled microcavity waveguides. To this end, the waveguide widths and their mutual couplings are carefully designed such that a constant energy gradient is induced perpendicular to the direction of motion of the propagating polaritons. This technique allows us to directly observe and study Bloch oscillations in real‐ and momentum‐space. Furthermore, the experimental findings are supported by numerical simulations based on a modified Gross–Pitaevskii approach. This work provides an important transfer of basic concepts of quantum mechanics to integrated solid state devices, using quantum fluids of light.
Diabolical points (spectral degeneracies) can naturally occur in spectra of two-dimensional quantum systems and classical wave resonators due to simple symmetries. Geometric Berry phase is associated with these spectral degeneracies. Here, we demonstrate a diabolical point and the corresponding Berry phase in the spectrum of hybrid light-matter quasiparticles—exciton-polaritons in semiconductor microcavities. It is well known that sufficiently strong optical pumping can drive exciton-polaritons to quantum degeneracy, whereby they form a macroscopically populated quantum coherent state similar to a Bose-Einstein condensate. By pumping a microcavity with a spatially structured light beam, we create a two-dimensional quantum billiard for the exciton-polariton condensate and demonstrate a diabolical point in the spectrum of the billiard eigenstates. The fully reconfigurable geometry of the potential walls controlled by the optical pump enables a striking experimental visualization of the Berry phase associated with the diabolical point. The Berry phase is observed and measured by direct imaging of the macroscopic exciton-polariton probability densities.
Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable childhood-onset neuropsychiatric condition, often persisting into adulthood. The genetic architecture of ADHD, particularly in adults, is largely unknown. We performed an exome-wide scan of adult ADHD using the Illumina Human Exome Bead Chip, which interrogates over 250 000 common and rare variants. Participants were recruited by the International Multicenter persistent ADHD CollaboraTion (IMpACT). Statistical analyses were divided into 3 steps: (1) gene-level analysis of rare variants (minor allele frequency (MAF)<1%); (2) single marker association tests of common variants (MAF⩾1%), with replication of the top signals; and (3) pathway analyses. In total, 9365 individuals (1846 cases and 7519 controls) were examined. Replication of the most associated common variants was attempted in 9847 individuals (2077 cases and 7770 controls) using fixed-effects inverse variance meta-analysis. With a Bonferroni-corrected significance level of 1.82E−06, our analyses of rare coding variants revealed four study-wide significant loci: 6q22.1 locus (P=4.46E−08), where NT5DC1 and COL10A1 reside; the SEC23IP locus (P=6.47E−07); the PSD locus (P=7.58E−08) and ZCCHC4 locus (P=1.79E−06). No genome-wide significant association was observed among the common variants. The strongest signal was noted at rs9325032 in PPP2R2B (odds ratio=0.81, P=1.61E−05). Taken together, our data add to the growing evidence of general signal transduction molecules (NT5DC1, PSD, SEC23IP and ZCCHC4) having an important role in the etiology of ADHD. Although the biological implications of these findings need to be further explored, they highlight the possible role of cellular communication as a potential core component in the development of both adult and childhood forms of ADHD.
In this work we present an extensive experimental and theoretical investigation of different regimes of strong field light–matter interaction for cavity-driven quantum dot (QD) cavity systems. The electric field enhancement inside a high-Q micropillar cavity facilitates exceptionally strong interaction with few cavity photons, enabling the simultaneous investigation for a wide range of QD-laser detuning. In case of a resonant drive, the formation of dressed states and a Mollow triplet sideband splitting of up to 45 μeV is measured for amean cavity photon number <n\(_c\)>\(\leq\) 1. In the asymptotic limit of the linear ACStark effect we systematically investigate the power and detuning dependence of more than 400 QDs. Some QD-cavity systems exhibit an unexpected anomalous Stark shift, which can be explained by an extended dressed 4-levelQDmodel.Weprovide a detailed analysis of the QD-cavity systems properties enabling this novel effect. The experimental results are successfully reproduced using a polaron master equation approach for the QD-cavity system, which includes the driving laser field, exciton-cavity and exciton-phonon interactions