Role of the N-terminal region in G protein-coupled receptor functions : negative modulation revealed by 5-HT2B receptor polymorphisms

The putative role of the N-terminal region of rhodopsin-like 7 transmembrane biogenic amine receptors in agonist-induced signaling has not yet been clarified despite recent advances in 7 transmembrane receptor structural biology. Given the existence of N-terminal nonsynonymous polymorphisms (R6G;E42G) within the HTR2B gene in a drug-abusing population, we assessed whether these polymorphisms affect 5-hydroxytryptamine 2B (5-HT2B) receptor in vitro pharmacologic and coupling properties in transfected COS-7 cells. Modification of the 5-HT2B receptor N terminus by the R6G;E42G polymorphisms increases such agonist signaling pathways as inositol phosphate accumulation as assessed by either classic or operational models. The N-terminal R6G;E42G mutations of the 5-HT2B receptor also increase cell proliferation and slow its desensitization kinetics compared with the wild-type receptor, further supporting a role for the N terminus in transduction efficacy. Furthermore, by coexpressing a tethered wild-type 5-HT2B receptor N terminus with a 5-HT2B receptor bearing a N-terminal deletion, we were able to restore original coupling. This reversion to normal activity of a truncated 5-HT2B receptor by coexpression of the membrane-tethered wild-type 5-HT2B receptor N terminus was not observed using a membrane-tethered 5-HT2B receptor R6G;E42G N terminus. These data suggest that the N terminus exerts a negative control over basal as well as agonist-stimulated receptor activity that is lost in the R6G;E42G mutant. Our findings reveal a new and unanticipated role of the 5-HT2B receptor N terminus as a negative modulator, affecting both constitutive and agonist-stimulated activity. Moreover, our data caution against excluding the N terminus and extracellular loops in structural studies of this 7 transmembrane receptor family

A Bit-Stream based space vector modulator

Bit-Stream based control, which uses one bit wide signals to control power electronics applications, is a new approach for controller design in power electronic systems. Bit-Stream signals are inherently high frequency in nature, and as such some form of down sampling or modulating is essential to avoid excessive switching losses. This paper presents a novel three-phase space vector modulator, which is based on the Bit-Stream technique and suitable for standard three-phase inverter systems. The proposed modulator simultaneously converts a two phase reference to the three-phase domain and reduces switching frequencies to reasonable levels. The modulator consumes relatively few logic elements and does not require sector detectors, carrier oscillators or trigonometric functions. The performance of the modulator was evaluated using ModelSim. Results indicate that, subject to limits on the modulation index, the proposed modulator delivers a spread-spectrum output with total harmonic distortion comparable to standard space vector pulse width modulation techniques.

Engineering the mechanical properties of graphene nanotube hybrid structures through structural modulation

The excellent multi-functional properties of carbon nanotube (CNT) and graphene have enabled them as appealing building blocks to construct 3D carbon-based nanomaterials or nanostructures. The recently reported graphene nanotube hybrid structure (GNHS) is one of the representatives of such nanostructures. This work investigated the relationships between the mechanical properties of the GNHS and its structure basing on large-scale molecular dynamics simulations. It is found that increasing the length of the constituent CNTs, the GNHS will have a higher Young’s modulus and yield strength. Whereas, no strong correlation is found between the number of graphene layers and Young’s modulus and yield strength, though more graphene layers intends to lead to a higher yield strain. In the meanwhile, the presences of multi-wall CNTs are found to greatly strengthen the hybrid structure. Generally, the hybrid structures exhibit a brittle behavior and the failure initiates from the connecting regions between CNT and graphene. More interestingly, affluent formations of monoatomic chains and rings are found at the fracture region. This study provides an in-depth understanding of the mechanical performance of the GNHSs while varying their structures, which will shed lights on the design and also the applications of the carbon-based nanostructures.

Phonon modes of MgB2 : Super-lattice structures and spectral response

Micrometre-sized MgB2 crystals of varying quality, synthesized at low temperature and autogeneous pressure, are compared using a combination of Raman and Infra-Red (IR) spectroscopy. These data, which include new peak positions in both spectroscopies for high quality MgB2, are interpreted using DFT calculations on phonon behaviour for symmetry-related structures. Raman and IR activity additional to that predicted by point group analyses of the P6/mmm symmetry are detected. These additional peaks, as well as the overall shapes of calculated phonon dispersion (PD) models are explained by assuming a double super-lattice, consistent with a lower symmetry structure for MgB2. A 2x super-lattice in the c-direction allows a simple correlation of the pair breaking energy and the superconducting gap by activation of corresponding acoustic frequencies. A consistent physical interpretation of these spectra is obtained when the position of a phonon anomaly defines a super-lattice modulation in the a-b plane.

A novel method of Fiber Bragg Grating (FBG) strain modulation and its application in FBG accelerometers

This thesis has systemically investigated the possibility of improving one type of optical fiber sensors by using a novel mechanism. Many parameters of the sensor have been improved, and one outcome of this innovation is that civil structures, such as bridges and high-rise buildings, may be operated more safely and used longer.

Regulation of P-fimbrial phase variation frequencies in Escherichia coli CFT073

Adherence of uropathogenic Escherichia coli to host tissue is required for infection and is mediated by fimbriae, such as pyelonephritis-associated pili (Pap). Expression of P fimbriae is regulated by phase variation, and to date, phase transition frequencies have been measured only for pap regulatory region constructs integrated into the E. coli K-12 chromosome. The aim of this work was to measure P phase transition frequencies in clinical isolates for the first time, including frequencies for the sequenced strain E. coli CFT073. P fimbriation and associated phase transition frequencies were measured for two E. coli clinical isolates and compared with levels for homologous pap constructs in E. coli K-12. Fimbriation and off-to-on transition frequencies were always higher in the clinical isolate. It was concluded that the regulatory inputs controlling papI expression are likely to be different in E. coli CFT073 and E. coli K-12 as (i) phase variation could be stimulated in E. coli K-12 by induction of papI and (ii) the level of expression of a papI::gfp+ fusion was higher in E. coli CFT073 than in E. coli K-12. Furthermore, phase transition frequencies for the two E. coli CFT073 pap clusters were shown to be different depending on the culture conditions, indicating that there is a hierarchy of expression depending on signal inputs.

Thermal conductivity of configurable two-dimensional carbon nanotube architecture and strain modulation

We reported the thermal conductivity of the two-dimensional carbon nanotube (CNT)-based architecture, which can be constructed through welding of single-wall CNTs by electron beam. Using large-scale nonequilibrium molecular dynamics simulations, the thermal conductivity is found to vary with different junction types due to their different phonon scatterings at the junction. The strong length and strain dependence of the thermal conductivity suggests an effective avenue to tune the thermal transport properties of the CNT-based architecture, benefiting the design of nanoscale thermal rectifiers or phonon engineering.

Assessing rod, cone and melanopsin contributions to human pupil flicker responses

Purpose: To determine the relative contributions of rods, cones and melanopsin to pupil responses in humans using temporal sinusoidal stimulation for light levels spanning the low mesopic to photopic range. Methods: A four-primary Ganzfeld photostimulator controlled flicker stimulations at seven light levels (-2.7 to 2 log cd/m2) and five frequencies (0.5 to 8Hz). Pupil diameter was measured using a high-resolution eyetracker. Three kinds of sinusoidal photoreceptor modulations were generated using silent substitution: 1) rod modulation, 2) cone modulation, and 3) combined rod and cone modulation in phase (Experiment 1) or phase shifted (Experiment 2) from a fixed rod phase. The melanopsin excitation was computed for each condition. A vector sum model was used to estimate the relative contribution of rods, cones and melanopsin to the pupil response. Results: From Experiment 1, the pupil frequency response peaked at 1Hz at two mesopic light levels for the three modulation conditions. Analyzing the rod-cone phase difference for the combined modulations (Experiment 2) identified a V-shaped response amplitude with a minimum between 135° and 180°. The pupil response phases increased as cone modulation phase increased. The pupil amplitude increased with increasing light level for cone and combined in-phase rod and cone modulation, but not for the rod modulation. Conclusions: These results demonstrate that cone- and rod-pathway contributions are more predominant than melanopsin contribution to the phasic pupil response. The combined rod, cone and melanopsin inputs to the phasic state of the pupil light reflex follow linear summation.

Modulating power and 'new weapons': Taking aim at the education revolution

This paper looks at the emergent performative culture seducing education in the Australian context. It links this corporate discourse to Deleuzean theorising of control societies to postulate that what we are experiencing is a new form of power relations – that of the modulating mechanisms of power. These modulating mechanisms overlay disciplinary power such that the self is modulated through the amplification and frequencies of the instruments of modulation: the simulation, the categorical sorting and the sample. These instruments are increasingly utilised within the performative culture of the Australian Federal Government’s Education Revolution as examples of the performative ‘terror’ or the abstraction of the self from the terrain in which they move. Finally, some new weapons are suggested that may offer preliminary and tentative ‘movement’ in deterritorialising ways through the enclosed spaces of mass, compulsory school and the policy that shapes it.

Single layer lead iodide: Computational exploration of structural, electronic and optical properties, strain induced band modulation and the role of spin-orbital-coupling

Graphitic like layered materials exhibit intriguing electronic structures and thus the search for new types of two-dimensional (2D) monolayer materials is of great interest for developing novel nano-devices. By using density functional theory (DFT) method, here we for the first time investigate the structure, stability, electronic and optical properties of monolayer lead iodide (PbI2). The stability of PbI2 monolayer is first confirmed by phonon dispersion calculation. Compared to the calculation using generalized gradient approximation, screened hybrid functional and spin–orbit coupling effects can not only predicts an accurate bandgap (2.63 eV), but also the correct position of valence and conduction band edges. The biaxial strain can tune its bandgap size in a wide range from 1 eV to 3 eV, which can be understood by the strain induced uniformly change of electric field between Pb and I atomic layer. The calculated imaginary part of the dielectric function of 2D graphene/PbI2 van der Waals type hetero-structure shows significant red shift of absorption edge compared to that of a pure monolayer PbI2. Our findings highlight a new interesting 2D material with potential applications in nanoelectronics and optoelectronics.

A method for estimating intrinsic noise in electroretinographic (ERG) signals

Purpose To develop a signal processing paradigm for extracting ERG responses to temporal sinusoidal modulation with contrasts ranging from below perceptual threshold to suprathreshold contrasts. To estimate the magnitude of intrinsic noise in ERG signals at different stimulus contrasts. Methods Photopic test stimuli were generated using a 4-primary Maxwellian view optical system. The 4-primary lights were sinusoidally temporally modulated in-phase (36 Hz; 2.5 - 50% Michelson). The stimuli were presented in 1 s epochs separated by a 1 ms blank interval and repeated 160 times (160.16 s duration) during the recording of the continuous flicker ERG from the right eye using DTL fiber electrodes. After artefact rejection, the ERG signal was extracted using Fourier methods in each of the 1 s epochs where a stimulus was presented. The signal processing allows for computation of the intrinsic noise distribution in addition to the signal to noise (SNR) ratio. Results We provide the initial report that the ERG intrinsic noise distribution is independent of stimulus contrast whereas SNR decreases linearly with decreasing contrast until the noise limit at ~2.5%. The 1ms blank intervals between epochs de-correlated the ERG signal at the line frequency (50 Hz) and thus increased the SNR of the averaged response. We confirm that response amplitude increases linearly with stimulus contrast. The phase response shows a shallow positive relationship with stimulus contrast. Conclusions This new technique will enable recording of intrinsic noise in ERG signals above and below perceptual visual threshold and is suitable for measurement of continuous rod and cone ERGs across a range of temporal frequencies, and post-receptoral processing in the primary retinogeniculate pathways at low stimulus contrasts. The intrinsic noise distribution may have application as a biomarker for detecting changes in disease progression or treatment efficacy.

Channel selection in the short-time modulation domain for distant speech recognition

Automatic speech recognition from multiple distant micro- phones poses significant challenges because of noise and reverberations. The quality of speech acquisition may vary between microphones because of movements of speakers and channel distortions. This paper proposes a channel selection approach for selecting reliable channels based on selection criterion operating in the short-term modulation spectrum domain. The proposed approach quantifies the relative strength of speech from each microphone and speech obtained from beamforming modulations. The new technique is compared experimentally in the real reverb conditions in terms of perceptual evaluation of speech quality (PESQ) measures and word error rate (WER). Overall improvement in recognition rate is observed using delay-sum and superdirective beamformers compared to the case when the channel is selected randomly using circular microphone arrays.

An investigation into the effectiveness of sensory modulation in reducing seclusion within an acute mental health unit

In this paper we report the findings from an evaluation of the introduction of sensory modulation (SM) in an acute mental health inpatient unit. It was expected that SM could be used to help settle patients experiencing high levels of disturbance and that as a result, there would be less need for use of more restrictive seclusion practices. The evaluation took place in a hospital in south-east Queensland, Australia. SM was introduced in one acute unit while the other served as a control. The evaluation comprised two studies. In the first study we aimed to determine whether SM reduced the level of disturbance among patients given the opportunity to use it. In the second study we aimed to find out whether the introduction of SM reduced the frequency and duration of seclusion. In study 1, we found that most patients reported marked reduction in disturbance after using SM and there was a very large effect size for the group as a whole. In study 2, we found that frequency of seclusion dropped dramatically in the unit that introduced SM but rose slightly in the unit that did not have access to SM. The change in seclusion rate was highly significant (χ2 = 49.1, df = 1, p < 0.001). Results are discussed, having reference to the limitations inherent in a naturalistic study.

On the effect of Reynolds number for flow past three side-by-side square cylinders for unequal gap spacings

Flow patterns and aerodynamic characteristics behind three side-by-side square cylinders has been found depending upon the unequal gap spacing (g1 = s1/d and g2 = s2/d) between the three cylinders and the Reynolds number (Re) using the Lattice Boltzmann method. The effect of Reynolds numbers on the flow behind three cylinders are numerically studied for 75 ≤ Re ≤ 175 and chosen unequal gap spacings such as (g1, g2) = (1.5, 1), (3, 4) and (7, 6). We also investigate the effect of g2 while keeping g1 fixed for Re = 150. It is found that a Reynolds number have a strong effect on the flow at small unequal gap spacing (g1, g2) = (1.5, 1.0). It is also found that the secondary cylinder interaction frequency significantly contributes for unequal gap spacing for all chosen Reynolds numbers. It is observed that at intermediate unequal gap spacing (g1, g2) = (3, 4) the primary vortex shedding frequency plays a major role and the effect of secondary cylinder interaction frequencies almost disappear. Some vortices merge near the exit and as a result small modulation found in drag and lift coefficients. This means that with the increase in the Reynolds numbers and unequal gap spacing shows weakens wakes interaction between the cylinders. At large unequal gap spacing (g1, g2) = (7, 6) the flow is fully periodic and no small modulation found in drag and lift coefficients signals. It is found that the jet flows for unequal gap spacing strongly influenced the wake interaction by varying the Reynolds number. These unequal gap spacing separate wake patterns for different Reynolds numbers: flip-flopping, in-phase and anti-phase modulation synchronized, in-phase and anti-phase synchronized. It is also observed that in case of equal gap spacing between the cylinders the effect of gap spacing is stronger than the Reynolds number. On the other hand, in case of unequal gap spacing between the cylinders the wake patterns strongly depends on both unequal gap spacing and Reynolds number. The vorticity contour visualization, time history analysis of drag and lift coefficients, power spectrum analysis of lift coefficient and force statistics are systematically discussed for all chosen unequal gap spacings and Reynolds numbers to fully understand this valuable and practical problem.