Imitating micelles as a way to control coordination self-assembly: cage-polymer switching directed rationally by solvent polarity or pH

Disguising a metal complex as a micelle by using amphiphilic phosphine ligands enables it to switch between a coordination polymer and a discrete cage in response to solvent polarity or pH; this medium-dependent behaviour of the complex is rational because it parallels that of true micelles.

Adaptation and Reintegration of Proprioceptive Information in Young and Older Adults' Postural Control

We investigated age-related changes in adaptation and sensory reintegration in postural control without vision. In two sessions, participants adapted their posture to sway reference and to reverse sway reference conditions, the former reducing (near eliminating) and the latter enhancing (near doubling) proprioceptive information for posture by means of support-surface rotations in proportion to body sway. Participants stood on a stable platform for 3 min (baseline) followed by 18 min of sway reference or reverse sway reference (adaptation) and finally again on a stable platform for 3 min (reintegration). Results showed that when inaccurate proprioception was introduced, anterior-posterior (AP) sway path length increased in comparable levels in the two age groups. During adaptation, young and older adults reduced postural sway at the same rate. On restoration of the stable platform in the reintegration phase, a sizeable aftereffect of increased AP path length was observed in both groups, which was greater in magnitude and duration for older adults. In line with linear feedback models of postural control, spectral analyses showed that this aftereffect differed between the two platform conditions. In the sway-referenced condition, a switch from low- to high-frequency COP sway marked the transition from reduced to normal proprioceptive information. The opposite switch was observed in the reverse sway referenced condition. Our findings illustrate age-related slowing in participants' postural control adjustments to sudden changes in environmental conditions. Over and above differences in postural control, our results implicate sensory reweighting as a specific mechanism highly sensitive to age-related decline.

Exchange protein directly activated by cAMP 1 (Epac1) is expressed in human neutrophils and mediates cAMP-dependent activation of the monomeric GTPase Rap1

Epac1 and Epac2 bind cAMP and mediate cAMP-dependent activation of Rap1. cAMP is produced in neutrophils in response to many chemoattractants. This second messenger plays a key role in the regulation of the functions of neutrophils. However, it is still not known whether Epacs are expressed in human neutrophils. We found that stimulation of PLB-985 cells differentiated into neutrophil-like cells, human neutrophils with 8CPT-2Me-cAMP (a selective activator of Epacs), or FK (a diterpene that augments the intracellular level of cAMP) led to GTP-loading of Rap1. Epac1 mRNA was expressed in UND and DF PLB-985 cells, but Epac1 protein was only detected in DF PLB-985 cells. In human neutrophils, the Epac1 transcript was present, and Epac1 protein could be detected by Western blot analysis if the cells had been treated with the serine protease inhibitor PMSF. FK induced adhesion of PLB-985 cells and human neutrophils on fibrinogen, a ligand for beta 2 integrins. Interestingly, in DF PLB-985 cells, but not in human neutrophils, 8CPT-2Me-cAMP induced beta 2 integrin-dependent adhesion. The failure of 8CPT-2Me-cAMP to induce beta 2 integrin-dependent human neutrophil adhesion could be explained by the fact that this compound did not induce a switch of the beta 2 integrins from a low-affinity to a high-affinity ligand-binding conformation. We concluded that Epac1 is expressed in human neutrophils and is involved in cAMP-dependent regulation of Rap1. However, the loading of GTP on Rap1 per se is not sufficient to promote activation of beta 2 integrins. J. Leukoc. Biol. 90: 741-749; 2011.

Reducing the future threat from (liver) fluke: realistic prospect or quixotic fantasy?

The liver fluke remains an economically significant parasite of livestock and is emerging as an important zoonotic infection of humans. The incidence of the disease has increased in the last few years, as a possible consequence of changes to the World's climate. Future predictions suggest that this trend is likely to continue. Allied to the changing pattern of disease, reports of resistance to triclabendazole (TCBZ) have appeared in the literature, although they do not all represent genuine cases of resistance. Nevertheless, any reports of resistance are a concern, because triclabendazole is the only drug that has high activity against the migratory and damaging juvenile stages of infection. How to deal with the twin problems (of increasing incidence and drug resistance) is the overall theme of the session on “Trematodes: Fasciola hepatica epidemiology and control” and of this review to introduce the session.

Greater knowledge of fluke epidemiology and population genetics will highlight those regions where surveillance is most required and indicate how quickly resistant populations of fluke may arise. Models of disease risk are becoming increasingly sophisticated and precise, with more refined data analysis programmes and Geographic Information Systems (GIS) data. Recent improvements have been made in our understanding of the action of triclabendazole and the ways in which flukes have become resistant to it. While microtubules are the most likely target for drug action, tubulin mutations do not seem to be involved in the resistance mechanism. Rather, upregulation of drug uptake and metabolism processes appear to be more important and the data relating to them will be discussed. The information may help in the design of new treatment strategies or pinpoint potential molecular markers for monitoring fluke populations. Advances in the identification of novel targets for drugs and vaccines will be made by the various “-omics” technologies that are now being applied to Fasciola. A major area of concern in the current control of fasciolosis is the lack of reliable tests for the diagnosis of drug (TCBZ) resistance. This has led to inaccurate reports of resistance, which is hindering successful disease management, as farmers may be encouraged to switch to less effective drugs. Progress with the development of a number of new diagnostic tests will be reviewed.

Synthesis and SAR of novel, non-MPEP chemotype mGluR5 NAMs identified by functional HTS

This Letter describes the discovery and SAR of three novel series of mGluR5 non-competitive antagonists/negative allosteric modulators (NAMs) not based on manipulation of an MPEP/MTEP chemotype identified by a functional HTS approach. This work demonstrates fundamentally new mGluR5 NAM chemotypes with submicromolar potencies, and further examples of a mode of pharmacology 'switch' to provide PAMs with a non-MPEP scaffold. (C) 2009 Elsevier Ltd. All rights reserved.

Free-space optoelectronic switching cores with MPLS for SANs over WDM ring networks

With increasing demands on storage devices in the modern communication environment, the storage area network (SAN) has evolved to provide a direct connection allowing these storage devices to be accessed efficiently. To optimize the performance of a SAN, a three-stage hybrid electronic/optical switching node architecture based on the concept of a MPLS label switching mechanism, aimed at serving as a multi-protocol label switching (MPLS) ingress label edge router (LER) for a SAN-enabled application, has been designed. New shutter-based free-space multi-channel optical switching cores are employed as the core switch fabric to solve the packet contention and switching path conflict problems. The system-level node architecture design constraints are evaluated through self-similar traffic sourced from real gigabit Ethernet network traces and storage systems. The extension performance of a SAN over a proposed WDM ring network, aimed at serving as an MPLS-enabled transport network, is also presented and demonstrated.

Chemical structural effects on γ-ray spectra of positron annihilation in fluorobenzenes

Spectra of ?-ray Doppler shifts for positron annihilation in benzene and its fluoro-derivatives are simulated using low energy plane wave positron (LEPWP) approximation. The results are compared with available measurements. It is found that the Doppler shifts in these larger aromatic compounds are dominated by the contributions of the valence electrons and that the LEPWP model overestimates the measurements by approximately 30%, in agreement with previous findings in noble gases and small molecules. It is further revealed that the halogen atoms not only switch the sign of the charges on carbon atoms that they bond to, but that they also polarize other C-H bonds in the molecule leading to a redistribution of the molecular electrostatic potentials. As a result, it is likely that the halogen atoms contribute more significantly to the annihilation process. The present study also suggests that, while the Doppler shifts are sensitive to the number of valence electrons in the molecules, they are less sensitive to the chemical structures of isomers that have the same numbers and type of atoms and, hence, the same numbers of electrons. Further investigation of this effect is warranted. © EDP Sciences, Società Italiana di Fisica, Springer-Verlag 2012.

Investigating the efficiency of fitting Coxian phase-type distributions to health care data

Coxian phase-type distributions are becoming a popular means of representing survival times within a health care environment. They are favoured as they show a distribution as a system of phases and can allow for an easy visual representation of the rate of flow of patients through a system. Difficulties arise, however, in determining the parameter estimates of the Coxian phase-type distribution. This paper examines ways of making the fitting of the Coxian phase-type distribution less cumbersome by outlining different software packages and algorithms available to perform the fit and assessing their capabilities through a number of performance measures. The performance measures rate each of the methods and help in identifying the more efficient. Conclusions drawn from these performance measures suggest SAS to be the most robust package. It has a high rate of convergence in each of the four example model fits considered, short computational times, detailed output, convergence criteria options, along with a succinct ability to switch between different algorithms.

Structural effects on the pH-dependent fluorescence of naphthalenic derivatives and consequences for sensing/switching

Naphthalenic compounds are a rich resource for designers of fluorescent sensing/switching/logic systems. The degree of internal charge transfer (ICT) character in the fluorophore excited states can vary from negligible to substantial. Naphthalene-1,8;4,5-diimides (11–13), 1,8-naphthalimides (16) and 4-chloro-1,8-naphthalimides (15) are of the former type. The latter type is represented by the 4-alkylamino-1,8-naphthalimides (1). Whether ICT-based or not, these serve as the fluorophore in ‘fluorophore-spacer-receptor’ switching systems where PET holds sway until the receptor is bound to H+. On the other hand, 4-dialkylamino-1,8-naphthalimides (3–4) show modest H+-induced fluorescence switching unless the 4-dialkylamino group is a part of a small ring (5). Electrostatic destabilization of a non-emissive twisted internal charge transfer (ICT) excited state is the origin of this behaviour. An evolution to the non-emissive twisted ICT excited state is responsible for the weak emission of the model compound 6 (and related structures 7 and 8) across the pH range. Twisted ICT excited states are also implicated in the switch 9 and its model compound 10, which are based on the 6-dialkylamino-3H-benzimidazo[2,1-a]benz[d,e]isoquinolin-3-one fluorophore.

Capturing mode-switching in postbuckling composite panels using a modified explicit procedure

A postbuckling blade-stiffened composite panel was loaded in uniaxial compression, until failure. During loading beyond initial buckling, this panel was observed to undergo a secondary instability characterised by a dynamic mode shape change. These abrupt changes cause considerable numerical difficulties using standard path-following quasi-static solution procedures in finite element analysis. Improved methods such as the arc-length-related procedures do better at traversing certain critical points along an equilibrium path but these procedures may also encounter difficulties in highly non-linear problems. This paper presents a robust, modified explicit dynamic analysis for the modelling of postbuckling structures. This method was shown to predict the mode-switch with good accuracy and is more efficient than standard explicit dynamic analysis. (C) 2003 Elsevier Science Ltd. All rights reserved.

Design and analysis of dual-rail circuits for security applications

Dual-rail encoding, return-to-spacer protocol, and hazard-free logic can be used to resist power analysis attacks by making energy consumed per clock cycle independent of processed data. Standard dual-rail logic uses a protocol with a single spacer, e.g., all-zeros, which gives rise to energy balancing problems. We address these problems by incorporating two spacers; the spacers alternate between adjacent clock cycles. This guarantees that all gates switch in every clock cycle regardless of the transmitted data values. To generate these dual-rail circuits, an automated tool has been developed. It is capable of converting synchronous netlists into dual-rail circuits and it is interfaced to industry CAD tools. Dual-rail and single-rail benchmarks based upon the advanced encryption standard (AES) have been simulated and compared in order to evaluate the method and the tool.

High-efficiency low-voltage-stress Class-EF PA with extended maximum operating frequency

The Class-EF power amplifier (PA) introduced recently has a peak switch voltage much lower than the well-known Class-E PA. However, the value of the transistor output capacitance at high frequencies is typically larger than the required Class-EF optimum shunt capacitance. As a result, softswitching operation that minimizes power dissipation during OFF-to-ON transient cannot be achieved at high frequencies. A novel Class-EF topology with transmission-line load network proposed in this paper allows the PA to operate at much higher frequencies without trading the other figures of merit. Closed-form formulations are derived to simultaneously satisfy the Class-EF impedances requirement at fundamental frequency, all even harmonics, and the first two odd harmonics as well as to provide matching to 50O load. © 2011 Institut fur Mikrowellen.

40-70 GHz 13 Gbps 1-dB loss SPST and SPDT differential switches in 0.35 μm SiGe technology

This paper presents the design and characterization of ultrafast wideband low-loss single-pole single-throw (SPST) and single-pole double-throw (SPDT) differential switches. The SPDT switch exhibits insertion loss of lower than 1.25 dB from 42 to 70 GHz and isolation of better than 20 dB from 40 to 65 GHz. Similar low-loss and broadband characteristics are also observed from the measured SPST switch. The proposed switch topologies adopting current-steering technique and implemented in 0.35 µm SiGe bipolar technology result in a switching time of only 75 ps. This suggests a maximum switching speed of 13 Gbps, the fastest ever reported at V-band.

Simulations of magnetic microstructure in thin film elements used for programmable motion of magnetic particles

The results of two-dimensional micromagnetic modeling of magnetization patterns in Permalloy ellipses under the influence of rotating constant-amplitude magnetic fields are discussed. Ellipses of two different lateral sizes have been studied, 0.5m x 1.5m and 1m x 3m. The amplitude of the rotating magnetic field was varied between simulations with the condition that it must be large enough to saturate or nearly saturate the ellipse with the field applied along the long axis of the ellipse. For the smaller ellipse size it is found that the magnetization pattern forms an S state and the direction of the net magnetization lags behind the direction of the applied field. At a critical angle of the rotating magnetic field the direction of the magnetization switches by a large angle to a new S state. Both the critical angle and the angle interval of the switch depend on field amplitude. For this new state, it is instead the applied field direction that lags behind the magnetization direction. The transient magnetization patterns correspond to multi-domain patterns including two vortices, but this state never exists for the equilibrated magnetization patterns. The behavior of the larger ellipse in rotating field is different. With the field applied along the long-axis of the ellipse, the magnetization of the ellipse is nearly saturated with a vortex close to each apex of the ellipse. As the field is rotated, this magnetization pattern remains and the net-magnetization direction lags behind the direction of the field until for a certain angle of the applied field an equilibrium multi-domain state is created. Comparisons are made with corresponding experimental results obtained by performing in-field magnetic force microscopy on Permalloy ellipses.

Metamaterial as a controllable template for nanoscale field localization

We report that subwavelength localization of light in the near-field of a double-periodic photonic metamaterial may be efficiently controlled by the polarization and wavelength of the incident radiation. A dramatic variation in the periodic near-field landscapes, including a transition from a pattern of isolated subwavelength plasmon hot-spots to a blurred, low contrast pattern, accompanied by a change in the pattern's symmetry has been observed in the proximity of an aluminum nanowire "fish-scale" nanostructure. Hot-spots as small as 0.23 lambda have been achieved and their position has been controlled by tuning the wavelength of incident light across the dipole absorption resonance of the metamaterial. A simple switch of the polarization state can lead to a spatial period doubling in the landscape pattern.