Development and in-vitro characterization of an implantable flow sensing transducer for hydrocephalus

An implantable transducer for monitoring the flow of Cerebrospinal fluid (CSF) for the treatment of hydrocephalus has been developed which is based on measuring the heat dissipation of a local thermal source. The transducer uses passive telemetry at 13.56 MHz for power supply and read out of the measured flow rate. The in vitro performance of the transducer has been characterized using artificial Cerebrospinal Fluid (CSF) with increased protein concentration and artificial CSF with 10\% fresh blood. After fresh blood was added to the artificial CSF a reduction of flow rate has been observed in case that the sensitive surface of the flow sensor is close to the sedimented erythrocytes. An increase of flow rate has been observed in case that the sensitive surface is in contact with the remaining plasma/artificial CSF mix above the sediment which can be explained by an asymmetric flow profile caused by the sedimentation of erythrocythes having increased viscosity compared to artificial CSF. After removal of blood from artificial CSF, no drift could be observed in the transducer measurement which could be associated to a deposition of proteins at the sensitive surface walls of the packaged flow transducer. The flow sensor specification requirement of +-10\% for a flow range between 2 ml/h and 40 ml/h. could be confirmed at test conditions of 37 degrees C.

Pi release from myosin: a simulation analysis of possible pathways

The release of phosphate (Pi) is an important element in actomyosin function and has been shown to be accelerated by the binding of myosin to actin. To provide information about the structural elements important for Pi release, possible escape pathways from various isolated myosin II structures have been determined by molecular dynamics simulations designed for studying such slow processes. The residues forming the pathways were identified and their role was evaluated by mutant simulations. Pi release is slow in the pre-powerstroke structure, an important element in preventing the powerstroke prior to actin binding, and is much more rapid for Pi modeled into the post-rigor and rigor-like structures. The previously proposed backdoor route is dominant in the pre-powerstroke and post-rigor states, whereas a different path is most important in the rigor-like state. This finding suggests a mechanism for the actin-activated acceleration of Pi release.

Outcomes of patients on dual-boosted PI regimens: experience of the Swiss HIV cohort study

Dual-boosted protease inhibitors (DBPI) are an option for salvage therapy for HIV-1 resistant patients. Patients receiving a DBPI in the Swiss HIV Cohort Study between January1996 and March 2007 were studied. Outcomes of interest were viral suppression at 24 weeks. 295 patients (72.5%) were on DBPI for over 6 months. The median duration was 2.2 years. Of 287 patients who had HIV-RNA >400?copies/ml at the start of the regimen, 184 (64.1%) were ever suppressed while on DBPI and 156 (54.4%) were suppressed within 24 weeks. The median time to suppression was 101 days (95% confidence interval 90-125 days). The median number of past regimens was 6 (IQR, 3-8). The main reasons for discontinuing the regimen were patient's wish (48.3%), treatment failure (22.5%), and toxicity (15.8%). Acquisition of HIV through intravenous drug use and the use of lopinavir in combination with saquinavir or atazanavir were associated with an increased likelihood of suppression within 6 months. Patients on DBPI are heavily treatment experienced. Viral suppression within 6 months was achieved in more than half of the patients. There may be a place for DBPI regimens in settings where more expensive alternates are not available.

PM(10) remote sensing from geostationary SEVIRI and polar-orbiting MODIS sensors over the complex terrain of the European Alpine region

The subject of this study is to investigate the capability of spaceborne remote sensing data to predict ground concentrations of PM10 over the European Alpine region using satellite derived Aerosol Optical Depth (AOD) from the geostationary Spinning Enhanced Visible and InfraRed Imager (SEVIRI) and the polar-orbiting MODerate resolution Imaging Spectroradiometer (MODIS). The spatial and temporal resolutions of these aerosol products (10 km and 2 measurements per day for MODIS, ∼ 25 km and observation intervals of 15 min for SEVIRI) permit an evaluation of PM estimation from space at different spatial and temporal scales. Different empirical linear relationships between coincident AOD and PM10 observations are evaluated at 13 ground-based PM measurement sites, with the assumption that aerosols are vertically homogeneously distributed below the planetary Boundary Layer Height (BLH). The BLH and Relative Humidity (RH) variability are assessed, as well as their impact on the parameterization. The BLH has a strong influence on the correlation of daily and hourly time series, whilst RH effects are less clear and smaller in magnitude. Despite its lower spatial resolution and AOD accuracy, SEVIRI shows higher correlations than MODIS (rSEV∼ 0.7, rMOD∼ 0.6) with regard to daily averaged PM10. Advantages from MODIS arise only at hourly time scales in mountainous locations but lower correlations were found for both sensors at this time scale (r∼ 0.45). Moreover, the fraction of days in 2008 with at least one satellite observation was 27% for SEVIRI and 17% for MODIS. These results suggest that the frequency of observations plays an important role in PM monitoring, while higher spatial resolution does not generally improve the PM estimation. Ground-based Sun Photometer (SP) measurements are used to validate the satellite-based AOD in the study region and to discuss the impact of aerosols' micro-physical properties in the empirical models. A lower error limit of 30 to 60% in the PM10 assessment from space is estimated in the study area as a result of AOD uncertainties, variability of aerosols properties and the heterogeneity of ground measurement sites. It is concluded that SEVIRI has a similar capacity to map PM as sensors on board polar-orbiting platforms, with the advantage of a higher number of observations. However, the accuracy represents a serious limitation to the applicability of satellites for ground PM mapping, especially in mountainous areas.

Acid-sensing channels in human bladder: expression, function and alterations during bladder pain syndrome

We examined the possible role of H(+) activated acid-sensing ion channels in pain perception. We characterized expression in bladder dome biopsies from patients with bladder pain syndrome and controls, in cultured human urothelium and in urothelial TEU-2 cells.

Urban Expansion and its impact on urban agriculture - remote sensing based change analysis of Kizinga and Mzinga Valley - Dar Es Salaam, Tanzania

Urban agriculture is a phenomenon that can be observed world-wide, particularly in cities of devel- oping countries. It is contributing significantly to food security and food safety and has sustained livelihood of the urban and peri-urban low income dwe llers in developing countries for many years. Population increase due to rural-urban migration and natural - formal as well as informal - urbani- sation are competing with urban farming for available space and scarce water resources. A mul- titemporal and multisensoral urban change analysis over the period of 25 years (1982-2007) was performed in order to measure and visualise the urban expansion along the Kizinga and Mzinga valley in the south of Dar Es Salaam. Airphotos and VHR satellite data were analysed by using a combination of a composition of anisotropic textural measures and spectral information. The study revealed that unplanned built-up area is expanding continuously, and vegetation covers and agricultural lands decline at a fast rate. The validation showed that the overall classification accuracy varied depending on the database. The extracted built-up areas were used for visual in- terpretation mapping purposes and served as information source for another research project. The maps visualise an urban congestion and expansion of nearly 18% of the total analysed area that had taken place in the Kizinga valley between 1982 and 2007. The same development can be ob- served in the less developed and more remote Mzinga valley between 1981 and 2002. Both areas underwent fast changes where land prices still tend to go up and an influx of people both from rural and urban areas continuously increase the density with the consequence of increasing multiple land use interests.

N-H center dot center dot center dot pi hydrogen-bonding and large-amplitude tipping vibrations in jet-cooled pyrrole-benzene

The N-H center dot center dot center dot pi hydrogen bond is an important intermolecular interaction in many biological systems. We have investigated the infrared (IR) and ultraviolet (UV) spectra of the supersonic-jet cooled complex of pyrrole with benzene and benzene-d(6) (Pyr center dot Bz, Pyr center dot Bz-d(6)). DFT-D density functional, SCS-MP2 and SCS-CC2 calculations predict a T-shaped and (almost) C(s) symmetric structure with an N-H center dot center dot center dot pi hydrogen bond to the benzene ring. The pyrrole is tipped by omega(S(0)) = +/- 13 degrees relative to the surface normal of Bz. The N center dot center dot center dot ring distance is 3.13 angstrom. In the S(1) excited state, SCS-CC2 calculations predict an increased tipping angle omega(S(1)) = +/- 21 degrees. The IR depletion spectra support the T-shaped geometry: The NH stretch is redshifted by -59 cm(-1), relative to the "free" NH stretch of pyrrole at 3531 cm(-1), indicating a moderately strong N-H center dot center dot center dot pi interaction. The interaction is weaker than in the (Pyr)(2) dimer, where the NH donor shift is -87 cm(-1) [Dauster et al., Phys. Chem. Chem. Phys., 2008, 10, 2827]. The IR C-H stretch frequencies and intensities of the Bz subunit are very similar to those of the acceptor in the (Bz)(2) dimer, confirming that Bz acts as the acceptor. While the S(1) <- S(0) electronic origin of Bz is forbidden and is not observable in the gas-phase, the UV spectrum of Pyr center dot Bz in the same region exhibits a weak 0(0)(0) band that is red-shifted by 58 cm(-1) relative to that of Bz (38 086 cm(-1)). The origin appears due to symmetry-breaking of the p-electron system of Bz by the asymmetric pyrrole NH center dot center dot center dot pi hydrogen bond. This contrasts with (Bz)(2), which does not exhibit a 0(0)(0) band. The Bz moiety in Pyr center dot Bz exhibits a 6a(0)(1) band at 0(0)(0) + 518 cm(-1) that is about 20x more intense than the origin band. The symmetry breaking by the NH center dot center dot center dot pi hydrogen bond splits the degeneracy of the v(6)(e(2g)) vibration, giving rise to 6a' and 6b' sub-bands that are spaced by similar to 6 cm(-1). Both the 0(0)(0) and 6(0)(1) bands of Pyr center dot Bz carry a progression in the low-frequency (10 cm(-1)) excited-state tipping vibration omega', in agreement with the change of the omega tipping angle predicted by SCS-MP2 and SCS-CC2 calculations.

Homo-DNA templated chemistry and its application to nucleic acid sensing

We have investigated the homo-DNA templated Staudinger reduction of the profluorophore rhodamine azide and have applied this reaction to the detection of natural DNA with a hybrid homo-DNA/DNA molecular beacon. In this system the sensing and the reporting unit are bioorthogonal to each other which facilitates sequence design and increases fidelity.