High accuracy of external ventricular drainage placement using anatomical landmarks.

BACKGROUND: The conventional approach for external ventricular drainage (EVD) application is the freehand method. Technical devices can improve the accuracy of placement, but they have not yet replaced anatomical landmarks owing to the cost and effort that they entail. There is disagreement as to whether freehand EVD application is safe enough to be accepted as a standard technique. Many authors have investigated the final catheter position in retrospect. They describe variable rates of malpositioning. However, few studies have assessed in how far cranial surface anatomy has really been respected during burr-hole drilling and catheter insertion. The aim of this study was to investigate parameters that might play a part in determining the final intracranial catheter position. METHODS: In all, 100 pre- and postprocedural thin-layer computed-tomography (CT) scans of EVD patients were analysed with the help of JiveX® and OsiriX Lite® software. A series of anatomical and catheter-related parameters, including inter alia intraventricular blood, midline shift, burr-hole location and catheter entrance angle, were correlated with the final catheter position. RESULTS: A majority of EVDs show an optimal or nearly optimal position. Only the deviation of catheter entrance angle has a significant influence on catheter malpositioning. The burr-hole location can vary within an area of several centimetres around the coronary suture. CONCLUSIONS: The freehand application of EVD is safe as long as the intracranial anatomy is not disfigured to a large extent, the surface measurements are carried out precisely and the puncturing is done perpendicularly to the skull.

Whispering gallery resonators with broken axial symmetry: Theory and experiment.

Axial symmetry is the cornerstone for theory and applications of high-Q optical whispering gallery resonators (WGRs). Nevertheless, research on birefringent crystalline material persistently pushes towards breaking this symmetry. We show theoretically and experimentally that the effect of broken axial symmetry, caused by optical anisotropy, is modest for the resonant frequencies and Q-factors of the WGR modes. Thus, the most important equatorial whispering gallery modes can be quantitatively described and experimentally identified. At the same time, the effect of broken axial symmetry on the light field distribution of the whispering gallery modes is typically very strong. This qualitatively modifies the phase-matching for the χ(2) nonlinear processes and enables broad-band second harmonic generation and optical parametric oscillation. The effect of weak geometric ellipticity in nominally symmetric WGRs is also considered. Altogether our findings pave the way for an extensive use of numerous birefringent (uniaxial and biaxial) crystals with broad transparency window and large χ(2) coefficients in nonlinear optics with WGRs.

Quantum light from a whispering-gallery-mode disk resonator.

Optical parametric down-conversion has proven to be a valuable source of nonclassical light. The process is inherently able to produce twin-beam correlations along with individual intensity squeezing of either parametric beam, when pumped far above threshold. Here, we present for the first time the direct observation of intensity squeezing of -1.2 dB of each of the individual parametric beams in parametric down-conversion by use of a high quality whispering-gallery-mode disk resonator. In addition, we observed twin-beam quantum correlations of -2.7 dB with this cavity. Such resonators feature strong optical confinement and offer tunable coupling to an external optical field. This work exemplifies the potential of crystalline whispering-gallery-mode resonators for the generation of quantum light. The simplicity of this device makes the application of quantum light in various fields highly feasible.

Naturally phase-matched second-harmonic generation in a whispering-gallery-mode resonator.

We demonstrate for the first time natural phase matching for optical frequency doubling in a high-Q whispering-gallery-mode resonator made of lithium niobate. A conversion efficiency of 9% is achieved at 30 microW in-coupled continuous wave pump power. The observed saturation pump power of 3.2 mW is almost 2 orders of magnitude lower than the state-of-the-art value. This suggests an application of our frequency doubler as a source of nonclassical light requiring only a low-power pump, which easily can be quantum noise limited. Our theoretical analysis of the three-wave mixing in a whispering-gallery-mode resonator provides the relative conversion efficiencies for frequency doubling in various modes.

Localized edge vibrations and edge reconstruction by joule heating in graphene nanostructures.

Control of the edge topology of graphene nanostructures is critical to graphene-based electronics. A means of producing atomically smooth zigzag edges using electronic current has recently been demonstrated in experiments [Jia, Science 323, 1701 (2009)10.1126/science.1166862]. We develop a microscopic theory for current-induced edge reconstruction using density functional theory. Our calculations provide evidence for localized vibrations at edge interfaces involving unpassivated armchair edges. We demonstrate that these vibrations couple to the current, estimate their excitation by Joule heating, and argue that they are the likely cause of the reconstructions observed in the experiments.

Low-threshold optical parametric oscillations in a whispering gallery mode resonator.

In whispering gallery mode (WGM) resonator light is guided by continuous total internal reflection along a curved surface. Fabricating such resonators from an optically nonlinear material one takes advantage of their exceptionally high quality factors and small mode volumes to achieve extremely efficient optical frequency conversion. Our analysis of the phase-matching conditions for optical parametric down-conversion (PDC) in a spherical WGM resonator shows their direct relation to the sum rules for photons' angular momenta and predicts a very low parametric oscillation threshold. We realized such an optical parametric oscillator (OPO) based on naturally phase-matched PDC in lithium niobate. We demonstrated a single-mode, strongly nondegenerate OPO with a threshold of 6.7 µW and linewidth under 10 MHz. This work demonstrates the remarkable capabilities of WGM-based OPOs.

Density functional theory based screening of ternary alkali-transition metal borohydrides: a computational material design project.

We present a computational screening study of ternary metal borohydrides for reversible hydrogen storage based on density functional theory. We investigate the stability and decomposition of alloys containing 1 alkali metal atom, Li, Na, or K (M(1)); and 1 alkali, alkaline earth or 3d/4d transition metal atom (M(2)) plus two to five (BH(4))(-) groups, i.e., M(1)M(2)(BH(4))(2-5), using a number of model structures with trigonal, tetrahedral, octahedral, and free coordination of the metal borohydride complexes. Of the over 700 investigated structures, about 20 were predicted to form potentially stable alloys with promising decomposition energies. The M(1)(Al/Mn/Fe)(BH(4))(4), (Li/Na)Zn(BH(4))(3), and (Na/K)(Ni/Co)(BH(4))(3) alloys are found to be the most promising, followed by selected M(1)(Nb/Rh)(BH(4))(4) alloys.

Oligonucleotide microarray identification of Bacillus anthracis strains using support vector machines.

The capability of a custom microarray to discriminate between closely related DNA samples is demonstrated using a set of Bacillus anthracis strains. The microarray was developed as a universal fingerprint device consisting of 390 genome-independent 9mer probes. The genomes of B. anthracis strains are monomorphic and therefore, typically difficult to distinguish using conventional molecular biology tools or microarray data clustering techniques. Using support vector machines (SVMs) as a supervised learning technique, we show that a low-density fingerprint microarray contains enough information to discriminate between B. anthracis strains with 90% sensitivity using a reference library constructed from six replicate arrays and three replicates for new isolates.

The ICln interactome.

The many different functional phenotypes described in mammalian cells can only be explained by an intense interaction of the underlying proteins, substantiated by the fact that the number of independently expressed proteins in living cells seems not to exceed 25 K, a number way too small to explain the >250 K different phenotypes on a one-protein-one-function base. Therefore, the study of the interactome of the different proteins is of utmost importance. Here, we describe the present knowledge of the ICln interactome. ICln is a protein, we cloned and whose function was reported to be as divers as (i) ion permeation, (ii) cytoskeletal organization, and (iii) RNA processing. The role of ICln in these different functional modules can be described best as being a 'connector hub' with 'date hub' function.

Molecular and functional aspects of anionic channels activated during regulatory volume decrease in mammalian cells.

The ability of cells to readjust their volume after swelling, a phenomenon known as regulatory volume decrease (RVD), is a fundamental biological achievement guaranteeing survival and function of cells under osmotic stress. This article reviews the mechanisms of RVD in mammalian cells with special emphasis on the activation of ion channels during RVD.

Fusion pore expansion is a slow, discontinuous, and Ca2+-dependent process regulating secretion from alveolar type II cells.

In alveolar type II cells, the release of surfactant is considerably delayed after the formation of exocytotic fusion pores, suggesting that content dispersal may be limited by fusion pore diameter and subject to regulation at a postfusion level. To address this issue, we used confocal FRAP and N-(3-triethylammoniumpropyl)-4-(4-[dibutylamino]styryl) pyridinium dibromide (FM 1-43), a dye yielding intense localized fluorescence of surfactant when entering the vesicle lumen through the fusion pore (Haller, T., J. Ortmayr, F. Friedrich, H. Volkl, and P. Dietl. 1998. Proc. Natl. Acad. Sci. USA. 95:1579-1584). Thus, we have been able to monitor the dynamics of individual fusion pores up to hours in intact cells, and to calculate pore diameters using a diffusion model derived from Fick's law. After formation, fusion pores were arrested in a state impeding the release of vesicle contents, and expanded at irregular times thereafter. The expansion rate of initial pores and the probability of late expansions were increased by elevation of the cytoplasmic Ca2+ concentration. Consistently, content release correlated with the occurrence of Ca2+ oscillations in ATP-treated cells, and expanded fusion pores were detectable by EM. This study supports a new concept in exocytosis, implicating fusion pores in the regulation of content release for extended periods after initial formation.

Determination of protein-protein interactions of ICIn by the yeast two-hybrid system.

ICln is a ubiquitously expressed eukaryotic protein. Expression of the protein in Xenopus laevis oocytes, the knocking-down of the protein in fibroblasts, or the reconstitution of the protein in lipid bilayer led to the assumption that this protein is an ionic channel or a significant part thereof. However, other possible roles for ICln in potential regulatory mechanisms have been postulated, as diverse as regulator of cell morphology by interacting with the Skb1 protein and/or interaction with core spliceosomal proteins. Here we show that ICln is able to interact with SnRNP core proteins SmD1, SmD2, SmD3, SmX5 and SmB/B'.

Structure and function of the ion channel ICln.

Normal function of organs and cells is tightly linked to the cytoarchitecture. Control of the cell volume is therefore vital for the organism. A widely established strategy of cells to counteract swelling is the activation of chloride and potassium channels, which leads to a net efflux of salt followed by water - a process termed regulatory volume decrease. Since there is evidence for swelling-dependent chloride channels (IClswell) being activated also during pathological processes, the identification of the molecular entity underlying IClswell is of utmost importance. Several proteins are discussed as the channel forming IClswell, i.e. phospholemman, p-glycoprotein, CLC-3 and ICln. In this review we would like to focus on the properties of ICln, a protein cloned from a Madin Darby canine kidney (MDCK) cell library whose expression in Xenopus laevis oocytes resulted in a nucleotide sensitive outwardly rectifying chloride current closely resembling the biophysical properties of IClswell.

Impact of enoxaparin low molecular weight heparin in patients with Q-wave myocardial infarction.

A subgroup meta-analysis from the Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events (ESSENCE) and the Thrombolysis in Myocardial Infarction (TIMI) 11B studies has shown that enoxaparin is superior to unfractionated heparin in reducing the composite end points of death, myocardial infarction, and emergency revascularization in patients with Q-wave myocardial infarction. The beneficial treatment effect was significant at 43 days.

Functional reconstitution of ICln in lipid bilayers.

Reconstitution of purified ICln in lipid bilayer leads to functional ion channels showing varying rectification. The reconstituted single channels have a conductance of approximately equal to 3 pS and their open probability is sensitive to nucleoside analogues. Mutation of a putative nucleotide binding site identified at the predicted extracellular mouth of the ICln channel protein leads to the reduction of the nucleoside-analogue sensitivity. Reconstituted ICln channels can be permeated both by cations and anions. The relative permeability of cations over anions depends on the presence of calcium. In the presence of calcium reconstituted ICln channels are more permeable to bromide than chloride, and more permeable to potassium than sodium. Similarly in NIH3T3 fibroblasts, the relative permeability of cations over anions of swelling-dependent chloride channels depends on extracellular calcium. Site-directed mutagenesis revealed the calcium-binding site responsible for the shift of the selectivity from cations towards anions of reconstituted ICln channels. Additional indirect structural information has been obtained by mutating a histidine in the predicted pore region of ICln. This histidine seems to have access to the ion-conducting tunnel of the pore. Our experiments show that ICln can act as an ionic channel, which does not exclude additional functions of the protein in regulatory mechanisms of the cell. Since knocking down the ICln protein in fibroblasts and epithelial cells leads to an impaired regulatory volume decrease (RVD) after cytoplasmic swelling and reconstituted ICln channels show several biophysical features of ion channels activated after swelling, ICln is a molecular candidate for these channels.

The promoter for constitutive expression of the human ICln gene CLNS1A.

The ICln protein is expressed ubiquitously in mammals. Experiments designed to knock down the ICln protein in NIH 3T3 fibroblasts as well as in epithelial cells led to the conclusion that this protein is crucially involved in volume regulation after cytoplasmic swelling. Reconstitution of the ICln protein in lipid bilayers revealed the ion channel nature of ICln. Here we describe a new human promoter sequence, composed of 89 nucleotides, which is responsible for a highly constitutive expression of the ICln protein. The promoter sequence lacks a TATA box, and the transcription can be effected at multiple sites. In addition to the starting sites, upstream sequence elements are mandatory for an efficient transcription of the ICln gene (CLNS1A). These new nucleotide elements were defined by site-directed mutagenesis.

The gastric H,K-ATPase blocker lansoprazole is an inhibitor of chloride channels.

1. It was postulated that swelling dependent chloride channels are involved in the proton secretion of parietal cells. Since omeprazole, lansoprazole and its acid activated sulphenamide form AG2000 are structurally related to phenol derivatives known to block swelling dependent chloride channels, we set out to test, whether these substances--which are known to block the H,K-ATPase--could also lead to an inhibition of swelling-dependent chloride channels. Swelling-dependent chloride channels--characterized in many different cell types--show highly conserved biophysical and pharmacological features, therefore we investigated the effect of omeprazole, lansoprazole and its acid activated sulphenamide form AG2000 on swelling-dependent chloride channels elicited in fibroblasts, after the reduction of the extracellular osmolarity. 2. Omeprazole, lansoprazole and its acid activated sulphenamide form AG2000 are able to block swelling-dependent chloride channels (IClswell). 3. Lansoprazole and its protonated metabolite AG2000 act on at least two different sites of the IClswell protein: on an extracellular site which seems to be in a functional proximity to the nucleotide binding site, and on an intracellular site which allows the formation of disulfide-bridges. 4. The inhibition of the proton pump and the simultaneous blocking of chloride channels by omeprazole, lansoprazole and its acid activated sulphenamide form AG2000, as described here could be an effective mode to restrict proton secretion in parietal cells.