Tissue fusion, a new opportunity for sutureless bypass surgery

Microsurgical suturing is the standard for cerebral bypass surgery, a technique where temporary occlusion is usually necessary. Non-occlusive techniques such as excimer laser-assisted non-occlusive anastomosis (ELANA) have certainly widened the spectrum of treatment of complex cerebrovascular situations, such as giant cerebral aneurysms, that were otherwise non-treatable. Nevertheless, the reduction of surgical risks while widening the spectrum of indications, such as a prophylactic cerebral bypass, is still a main aim, that we would like to pursue with our sutureless tissue fusion research. The primary concern in sutureless tissue fusion- and especially in tissue fusion of cerebral vessels- is the lack of reproducibility, often caused by variations in the thermal damage of the vessel. This has prevented this novel fusion technique from being applicable in daily surgical use. In this overview, we present three ways to further improve the laser tissue soldering technique.In the first section entitled "Laser Tissue Soldering Using a Biodegradable Polymer," a porous polymer scaffold doped with albumin (BSA) and indocyanine green (ICG) is presented, leading to strong and reproducible tensile strengths in tissue soldering. Histologies and future developments are discussed.In the section "Numerical Simulation for Improvement of Laser Tissue Soldering," a powerful theoretical simulation model is used to calculate temperature distribution during soldering. The goal of this research is to have a tool in hand that allows us to determine laser irradiation parameters that guarantee strong vessel fusion without thermally damaging the inner structures such as the intima and endothelium.In a third section, "Nanoparticles in Laser Tissue Soldering," we demonstrate that nanoparticles can be used to produce a stable and well-defined spatial absorption profile in the scaffold, which is an important step towards increasing the reproducibility. The risks of implanting nanoparticles into a biodegradable scaffold are discussed.Step by step, these developments in sutureless tissue fusion have improved the tensile strength and the reproducibility, and are constantly evolving towards a clinically applicable anastomosis technique.

The international spine registry SPINE TANGO: status quo and first results

With an official life time of over 5 years, Spine Tango can meanwhile be considered the first international spine registry. In this paper we present an overview of frequency statistics of Spine Tango for demonstrating the genesis of questionnaire development and the constantly increasing activity in the registry. Results from two exemplar studies serve for showing concepts of data analysis applied to a spine registry. Between 2002 and 2006, about 6,000 datasets were submitted by 25 centres. Descriptive analyses were performed for demographic, surgical and follow-up data of three generations of the Spine Tango surgery and follow-up forms. The two exemplar studies used multiple linear regression models to identify potential predictor variables for the occurrence of dura lesions in posterior spinal fusion, and to evaluate which covariates influenced the length of hospital stay. Over the study period there was a rise in median patient age from 52.3 to 58.6 years in the Spine Tango data pool and an increasing percentage of degenerative diseases as main pathology from 59.9 to 71.4%. Posterior decompression was the most frequent surgical measure. About one-third of all patients had documented follow-ups. The complication rate remained below 10%. The exemplar studies identified "centre of intervention" and "number of segments of fusion" as predictors of the occurrence of dura lesions in posterior spinal fusion surgery. Length of hospital stay among patients with posterior fusion was significantly influenced by "centre of intervention", "surgeon credentials", "number of segments of fusion", "age group" and "sex". Data analysis from Spine Tango is possible but complicated by the incompatibility of questionnaire generations 1 and 2 with the more recent generation 3. Although descriptive and also analytic studies at evidence level 2++ can be performed, findings cannot yet be generalised to any specific country or patient population. Current limitations of Spine Tango include the low number and short duration of follow-ups and the lack of sufficiently detailed patient data on subgroup levels. Although the number of participants is steadily growing, no country is yet represented with a sufficient number of hospitals. Nevertheless, the benefits of the project for the whole spine community become increasingly visible.

Multi-node TOA-DOA cooperative LOS-NLOS localization : enabling high accuracy and reliability

This dissertation investigates high performance cooperative localization in wireless environments based on multi-node time-of-arrival (TOA) and direction-of-arrival (DOA) estimations in line-of-sight (LOS) and non-LOS (NLOS) scenarios. Here, two categories of nodes are assumed: base nodes (BNs) and target nodes (TNs). BNs are equipped with antenna arrays and capable of estimating TOA (range) and DOA (angle). TNs are equipped with Omni-directional antennas and communicate with BNs to allow BNs to localize TNs; thus, the proposed localization is maintained by BNs and TNs cooperation. First, a LOS localization method is proposed, which is based on semi-distributed multi-node TOA-DOA fusion. The proposed technique is applicable to mobile ad-hoc networks (MANETs). We assume LOS is available between BNs and TNs. One BN is selected as the reference BN, and other nodes are localized in the coordinates of the reference BN. Each BN can localize TNs located in its coverage area independently. In addition, a TN might be localized by multiple BNs. High performance localization is attainable via multi-node TOA-DOA fusion. The complexity of the semi-distributed multi-node TOA-DOA fusion is low because the total computational load is distributed across all BNs. To evaluate the localization accuracy of the proposed method, we compare the proposed method with global positioning system (GPS) aided TOA (DOA) fusion, which are applicable to MANETs. The comparison criterion is the localization circular error probability (CEP). The results confirm that the proposed method is suitable for moderate scale MANETs, while GPS-aided TOA fusion is suitable for large scale MANETs. Usually, TOA and DOA of TNs are periodically estimated by BNs. Thus, Kalman filter (KF) is integrated with multi-node TOA-DOA fusion to further improve its performance. The integration of KF and multi-node TOA-DOA fusion is compared with extended-KF (EKF) when it is applied to multiple TOA-DOA estimations made by multiple BNs. The comparison depicts that it is stable (no divergence takes place) and its accuracy is slightly lower than that of the EKF, if the EKF converges. However, the EKF may diverge while the integration of KF and multi-node TOA-DOA fusion does not; thus, the reliability of the proposed method is higher. In addition, the computational complexity of the integration of KF and multi-node TOA-DOA fusion is much lower than that of EKF. In wireless environments, LOS might be obstructed. This degrades the localization reliability. Antenna arrays installed at each BN is incorporated to allow each BN to identify NLOS scenarios independently. Here, a single BN measures the phase difference across two antenna elements using a synchronized bi-receiver system, and maps it into wireless channel’s K-factor. The larger K is, the more likely the channel would be a LOS one. Next, the K-factor is incorporated to identify NLOS scenarios. The performance of this system is characterized in terms of probability of LOS and NLOS identification. The latency of the method is small. Finally, a multi-node NLOS identification and localization method is proposed to improve localization reliability. In this case, multiple BNs engage in the process of NLOS identification, shared reflectors determination and localization, and NLOS TN localization. In NLOS scenarios, when there are three or more shared reflectors, those reflectors are localized via DOA fusion, and then a TN is localized via TOA fusion based on the localization of shared reflectors.

Measurement of Higgs boson production in the diphoton decay channel in pp collisions at center-of-mass energies of 7 and 8 TeV with the ATLAS detector

A measurement of the production processes of the recently discovered Higgs boson is performed in the two-photon final state using 4.5  fb −1 of proton-proton collisions data at s √ =7  TeV and 20.3  fb −1 at s √ =8  TeV collected by the ATLAS detector at the Large Hadron Collider. The number of observed Higgs boson decays to diphotons divided by the corresponding Standard Model prediction, called the signal strength, is found to be μ=1.17±0.27 at the value of the Higgs boson mass measured by ATLAS, m H =125.4  GeV . The analysis is optimized to measure the signal strengths for individual Higgs boson production processes at this value of m H . They are found to be μ ggF =1.32±0.38 , μ VBF =0.8±0.7 , μ WH =1.0±1.6 , μ ZH =0.1 +3.7 −0.1 , and μ tt ¯ H =1.6 +2.7 −1.8 , for Higgs boson production through gluon fusion, vector-boson fusion, and in association with a W or Z boson or a top-quark pair, respectively. Compared with the previously published ATLAS analysis, the results reported here also benefit from a new energy calibration procedure for photons and the subsequent reduction of the systematic uncertainty on the diphoton mass resolution. No significant deviations from the predictions of the Standard Model are found.

Influence of muscle fiber orientation on water and metabolite relaxation times, magnetization transfer, and visibility in human skeletal muscle

PURPOSE To gain a deeper understanding of the influence of skeletal muscle fiber orientation on metabolite visibility, magnetization transfer from water, and water proton relaxation rates in (1) H MR spectra. METHODS Non-water-suppressed MR spectroscopy was performed in tibialis anterior muscle (TA) of 10 healthy adults, with the TA oriented either parallel or at the magic angle to the 3T field. Spectra were acquired with metabolite-cycled PRESS, and water inversion from 50 to 2510 ms before excitation. Water proton T2 relaxation was sampled with STEAM with echo times from 12 to 272 ms. RESULTS Apparent concentrations of total creatine (tCr), taurine, and trimethylammonium compounds were reduced by 29% to 67% when TA was parallel to B0 . Both tCr peak areas were strongly correlated to the methylene peak splitting. Magnetization transfer rates from water to tCr CH3 were not significantly different between orientations. Water T1 s were similar between orientations, but T2 s were statistically significantly shorter by 1 ms in the parallel orientation (P = 0.002). CONCLUSION Muscle metabolite visibilities in MR spectroscopy and water T2 times depend substantially on muscle fiber orientation relative to B0 . In contrast, magnetization transfer rates appear to depend on muscle composition, rather than fiber orientation. Magn Reson Med, 2015. © 2015 Wiley Periodicals, Inc.

Cell-cell fusion induced by the Ig3 domain of receptor FGFRL1 in CHO cells.

FGFRL1 is a single-pass transmembrane protein with three extracellular Ig domains. When overexpressed in CHO cells or related cell types, it induces cell-cell fusion and formation of large, multinucleated syncytia. For this fusion-promoting activity, only the membrane-proximal Ig domain (Ig3) and the transmembrane domain are required. It does not matter whether the transmembrane domain is derived from FGFRL1 or from another receptor, but the distance of the Ig3 domain to the membrane is crucial. Fusion can be inhibited with soluble recombinant proteins comprising the Ig1-Ig2-Ig3 or the Ig2-Ig3 domains as well as with monoclonal antibodies directed against Ig3. Mutational analysis reveals a hydrophobic site in Ig3 that is required for fusion. If a single amino acid from this site is mutated, fusion is abolished. The site is located on a β-sheet, which is part of a larger β-barrel, as predicted by computer modeling of the 3D structure of FGFRL1. It is possible that this site interacts with a target protein of neighboring cells to trigger cell-cell fusion.

Radiative properties for warm and hot dense matter

We will present calculations of opacities for matter under LTE conditions. Opacities are needed in radiation transport codes to study processes like Inertial Confinement Fusion and plasma amplifiers in X-ray secondary sources. For the calculations we use the code BiGBART, with either a hydrogenic approximation with j-splitting or self-consistent data generated with the atomic physics code FAC. We calculate the atomic structure, oscillator strengths, radiative transition energies, including UTA computations, and photoionization cross-sections. A DCA model determines the configurations considered in the computation of the opacities. The opacities obtained with these two models are compared with experimental measurements.

Modelling of spectral properties and population kinetics studies of inertial fusión and laboratory astrophysical plasmas

Fundamental research and modelling in plasma atomic physics continue to be essential for providing basic understanding of many different topics relevant to high-energy-density plasmas. The Atomic Physics Group at the Institute of Nuclear Fusion has accumulated experience over the years in developing a collection of computational models and tools for determining the atomic energy structure, ionization balance and radiative properties of, mainly, inertial fusion and laser-produced plasmas in a variety of conditions. In this work, we discuss some of the latest advances and results of our research, with emphasis on inertial fusion and laboratory-astrophysical applications.

Regularized logistic regression and multi-objective variable selection for classifying MEG data

This paper addresses the question of maximizing classifier accuracy for classifying task-related mental activity from Magnetoencelophalography (MEG) data. We propose the use of different sources of information and introduce an automatic channel selection procedure. To determine an informative set of channels, our approach combines a variety of machine learning algorithms: feature subset selection methods, classifiers based on regularized logistic regression, information fusion, and multiobjective optimization based on probabilistic modeling of the search space. The experimental results show that our proposal is able to improve classification accuracy compared to approaches whose classifiers use only one type of MEG information or for which the set of channels is fixed a priori.

Estudio teórico de propiedades termodinámicas y optoelectronicas de nuevos materiales fotovoltaicos de banda intermedia = Theoretical study of thermodynamic and optoelectronic properties of new intermediate band photovoltaic materials

Los materiales de banda intermedia han atraido la atención de la comunidad científica en el campo de la energía solar fotovoltaica en los últimos años. Sin embargo, con el objetivo de entender los fundamentos de las células solares de banda intermedia, se debe llevar a cabo un estudio profundo de la características de los materiales. Esto se puede hacer mediante un modelo teórico usando Primeros Principios. A partir de este enfoque se pueden obtener resultados tales como la estructura electrónica y propiedades ópticas, entre otras, de los semiconductores fuertemente dopados y sus precursores. Con el fin de desentrañar las estructuras de estos sistemas electrónicos, esta tesis presenta un estudio termodinámico y optoelectrónico de varios materiales fotovoltaicos. Específicamente se caracterizaron los materiales avanzados de banda intermedia y sus precursores. El estudio se hizo en términos de caracterización teórica de la estructura electrónica, la energética del sistema, entre otros. Además la estabilidad se obtuvo usando configuraciones adaptadas a la simetría del sistema y basado en la combinatoria. Las configuraciones de los sitios ocupados por defectos permiten obtener información sobre un espacio de configuraciones donde las posiciones de los dopantes sustituidos se basan en la simetría del sólido cristalino. El resultado puede ser tratado usando elementos de termodinámica estadística y da información de la estabilidad de todo el espacio simétrico. Además se estudiaron otras características importantes de los semiconductores de base. En concreto, el análisis de las interacciones de van der Waals fueron incluidas en el semiconductor en capas SnS2, y el grado de inversión en el caso de las espinelas [M]In2S4. En este trabajo además realizamos una descripción teórica exhaustiva del sistema CdTe:Bi. Este material de banda-intermedia muestra características que son distintas a las de los otros materiales estudiados. También se analizó el Zn como agente modulador de la posición de las sub-bandas prohibidas en el material de banda-intermedia CuGaS2:Ti. Analizándose además la viabilidad termodinámica de la formación de este compuesto. Finalmente, también se describió el GaN:Cr como material de banda intermedia, en la estructura zinc-blenda y en wurtztite, usando configuraciones de sitios ocupados de acuerdo a la simetría del sistema cristalino del semiconductor de base. Todos los resultados, siempre que fue posible, fueron comparados con los resultados experimentales. ABSTRACT The intermediate-band materials have attracted the attention of the scientific community in the field of the photovoltaics in recent years. Nevertheless, in order to understand the intermediate-band solar cell fundamentals, a profound study of the characteristics of the materials is required. This can be done using theoretical modelling from first-principles. The electronic structure and optical properties of heavily doped semiconductors and their precursor semiconductors are, among others, results that can be obtained from this approach. In order to unravel the structures of these crystalline systems, this thesis presents a thermodynamic and optoelectronic study of several photovoltaic materials. Specifically advanced intermediate-band materials and their precursor semiconductors were characterized. The study was made in terms of theoretical characterization of the electronic structure, energetics among others. The stability was obtained using site-occupancy-disorder configurations adapted to the symmetry of the system and based on combinatorics. The site-occupancy-disorder method allows the formation of a configurational space of substitutional dopant positions based on the symmetry of the crystalline solid. The result, that can be treated using statistical thermodynamics, gives information of the stability of the whole space of symmetry of the crystalline lattice. Furthermore, certain other important characteristics of host semiconductors were studied. Specifically, the van der Waal interactions were included in the SnS2 layered semiconductor, and the inversion degree in cases of [M]In2S4 spinels. In this work we also carried out an exhaustive theoretical description of the CdTe:Bi system. This intermediate-band material shows characteristics that are distinct from those of the other studied intermediate-band materials. In addition, Zn was analysed as a modulator of the positions of the sub-band gaps in the CuGaS2:Ti intermediate-band material. The thermodynamic feasibility of the formation of this compound was also carried out. Finally GaN:Cr intermediate-band material was also described both in the zinc-blende and the wurtztite type structures, using the symmetry-adapted-space of configurations. All results, whenever possible, were compared with experimental results.

Measurement of cytosolic, mitochondrial, and Golgi pH in single living cells with green fluorescent proteins

Many cellular events depend on a tightly compartmentalized distribution of H+ ions across membrane-bound organelles. However, measurements of organelle pH in living cells have been scarce. Several mutants of the Aequorea victoria green fluorescent protein (GFP) displayed a pH-dependent absorbance and fluorescent emission, with apparent pKa values ranging from 6.15 (mutations F64L/S65T/H231L) and 6.4 (K26R/F64L/S65T/Y66W/N146I/M153T/V163A/N164H/H231L) to a remarkable 7.1 (S65G/S72A/T203Y/H231L). We have targeted these GFPs to the cytosol plus nucleus, the medial/trans-Golgi by fusion with galactosyltransferase, and the mitochondrial matrix by using the targeting signal from subunit IV of cytochrome c oxidase. Cells in culture transfected with these cDNAs displayed the expected subcellular localization by light and electron microscopy and reported local pH that was calibrated in situ with ionophores. We monitored cytosolic and nuclear pH of HeLa cells, and mitochondrial matrix pH in HeLa cells and in rat neonatal cardiomyocytes. The pH of the medial/trans-Golgi was measured at steady-state (calibrated to be 6.58 in HeLa cells) and after various manipulations. These demonstrated that the Golgi membrane in intact cells is relatively permeable to H+, and that Cl− serves as a counter-ion for H+ transport and likely helps to maintain electroneutrality. The amenability to engineer GFPs to specific subcellular locations or tissue targets using gene fusion and transfer techniques should allow us to examine pH at sites previously inaccessible.

Studies using double mutants of the conformational transitions in influenza hemagglutinin required for its membrane fusion activity

Amino acid substitutions widely distributed throughout the influenza hemagglutinin (HA) influence the pH of its membrane fusion activity. We have combined a number of these substitutions in double mutants and determined the effects on the pH of fusion and on the pH at which the refolding of HA required for fusion occurs. By analyzing combinations of mutations in three regions of the metastable neutral-pH HA that are rearranged at fusion pH we obtain evidence for both additive and nonadditive effects and for an apparent order of dominance in the effects of amino acid substitutions in particular regions on the pH of fusion. We conclude that there are at least three components in the structural transition required for membrane fusion activity and consider possible pathways for the transition in relation to the known differences between neutral and fusion pH HA structures.

An in vivo membrane fusion assay implicates SpoIIIE in the final stages of engulfment during Bacillus subtilis sporulation

Shortly after the synthesis of the two cells required for sporulation in Bacillus subtilis, the membranes of the larger mother cell begin to migrate around and engulf the smaller forespore cell. At the completion of this process the leading edges of the migrating membrane meet and fuse, releasing the forespore into the mother cell cytoplasm. We developed a fluorescent membrane stain-based assay for this membrane fusion event, and we isolated mutants defective in the final stages of engulfment or membrane fusion. All had defects in spoIIIE, which is required for translocation of the forespore chromosome across the polar septum. We isolated one spoIIIE mutant severely defective in chromosome translocation, but not in membrane fusion; this mutation disrupts the ATP/GTP-binding site of SpoIIIE, suggesting that ATP binding and hydrolysis are required for DNA translocation but not for the late engulfment function of SpoIIIE. We also correlated relocalization of SpoIIIE-green fluorescent protein from the sporulation septum to the forespore pole with the completion of membrane fusion and engulfment. We suggest that SpoIIIE is required for the final steps of engulfment and that it may regulate or catalyze membrane fusion events.

The mating-type and pathogenicity locus of the fungus Ustilago hordei spans a 500-kb region

The fungal pathogen Ustilago hordei causes the covered smut disease of barley and oats. Mating and pathogenicity in this fungus are controlled by the MAT locus, which contains two distinct gene complexes, a and b. In this study, we tagged the a and b regions with the recognition sequence for the restriction enzyme I-SceI and determined that the distance between the complexes is 500 kb in a MAT-1 strain and 430 kb in a MAT-2 strain. Characterization of the organization of the known genes within the a and b gene complexes provided evidence for nonhomology and sequence inversion between MAT-1 and MAT-2. Antibiotic-resistance markers also were used to tag the a gene complex in MAT-1 strains (phleomycin) and the b gene complex in MAT-2 strains (hygromycin). Crosses were performed with these strains and progeny resistant to both antibiotics were recovered at a very low frequency, suggesting that recombination is suppressed within the MAT region. Overall, the chromosome homologues carrying the MAT locus of U. hordei share features with primitive sex chromosomes, with the added twist that the MAT locus also controls pathogenicity.