On seeing the trees and the forest: Single-signal and multisignal analysis of periictal intracranial EEG

Epileptic seizures are associated with a dysregulation of electrical brain activity on many different spatial scales. To better understand the dynamics of epileptic seizures, that is, how the seizures initiate, propagate, and terminate, it is important to consider changes of electrical brain activity on different spatial scales. Herein we set out to analyze periictal electrical brain activity on comparatively small and large spatial scales by assessing changes in single intracranial electroencephalography (EEG) signals and of averaged interdependences of pairs of EEG signals.

Taking an Object-Centric View on Dynamic Information with Object Flow Analysis

A large body of research analyzes the runtime execution of a system to extract abstract behavioral views. Those approaches primarily analyze control flow by tracing method execution events or they analyze object graphs of heap snapshots. However, they do not capture how objects are passed through the system at runtime. We refer to the exchange of objects as the object flow, and we claim that object flow is necessary to analyze if we are to understand the runtime of an object-oriented application. We propose and detail Object Flow Analysis, a novel dynamic analysis technique that takes this new information into account. To evaluate its usefulness, we present a visual approach that allows a developer to study classes and components in terms of how they exchange objects at runtime. We illustrate our approach on three case studies.

Continuous Flow Analysis of labile iron in ice-cores

The important active and passive role of mineral dust aerosol in the climate and the global carbon cycle over the last glacial/interglacial cycles has been recognized. However, little data on the most important aeolian dust-derived biological micronutrient, iron (Fe), has so far been available from ice-cores from Greenland or Antarctica. Furthermore, Fe deposition reconstructions derived from the palaeoproxies particulate dust and calcium differ significantly from the Fe flux data available. The ability to measure high temporal resolution Fe data in polar ice-cores is crucial for the study of the timing and magnitude of relationships between geochemical events and biological responses in the open ocean. This work adapts an existing flow injection analysis (FIA) methodology for low-level trace Fe determinations with an existing glaciochemical analysis system, continuous flow analysis (CFA) of ice-cores. Fe-induced oxidation of N,N′-dimethyl-p-pheylenediamine (DPD) is used to quantify the biologically more important and easily leachable Fe fraction released in a controlled digestion step at pH ∼1.0. The developed method was successfully applied to the determination of labile Fe in ice-core samples collected from the Antarctic Byrd ice-core and the Greenland Ice-Core Project (GRIP) ice-core.

Continuous Flow Analysis Method for Determination of Dissolved Reactive Phosphorus in Ice Cores

Phosphorus (P) is an essential macronutrient for all living organisms. Phosphorus is often present in nature as the soluble phosphate ion PO43– and has biological, terrestrial, and marine emission sources. Thus PO43– detected in ice cores has the potential to be an important tracer for biological activity in the past. In this study a continuous and highly sensitive absorption method for detection of dissolved reactive phosphorus (DRP) in ice cores has been developed using a molybdate reagent and a 2-m liquid waveguide capillary cell (LWCC). DRP is the soluble form of the nutrient phosphorus, which reacts with molybdate. The method was optimized to meet the low concentrations of DRP in Greenland ice, with a depth resolution of approximately 2 cm and an analytical uncertainty of 1.1 nM (0.1 ppb) PO43–. The method has been applied to segments of a shallow firn core from Northeast Greenland, indicating a mean concentration level of 2.74 nM (0.26 ppb) PO43– for the period 1930–2005 with a standard deviation of 1.37 nM (0.13 ppb) PO43– and values reaching as high as 10.52 nM (1 ppb) PO43–. Similar levels were detected for the period 1771–1823. Based on impurity abundances, dust and biogenic particles were found to be the most likely sources of DRP deposited in Northeast Greenland.

High-resolution glacial and deglacial record of atmospheric methane by continuous-flow and laser spectrometer analysis along the NEEM ice core

The Greenland NEEM (North Greenland Eemian Ice Drilling) operation in 2010 provided the first opportunity to combine trace-gas measurements by laser spectroscopic instruments and continuous-flow analysis along a freshly drilled ice core in a field-based setting. We present the resulting atmospheric methane (CH4) record covering the time period from 107.7 to 9.5 ka b2k (thousand years before 2000 AD). Companion discrete CH4 measurements are required to transfer the laser spectroscopic data from a relative to an absolute scale. However, even on a relative scale, the high-resolution CH4 data set significantly improves our knowledge of past atmospheric methane concentration changes. New significant sub-millennial-scale features appear during interstadials and stadials, generally associated with similar changes in water isotopic ratios of the ice, a proxy for local temperature. In addition to the midpoint of Dansgaard–Oeschger (D/O) CH4 transitions usually used for cross-dating, sharp definition of the start and end of these events brings precise depth markers (with ±20 cm uncertainty) for further cross-dating with other palaeo- or ice core records, e.g. speleothems. The method also provides an estimate of CH4 rates of change. The onsets of D/O events in the methane signal show a more rapid rate of change than their endings. The rate of CH4 increase associated with the onsets of D/O events progressively declines from 1.7 to 0.6 ppbv yr−1 in the course of marine isotope stage 3. The largest observed rate of increase takes place at the onset of D/O event #21 and reaches 2.5 ppbv yr−1.

Water isotopic ratios from a continuously melted ice core sample

A new technique for on-line high resolution isotopic analysis of liquid water, tailored for ice core studies is presented. We built an interface between a Wavelength Scanned Cavity Ring Down Spectrometer (WS-CRDS) purchased from Picarro Inc. and a Continuous Flow Analysis (CFA) system. The system offers the possibility to perform simultaneuous water isotopic analysis of δ18O and δD on a continuous stream of liquid water as generated from a continuously melted ice rod. Injection of sub μl amounts of liquid water is achieved by pumping sample through a fused silica capillary and instantaneously vaporizing it with 100% efficiency in a~home made oven at a temperature of 170 °C. A calibration procedure allows for proper reporting of the data on the VSMOW–SLAP scale. We apply the necessary corrections based on the assessed performance of the system regarding instrumental drifts and dependance on the water concentration in the optical cavity. The melt rates are monitored in order to assign a depth scale to the measured isotopic profiles. Application of spectral methods yields the combined uncertainty of the system at below 0.1‰ and 0.5‰ for δ18O and δD, respectively. This performance is comparable to that achieved with mass spectrometry. Dispersion of the sample in the transfer lines limits the temporal resolution of the technique. In this work we investigate and assess these dispersion effects. By using an optimal filtering method we show how the measured profiles can be corrected for the smoothing effects resulting from the sample dispersion. Considering the significant advantages the technique offers, i.e. simultaneuous measurement of δ18O and δD, potentially in combination with chemical components that are traditionally measured on CFA systems, notable reduction on analysis time and power consumption, we consider it as an alternative to traditional isotope ratio mass spectrometry with the possibility to be deployed for field ice core studies. We present data acquired in the field during the 2010 season as part of the NEEM deep ice core drilling project in North Greenland.

Homozygous Cys542-->Arg substitution in GPIIIa in a Swiss patient with type I Glanzmann's thrombasthenia

Glanzmann's thrombasthenia (GT) arises from a qualitative or quantitative defect in the GPIIb-IIIa complex (integrin alphaIIbbeta3), the mediator of platelet aggregation. We describe a patient in whom clinical and laboratory findings typical of type I GT were found together with a second pathology involving neurological and other complications symptomatic of tuberous sclerosis. Analysis of platelet proteins by Western blotting revealed trace amounts of normally migrating GPIIb and equally small amounts of GPIIIa of slightly slower than normal migration. Flow cytometry confirmed a much decreased binding to platelets of monoclonal antibodies to GPIIb, GPIIIa or GPIIb-IIIa, and an antibody to the alphav subunit also showed decreased binding. Nonradioactive PCR single-strand conformation polymorphism analysis followed by direct sequencing of PCR-amplified DNA fragments showed a homozygous point mutation (T to C) at nucleotide 1722 of GPIIIa cDNA and which led to a Cys542-->Arg substitution in the GPIIIa protein. The mutation gave rise to a HinP1 I restriction site in exon 11 of the GPIIIa gene and allele-specific restriction enzyme analysis of family members confirmed that a single mutated allele was inherited from each parent. This amino acid substitution presumably changes the capacity for disulphide bond formation within the cysteine-rich core region of GPIIIa and its study will provide new information on GPIIb-IIIa and alphavbeta3 structure and biosynthesis.

In Situ SHINERS at Electrochemical Single-Crystal Electrode/Electrolyte Interfaces: Tuning Preparation Strategies and Selected Applications

We have studied Au(55 nm)@SiO2 nanoparticles (NPs) on two low-index phases of gold and platinum single crystal electrodes in ClO4– and SO42– ion-containing electrolytes by both electrochemical methods and in-situ shell-isolated nanoparticle enhanced Raman spectroscopy (SHINERS). We showed the blocking of the electrode with surfactants originating from the synthesis of as-prepared SHINERS NPs. We introduce an efficient procedure to overcome this problem, which provides a fundamental platform for the application of SHINERS in surface electrochemistry and beyond. Our method is based on a hydrogen evolution treatment of the SHINERS-NP-modified single-crystal surfaces. The reliability of our preparation strategy is demonstrated in electrochemical SHINERS experiments on the potential-controlled adsorption and phase formation of pyridine on Au(hkl) and Pt(hkl). We obtained high-quality Raman spectra on these well-defined and structurally carefully characterized single-crystal surfaces. The analysis of the characteristic A1 vibrational modes revealed perfect agreement with the interpretation of single-crystal voltammetric and chronoamperometric experiments. Our study demonstrates that the SHINERS protocol developed in this work qualifies this Raman method as a pioneering approach with unique opportunities for in situ structure and reactivity studies at well-defined electrochemical solid/liquid interfaces.

Oligo(aryleneethynylene)s with Terminal Pyridyl Groups: Synthesis and Length Dependence of the Tunneling-to-Hopping Transition of Single-Molecule Conductances

The synthesis is reported of a new series of oligo(aryleneethynylene) (OAE) derivatives of up to ca. 6 nm in molecular length (OAE9) using iterative Pd-mediated Sonogashira cross-coupling methodology. The oligo-p-phenyleneethynylene cores of the molecular wires are functionalized at both termini with pyridyl units for attachment to gold leads. The molecular structures determined by single-crystal X-ray analysis are reported for OAE4, OAE5, OAE7, and OAE8a. The charge transport characteristics of derivatives OAE3–OAE9 in single-molecular junctions have been studied using the mechanically controlled break junction technique. The data demonstrate that the junction conductance decreases with increasing molecular length. A transition from coherent transport via tunneling to a hopping mechanism is found for OAE wires longer than ca. 3 nm.

K-t GRAPPA-accelerated 4D flow MRI of liver hemodynamics: influence of different acceleration factors on qualitative and quantitative assessment of blood flow.

OBJECTIVE We sought to evaluate the feasibility of k-t parallel imaging for accelerated 4D flow MRI in the hepatic vascular system by investigating the impact of different acceleration factors. MATERIALS AND METHODS k-t GRAPPA accelerated 4D flow MRI of the liver vasculature was evaluated in 16 healthy volunteers at 3T with acceleration factors R = 3, R = 5, and R = 8 (2.0 × 2.5 × 2.4 mm(3), TR = 82 ms), and R = 5 (TR = 41 ms); GRAPPA R = 2 was used as the reference standard. Qualitative flow analysis included grading of 3D streamlines and time-resolved particle traces. Quantitative evaluation assessed velocities, net flow, and wall shear stress (WSS). RESULTS Significant scan time savings were realized for all acceleration factors compared to standard GRAPPA R = 2 (21-71 %) (p < 0.001). Quantification of velocities and net flow offered similar results between k-t GRAPPA R = 3 and R = 5 compared to standard GRAPPA R = 2. Significantly increased leakage artifacts and noise were seen between standard GRAPPA R = 2 and k-t GRAPPA R = 8 (p < 0.001) with significant underestimation of peak velocities and WSS of up to 31 % in the hepatic arterial system (p <0.05). WSS was significantly underestimated up to 13 % in all vessels of the portal venous system for k-t GRAPPA R = 5, while significantly higher values were observed for the same acceleration with higher temporal resolution in two veins (p < 0.05). CONCLUSION k-t acceleration of 4D flow MRI is feasible for liver hemodynamic assessment with acceleration factors R = 3 and R = 5 resulting in a scan time reduction of at least 40 % with similar quantitation of liver hemodynamics compared with GRAPPA R = 2.