Efstratios K. Kosmidis

Effect of aerosols on solar UV irradiances during the Photochemical Activity and Solar Ultraviolet Radiation campaign

Surface UV irradiances were measured at two different sites in Greece during June 1996 under noncloudy conditions. The measured UV irradiances are simulated by a radiative transfer model using measured ozone density and aerosol optical depth profiles. The absolute difference between model and measurements ranges between −5% and +5% with little dependence on wavelength. The temporal and solar zenith angle dependence in the difference between model and measurement suggests that part of this difference may be explained by assumptions made about the aerosol single-scattering albedo and phase function. Simulated spectra including aerosols are compared with calculated spectra excluding aerosols. It is found that for otherwise similar atmospheric conditions the UVB irradiance is reduced with respect to aerosol free conditions by 5% to 35% depending on the aerosol optical depth and single-scattering albedo. For the campaign period, changes in the aerosol loading gave larger variations in the surface UV irradiances than the changes seen in the ozone column.

Imaging brain activity with voltage- and calcium-sensitive dyes

This paper presents three examples of imaging brain activity with voltage- or calcium-sensitive dyes and then discusses the methodological aspects of the measurements that are needed to achieve an optimal signal-to-noise ratio.Internally injected voltage-sensitive dye can be used to monitor membrane potential in the dendrites of invertebrate and vertebrate neurons in in vitro preparations.Both invertebrate and vertebrate ganglia can be bathed in voltage-sensitive dyes to stain all of the cell bodies in the preparation. These dyes can then be used to follow the spike activity of many neurons simultaneously while the preparations are generating behaviors.Calcium-sensitive dyes that are internalized into olfactory receptor neurons in the nose will, after several days, be transported to the nerve terminals of these cells in the olfactory bulb. There they can be used to measure the input from the nose to the bulb.Three kinds of noise are discussed. a. Shot noise from the random emission of photons from the preparation. b. Vibrational noise from external sources. c. Noise that occurs in the absence of light, the dark noise.Three different parts of the light measuring apparatus are discussed: the light sources, the optics, and the cameras.The major effort presently underway to improve the usefulness of optical recordings of brain activity are to find methods for staining individual cell types in the brain. Most of these efforts center around fluorescent protein sensors of activity.

Three fluorescent protein voltage sensors exhibit low plasma membrane expression in mammalian cells

Three first-generation fluorescent protein voltage sensitive probes (FP-voltage sensors) were characterized in mammalian cells. Flare, a Kv1.4 variant of FlaSh [Siegel MS, Isacoff EY. Neuron 1997;19(October (4)):735-41], SPARC [Ataka K, Pieribone VA. Biophys J 2002;82(January (1 Pt 1)):509-16], and VSFP-1 [Sakai R, Repunte-Canonigo V, Raj CD, Knopfel T. Eur J Neurosci 2001;13(June (12)):2314-18] were expressed, imaged and voltage clamped in HEK 293 cells and in dissociated hippocampal neurons. We were unable to detect a signal in response to changes in membrane potential after averaging16 trials with any of the three constructs. Using the hydrophobic voltage sensitive dye, di8-ANEPPS, as a surface marker, confocal analyses demonstrated poor plasma membrane expression for Flare, SPARC and VSFP-1 in both HEK 293 cells and dissociated hippocampal neurons. Almost all of the expressed FP-voltage sensors reside in internal membranes in both cell types. This internal expression generates a background fluorescence that increases the noise in the optical measurement.

Performance evaluation of PCA-based spike sorting algorithms

Deciphering the electrical activity of individual neurons from multi-unit noisy recordings is critical for understanding complex neural systems. A widely used spike sorting algorithm is being evaluated for single-electrode nerve trunk recordings. The algorithm is based on principal component analysis (PCA) for spike feature extraction. In the neuroscience literature it is generally assumed that the use of the first two or most commonly three principal components is sufficient. We estimate the optimum PCA-based feature space by evaluating the algorithms performance on simulated series of action potentials. A number of modifications are made to the open source nev2lkit software to enable systematic investigation of the parameter space. We introduce a new metric to define clustering error considering over-clustering more favorable than under-clustering as proposed by experimentalists for our data. Both the program patch and the metric are available online. Correlated and white Gaussian noise processes are superimposed to account for biological and artificial jitter in the recordings. We report that the employment of more than three principal components is in general beneficial for all noise cases considered. Finally, we apply our results to experimental data and verify that the sorting process with four principal components is in agreement with a panel of electrophysiology experts.

On the turnaround of stratospheric ozone trends deduced from the reevaluated Umkehr record of Arosa, Switzerland

[1]xa0In this work, we investigate the issue of the turnaround in ozone trends of the recently homogenized Umkehr ozone record of Arosa, Switzerland, which is the longest Umkehr data set, extending from 1956 to date, using different statistical methods. All methods show statistically significant negative ozone trends from 1970 to 1995 in the upper stratosphere (above 32.6 km) throughout the course of the year as well as in the lower stratosphere (below 23.5 km) mainly during winter to spring, which can be partially attributed to dynamical changes. Over the recent period (1996–2004) the year-round trends in the lower stratosphere become positive and are more positive during the winter to spring period. The results also show changes in upper stratospheric ozone trends after 1996, which are, however, not statistically significant at 95% if aerosol correction is applied on the retrieved data. This lack of significant trend changes during the recent period in the upper stratosphere is regionally coherent with recent results derived from upper stratospheric ozone data recorded by lidars, microwave radiometers, and satellite instruments at an adjacent location. Although the positive change in trends after 1996 both for upper and lower stratospheric ozone is in line with the reduction of the emissions of ozone-depleting substances from the successful implementation of the Montreal Protocol and its amendments, we recommend, because of lack of significance for the upper stratospheric trends, repeating this analysis in a few years in order to overcome ambiguous results for documentation of the turnaround of upper stratospheric ozone.

Comparison of Model Calculations with Spectral UV Measurements during the SUSPEN Campaign: The Effect of Aerosols

Spectral measurements of global solar irradiance, obtained under cloud-free conditions during the SUSPEN campaign (July 1997) in Thessaloniki, Greece, are compared with radiative transfer model calculations, showing an agreement to within 65% for wavelengths higher that 305 nm. The uncertainties in the modeled spectra were analyzed with respect to the aerosol-related model input parameters (single-scattering albedo and asymmetry factor), which were not derivable from measurements. A range of single-scattering albedo values was used to investigate its impact on surface UV irradiance through comparison of measurements with model calculations. It was found that a difference in the single-scattering albedo of 0.1 changes the model‐measurement ratio by 7%‐14%, depending on solar zenith angle. Finally, an attempt was made to relate the estimated values of singlescattering albedo to wind direction and relative humidity, which control the origin and type of the aerosols in the area.

Prognostic biomarkers in phase II trial of cetuximab-containing induction and chemoradiation in resectable HNSCC: Eastern cooperative oncology group E2303.

Purpose: We sought to evaluate the correlation between tissue biomarker expression (using standardized, quantitative immunofluorescence) and clinical outcome in the E2303 trial. Experimental Design: Sixty-three eligible patients with operable stage III/IV head and neck squamous cell cancer (HNSCC) participated in the Eastern Cooperative Oncology Group (ECOG) 2303 phase II trial of induction chemotherapy with weekly cetuximab, paclitaxel, and carboplatin followed by chemoradiation with the same regimen. A tissue microarray (TMA) was constructed and EGF receptor (EGFR), ERK1/2, Met, Akt, STAT3, β-catenin, E-cadherin, EGFR Variant III, insulin-like growth factor-1 receptor, NF-κB, p53, PI3Kp85, PI3Kp110a, PTEN, NRAS, and pRb protein expression levels were assessed using automated quantitative protein analysis (AQUA). For each dichotomized biomarker, overall survival (OS), progression-free survival (PFS), and event-free survival (EFS) were estimated by the Kaplan–Meier method and compared using log-rank tests. Multivariable Cox proportional hazards models were used to estimate HRs and test for significance. Results: Forty-two of 63 patients with TMA data on at least one biomarker were included in the biomarker analysis. Tumor extracellular signal–regulated kinase (ERK)1/2 levels were significantly associated with PFS [HR (low/high), 3.29; P = 0.026] and OS [HR (low/high), 4.34; P = 0.008]. On multivariable Cox regression analysis, ERK1/2 remained significantly associated with OS (P = 0.024) and PFS (P = 0.022) after controlling for primary site (oropharynx vs. non-oropharynx) and disease stage (III vs. IV), respectively. Clustering analysis revealed that clusters indicative of activated RAS/MAPK/ERK and/or PI3K/Akt pathways were associated with inferior OS and/or PFS and maintained significance in multivariable analysis. Conclusions: These results implicate PI3K/Akt and RAS/MAPK/ERK pathways in resistance to cetuximab-containing chemoradiation in HNSCC. Large prospective studies are required to validate these results. Clin Cancer Res; 20(11); 3023–32. ©2014 AACR.

NASS: An empirical approach to spike sorting with overlap resolution based on a hybrid noise-assisted methodology

Background noise and spike overlap pose problems in contemporary spike-sorting strategies. We attempted to resolve both issues by introducing a hybrid scheme that combines the robust representation of spike waveforms to facilitate the reliable identification of contributing neurons with efficient data learning to enable the precise decomposition of coactivations. The isometric feature mapping (ISOMAP) technique reveals the intrinsic data structure, helps with recognising the involved neurons and, simultaneously, identifies the overlaps. Exemplar activation patterns are first estimated for all detected neurons and consecutively used to build a synthetic database in which spike overlaps are systematically varied and realistic noise is added. An Extreme Learning Machine (ELM) is then trained with the ISOMAP representation of this database and learns to associate the synthesised waveforms with the corresponding source neurons. The trained ELM is finally applied to the actual overlaps from the experimental data and this completes the entire spike-sorting process. Our approach is better characterised as semi-supervised, noise-assisted strategy of an empirical nature. The users engagement is restricted at recognising the number of active neurons from low-dimensional point-diagrams and at deciding about the complexity of overlaps. Efficiency is inherited from the incorporation of well-established algorithms. Moreover, robustness is guaranteed by adaptation to the actual noise properties of a given data set. The validity of our work has been verified via extensive experimentation, using realistically simulated data, under different levels of noise.

Perceptual stability during dramatic changes in olfactory bulb activation maps and dramatic declines in activation amplitudes

We compared the concentration dependence of the ability of rats to identify odorants with the calcium signals in the nerve terminals of the olfactory receptor neurons. Although identification performance decreased with concentrations both above and below the training stimuli it remained well above random at all concentrations tested (between 0.0006% and 35% of saturated vapor). In contrast, the calcium signals in the same awake animals were much smaller than their maximum values at odorant concentrations <1% of saturated vapor. In addition, maps of activated glomeruli changed dramatically as odorant concentration was reduced. Thus perceptual stability exists in the face of dramatic changes in both the amplitude and the maps of the input to the olfactory bulb. The data for the concentration dependence of the response of the most sensitive glomeruli for each of five odorants was fitted with a Michaelis–Menten (Hill) equation. The fitted curves were extrapolated to odorant concentrations several orders of magnitude lower the smallest observed signals and suggest that the calcium response at low odorant concentrations is >u20031000u2003times smaller than the response at saturating odorant concentrations. We speculate that only a few spikes in olfactory sensory neurons may be sufficient for correct odorant identification.

Oxaliplatin-induced hyperexcitation of rat sciatic nerve fibers: an intra-axonal study.

Oxaliplatin is an agent that is used extensively in gastrointestinal cancer chemotherapy. The agents major dose-limiting toxicity is peripheral neuropathy that can manifest as a chronic or an acute syndrome. Oxaliplatin-induced acute neuropathy is purportedly caused by an alteration of the biophysical properties of voltage-gated sodium channels. However, sodium channel blockers have not been successful at preventing acute neuropathy in the clinical setting. We report intra-axonal recordings from the isolated rat sciatic nerve preparation under the effect of oxaliplatin. The depolarization phase of single action potentials remains intact with a duration of 0.52 ± 0.02 ms (n=68) before and 0.55 ± 0.01 ms (n=68) after 1-5 h of exposure to 150 μM oxaliplatin (unpaired t-test, P > 0.05) whereas there is a significant broadening of the repolarization phase (2.16 ± 0.10 ms, n=68, before and 5.90 ± 0.32 ms after, n=68, unpaired t-test, P < 0.05). Apart from changes in spike shape, oxaliplatin also had drastic concentration- and time-dependent effects on the firing responses of fibers to short stimuli. In the intra-axonal recordings, three groups of firing patterns were indentified. The first group shows bursting (internal frequency 90 - 130 Hz, n=88), the second shows a characteristic plateau (at -19.27�2.84 mV, n=31, with durations ranging from 45 - 140 ms depending on the exposure time), and the third combines a plateau and a bursting period. Our results implicate the voltage-gated potassium channels as additional oxaliplatin targets, opening up new perspectives for the pharmacological prevention of peripheral neuropathy.