Millimeter wave-induced suppression of B16 F10 melanoma growth in mice: involvement of endogenous opioids

Millimeter wave treatment (MMWT) is widely used in Eastern European countries, but is virtually unknown in Western medicine. Among reported MMWT effects is suppression of tumor growth. The main aim of the present "blind" and dosimetrically controlled experiments was to evaluate quantitatively the ability of MMWT to influence tumor growth and to assess whether endogenous opioids are involved. The murine experimental model of B16 F10 melanoma subcutaneous growth was used. MMWT characteristics were: frequency, 61.22 GHz; average incident power density, 13.3 x 10(-3) W/cm2; single exposure duration, 15 min; and exposure area, nose. Naloxone (1 mg/kg, intraperitoneally, 30 min prior to MMWT) was used as a nonspecific blocker of opioid receptors. Five daily MMW exposures, if applied starting at the fifth day following B16 melanoma cell injection, suppressed subcutaneous tumor growth. Pretreatment with naloxone completely abolished the MMWT-induced suppression of melanoma growth. The same course of 5 MMW treatments, if started on day 1 or day 10 following tumor inoculations, was ineffective. We concluded that MMWT has an anticancer therapeutic potential and that endogenous opioids are involved in MMWT-induced suppression of melanoma growth in mice. However, appropriate indications and contraindications have to be developed experimentally before recommending MMWT for clinical usage.     

Mathematical analysis of a model describing evolution of an asexual population in a changing environment

We investigate a mathematical model for an asexual population with non-overlapping (discrete) generations, that exists in a changing environment. Sexual populations are also briefly discussed at the end of the paper. It is assumed that selection occurs on the value of a single polygenic trait, which is controlled by a finite number of loci with discrete-effect alleles. The environmental change results in a moving fitness optimum, causing the trait to be subject to a combination of stabilising and directional selection.This model is different from that investigated by Waxman and Peck [Genetics 153 (1999) 1041] where overlapping generations and continuous effect alleles were considered. In this paper, we consider non-overlapping generations and discrete effect alleles. However in [Genetics 153 (1999) 1041] and the present work, there is the same pattern of environmental change, namely a constant rate of change of the optimum.From [Genetics 153 (1999) 1041], no rigorous theoretical conclusion can be drawn about the form of the solutions as t grows large. Numerical work carried out in [Genetics 153 (1999) 1041] suggests that the solution is a lagged travelling wave solution, but no mathematical proof exists for the continuous model. Only partial results, regarding existence of travelling wave solutions and perturbed solutions, have been established (see [Nonlin. Anal. 53 (2003) 683; An integral equation describing an asexual population in a changing environment, Preprint]). For the discrete case of this paper, under the assumption that the ratio between the unit of genotypic value and the speed of environment change is a rational number, we are able to give rigorous proof of the following conclusion: the population follows the environmental change with a small lag behind, moreover, the lag is represented using a calculable quantity.     

Self-aggregation properties of spin-labeled zervamicin IIA as studied by PELDOR spectroscopy

In this article, the pulsed double electron-electron resonance in electron spin-echo (PELDOR) technique is applied to study the self-aggregation of spin-labeled zervamicin IIA, a hexadecapeptide antibiotic of fungal origin, which is known to form ion channels in a phospholipid double layer. Measurements of the ion channel forming properties and the antibiotic activity of the analog indicate that replacement of the C-terminal phenylalaninol by the amino-2,2,6,6-tetramethylpiperidinyloxy (TEMPO) residue does not influence the biophysical and biological properties. The dipole-dipole interaction between the spin labels of the fully biologically active peptide analog was studied in frozen (77 K) glassy solutions in different ratios of toluene-methanol. The spin-labeled zervamicin IIA molecules were shown to form aggregates. An average distance between the spin labels in the aggregates was estimated to be in the range of 25-35 A (depending on the solvent composition), indicating that the amphiphilic helical peptide molecules are oriented in an antiparallel fashion. Increasing of methanol content in the solution results in a loosening of the aggregate structure. It was shown that the fraction of aggregated zervamicin IIA molecules is less than 44-67% depending on the solvent composition. The general usefulness of the method to obtain structural long-range information in a range of several tens of angstroms is demonstrated by comparison with the peptide cluster of trichogin GA IV.     

Fluorescence imaging with two-photon evanescent wave excitation

We demonstrate broad-field, non-scanning, two-photon excitation fluorescence (2PEF) close to a glass/cell interface by total internal reflection of a femtosecond-pulsed infrared laser beam. We exploit the quadratic intensity dependence of 2PEF to provide non-linear evanescent wave (EW) excitation in a well-defined sample volume and to eliminate scattered background excitation. A simple model is shown to describe the resulting 2PEF intensity and to predict the effective excitation volume in terms of easily measurable beam, objective and interface properties. We demonstrate non-linear evanescent wave excitation at 860 nm of acridine orange-labelled secretory granules in live chromaffin cells, and excitation at 900 nm of TRITC-phalloidin-actin/GPI-GFP double-labelled fibroblasts. The confined excitation volume and the possibility of simultaneous multi-colour excitation of several fluorophores make EW 2PEF particularly advantageous for quantitative microscopy, imaging biochemistry inside live cells, or biosensing and screening applications in miniature high-density multi-well plates.Abbreviations 1PEF one-photon excited fluorescence - 2PEF two-photon excited fluorescence - APD avalanche photo diode - CHO Chinese hamster ovary - DMEM Dulbecco's modified Eagle's medium - EGFP enhanced green fluorescent protein - EW evanescent wave - FCS fetal calf serum - GPI glycosylphosphatidylinositol - TIR total internal reflectionThis paper is dedicated to the memory of Prof. Horst Harreis (1940–2002)     

Tracking chromaffin granules on their way through the actin cortex

Quantitative time-lapse evanescent-wave imaging of individual fluorescently labelled chromaffin granules was used for kinetic analysis of granule trafficking through a ∼300-nm (1/e²) optical section beneath the plasma membrane. The mean squared displacement (MSD) was used to estimate the three-dimensional diffusion coefficient (D ⁽³⁾). We calculated the granules' speed, frame-to-frame displacement and direction and their autocorrelation to identify different stages of approach to the membrane. D ⁽³⁾ was about 10,000 times lower than expected for free diffusion. Granules located ∼60 nm beneath the plasma membrane moved on random tracks (D ⁽³⁾≈10⁻¹⁰ cm² s⁻¹) with several reversals in direction before they approached their docking site at angles larger than 45^∘. Docking was observed as a loss of vesicle mobility by two orders of magnitude within <100 ms. For longer observation times the MSD saturated, as if the granules' movement was confined to a volume only slightly larger than the granule. Rarely, the local random motion was superimposed with a directed movement in a plane beneath the membrane. Stimulation of exocytosis selectively depleted the immobile, near-membrane granule population and caused a recruitment of distant granules to sites at the plasma membrane. Their absolute mobility levels were not significantly altered. Application of latrunculin or jasplakinolide to change F-actin polymerisation caused a change in D ⁽³⁾ of the mobile granule population as well as a reduction of the rate of release, suggesting that granule mobility is constrained by the filamentous actin meshwork and that stimulation-dependent changes in actin viscosity propel granules through the actin cortex. Received: 18 November 1999 / Revised version: 26 January 2000 / Accepted: 2 February 2000     

Single-pad scheme for integrated optical fluorescence sensing

A new scheme for integrated optical fluorescence sensing is presented. The principle is based on a planar waveguide containing multiple sensing units, each consisting of a single-pad grating coupler structure. Single-pad means that all the following functions are incorporated in one single pad: laser light input, excitation of the labeled analyte molecules, efficient collection of the emitted fluorescent light into the waveguide, background suppression, and coupling the guided wave out to the detector. The results demonstrate a high efficiency of the fluorescence light excitation and collection, as well as a good suppression of the volume background.     

Stress Reduction by Technology? An Experimental Study into the Effects of Brainmachines on Burnout and State Anxiety

Stress and burnout are widely acknowledged as major causes of societal and individual problems in the Western world. In order to reduce material and immaterial expenses, increased efforts are made to enhance relaxation and stress reduction. Based on neuropsychological findings, alternative ways have been explored, one of them being the application of so-called brain wave synchronizers, which are said to induce a relaxation response by entraining alpha brain-wave activity (8–13 Hz) through audiovisual stimulation. A double blind, quasi-experiment was conducted among employees at a Dutch addiction care center to investigate the possible effects of two distinct brainmachine programs on burnout and anxiety. Subjects in both conditions showed a significant, immediate decrease in state anxiety as assessed by Spielberger's State-Trait Anxiety Inventory (STAI) and reported a range of subjective effects. However, a long-term effect on burnout, as measured with Maslach's Burnout Inventory (MBI-NL), could not be established. A long-term effect on anxiety (STAI), as investigated by interrupted time-series measurement, could not be established either. These and other findings suggest that the major claims with respect to these machines cannot hold over time, although pleasant short-term effects do occur. Individual differences in baseline responsivity, the stable character of burnout dimensions, or the ill-defined nature of relaxation, or a combination of these, may account for these results.     

果蝇复眼形成过程中的靶波

本文用数值方法,求出了果蝇复眼形成过程的靶波解并对解的稳定性和临界点的分叉问题进行了分析．     

神经干复合动作电位实验的软件设计

本文描述神经干复合动作电位实验的软件设计及其主要特点,友好的人机界面和简便的波形处理,并给出了实际实验结果,由于软件设计在智能化仪器中的重要作用,所以应加以仔细考虑。     

Travelling wave dynamics and self-organization in a spatio-temporally structured population

We analyse spatial population dynamics showing that periodic or period-like chaotic dynamics produce self-organization structures, such as travelling waves. We suggest that self-organized patterns are associated with spatial synchrony patterns that often depend on geographical distance between subpopulations. The population dynamics also show statistical spatial autocorrelation patterns. We contrast our theoretical simulations with empirical data on annual damages in young sapling stands caused by voles. We conclude, on the basis of the periodicity, synchrony, and spatial autocorrelation patterns, and our simulation results, that vole dynamics represent travelling waves in population dynamics. We suggest that because such synchrony patterns are frequently observed in natural populations, spatial self-organization may be more common in population dynamics than reported in the literature.