On the reason for the kink in the rigidity spectra of cosmic-ray protons and helium nuclei near 230 GV

A three-component phenomenological model describing the specific features of the spectrum of cosmic-ray protons and helium nuclei in the rigidity range of 30–2×10⁵ GV is proposed. The first component corresponds to the constant background; the second, to the variable “soft” (30–500 GV) heliospheric source; and the third, to the variable “hard” (0.5–200 TV) source located inside a local bubble. The existence and variability of both sources are provided by the corresponding “surfatron accelerators,” whose operation requires the presence of an extended region with an almost uniform (in both magnitude and direction) magnetic field, orthogonally (or obliquely) to which electromagnetic waves propagate. The maximum energy to which cosmic rays can be accelerated is determined by the source size. The soft source with a size of ～100 AU is located at the periphery of the heliosphere, behind the front of the solar wind shock wave. The hard source with a size of >0.1 pc is located near the boundary of an interstellar cloud at a distance of ～0.01 pc from the Sun. The presence of a kink in the rigidity spectra of p and He near 230 GV is related to the variability of the physical conditions in the acceleration region and depends on the relation between the amplitudes and power-law exponents in the dependences of the background, soft heliospheric source, and hard near galactic source. The ultrarelativistic acceleration of p and He by an electromagnetic wave propagating in space plasma across the external magnetic field is numerically analyzed. Conditions for particle trapping by the wave and the dynamics of the particle velocity and momentum components are considered. The calculations show that, in contrast to electrons and positrons (e ⁺), the trapped protons relatively rapidly escape from the effective potential well and cease to accelerate. Due to this effect, the p and He spectra are softer than that of e ⁺. The possibility that the spectra of accelerated protons deviate from standard power-law dependences due to the surfatron mechanism is discussed.     

Novel mtDNA mutations and oxidative phosphorylation dysfunction in Russian LHON families

Leber's hereditary optic neuropathy (LHON) is characterized by maternally transmitted, bilateral, central vision loss in young adults. It is caused by mutations in the mitochondrial DNA (mtDNA) encoded genes that contribute polypeptides to NADH dehydrogenase or complex I. Four mtDNA variants, the nucleotide pair (np) 3460A, 11778A, 14484C, and 14459A mutations, are known as "primary" LHON mutations and are found in most, but not all, of the LHON families reported to date. Here, we report the extensive genetic and biochemical analysis of five Russian families from the Novosibirsk region of Siberia manifesting maternally transmitted optic atrophy consistent with LHON. Three of the five families harbor known LHON primary mutations. Complete sequence analysis of proband mtDNA in the other two families has revealed novel complex I mutations at nps 3635A and 4640C, respectively. These mutations are homoplasmic and have not been reported in the literature. Biochemical analysis of complex I in patient lymphoblasts and transmitochondrial cybrids demonstrated a respiration defect with complex-I-linked substrates, although the specific activity of complex I was not reduced. Overall, our data suggests that the spectrum of mtDNA mutations associated with LHON in Russia is similar to that in Europe and North America and that the np 3635A and 4640C mutations may be additional mtDNA complex I mutations contributing to LHON expression.     

Influence of modified gas mixtures on the acoustic parameters of human forced exhalation

It was earlier demonstrated that the duration of tracheal noises of forced exhalation (FE) looks to be promising to determine adverse changes in the lung function after a dive. This study dealt with the parameters of tracheal expiratory noises (FE) as dependent of the composition of breathing gas mixtures. In the first type of experiments, 25 volunteers aged from 22 to 60 years carried out forced exhalation under a normal pressure of air or of an oxygen-helium or oxygen-krypton mixture. In the second type of experiments, six volunteers from 25 to 46 years of age performed forced exhalation with air in an altitude chamber under a normal pressure (0.1 MPa); the same subjects performed FE under an elevated pressure (0.263 MPa) while breathing air or an oxygen-helium mixture. In the first type of experiments, the total duration of tracheal FE noises in the frequency range 200?C2000 Hz and 200-Hz bands FE noises depended directly and linearly on the density of the gas mixture; this was not the case in the high-frequency band from 1400 to 2000 Hz. In the second type of experiments, the high-frequency durations and spectral energies of tracheal FE noises (1600?C2000 Hz) depended inversely and significantly on the adiabatic gas compressibility. In a simulated dive to a depth of 16.3 m (0.263 MPa), individual changes in the total duration of tracheal FE noises exceeded the diagnostic threshold of deterioration of the lung function in divers that was determined earlier under normal pressure.     

On the cause of variability of the cosmic ray spectrum in the knee region

Cosmic ray (CR) energy spectra for H, He, Si, and Fe nuclei with energy-to-charge number ratios ?/Z in the range from 10 to 5 × 10⁷ GeV are studied using observational data obtained at different times in different energy ranges: AMS-02, CREAM, Tibet ASγ, Tibet (hybrid), GRAPES-3, KASCADE, and KASCADE-Grande. Comparison of the H and He CR fluxes according to the KASCADE and KASCADE-Grande data (for different models of deconvolving CR spectra) with the Tibet ASγ and Tibet (hybrid) data obtained at another time in the range of ?/Z ～ 3 × 10⁶ GeV demonstrates space weather-caused variability of the CR flux. This feature of CR energy spectra in the Tibet ASγ data is most clearly observed in the spectra of heavier nuclei (Si and Fe) according to the KASCADE-Grande and GRAPES-3 data. The variability in the energy spectra of all CRs in the vicinity of the “knee” is shown in the data of Yakutsk EAS, CASA-BLANCA, and Tibet-III experiments. The variability of the CR flux on a time scale on the order of several years exists only if the source corresponding to the peak in the energy spectrum is situated at a distance of no more than 1 pc from the Sun. Rapid surfatron acceleration of CRs may result from colliding interstellar clouds nearest to the Sun (LIC and G). This acceleration mechanism allows one to explain the variability of the CR spectrum in the range 10³ GeV < ?/Z < 10⁸ GeV. Conditions for the trapping of strongly relativistic Fe nuclei by an electromagnetic wave, the dynamics of the components of the particle velocity and momentum, and the dependence of the particle acceleration rate on the initial parameters of the problem are analyzed using numerical calculations. The structure of the phase plane of the accelerated Fe nuclei is examined. Optimal conditions for the implementation of ultrarelativistic surfatron acceleration of Fe nuclei by an electromagnetic wave are formulated.     

The Mitochondrial Genome and Human Mitochondrial Diseases

To date, more than 100 point mutations and several hundreds of structural rearrangements of mitochondrial DNA (mtDNA) are known too be connected with characteristic neuromuscular and other mitochondrial syndromes varying form those causing death at the neonatal stage to diseases with late ages of onset. The immediate cause of mitochondrial disorders is a defective oxidative phosphorylation. Wide phenotypic variation and the heteroplasmy phenomenon, which some authors include in mutation load, are characteristic of human mitochondrial diseases. As the numbers of cases identified and pedigrees described increase, data on the genotype–phenotype interaction and the structure and frequency of pathogenic and conditionally pathogenic mtDNA mutations in human populations are rapidly accumulated. The data on the genetics and epidemiology of mitochondrial diseases are not only important for differential diagnosis and genetic counseling. Since both neutral and mildly pathogenic mutations of mtDNA are progressively accumulated in maternal phyletic lines, molecular analysis of these mutations permits not only reconstruction of the genealogical tree of modern humans, but also estimation of the role that these mutations play in natural selection.     

Spectrum of pathogenic mtDNA mutations in Leber’s hereditary optic neuropathy families from Siberia

The results of clinical, genealogical and molecular investigation of eighteen families with Leber’s hereditary optic neuropathy (LHON), identified on the territory of Siberia during the period from 1997 to 2005, are presented. Comprehensive analysis of mitochondrial genome variations in probands and their matrilineal relatives revealed the presence of relatively frequent (G11778A, G3460A, and T14484C), as well as rare and new mutations with the established or presumptive pathological effect (T10663C, G3535A, C4640A, and A14619G). The G11778A mutation was detected in nine pedigrees (50%), mostly in the families of ethnic Russians. In eight of these families G11778A was found in preferred association with the coding-region substitutions, typical of western Eurasian mtDNA lineage (haplogroup) TJ. On the contrary, the G3460A mutation was detected in the three families belonging to the indigenous Siberian populations (Tuvinians, Altaians, and Buryats). It was associated with clearly different haplotypes of eastern Eurasian haplogroups, C3, D5, and D8. Unexpectedly, the G3460A de novo mutation was found in a large Tuvinian pedigree. At the same time, in eleven out of fourteen families of Caucasoid origin pathogenic mutations in the ND genes were associated with the T4216C and C15445A coding-region mutations, marking the root motif of haplogoup TJ. It is suggested that phylogenetically ancient mutations could have provided their carriers with the adaptive advantages upon the development of Central and Northern Europe at the end of the last glaciation (10 000 to 9000 years ago), thereby, contributing to the preservation of weekly pathogenic LHON mutations, appearing at specific genetic background.     

The role of mtDNA background in disease expression: a new primary LHON mutation associated with Western Eurasian haplogroup J

Leber's hereditary optic neuropathy (LHON) is a maternally transmitted form of blindness caused by mitochondrial DNA (mtDNA) mutations. Approximately 90% of LHON cases are caused by 3460A, 11778A, or 14484C mtDNA mutations. These are designated "primary" mutations because they impart a high risk for LHON expression. Although the 11778A and 14484C mutations unequivocally predispose carriers to LHON, they are preferentially associated with mtDNA haplogroup J, one of nine Western Eurasian mtDNA lineages, suggesting a synergistic and deleterious interaction between these LHON mutations and haplogroup J polymorphism(s). We report here the characterization of a new primary LHON mutation in the mtDNA ND4L gene at nucleotide pair 10663. The homoplasmic 10663C mutation has been found in three independent LHON patients who lack a known primary mutation and all of which belong to haplogroup J. This mutation has not been found in a large number of haplotype-matched or non-haplogroup-J control mtDNAs. Phylogenetic analysis with primarily complete mtDNA sequence data demonstrates that the 10663C mutation has arisen at least three independent times in haplogroup J, indicating that it is not a rare lineage-specific polymorphism. Analysis of complex I function in patient lymphoblasts and transmitochondrial cybrids has revealed a partial complex I defect similar in magnitude to the 14484C mutation. Thus, the 10663C mutation appears to be a new primary LHON mutation that is pathogenic when co-occurring with haplogroup J. These results strongly support a role for haplogroup J in the expression of certain LHON mutations.     

Surfatron acceleration of protons by an electromagnetic wave at the heliosphere periphery

The trapping and subsequent efficient surfatron acceleration of weakly relativistic protons by an electromagnetic wave propagating across an external magnetic field in plasma at the heliosphere periphery is considered. The problem is reduced to analysis of a second-order time-dependent nonlinear equation for the wave phase on the particle trajectory. The conditions of proton trapping by the wave, the dynamics of the components of the particle momentum and velocity, the structure of the phase plane, the particle trajectories, and the dependence of the acceleration rate on initial parameters of the problem are analyzed. The asymptotic behavior of the characteristics of accelerated particles for the heliosphere parameters is investigated. The optimum conditions for surfatron acceleration of protons by an electromagnetic wave are discussed. It is demonstrated that the experimentally observed deviation of the spectra of cosmic-ray protons from standard power-law dependences can be caused by the surfatron mechanism. It is shown that protons with initial energies of several GeV can be additionally accelerated in the heliosphere (the region located between the shock front of the solar wind and the heliopause at distances of about 100 astronomical units (a.u.) from the Sun) up to energies on the order of several thousands of GeV. In order to explain the proton spectra in the energy range of ～20–500 GeV, a two-component phenomenological model is proposed. The first component corresponds to the constant (in this energy range) galactic contribution, while the second (variable) component corresponds to the heliospheric contribution, which appears due to the additional acceleration of soft cosmic-ray protons at the heliosphere periphery. Variations in the proton spectra measured on different time scales between 1992 and 2008 in the energy range from several tens to several hundred GeV, as well as the dependence of these spectra on the heliospheric weather, can be explained by surfatron acceleration of protons in the heliosphere.     

Surfatron accelerator in the local interstellar cloud

Taking into account results of numerous experiments, the variability of the energy spectra of cosmic rays (protons and helium nuclei) in the energy range of 10 GeV to ~10⁷ GeV is explained on the basis of a hypothesis of the existence of two variable sources close to the Sun. The first (soft) surfatron source (with a size of ~100 AU) is located at the periphery of the heliosphere. The second (hard) surfatron source (with a size of ~1 pc) is situated in the Local Interstellar Cloud (LIC) at a distance of <1 pc. The constant background is described by a power-law spectrum with a slope of ~2.75. The variable heliospheric surfatron source is described by a power-law spectrum with a variable amplitude, slope, and cutoff energy, the maximum cutoff energy being in the range of E _СН/Z < 1000 GeV. The variable surfatron source in the LIC is described by a power-law spectrum with a variable amplitude, slope, and cut-off energy, the maximum cut-off energy being E _СL/Z ≤ 3 × 10⁶ GeV. The proposed model is used to approximate data from several experiments performed at close times. The energy of each cosmic-ray component is calculated. The possibility of surfatron acceleration of Fe nuclei (Z = 26) in the LIC up to an energy of E _CL ~ 10¹⁷ eV and electron and positrons to the “knee” in the energy spectrum is predicted. By numerically solving a system of nonlinear equations describing the interaction between an electromagnetic wave and a charged particle with an energy of up to E/Z ~ 3 × 10⁶ GeV, the possibility of trapping, confinement, and acceleration of charged cosmic-ray particles by a quasi-longitudinal plasma wave is demonstrated.     

Acoustic and spirometry parameters of forced expiratory sounds during a five-day dry immersion

The dynamic studies of the parameters of forced expiration under the conditions of a five-day dry immersion involved seven healthy male subjects aged 20 to 25 years. During forced expiration, spirometry tests were performed simultaneously with tracheal sounds being recorded by a microphone. A number of parameters, including the acoustic duration of the forced-expiration tracheal sounds, the lungs’ forced vital capacity, the 1-s forced expiration volume, the peak expiratory flow, and time of achieving the peak expiratory flow, were recorded before dry immersion, on days 1 and 4 of immersion, and the next day after the termination of immersion. There was a significant decrease (by 8.4%) in the peak expiratory flow on day 1 of immersion; however, by day 4 of immersion, the peak expiratory flow increased by 8.9%, reaching its baseline values. The lungs’ forced vital capacity and the forced expiration volume during 1 second, on the average, did not change throughout the experiment. There was a significant increase (by 17%) in the duration of the forced expiration tracheal sounds after the immersion, which suggests an increase in respiratory resistance and needs further studies. A moderate negative correlation between the duration of the forced expiration tracheal sounds and Gensler’s index (r = ?0.63) was found, whereas the correlation with other spirometry parameters was weak or absent.