A sufficient criterion for Kelvin–Helmholtz instability in the magnetopause boundary‐layer region

The Kelvin–Helmholtz instability has been investigated for the magnetopause boundary‐layer region by the linearized method. The plasma in magnetosheath and magnetopause is assumed to be semi‐infinitely extended homogeneous, nondissipative, and incompressible. It is observed that, if one relation of two plasma speeds on the two sides of the magnetopause, wave number, and boundary‐layer thickness exceeds a certain threshold, the instability sets in. This new analytically sufficient criterion for excitation of instability in the three‐layer plasma flow generalizes the corresponding Chandrasekhar’s instability criterion for two‐layer plasma flow. The known results have been recovered and modified, the new results have been discovered. It is proved that the velocity threshold for the onset of instability is low when the magnitude of the magnetosheath and boundary‐layer region magnetic field and the angle between them are small. Also the threshold depends on the direction of plasma flow. The following results are observed numerically. The growth of the instability is sensitive to the magnetic field direction in the magnetosheath. A slight variation in the magnetic field direction in the second region can substantially change the relative velocity threshold for instability. When the ratio of the density of the second and third layer (magnetosphere) increases or that of the first and third layer decreases, the threshold decreases. Apart from this a necessary criterion for instability is obtained for a particular case.

Hantavirus infection: Insights into entry, assembly and pathogenesis

Hantaviruses (family Bunyaviridae, genus Hantavirus) are enveloped viruses incorporating a segmented, negative-sense RNA genome. Each hantavirus is carried by its specific host, either a rodent or an insectivore (shrew), in which the infection is asymptomatic and persistent. In humans, hantaviruses cause Hemorrhagic fever with renal syndrome (HFRS) in Eurasia and Hantavirus cardiopulmonary syndrome (HCPS) in the Americas. In Finland, Puumala virus (genus Hantavirus) is the causative agent of NE, a mild form of HFRS. The HFRS-type diseases are often associated with renal failure and proteinuria that might be mechanistically explained by infected kidney tubular cell degeneration in patients. Previously, it has been shown that non-pathogenic hantavirus, Tula virus (TULV), could cause programmed cell death, apoptosis, in cell cultures. This suggested that the infected kidney tubular degeneration could be caused directly by virus replication. In the first paper of this thesis the molecular mechanisms involved in TULV-induced apoptosis was further elucidated. A virus replication-dependent down-regulation of ERK1/2, concomitantly with the induced apoptosis, was identified. In addition, this phenomenon was not restricted to TULV or to non-pathogenic hantaviruses in general since also a pathogenic hantavirus, Seoul virus, could inhibit ERK1/2 activity. Hantaviruses consist of membrane-spanning glycoproteins Gn and Gc, RNA-dependent RNA polymerase (L protein) and nucleocapsid protein N, which encapsidates the viral genome, and thus forms the ribonucleoprotein (RNP). Interaction between the cytoplasmic tails of viral glycoproteins and RNP is assumed to be the only means how viral genetic material is incorporated into infectious virions. In the second paper of this thesis, it was shown by immunoprecipitation that viral glycoproteins and RNP interact in the purified virions. It was further shown that peptides derived from the cytoplasmic tails (CTs) of both Gn and Gc could bind RNP and recombinant N protein. In the fourth paper the cytoplamic tail of Gn but not Gc was shown to interact with genomic RNA. This interaction was probably rather unspecific since binding of Gn-CT with unrelated RNA and even single-stranded DNA were also observed. However, since the RNP consists of both N protein and N protein-encapsidated genomic RNA, it is possible that the viral genome plays a role in packaging of RNPs into virions. On the other hand, the nucleic acid-binding activity of Gn may have importance in the synthesis of viral RNA. Binding sites of Gn-CT with N protein or nucleic acids were also determined by peptide arrays, and they were largely found to overlap. The Gn-CT of hantaviruses contain a conserved zinc finger (ZF) domain with an unknown function. Some viruses need ZFs in entry or post-entry steps of the viral life cycle. Cysteine residues are required for the folding of ZFs by coordinating zinc-ions, and alkylation of these residues can affect virus infectivity. In the third paper, it was shown that purified hantavirions could be inactivated by treatment with cysteine-alkylating reagents, especially N-ethyl maleimide. However, the effect could not be pin-pointed to the ZF of Gn-CT since also other viral proteins reacted with maleimides, and it was, therefore, impossible to exclude the possibility that other cysteines besides those that were essential in the formation of ZF are required for hantavirus infectivity.

DNA damage recognition in the normal epithelium of human prostate and seminal vesicles

Prostate cancer is one of the most prevalent cancer types in men. The development of prostate tumors is known to require androgen exposure, and several pathways governing cell growth are deregulated in prostate tumorigenesis. Recent genetic studies have revealed that complex gene fusions and copy - number alterations are frequent in prostate cancer, a unique feature among solid tumors. These chromosomal aberrations are though to arise as a consequence of faulty repair of DNA double strand breaks (DSB). Most repair mechanisms have been studied in detail in cancer cell lines, but how DNA damage is detected and repaired in normal differentiated human cells has not been widely addressed. The events leading to the gene fusions in prostate cancer are under rigorous studies, as they not only shed light on the basic pathobiologic mechanisms but may also produce molecular targets for prostate cancer treatment and prevention. Prostate and seminal vesicles are part of the male reproductive system. They share similar structure and function but differ dramatically in their cancer incidence. Approximately fifty primary seminal vesicle carcinomas have been reported worldwide. Surprisingly, only little is known on why seminal vesicles are resistant to neoplastic changes. As both tissues are androgen dependent, it is a mystery that androgen signaling would only lead to tumors in prostate tissue. In this work, we set up novel ex vivo human tissue culture models of prostate and seminal vesicles, and used them to study how DNA damage is recognized in normal epithelium. One of the major DNA - damage inducible pathways, mediated by the ATM kinase, was robustly activated in all main cell types of both tissues. Interestingly, we discovered that secretory epithelial cells had less histone variant H2A.X and after DNA damage lower levels of H2AX were phosphorylated on serine 139 (γH2AX) than in basal or stromal cells. γH2AX has been considered essential for efficient DSB repair, but as there were no significant differences in the γH2AX levels between the two tissues, it seems more likely that the role of γH2AX is less important in postmitotic cells. We also gained insight into the regulation of p53, an important transcription factor that protects genomic integrity via multiple mechanisms, in human tissues. DSBs did not lead to a pronounced activation of p53, but treatments causing transcriptional stress, on the other hand, were able to launch a notable p53 response in both tissue types. In general, ex vivo culturing of human tissues provided unique means to study differentiated cells in their relevant tissue context, and is suited for testing novel therapeutic drugs before clinical trials. In order to study how prostate and seminal vesicle epithelial cells are able to activate DNA damage induced cell cycle checkpoints, we used primary cultures of prostate and seminal vesicle epithelial cells. To our knowledge, we are the first to report isolation of human primary seminal vesicle cells. Surprisingly, human prostate epithelial cells did not activate cell cycle checkpoints after DSBs in part due to low levels of Wee1A, a kinase regulating CDK activity, while primary seminal vesicle epithelial cells possessed proficient cell cycle checkpoints and expressed high levels of Wee1A. Similarly, seminal vesicle cells showed a distinct activation of the p53 - pathway after DSBs that did not occur in prostate epithelial cells. This indicates that p53 protein function is under different control mechanisms in the two cell types, which together with proficient cell cycle checkpoints may be crucial in protecting seminal vesicles from endogenous and exogenous DNA damaging factors and, as a consequence, from carcinogenesis. These data indicate that two very similar organs of male reproductive system do not respond to DNA damage similarly. The differentiated, non - replicating cells of both tissues were able to recognize DSBs, but under proliferation human prostate epithelial cells had deficient activation of the DNA damage response. This suggests that prostate epithelium is most vulnerable to accumulating genomic aberrations under conditions where it needs to proliferate, for example after inflammatory cellular damage.

Arabidopsis GRI is involved in the regulation of cell death induced by extracellular ROS

Reactive oxygen species (ROS) have important functions in plant stress responses and development. In plants, ozone and pathogen infection induce an extracellular oxidative burst that is involved in the regulation of cell death. However, very little is known about how plants can perceive ROS and regulate the initiation and the containment of cell death. We have identified an Arabidopsis thaliana protein, GRIM REAPER (GRI), that is involved in the regulation of cell death induced by extracellular ROS. Plants with an insertion in GRI display an ozone-sensitive phenotype. GRI is an Arabidopsis ortholog of the tobacco flower-specific Stig1 gene. The GRI protein appears to be processed in leaves with a release of an N-terminal fragment of the protein. Infiltration of the N-terminal fragment of the GRI protein into leaves caused cell death in a superoxide-and salicylic acid-dependent manner. Analysis of the extracellular GRI protein yields information on how plants can initiate ROS-induced cell death during stress response and development.

Criteria for prediction of flow instabilities and microstructural manifestations during warm working of AISI 304L stainless steel

The deformation characteristics of 304L stainless steel in compression in the temperature range 20–700°C and strain rate range 0·001–100 s−1 have been studied with the aim of characterising the .flow instabilities occurring in the microstructure. At higher temperatures and strain rates the stainless steel exhibits flow localisation, whereas at temperatures below 500°C and strain rates lower than 0·1 s−1 the flow instabilities are due to dynamic strain aging. Strain induced martensite formation is responsible for the flow instabilities at room temperature and low strain rates (0·01 s−1). In view of the occurrence of these instabilities, cold working is preferable to warm working to achieve dimensional tolerance and reproducible properties in the product. Among the different criteria tested to explain the occurrence of instabilities, the continuum criterion, developed on the basis of the principles of maximum rate of entropy production and separability of the dissipation function, predicts accurately all the above instability features.

Do the Hydrolysis Products, Methylamine and N,N'-Dimethylurea, Play any Role in the Methyl Isocyanate-Induced Haematological and Biochemical Changes in Rabbits?

The subcutaneous administration of methyl isocyanate (MIC) to female rabbits, resulted in significant increases in haemoglobin concentration, erythrocyte volume fraction and leucocyte number in blood, as well as plasma total proteins, and urea. The present study was designed to investigate whether the hydrolytic products of MIC, methylamine (MA) and N,N'-dimethylurea (DMU) play any role in eliciting these changes. Both MA and DMU administered subcutaneously in an equimolar dose to that of 1.0 LD50 MIC, 2.2 mmol kg-1, had no influence on these parameters, although there was a marginal increase in the plasma urea level shortly after the administration of DMU. This study establishes that the observed haematological and biochemical changes induced by MIC intoxication in rabbits are mostly due to MIC.

Magnetorotational instability driven dynamos at low magnetic Prandtl numbers

Numerical simulations of the magnetorotational instability (MRI) with zero initial net flux in a non-stratified isothermal cubic domain are used to demonstrate the importance of magnetic boundary conditions. In fully periodic systems the level of turbulence generated by the MRI strongly decreases as the magnetic Prandtl number (Pm), which is the ratio of kinematic viscosity and magnetic diffusion, is decreased. No MRI or dynamo action below Pm=1 is found, agreeing with earlier investigations. Using vertical field conditions, which allow magnetic helicity fluxes out of the system, the MRI is found to be excited in the range 0.1

Influence of methylamine and N,N'-dimethylurea, the hydrolysis products of methyl isocyanate, on its systemic toxicity

Subcutaneous administration of the LD50 dose of methyl isocyanate (MIC) to rats induced severe hyperglycaemia, lactic acidosis and uraemia in rats. Neither methylamine (MA) nor N,N′-dimethylurea (DMU), the hydrolysis products of MIC, administered in equimolar doses had any influence on these parameters except for a marginal transient increase in plasma urea by DMU. Methyl isocyanate administration led to haemoconcentration, resulting in an increase in the plasma concentration of total proteins and a decrease in both the plasma concentration of albumin and the plasma cholinesterase activity. The hydrolysis products of MIC had no influence on any of these parameters. Thus, it seems reasonable to suggest that the systemic effects of MIC are caused by MIC per se, in spite of its high hydrolytic instability.

Microstructural features of flow instability in α-titanium cylinders under high strain rate compression at 25°C to 400°C

Cylindrical specimens of commercial pure titanium have been compressed at strain rates in the range of 0.1 to 100 s-1 and temperatures in the range of 25-degrees-C to 400-degrees-C. At strain rates of 10 and 100 s-1, the specimens exhibited adiabatic shear bands. At lower strain rates, the material deformed in an inhomogeneous fashion. These material-related instabilities are examined in the light of the ''phenomenological model'' and the ''dynamic materials mode.'' It is found that the regime of adiabatic shear band formation is predicted by the phenomenological model, while the dynamic materials model is able to predict the inhomogeneous deformation zone. The criterion based on power partitioning is competent to predict the variations within the inhomogeneous deformation zone.

Parametric instability of stochastic columns

Columns which have stochastically distributed Young's modulus and mass density and are subjected to deterministic periodic axial loadings are considered. The general case of a column supported on a Winkler elastic foundation of random stiffness and also on discrete elastic supports which are also random is considered. Material property fluctuations are modeled as independent one-dimensional univariate homogeneous real random fields in space. In addition to autocorrelation functions or their equivalent power spectral density functions, the input random fields are characterized by scale of fluctuations or variance functions for their second order properties. The foundation stiffness coefficient and the stiffnesses of discrete elastic supports are treated to constitute independent random variables. The system equations of boundary frequencies are obtained using Bolotin's method for deterministic systems. Stochastic FEM is used to obtain the discrete system with random as well as periodic coefficients. Statistical properties of boundary frequencies are derived in terms of input parameter statistics. A complete covariance structure is obtained. The equations developed are illustrated using a numerical example employing a practical correlation structure.

Bacteriophage therapy for Staphylococcus aureus bacteremia in streptozotocin-induced diabetic mice

The protective effect of bacteriophage was assessed against experimental Staphylococcus aureus lethal bacteremia in streptozotocin (STZ) induced-diabetic and non-diabetic mice. Intraperitoneal administrations of S. aureus (RCS21) of 2 x 10(8) CFU caused lethal bacteremia in both diabetic and non-diabetic mice. A single administration of a newly isolated lytic phage strain (GRCS) significantly protected diabetic and nondiabetic mice from lethal bacteremia (survival rate 90% and 100% for diabetic and non-diabetic bacteremic groups versus 0% for saline-treated groups). Comparison of phage therapy to oxacillin treatment showed a significant decrease in RCS21 of 5 and 3 log units in diabetic and nondiabetic bacteremic mice, respectively. The same protection efficiency of phage GRCS was attained even when the treatment was delayed up to 4 h in both diabetic and non-diabetic bacteremic mice. Inoculation of mice with a high dose (10(10) PFU) of phage GRCS alone produced no adverse effects attributable to the phage per se. These results suggest that phages could constitute valuable prophylaxis against S. aureus infections, especially in immunocompromised patients. (C) 2010 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Potassamide induced in situ alkylation of 5,6-dihydroisoquinolines: Structure of products

Potassamide induced in situ alkylation of 1-alkyl- 4-cyano-3-methoxy-5,6-dihydroisoquinolines (2a & 2b) with alkyl iodides (CH3I, CH3CH2I & cyclohexyl iodide) gave the 5-alkyl- and 5,9-dialkyl-5,6-dihydroisoquinolines (4–ad & 3a–e), isoquinoline derivatives, (5a–b) and diastereomeric mixture of 4- alkyl-1,2,3,4-tetrahydroisoquinolin-3(2H)-ones (6a–e & 6′a–e). Structures were assigned on the basis of spectral data [Mass, 1H & 13C NMR, 2D NOESY & HC-COLOC]. Amide induced in situ alkylation of compounds 3a and 4a with CH3I gave in almost quantitative yield the dimethylated compounds 3d and 3a respectively. While KNH2/liq.NH3 methylation of 1,2- dihydroisoquinoline, 1 with CH3I gave the mixture of compounds, 6a & 6′a and the isoquinoline derivative 5a, NaH/benzene reaction of 1 with CH3I gave exclusively 5a. N-methylation of the mixture of compounds 6a & 6′a with NaH/CH3I gave the methylated derivatives, 7 & 8. A suitable mechanism has been proposed for the formation of products.

Pressure-induced phase transitions in LiRbSO4: a Raman spectroscopic study

Room-temperature Raman spectra of LiRbSO4 were studied as a function of pressure up to 170 kbar for two different orientations of the crystal. Four pressure-induced phase transitions at about 2, 17, 32 and 57 kbar were observed. The transitions at 17 and 57 kbar have slow kinetics, taking about 4 h for their completion. These phase transitions are associated with the orientations of the SO4 ions in the unit cell.

Dependence of the large-scale vortex instability on latitude, stratification and domain size

In an earlier study, we reported on the excitation of large-scale vortices in Cartesian hydrodynamical convection models subject to rapid enough rotation. In that study, the conditions for the onset of the instability were investigated in terms of the Reynolds (Re) and Coriolis (Co) numbers in models located at the stellar North pole. In this study, we extend our investigation to varying domain sizes, increasing stratification, and place the box at different latitudes. The effect of the increasing box size is to increase the sizes of the generated structures, so that the principal vortex always fills roughly half of the computational domain. The instability becomes stronger in the sense that the temperature anomaly and change in the radial velocity are observed to be enhanced. The model with the smallest box size is found to be stable against the instability, suggesting that a sufficient scale separation between the convective eddies and the scale of the domain is required for the instability to work. The instability can be seen upto the colatitude of 30 degrees, above which value the flow becomes dominated by other types of mean flows. The instability can also be seen in a model with larger stratification. Unlike the weakly stratified cases, the temperature anomaly caused by the vortex structures is seen to depend on depth.