Sex steroids in Sjögren's syndrome

Sjögren s syndrome (SS) is a strongly female dominant autoimmune disease. SS targets mainly salivary and lacrimal glands and leads to loss of the secreting acinar cells of these glands. Accordingly, secretion of the affected glands is diminished and the main symptoms of SS, dryness of mouth and eyes, follow. In addition to these sicca symptoms, SS patients suffer from severe fatigue and can have various extraglandular symptoms. To date, the etiology of SS still remains unknown. Female dominance and the late onset of the disease simultaneously with remarkable hormonal changes in the body (menopause, adrenopause) encouraged us to hypothesize that sex steroids, especially androgens, are involved in the onset and progression of SS. We confirmed our hypothesis and showed that patients with SS suffer from androgen depletion both systemically and locally in the target tissue of SS, salivary glands. We especially focused on the local androgen environment in salivary glands and demonstrated that healthy salivary glands contain a complete enzymatic machinery for local synthesis of androgens and estrogens from pro-hormone dehydroepiandrosterone (DHEA). However, in SS salivary glands the enzymes catalyzing the local androgen synthesis are defective and, in a subgroup of patients, practically non-functional. Probably due to this local defect in DHEA processing, therapy with DHEA was found unbeneficial for SS patients in the treatment of fatigue. We also studied the effect of the local androgen depletion on salivary glands. We found that in salivary gland cells and healthy labial salivary glands androgens upregulate integrin subunits α1 and α2, which are important for the communication, differentiation and function of the acinar cells. On the contrary, in SS salivary glands DHEA failed to upregulate these signaling molecules, again probably due to defective processing of DHEA into active androgens. Our finding highlights the importance of the local androgen environment and local DHEA processing for the function and welfare of salivary glands. In conclusion, this study showed that patients with SS are androgen depleted both systemically and locally in salivary glands. SS patients also have a defective local sex steroid synthesizing enzymatic machinery further impairing the local androgen depletion. We also showed that the local androgen defect leads to decreased expression of acinar cell specific integrin molecules, which impairs the signaling between the acinar cells and basement membrane and might thus explain the acinar cell loss seen in SS salivary glands. By showing the importance of the local sex steroid imbalance in SS we have clarified some etiopathogenetic mechanisms of SS, which have thus far remained unknown.

Ab initio studies on proton transfer involving Schiff base and related nitrogen compounds

Proton transfer across cationic hydrogen bonds involving Schiff base, ammonia and related compounds has been studied at the 4-31G level. Proton transfer characteristics are correlated to the proton affinities of the species involved. Hydrogen bond strengths of these hydrogen bonds are correlated to the differences in the proton affinity of the donor and the acceptor. Influence of a neighbouring hydrogen bond on the proton transfer from Schiff base to ammonia and Schiff base to water is also discussed.

Positional dependence of material flow in friction stir welding: analysis of joint line remnant and its relevance to dissimilar metal welding

Understanding material flow in friction stir welding is important for production of sound dissimilar metal welding that control the intermixing of two alloys being welded and consequent formation of new constituents which influences the weld properties. In the present experimental investigation material flow patterns are visualised using dissimilar and similar aluminium alloys using a simple innovative ,experiment. The experimental results reveal that only a portion of material transported from the leading edge undergoes chaotic flow and the remaining is deposited systematically in the trailing edge of the weld. Using this information it is shown that the formation of a friction stir welding defect, joint line remnant, does not occur only when the weld interface is on the advancing side. The material flow visualisation study has been utilised to analyse the mechanism of weld formation and its usefulness in improving fatigue properties and for dissimilar metal welds.

Generators contribution towards loads and line flows - A case study

n many parts of the world, the goal of electricity supply industries is always the introduction of competition and a lowering of the average consumer price. Because of this it has become much more important to be able to determine which generators are supplying a particular load, how much use each generator is making of a transmission line and what is generator's contribution to the system losses. In this paper a case study on generator contributions towards loads and transmission flows are illustrated with an equivalent 11-bus system, a part of Indian Southern Grid, based on the concepts of circuit flow directions, for normal and network contingency conditions.

Photocatalytic degradation of phenol by base metal-substituted orthovanadates

Base metal (Cr, Mn, Fe, Ni, Cu) substituted CeVO4 compounds were synthesized by the solution combustion technique. These compounds were characterized by X-ray diffraction, X-ray photoelectron spectroscopy, UV-vis spectroscopy, transmission electron microscopy and BET surface area analyzer. The characterization indicated that the base metals were substituted in the ionic state in all the compounds. These compounds were used for the photocatalytic degradation of phenol and the degradation rates obtained in the presence of these compounds werecompared against that obtained with the commercial Degussa P-25 TiO2 catalyst. Fe and Cr substituted CeVO4 showed photocatalytic activity that was comparable with that of Degussa P-25 TiO2. The concentration of toxic intermediates was high when the reaction was carried out in presence of Degussa P-25 TiO2 but it was found to be insignificant when the reaction was carried out in presence of base metal-substituted CeVO4. The effect of % Fe-substitution (varied from 1 to 5 at%) in CeVO4 on the photocatalytic activity was also investigated and it was observed that 1 at% Fe-substituted compound showed the highest activity. A mathematical model describing the kinetics of the photocatalytic degradation of phenol was developed on the basis of the catalyst structure and taking into account the formation of all the possible intermediates. The variation of the concentration of phenol and the intermediates was described by the model and the reaction rateconstants were determined. (C) 2010 Elsevier B.V. All rights reserved.

Mode-dependent dispersion in Raman line shapes: Observation and implications from ultrafast Raman loss spectroscopy

Ultrafast Raman loss spectroscopy (URLS) enables one to obtain the vibrational structural information of molecular systems including fluorescent materials. URLS, a nonlinear process analog to stimulated Raman gain, involves a narrow bandwidth picosecond Raman pump pulse anda femtosecond broadband white light continuum. Under nonresonant condition, the Raman response appears as a negative (loss) signal, whereas, on resonance with the electronic transition the line shape changes from a negative to a positive through a dispersive form. The intensities observed and thus, the Franck-Condon activity (coordinate dependent), are sensitive to the wavelength of the white light corresponding to a particular Raman frequency with respect to the Raman pump pulse wavelength, i.e., there is a mode-dependent response in URLS. (C) 2010 American Institute of Physics.

Synthesis, X-ray structure and catalytic properties of a copper(II) Schiff base complex modeling the activity of the Cu-B site of dopamine beta-hydroxylase

The copper(II) complex [Cu(salgly) (bpy)] . 4H(2)O (1), where salgly is a tridentate glycinatosalicylaldimine Schiffbase Ligand, is prepared and structurally characterized. The complex is found to be catalytically active in the oxidation of ascorbic acid by dioxygen and the process is also effective in the presence of benzylamine giving benzaldehyde as a product, thus modeling the activity of the Cu-B site of dopamine beta-hydroxylase. (C) 2000 Elsevier Science S.A. All rights reserved.

Slip line field analysis of a simple plane strain closed‐die forging

A slip line field is proposed for symmetrical single‐cavity closed‐die forging by rough dies. A compatible velocity field is shown to exist. Experiments were conducted using lead workpiece and rough dies. Experimentally observed flow and load were used to validate the proposed slip line field. The slip line field was used to simulate the process in the computer with the objective of studying the influence of flash geometry on cavity filling.

Photocytotoxicity and DNA cleavage activity of L-arg and L-lys Schiff base oxovanadium(IV) complexes having phenanthroline bases

Oxovanadium(IV) complexes [VO(sal-argH)(B)] Cl (1-3) and [VO(sal-lysH)(B)] Cl (4-6), where sal-argH2 and sal-lysH(2) are N-salicylidene-L-arginine and N-salicylidene-L-lysine Schiff bases and B is a phenanthroline base, viz. 1,10-phenanthroline (phen in 1 and 4); dipyrido[3,2-d: 2', 3'-f] quinoxaline (dpq in 2 and 5) and dipyrido[3,2-a: 2', 3'-c] phenazine (dppz in 3 and 6), have been prepared, characterized and their DNA photocleavage activity studied. Complex 1, characterized by X-ray crystallography, shows the presence of a vanadyl group in VIVO3N3 coordination geometry with a tridentate Schiff base having a pendant guanidinium moiety and bidentate phen ligand. The complexes exhibit a d-d band at similar to 715 nm in 20% DMF-Tris-HCl buffer. The complexes are redox active showing cathodic and anodic responses near -1.0 V and 0.85 V (vs. SCE) for the V(IV)-V(III) and V(V)-V(IV) couples, respectively, in DMF-Tris-HCl buffer. The complexes bind to calf thymus DNA giving Kb values in the range of 3.8 x 10(4) to 1.6 x 10(5) M-1. Thermal denaturation and viscosity data suggest DNA groove binding nature of the complexes. The complexes do not show any `chemical nuclease'' activity in dark in the presence of 3-mercaptopropionic acid or H2O2. The dpq and dppz complexes are efficient photocleavers of plasmid DNA in UV-A (365 nm) and red light (676 nm) via singlet oxygen pathway. The dppz complexes exhibit photocytotoxicity in HeLa cancer cells giving IC50 values of 15.4 mu M for 3 and 17.5 mu M for 6 in visible light while being non-toxic in dark giving IC50 values of > 100 mu M.

Accelerating Waves in Polar Coronal Holes as Seen by EIS and SUMER

We present EIS/Hinode and SUMER/SOHO observations of propagating disturbances detected in coronal lines in inter-plume and plume regions of a polar coronal hole. The observation was carried out on 2007 November 13 as part of the JOP196/HOP045 program. The SUMER spectroscopic observation gives information about fluctuations in radiance and on both resolved (Doppler shift) and unresolved (Doppler width) line-of-sight velocities, whereas EIS 40 `'wide slot images detect fluctuations only in radiance but maximize the probability of overlapping field of view between the two instruments. From distance-time radiance maps, we detect the presence of propagating waves in a polar inter-plume region with a period of 15-20 minutes and a propagation speed increasing from 130 +/- 14 km s(-1) just above the limb to 330 +/- 140 km s(-1) around 160 `' above the limb. These waves can be traced to originate from a bright region of the on-disk part of the coronal hole where the propagation speed is in the range of 25 +/- 1.3 to 38 +/- 4.5 km s(-1), with the same periodicity. These on-disk bright regions can be visualized as the base of the coronal funnels. The adjacent plume region also shows the presence of propagating disturbances with the same range of periodicity but with propagation speeds in the range of 135 +/- 18 to 165 +/- 43 km s(-1) only. A comparison between the distance-time radiance map of the two regions indicates that the waves within the plumes are not observable (may be getting dissipated) far off-limb, whereas this is not the case in the inter-plume region. A correlation analysis was also performed to find out the time delay between the oscillations at several heights in the off-limb region, finding results consistent with those from the analysis of the distance-timemaps. To our knowledge, this result provides first spectroscopic evidence of the acceleration of propagating disturbances in the polar region close to the Sun (within 1.2 R/R-circle dot), which provides clues to the understanding of the origin of these waves. We suggest that the waves are likely either Alfvenic or fast magnetoacoustic in the inter-plume region and slow magnetoacoustic in the plume region. This may lead to the conclusion that inter-plumes are a preferred channel for the acceleration of the fast solar wind.

An ab-initio study of the proton affinity of conjugated schiff-base and related nitrogen compounds: an analysis of the triggering site of bacteriorhodopsin

The chemical groups which take part in the proton transfer reaction in bacteriorhodopsin have been studied by ab initio quantum chemical methods. The various factors such as conjugation with a linear system, electron delocalization of the guanidine type, cis-trans isomerism, geometry distortion and hydrogen bonding with charged groups can influence the properties of a given chemical group. Several systems are studied at 4-31G and STO-3G levels. Some of the Schiff-base analogues and guanidine type molecules are characterized by their molecular orbital diagrams, energy levels and the nature of charge distribution. Also, the effects of the above-mentioned factors on proton affinity are studied. It is hoped that the values thus obtained can be helpful in evaluating various structural models for proton transfer.

Reactions of coordinated bivalent tetradentate schiff-base chelates of nickel (II) and palladium (II)

Reactions of N,N′-n-propylene-bis(acetylacetoneimino) metal (II), M[n-P-(AI)2], where M=Ni(II) or Pd(II), with nitrosating reagents have been investigated. Mono- and di-nitrosated complexes were obtained selectively, depending upon the concentration of the nitrosating reagents and the reaction time. In both the cases, the γ-CH group is transformed to an ambidentate isonitroso group (>C=NOH), which coordinates to the metal ion by dislodging the already coordinated carbonyl group. The factors influencing the mode of binding of the isonitroso group have been discussed. The bromination reactions of the mono-nitrosated products of M[n-P-(AI)2] and Pd (II) complexes, Pd [E/i-P-(AI)2], where E/i-P-(AI)2 is a dianion of ethylene/i-propylene-bis (acetylacetoneimine), are also reported. The reaction products have been characterized by elemental analyses, electrical conductivity molecular weight determination, and ir, pmr and electronic spectral data.

Isobaric electrical resistance along the critical line in nickel: An experimental test of universality

High-precision measurement of the electrical resistance of nickel along its critical line, a first attempt of this kind, as a function of pressure to 47.5 kbar is reported. Our analysis yields the values of the critical exponents α=α’=-0.115±0.005 and the amplitude ratios ‖A/A’‖=1.17±0.07 and ‖D/D’‖=1.2±0.1. These values are in close agreement with those predicted by renormalization-group (RG) theory. Moreover, this investigation provides an unambiguous experimental verification to one of the key consequences of RG theory that the critical exponents and amplitudes ratios are insensitive to pressure variation in nickel, a Heisenberg ferromagnet.

A novel fiber-coated strong base-type anion exchanger with superfast kinetics. Removal and recovery of silver thiosulfate from aqueous solutions

A commercial acrylic fiber with 92% (w/w) acrylonitrile content was partially hydrolyzed converting a fraction of the nitrile (-CN) groups to carboxylic acid (-COOH) groups, to coat the fiber with polyethylenimine (PEI) resin, which was then crosslinked with glutaraldehyde and further quaternized with ethyl chloroacetate to produce a novel strong-base anionic exchanger in the form of fiber. Designated as PAN(QPEI.XG)(Cl-), the fibrous sorbent was compared with a commercial bead-form resin Amberlite IRA-458(Cl-) in respect of sorption capacity, selectivity, and kinetics for removal of silver thiosulfate complexes from aqueous solutions. Though the saturation level of [Ag(S2O3)(2)](3-) on PAN(QPEI.XG)(Cl-) is considerably less than that on IRA-458(Cl-), the gel-coated fibrous sorbent exhibits, as compared to the bead-form sorbent, a significantly higher sorption selectivity for the silver thiosulfate complex in the presence of excess of other anions Such as S2O32-, SO42-, and Cl-, and a remarkably faster rate of both sorption and stripping. The initial uptake of the sorbate by the fibrous sorbent is nearly instantaneous, reaching up to similar to 80% of the saturation capacity within 10 s, as compared to only similar to 12% on the bead-form sorbent. The high initial rate of uptake fits a shell-core kinetic model for sorption on fiber of cylindrical geometry. With 4M HCl, the stripping of the sorbed silver complex from the fibrous sorbent is clean and nearly instantaneous, while, in contrast, a much slower rate of stripping on the bead-form sorbent leads to its fouling due to a slow decomposition of the silver thiosulfate complex in the acidic medium.

Real-Time PCR : A Molecular Approach to Investigate the Role of Intestinal Microbiota in the Pathophysiology of Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) is a common multifactorial functional intestinal disorder, the pathogenesis of which is not completely understood. Increasing scientific evidence suggests that microbes are involved in the onset and maintenance of IBS symptoms. The microbiota of the human gastrointestinal (GI) tract constitutes a massive and complex ecosystem consisting mainly of obligate anaerobic microorganisms making the use of culture-based methods demanding and prone to misinterpretation. To overcome these drawbacks, an extensive panel of species- and group-specific assays for an accurate quantification of bacteria from fecal samples with real-time PCR was developed, optimized, and validated. As a result, the target bacteria were detectable at a minimum concentration range of approximately 10 000 bacterial genomes per gram of fecal sample, which corresponds to the sensitivity to detect 0.000001% subpopulations of the total fecal microbiota. The real-time PCR panel covering both commensal and pathogenic microorganisms was assessed to compare the intestinal microbiota of patients suffering from IBS with a healthy control group devoid of GI symptoms. Both the IBS and control groups showed considerable individual variation in gut microbiota composition. Sorting of the IBS patients according to the symptom subtypes (diarrhea, constipation, and alternating predominant type) revealed that lower amounts of Lactobacillus spp. were present in the samples of diarrhea predominant IBS patients, whereas constipation predominant IBS patients carried increased amounts of Veillonella spp. In the screening of intestinal pathogens, 17% of IBS samples tested positive for Staphylococcus aureus, whereas no positive cases were discovered among healthy controls. Furthermore, the methodology was applied to monitor the effects of a multispecies probiotic supplementation on GI microbiota of IBS sufferers. In the placebo-controlled double-blind probiotic intervention trial of IBS patients, each supplemented probiotic strain was detected in fecal samples. Intestinal microbiota remained stable during the trial, except for Bifidobacterium spp., which increased in the placebo group and decreased in the probiotic group. The combination of assays developed and applied in this thesis has an overall coverage of 300-400 known bacterial species, along with the number of yet unknown phylotypes. Hence, it provides good means for studying the intestinal microbiota, irrespective of the intestinal condition and health status. In particular, it allows screening and identification of microbes putatively associated with IBS. The alterations in the gut microbiota discovered here support the hypothesis that microbes are likely to contribute to the pathophysiology of IBS. The central question is whether the microbiota changes described represent the cause for, rather than the effect of, disturbed gut physiology. Therefore, more studies are needed to determine the role and importance of individual microbial species or groups in IBS. In addition, it is essential that the microbial alterations observed in this study will be confirmed using a larger set of IBS samples of different subtypes, preferably from various geographical locations.