A search for solar related changes in tropospheric weather

The possibility that solar variations associated with the 11-year solar cycle may be the cause of the changes in tropospheric weather and climate has been the subject to scientific investigation for several decades. Meteorologists are greatly concerned with the changes in tropospheric phenomena. An attempt was made to find solar activity related changes in tropospheric weather, by the modulation of the quasi-biennial oscillation (QBO) of zonal wind at 50 mb. Rainfall and surface temperature data for a period of about three solar cycles, 1953 to 1988, from various stations in the Indian subcontinent were utilized. By extension, a possible teleconnection was looked for between the temperature changes in middle atmospheric levels and surface temperature when the data are stratified according to east or west phase of the QBO. The temperature data were averaged for January and February to represent the winter temperature and for July and August to represent the summer temperature

Influence of solar activity on middle atmosphere associated with phases of equatorial quasi-biennial oscillation

Earlier studies on the influence of solar activity variations within a 11-year solar cycle on temperature changes in the middle atmosphere revealed that while the temperature in the mesosphere showed strong responses to changes in solar activity, the stratosphere remained almost unaffected. Recent studies showed that when the temperature data were grouped into east or west phase of the equatorial quasi-biennial oscillation (QBO) in stratospheric zonal wind, significant relationships of temperature in the lower stratosphere and troposphere could be obtained with 10.7 cm solar radio flux. Positive correlations in high latitude regions and negative correlations in mid-latitude and tropical regions were obtained during winter when the QBO was in its west phase. During the east phase, converse relationships were indicated. These results inspired this study on the response of solar activity in 11-year cycle on the temperature structure of the middle atmosphere in the two phases of equatorial QBO of zonal wind at 50 mb, in tropics, mid-latitude and antarctic regions

Thermophoresis of electrolyte solutions and protein-ligand systems

Thermophoresis or thermodiffusion is the mass transport driven by a temperature gradient. This thesis focuses on the thermophoretic motion of ionic compounds in a biological context and is motivated by a practical application, in which thermodiffusion is used to monitor protein-ligand reactions. Proteins are complex molecules containing non-ionic and ionic groups. While recent studies of non-ionic compounds found a strong correlation between thermodiffusion and hydration, it is unclear how this correlation changes when molecules are charged. To separate ionic from non-ionic contributions, it is reasonable to look first into the thermophoretic motion of simple salts without large organic side groups and to study in the next step complex protein-ligand systems, which typically contain hydrophobic and hydrophilic groups. The systematic studies of aqueous solutions of simple salts should reveal differences between ionic and non-ionic systems and should give further information about ion and ion specific effects. Due to the high complexity of protein-ligand systems, complementary methods should be used to gain a better understanding of the interactions between different components that are present in the system. This will help to understand how the thermophoretic behavior of the free protein differs from that of the protein-ligand complex formed. Study of the thermophoretic behavior of ionic systems indicates that several correlations, which were found for aqueous solutions of non-ionic solutes are no longer valid for ionic solutes. For non-ionic solutes hydrogen bonds primarily influence the thermophoretic behavior. In case of ionic solutes, although both electrostatic interactions and hydrogen bonds are present, it is found that thermophoretic behavior is influenced by electrostatic interactions. Focusing on the specific ion effects for ionic systems in the context of the Hofmeister series, a change of the anion is found to influence the thermophoretic behavior more than a change of the cation. Further, a correlation between thermophoretic behavior and hydrophilicity of the ionic solutes is found, which underlines the sensitivity of thermodiffusion to changes in hydration. Based on this sensitivity, a preliminary model is developed for describing the non-monotonous variation of Soret coefficient ST with concentration for aqueous solutions of alkali iodide salts. To study the thermodiffusion of binding reactions, we also use complementary methods such as Isothermal Titration Calorimetry (ITC) and a thermophoretic microfluidic cell. As systems, we have chosen EDTA-CaCl2 and protein-ligand systems (binding of Bovine Carbonic Anhydrase I (BCA I) with two aryl sulfonamide ligands). To gain deeper insight into the complex formation reactions thermophoretic data (non-equilibrium process) are compared with thermodynamic data (equilibrium process) to establish a mathematical relation between ST and Gibb’s free energy ΔG. For EDTA-CaCl2 and protein-ligand systems, the derived relation holds valid, which enables calculation of ΔG at a particular temperature from ST

Complementary experimental methods to obtain thermodynamic parameters of protein ligand systems

In recent years, thermophoresis has emerged as a promising tool for quantifying biomolecular interactions. The underlying physical effect is still not understood. To gain deeper insight, we investigate whether non-equilibrium coefficients can be related to equilibrium properties. Therefore, we compare thermophoretic data measured by thermal diffusion forced Rayleigh scattering (TDFRS) (which is a non-equilibrium process) with thermodynamic data obtained by isothermal titration calorimetry (ITC) (which is an equilibrium process). As a reference system, we studied chelation reaction between ethylenediaminetetraacetic acid (EDTA) and calcium chloride (CaCl$_2$) to relate the thermophoretic behavior quantified by the Soret coefficient $S_{\mathrm T}$ to the Gibb's free energy $\Delta G$ determined in the ITC experiment using an expression proposed by Eastman [J. Am. Chem. Soc. 50, 283 (1928)]. Finally, we have studied the binding of the protein Bovine Carbonic Anhydrase I (BCA I) to two different benzenesulfonamide derivatives: 4-fluorobenzenesulfonamide (4FBS) and pentafluorobenzenesulfonamide (PFBS). For all three systems, we find that the Gibb' free energies calculated from $S_{\mathrm T}$ agree with $\Delta G$ from the ITC experiment. In addition, we also investigate the influence of fluorescent labeling, which allows measurements in a thermophoretic microfluidic cell. Re-examination of the fluorescently labeled system using ITC showed a strong influence of the dye on the binding behavior

L-deprenyl attenuates the rotenone-induced dopaminergic neurotoxicity: experimental evidences in rats

Parkinson disease (PD) is progressive neurological disorder because of massive degeneration of nigrostriatal dopaminergic neurons. The pathogenesis of PD is unknown, but considerable evidence suggests multifactorial factors including genetic, mitochondrial dysfunction, oxidative stress, excitotoxicity, calcium cytotoxicity, environmental factors and apoptosis. We investigated the role of oxidative damage produced by intranigral infusion of a potent mitochondrial complex-I inhibitor, rotenone and studied the neuroprotective effects with a well-known antiparkinsonian drug L-deprenyl in rats. Unilateral stereotaxic intranigral infusion of rotenone 6 lg caused significant decrease in dopamine levels. L-deprenyl (10 mg/kg) treatment significantly attenuated the DA depletion caused by rotenone. Parallely, a significant decrease in the concentration of GSH was also observed in the SN was reverted by L-deprenyl treatment. L-deprenyl significantly attenuated the rotenone-induced decrease in tyrosine hydroxylase immunoreactivity in striatum. The results suggest that L-deprenyl can rescue the dopaminergic neurons from the rotenone mediated neurodegeneration in this experimental animal model

The economic implications of HLA matching in cadaveric renal transplantation.

Abstract Background: The potential economic effects of the allocation of cadaveric kidneys on the basis of tissue-matching criteria are controversial. We analyzed the economic costs associated with the transplantation of cadaveric kidneys with various numbers of HLA mismatches and examined the potential economic benefits of a local, as compared with a national, system designed to minimize HLA mismatches between donor and recipient in first cadaveric renal transplantations. Methods: All data were supplied by the U.S. Renal Data System. Data on all payments made by Medicare from 1991 through 1997 for the care of recipients of a first cadaveric renal transplant were analyzed according to the number of HLA-A, B, and DR mismatches between donor and recipient and the duration of cold ischemia before transplantation. Results: Average Medicare payments for renal-transplant recipients in the three years after transplantation increased from $60,436 per patient for fully HLA-matched kidneys (those with no HLA-A, B, or DR mismatches) to$80,807 for kidneys with six HLA mismatches between donor and recipient, a difference of 34 percent (P\u3c0.001). By three years after transplantation, the average Medicare payments were $64,119 for transplantations of kidneys with less than 12 hours of cold-ischemia time and$74,997 for those with more than 36 hours (P\u3c0.001). In simulations, the assignment of cadaveric kidneys to recipients by a method that minimized HLA mismatching within a local geographic area (i.e., within one of the approximately 50 organ-procurement organizations, which cover widely varying geographic areas) produced the largest cost savings ($4,290 per patient over a period of three years) and the largest improvements in the graft-survival rate (2.3 percent) when the potential costs of longer cold-ischemia time were considered. Conclusions: Transplantation of better-matched cadaveric kidneys could have substantial economic advantages. In our simulations, HLA-based allocation of kidneys at the local level produced the largest estimated cost savings, when the duration of cold ischemia was taken into account. No additional savings were estimated to result from a national allocation program, because the additional costs of longer cold-ischemia time were greater than the advantages of optimizing HLA matching

PARTICIPATION OF DENDRITIC CELLS IN VASCULAR LESIONS OF CHRONIC REJECTION OF HUMAN ALLOGRAFTS

Immunohistochemical techniques were used to investigate the pathogenesis of obliterative arteriopathy, a major obstacle to long-term solid organ allograft survival. T-lymphocytes, macrophages, and proliferating smooth muscle cells made up most of the thickened intima. More importantly, S100-protein-positive dendritic cells were also present in the intima, especially during active inflammation and smooth muscle cell proliferation. These are phenotypic characteristics of tissue "dendritic" cells, pivotal accessory cells in T-dependent immune reactions. Their localisation in the arterial wall signals the presence of an ongoing immunological reaction directed at native constituents of the artery or at exogenous antigens which permeate the damaged vessel wall. © 1988

Role of defensins in the pathogenesis of chronic lung allograft rejection

Chronic rejection predominantly manifested as bronchiolitis obliterans syndrome (BOS), still remains a major problem affecting long-term outcomes in human lung transplantation (LTx). Donor specific antibodies (DSA) and infiltration of neutrophils in the graft have been associated with the development of BOS. This study determines the role of defensins, produced by neutrophils, and its interaction with α-1-antitrypsin (AAT) towards induction of airway inflammation and fibrosis which are characteristic hallmarks of BOS. Bronchoalveolar lavage (BAL) and serum from LTx recipients, BOS+ (n=28), BOS− (n=26) and normal healthy controls (n=24) were analyzed. Our results show that BOS+ LTx recipients had higher α-defensins (HNP1–3) and β-defensin2 HBD2 concentration in BAL and serum compared to BOS-DSA-recipients and normal controls (p=0.03). BOS+ patients had significantly lower serum AAT along with higher circulating concentration of HNP–AAT complexes in BAL (p=0.05). Stimulation of primary small airway epithelial cells (SAECs) with HNPs induced expression of HBD2, adhesion molecules (ICAM and VCAM), cytokines (IL-6, IL-1β, IL-13, IL-8 and MCP-1) and growth-factor (VEGF and EGF). In contrast, anti-inflammatory cytokine, IL-10 expression decreased 2-fold (p=0.002). HNPs mediated SAEC activation was completely abrogated by AAT. In conclusion, our results demonstrates that neutrophil secretory product, α-defensins, stimulate β-defensin production by SAECs causing upregulation of pro-inflammatory and pro-fibrotic signaling molecules. Hence, chronic stimulation of airway epithelial cells by defensins can lead to inflammation and fibrosis the central events in the development of BOS following LTx