Estimation of peak ground acceleration and spectral acceleration for South India with local site effects: probabilistic approach

In this work an attempt has been made to evaluate the seismic hazard of South India (8.0 degrees N-20 degrees N; 72 degrees E-88 degrees E) based on the probabilistic seismic hazard analysis (PSHA). The earthquake data obtained from different sources were declustered to remove the dependent events. A total of 598 earthquakes of moment magnitude 4 and above were obtained from the study area after declustering, and were considered for further hazard analysis. The seismotectonic map of the study area was prepared by considering the faults, lineaments and the shear zones in the study area which are associated with earthquakes of magnitude 4 and above. For assessing theseismic hazard, the study area was divided into small grids of size 0.1 degrees x0.1 degrees, and the hazard parameters were calculated at the centre of each of these grid cells by considering all the seismic sources with in a radius of 300 km. Rock level peak horizontal acceleration (PHA) and spectral acceleration (SA) values at 1 corresponding to 10% and 2% probability of exceedance in 50 years have been calculated for all the grid points. The contour maps showing the spatial variation of these values are presented here. Uniform hazard response spectrum (UHRS) at rock level for 5% damping and 10% and 2% probability of exceedance in 50 years were also developed for all the grid points. The peak ground acceleration (PGA) at surface level was calculated for the entire South India for four different site classes. These values can be used to find the PGA values at any site in South India based on site class at that location. Thus, this method can be viewed as a simplified method to evaluate the PGA values at any site in the study area.

Direct estimation of an element of order matrix from H-1 NMR spectra of strongly dipolar coupled spins

NMR spectra of molecules oriented in thermotropic liquid crystalline media provide information on the molecular structure and order. The spins are generally strongly dipolar coupled and the spectral analyse require the tedious and time consuming numerical iterative calculations. The present study demonstrates the application of multiple quantum spin state selective detection of single quantum transitions for mimicking the homonuclear decoupling and the direct estimation of an element of ordering matrix. This information is utilized to estimate the nearly accurate starting dipolar couplings for iterative calculations. The studies on the spectra of strongly dipolar coupled five and six interacting spin systems are reported.

Estimation of Cavitation Erosion with Incubation Periods and Material Properties

A detailed study of the normalized correlations between the incubation period tc and the properties of various materials tested in a rotating disk device indicates that, at very high intensities, the strength properties influence the duration of tc. The analysis of extensive data from other laboratories for cavitation and liquid impingement erosion also indicates that, while both energy and strength properties influence the duration of tc, the latter ones predominate for a majority of cases. A fatigue-type failure occurs during tc. For estimating the time required to pierce a metallic specimen in a rotating device a relationship tp = 160 tc0.44 is proposed. A detailed study of normalized correlations between erosion resistance (inverse of erosion rate) and tc values of different materials tested in the rotating disk shows that correlations are good. Analysis of data from eight other investigators clearly points out the validity and the usefulness of this type of prediction.

A rapid and sensitive method for the estimation of individual tRNA pools

A rapid and sensitive method is described to quantitatively compare tRNA pools for individual aminoacids in a single experiment. The procedure comprises of: (i) charging of total tRNA with a mixture of radiolabeled aminoacids, (ii) deacylation of the esterified tRNA with a volatile base and the recovery of the labeled aminoacid, (iii) derivatisation of the aminoacid with phenylisothiocyanate after mixing with excess of nonradioactive aminoacids, (iv) baseline separation of the phenylthiocarbamyl aminoacids by reverse phase high performance liquid chromatography monitored by A254nm and (v) quantitation of the radioactivity in individual aminoacid peaks. The radioactivity in the aminoacid peak corresponds to the quantity of the aminoacylated tRNA. The method has been successfully applied to quantitate the individual tRNA pools in the developing silk glands of Bombyx mori, a functionally adapted tissue which undergoes considerable variations in tRNA content. PSG, posterior silk gland; PITC, phenylisothiocyanate; DMAA, N,N-dimethyl-N-allylamine; APH, algal protein hydrolysate; ptc-, phenylthiocarbamyl; HPLC, high performance liquid chromatography.

Automated estimation of fatigue crack length and closure/opening stress

An experimental technique is proposed for the estimation of crack length as well as crack closure/opening stress during fatigue crack growth. A specially designed, single cantilever, crack opening displacement gauge is used to monitor these variables during fatigue crack propagation testing. The technique was experimentally validated through electronfractography.

Modeling dynamic demand response using Monte Carlo simulation and interval mathematics for boundary estimation

With the rapid development of various technologies and applications in smart grid implementation, demand response has attracted growing research interests because of its potentials in enhancing power grid reliability with reduced system operation costs. This paper presents a new demand response model with elastic economic dispatch in a locational marginal pricing market. It models system economic dispatch as a feedback control process, and introduces a flexible and adjustable load cost as a controlled signal to adjust demand response. Compared with the conventional “one time use” static load dispatch model, this dynamic feedback demand response model may adjust the load to a desired level in a finite number of time steps and a proof of convergence is provided. In addition, Monte Carlo simulation and boundary calculation using interval mathematics are applied for describing uncertainty of end-user's response to an independent system operator's expected dispatch. A numerical analysis based on the modified Pennsylvania-Jersey-Maryland power pool five-bus system is introduced for simulation and the results verify the effectiveness of the proposed model. System operators may use the proposed model to obtain insights in demand response processes for their decision-making regarding system load levels and operation conditions.

Correction factors for dynamic state estimation of aggregated generators

This paper presents an approach for dynamic state estimation of aggregated generators by introducing a new correction factor for equivalent inter-area power flows. The spread of generators from the center of inertia of each area is summarized by the correction term α on the equivalent power flow between the areas and is applied to the identification and estimation process. A nonlinear time varying Kalman filter is applied to estimate the equivalent angles and velocities of coherent areas by reducing the effect of local modes on the estimated states. The approach is simulated on two test systems and the results show the effect of the correction factor and the performance of the state estimation by estimating the inter-area dynamics of the system.

Net radiation dynamics: performance of 20 daily net radiation models as related to model structure and intricacy in two climates.

We compared daily net radiation (Rn) estimates from 19 methods with the ASCE-EWRI Rn estimates in two climates: Clay Center, Nebraska (sub-humid) and Davis, California (semi-arid) for the calendar year. The performances of all 20 methods, including the ASCE-EWRI Rn method, were then evaluated against Rn data measured over a non-stressed maize canopy during two growing seasons in 2005 and 2006 at Clay Center. Methods differ in terms of inputs, structure, and equation intricacy. Most methods differ in estimating the cloudiness factor, emissivity (e), and calculating net longwave radiation (Rnl). All methods use albedo (a) of 0.23 for a reference grass/alfalfa surface. When comparing the performance of all 20 Rn methods with measured Rn, we hypothesized that the a values for grass/alfalfa and non-stressed maize canopy were similar enough to only cause minor differences in Rn and grass- and alfalfa-reference evapotranspiration (ETo and ETr) estimates. The measured seasonal average a for the maize canopy was 0.19 in both years. Using a = 0.19 instead of a = 0.23 resulted in 6% overestimation of Rn. Using a = 0.19 instead of a = 0.23 for ETo and ETr estimations, the 6% difference in Rn translated to only 4% and 3% differences in ETo and ETr, respectively, supporting the validity of our hypothesis. Most methods had good correlations with the ASCE-EWRI Rn (r2 > 0.95). The root mean square difference (RMSD) was less than 2 MJ m-2 d-1 between 12 methods and the ASCE-EWRI Rn at Clay Center and between 14 methods and the ASCE-EWRI Rn at Davis. The performance of some methods showed variations between the two climates. In general, r2 values were higher for the semi-arid climate than for the sub-humid climate. Methods that use dynamic e as a function of mean air temperature performed better in both climates than those that calculate e using actual vapor pressure. The ASCE-EWRI-estimated Rn values had one of the best agreements with the measured Rn (r2 = 0.93, RMSD = 1.44 MJ m-2 d-1), and estimates were within 7% of the measured Rn. The Rn estimates from six methods, including the ASCE-EWRI, were not significantly different from measured Rn. Most methods underestimated measured Rn by 6% to 23%. Some of the differences between measured and estimated Rn were attributed to the poor estimation of Rnl. We conducted sensitivity analyses to evaluate the effect of Rnl on Rn, ETo, and ETr. The Rnl effect on Rn was linear and strong, but its effect on ETo and ETr was subsidiary. Results suggest that the Rn data measured over green vegetation (e.g., irrigated maize canopy) can be an alternative Rn data source for ET estimations when measured Rn data over the reference surface are not available. In the absence of measured Rn, another alternative would be using one of the Rn models that we analyzed when all the input variables are not available to solve the ASCE-EWRI Rn equation. Our results can be used to provide practical information on which method to select based on data availability for reliable estimates of daily Rn in climates similar to Clay Center and Davis.

Biophysical Characterization of Oxidized Phospholipids : Implications for Altered Membrane Structure and Function

The present study aims to elucidate the modifications in the structure and functionality of the phospholipid matrix of biological membranes brought about by free radical-mediated oxidative damage of its molecular constituents. To this end, the surface properties of two oxidatively modified phospholipids bearing an aldehyde or carboxyl function at the end of truncated sn-2 acyl chain were studied using a Langmuir balance. The results obtained reveal both oxidized species to have a significant impact on the structural dynamics of phospholipid monolayers, as illustrated by the progressive changes in force-area isotherms with increasing mole fraction of the oxidized lipid component. Moreover, surface potential measurements revealed considerable modifications in the electric properties of oxidized phospholipid containing monolayers during film compression, suggesting a packing state-controlled reorientation of the intramolecular electric dipoles of the lipid headgroups and acyl chains. Based on the above findings, a model describing the conformational state of oxidized phospholipid molecules in biological membranes is proposed, involving the protrusion of the acyl chains bearing the polar functional groups out from the hydrocarbon phase to the surrounding aqueous medium. Oxidative modifications alter profoundly the physicochemical properties of unsaturated phospholipids and are therefore readily anticipated to have important implications for their interactions with membrane-associating molecules. Along these lines, the carboxyl group bearing lipid was observed to bind avidly the peripheral membrane protein cytochrome c. The binding was reversed following increase in ionic strength or addition of polyanionic ATP, thus suggesting it to be driven by electrostatic interactions between cationic residues of the protein and the deprotonated lipid carboxyl exposed to the aqueous phase. The presence of aldehyde function bearing oxidized phospholipid was observed to enhance the intercalation of four antimicrobial peptides into phospholipid monolayers and liposomal bilayers. Partitioning of the peptides to monolayers was markedly attenuated by the aldehyde scavenger methoxyamine, revealing it to be mediated by the carbonyl moiety possibly through efficient hydrogen bonding or, alternatively, formation of covalent adduct in form of a Schiff base between the lipid aldehydes and primary amine groups of the peptide molecules. Lastly, both oxidized phospholipid species were observed to bind with high affinity three small membrane-partitioning therapeutic agents, viz. chlorpromazine, haloperidol, and doxorubicin. In conclusion, the results of studies conducted using biomimetic model systems support the notion that oxidative damage influences the molecular architecture as well as the bulk physicochemical properties of phospholipid membranes. Further, common polar functional groups carried by phospholipids subjected to oxidation were observed to act as molecular binding sites at the lipid-water interface. It is thus plausible that oxidized phospholipid species may elicit cellular level effects by modulating integration of various membrane-embedded and surface-associated proteins and peptides, whose conformational state, oligomerization, and functionality is known to be controlled by highly specific lipid-protein interactions and proper physical state of the membrane environment.

Expression and function of angiotensins in the regulation of intraocular pressure - an experimental study

Glaucoma is a multifactorial long-term ocular neuropathy associated with progressive loss of the visual field, retinal nerve fiber structural abnormalities and optic disc changes. Like arterial hypertension it is usually a symptomless disease, but if left untreated leads to visual disability and eventual blindness. All therapies currently used aim to lower intraocular pressure (IOP) in order to minimize cell death. Drugs with new mechanisms of action could protect glaucomatous eyes against blindness. Renin-angiotensin system (RAS) is known to regulate systemic blood pressure and compounds acting on it are in wide clinical use in the treatment of hypertension and heart failure but not yet in ophthalmological use. There are only few previous studies concerning intraocular RAS, though evidence is accumulating that drugs antagonizing RAS can also lower IOP, the only treatable risk factor in glaucoma. The main aim of this experimental study was to clarify the expression of the renin-angiotensin system in the eye tissues and to test its potential oculohypotensive effects and mechanisms. In addition, the possible relationship between the development of hypertension and IOP was evaluated in animal models. In conclusion, a novel angiotensin receptor type (Mas), as well as ACE2 enzyme- producing agonists for Mas, were described for the first time in the eye structures participating in the regulation of IOP. In addition, a Mas receptor agonist significantly reduced even normal IOP. The effect was abolished by a specific receptor antagonist. Intraocular, local RAS would thus to be involved in the regulation of IOP, probably even more in pathological conditions such as glaucoma though there was no unambiguous relationship between arterial and ocular hypertension. The findings suggest the potential as antiglaucomatous drugs of agents which increase ACE2 activity and the formation of angiotensin (1-7), or activate Mas receptors.

Analytical estimation of stress intensity factors in patched cracked plates

The fatigue and fracture performance of a cracked plate can be substantially improved by providing patches as reinforcements. The effectiveness of the patches is related to the reduction they cause in the stress intensity factor (SIF) of the crack. So, for reliable design, one needs an accurate evaluation of the SIF in terms of the crack, patch and adhesive parameters. In this investigation, a centrally cracked large plate with a pair of symmetric bonded narrow patches, oriented normally to the crack line, is analysed by a continuum approach. The narrow patches are treated as transversely flexible line members. The formulation leads to an integral equation which is solved numerically using point collocation. The convergence is rapid. It is found that substantial reductions in SIF are possible with practicable patch dimensions and locations. The patch is more effective when placed on the crack than ahead of the crack. The present analysis indicates that a little distance inwards of the crack tip, not the crack tip itself, is the ideal location, for the patch.

The mechanisms of human renal epithelial cell modulation of autologous dendritic cell phenotype and function

Proximal tubule epithelial cells (PTEC) of the kidney line the proximal tubule downstream of the glomerulus and play a major role in the re-absorption of small molecular weight proteins that may pass through the glomerular filtration process. In the perturbed disease state PTEC also contribute to the inflammatory disease process via both positive and negative mechanisms via the production of inflammatory cytokines which chemo-attract leukocytes and the subsequent down-modulation of these cells to prevent uncontrolled inflammatory responses. It is well established that dendritic cells are responsible for the initiation and direction of adaptive immune responses. Both resident and infiltrating dendritic cells are localised within the tubulointerstitium of the renal cortex, in close apposition to PTEC, in inflammatory disease states. We previously demonstrated that inflammatory PTEC are able to modulate autologous human dendritic cell phenotype and functional responses. Here we extend these findings to characterise the mechanisms of this PTEC immune-modulation using primary human PTEC and autologous monocyte-derived dendritic cells (MoDC) as the model system. We demonstrate that PTEC express three inhibitory molecules: (i) cell surface PD-L1 that induces MoDC expression of PD-L1; (ii) intracellular IDO that maintains the expression of MoDC CD14, drives the expression of CD80, PD-L1 and IL-10 by MoDC and inhibits T cell stimulatory capacity; and (iii) soluble HLA-G (sHLA-G) that inhibits HLA-DR and induces IL-10 expression by MoDC. Collectively the results demonstrate that primary human PTEC are able to modulate autologous DC phenotype and function via multiple complex pathways. Further dissection of these pathways is essential to target therapeutic strategies in the treatment of inflammatory kidney disorders.

Milk casein-derived tripeptides : A special focus on blood pressure and vascular function

Increased consumption of low-fat milk products is inversely associated with the risk of hypertension. The beneficial effect of milk on blood pressure is attributed to high calcium and potassium content but also to specific peptide sequences, which are cleaved from milk protein during gastrointestinal digestion, fermentation of milk with proteolytic starter cultures or enzymatic hydrolysis. Milk products fermented with Lactobacillus helveticus contain casein-derived tripeptides isoleucine-proline-proline (Ile-Pro-Pro) and valine-proline-proline (Val-Pro-Pro), which have been shown to possess antihypertensive effects in humans and in experimental animals. The aim of the present series of studies was to investigate the effects of tripeptides Ile-Pro-Pro and Val-Pro-Pro or fermented milk products containing them on vascular function and blood pressure and to elucidate the mechanisms behind them by using different experimental models of hypertension. Another aim was to characterize the acute effects of tripeptides on blood pressure and arterial stiffness in mildly hypertensive humans. Ile-Pro-Pro and Val-Pro-Pro or fermented milk products containing them attenuated the development of hypertension in two experimental models of hypertension, spontaneously hypertensive rat (SHR) and type 2 diabetic Goto-Kakizaki (GK) rat fed with high-salt diet. Significant differences in systolic blood pressure (SBP) were seen after 8 weeks treatment with tripeptide-containing products compared to control product. Plant sterols did not enhance this effect. Two differently produced tripeptide powders produced a similar attenuating effect on SBP in SHR. In mildly hypertensive subjects, a single administration of tripeptide- and plant sterol-containing fermented milk product decreased both SBP and diastolic blood pressure (DBP) over a period of 8 hours. Protective effect of tripeptides Ile-Pro-Pro and Val-Pro-Pro and fermented milk products containing them on vascular function was demonstrated in in vitro studies and long-term experimental studies. The effect was shown to be endothelium-dependent and possibly involving endothelium-derived hyperpolarizing factor (EDHF). In the clinical study, single administration of tripeptide-containing fermented milk product did not affect measures of arterial stiffness. Long-term treatment with fermented milk product containing Ile-Pro-Pro and Val-Pro-Pro inhibited angiotensin-converting enzyme (ACE) and decreased aldosterone levels thus showing beneficial effects on the renin-angiotensin system (RAS) in SHR and GK. No changes in the components of RAS were observed by the single administration of the same product in mildly hypertensive subjects. Increased levels of cGMP, NOx and citrulline suggest increased nitric oxide (NO) production by the tripeptides. Taken together, Ile-Pro-Pro and Val-Pro-Pro -containing products attenuate the development of hypertension after long-term treatment in experimental models of hypertension and possess an acute antihypertensive effect in mildly hypertensive subjects. In addition, these tripeptides show endothelium-mediated beneficial effects on vascular function. Attenuation of blood pressure increase by the tripeptides in experimental animals involves RAS, but its role in the antihypertensive effect in humans remains to be elucidated.

Function and regulation of Cdk7

Understanding the process of cell division is crucial for modern cancer medicine due to the central role of uncontrolled cell division in this disease. Cancer involves unrestrained proliferation as a result of cells loosing normal control and being driven through the cell cycle, where they normally would be non-dividing or quiescent. Progression through the cell cycle is thought to be dependent on the sequential activation of cyclin-dependent kinases (Cdks). The full activation of Cdks requires the phosphorylation of a conserved residue (threonine-160 on human Cdk2) on the T-loop of the kinase domain. In metazoan species, a trimeric complex consisting of Cdk7, cyclin H and Mat1 has been suggested to be the T-loop kinase of several Cdks. In addition, Cdk7 have also been implicated in the regulation of transcription. Cdk7, cyclin H, and Mat1 can be found as subunits of general transcription factor TFIIH. Cdk7, in this context, phosphorylates the Carboxy-terminal domain (CTD) of the large subunit of RNA polymerase II (RNA pol II), specifically on serine-5 residues of the CTD repeat. The regulation of Cdk7 in these and other functions is not well known and the unambiguous characterization of the in vivo role of Cdk7 in both T-loop activation and CTD serine-5 phosphorylation has proved challenging. In this study, the fission yeast Cdk7-cyclin H homologous complex, Mcs6-Mcs2, is identified as the in vivo T-loop kinase of Cdk1(Cdc2). It also identifies multiple levels of regulation of Mcs6 kinase activity, i.e. association with Pmh1, a novel fission yeast protein that is the apparent homolog of metazoan Mat1, and T-loop phosphorylation of Mcs6, mediated by Csk1, a monomeric T-loop kinase with similarity to Cak1 of budding yeast. In addition, Skp1, a component of the SCF (Skp1-Cullin-F box protein) ubiquitin ligase is identified by its interactions with Mcs2 and Pmh1. The Skp1 association with Mcs2 and Pmh1 is however SCF independent and does not involve proteolytic degradation but may reflect a novel mechanism to modulate the activity or complex assembly of Mcs6. In addition to Cdk7, also Cdk8 has been shown to have CTD serine-5 kinase activity in vitro. Cdk8 is not essential in yeast but has been shown to function as a transcriptional regulator. The function of Cdk8 is unknown in flies and mammals. This prompted the investigation of murine Cdk8 and its potential role as a redundant CTD serine-5 kinase. We find that Cdk8 is required for development prior to implantation, at a time that is co-incident with a burst of Cdk8 expression during normal development. The results does not support a role of Cdk8 as a serine-5 CTD kinase in vivo but rather shows an unexpected requirement for Cdk8, early in mammalian development. The results presented in this thesis extends our current knowledge of the regulation of the cell cycle by characterizing the function of two distinct cell cycle regulating T-loop kinases, including the unambiguous identification of Mcs6, the fission yeast Cdk7 homolog, as the T-loop kinase of Cdk1. The results also indicate that the function of Mcs6 is conserved from fission yeast to human Cdk7 and suggests novel mechanisms by which the distinct functions of Cdk7 and Mcs6 could be regulated. These findings are important for our understanding of how progression of the cell cycle and proper transcription is controlled, during normal development and tissue homeostasis but also under condition where cells have escaped these control mechanisms e.g. cancer.