Higher topoisomerase 2 alpha gene transcript levels predict better prognosis in GBM patients receiving temozolomide chemotherapy: identification of temozolomide as a TOP2A inhibitor

The search for molecular markers which predict response to chemotherapy is an important aspect of current neuro-oncology research. MGMT promoter methylation is the only proved marker of glioblastoma. The purpose of this study was to assess the effect of topoisomerase expression on glioblastoma survival and study the mechanisms involved. The transcript levels of all isoforms of the topoisomerase family in all grades of diffuse astrocytoma were assessed. A prospective study of patients with glioblastoma treated by a uniform treatment procedure was performed with the objective of correlating outcome with gene expression. The ability of TOP2A enzyme to relax the super coiled plasmid DNA in the presence of temozolomide was evaluated to assess its effect on TOP2A. The temozolomide cyctotoxicity of TOP2A-silenced U251 cells was assessed. The transcript levels of TOP2A, TOP2B, and TOP3A are upregulated significantly in GBM in comparison with lower grades of astrocytoma and normal brain samples. mRNA levels of TOP2A correlated significantly with survival of the patients. Higher TOP2A transcript levels in GBM patients predicted better prognosis (P = 0.043; HR = 0.889). Interestingly, we noted that temozolomide inhibited TOP2A activity in in-vitro enzyme assays. We also noted that siRNA knock down of TOP2A rendered a glioma cell line resistant to temozolomide chemotherapy. We demonstrated for the first time that temozolomide is also a TOP2A inhibitor and established that TOP2A transcript levels determine the chemosensitivity of glioblastoma to temozolomide therapy. Very high levels of TOP2A are a good prognostic indicator in GBM patients receiving temozolomide chemotherapy.

Gossypol-induced hypokalemia and role of exogenous potassium salt supplementation when used as an antispermatogenic agent in male langur monkey

In our earlier study, we have observed that hypokalemia in langur monkeys, following gossypol acetic acid (GAA) treatment (5 mg dose level) when used as an antispermatogenic agent, and potassium salt supplementation partially maintained body potassium level of the animals. The aims of the present investigation was to confirm further occurrence of hypokalemia in the monkey (comparatively at two higher dose levels) and the role of potassium salt in preventing occurrence of gossypol-induced hypokalemia. Highly purified gossypol acetic acid alone at two dose levels (7.5 and 10 mg/animal/day; oral) and in combination with potassium chloride (0.50 and 0.75 mg/animal/day; oral) was given for 180 days. Treatment with gossypol alone as well as with the supplementation of potassium salt resulted in severe oligospermia and azoospermia. Animals receiving gossypol alone showed significant potassium deficiency with signs of fatigue at both dose levels. Enhanced potassium loss through urine was found in potassium-deficient animals, whereas animals receiving gossypol acetic acid plus potassium salt showed normal serum potassium with a less significant increase in urine potassium level during treatment phases. Other parameters of the body remained within normal range except gradual and significant elevation in serum transaminases activity. The animals gradually returned to normalcy following 150 and 180 days of termination of the treatment.

Buoyant Jet Discharges into Finite Ambient Waters

The paper presents the results of an experimental study regarding the effect of the lateral dimension of the receiving water on the spreading, mixing, and temperature decay of a horizontal buoyant surface jet. The widths of the ambient water in the experiments have been 240, 120, 90 and 60 times the diameter of the jet nozzle. Based on the experimental data, correlations are carried out and empirical equations for prediction of jet width, thickness in vertical direction and longitudinal temperature decay are obtained. The available data of earlier investigators are included to obtain generalized equations for the spreading and temperature decay. Similarity of temperature profiles in the lateral and vertical directions is observed. The longitudinal temperature decay is found to vary inversely with distance in the flow direction and ¼th power of the densimetric Froude number.

Improving the optimum generalised stop-and-wait ARQ scheme

Instead of waiting for the acknowledgments from all the copies of a single data block sent, as in the optimum generalised stop-and-wait ARQ scheme, the transmitter in the proposed scheme starts sending an optimum number of copies of the next block in the queue, soon after receiving the positive acknowledgment from the receiver, thereby further improving the throughput efficiency.

Support vector machine approach for the switching transient peak overvoltages during line energization

At the time of restoration transmission line switching is one of the major causes, which creates transient overvoltages. Though detailed Electro Magnetic Transient studies are carried out extensively for the planning and design of transmission systems, such studies are not common in a day-today operation of power systems. However it is important for the operator to ensure during restoration of supply that peak overvoltages resulting from the switching operations are well within safe limits. This paper presents a support vector machine approach to classify the various cases of line energization in the category of safe or unsafe based upon the peak value of overvoltage at the receiving end of line. Operator can define the threshold value of voltage to assign the data pattern in either of the class. For illustration of proposed approach the power system used for switching transient peak overvoltages tests is a 400 kV equivalent system of an Indian southern gri

Effect of vitamins A and K on colon lysosomes

1. 1. Colon lysosome were separated by differential centrifugation and lysosomes with three different densities, probably arising from the three layers of colon, were found. 2. 2. Hypervitaminosis A resulted in a significant increase in prothrombin time which was restored to normal on vitamin K1 (20) supplementation. 3. 3. There was no appreciable change in the liver storage of vitamin A between hypervitaminotic rats receiving vitamin A and those rats receiving vitamin K1 (20) in addition to excess vitamin A. 4. 4. The colon lysosomes were unstable in hypervitaminosis A, showing an increased free activity of lysosomal enzymes like β-glucuronidase, acid phosphatase and arylsulphatase. This increase of free activity of lysoso3al enzymes in hypervitaminosis A could be prevented by oral supplementation of vitamin K1 (20). 5. 5. In "mild" vitamin A deficiency the release of arylsulphatase was significantly retarded, whereas the decreased free acid phosphatase activity was not significant. 6. 6. "Severe" vitamin A deficiency resulted in a significantly increased free activity of arylsulphatase and acid phosphatase, thus showing the instability of the lysosomal particles in this condition. 7. 7. Addition of vitamin K1 (20) to the incubation medium in vitro could prevent the vitamin A-induced release of arylsulphatase from liver lysosomes, whereas α-tocopherol was inactive. 8. 8. Retinol and retinoic acid were nearly twice as active as ethanol in the release of arylsulphatase from lysosomes in vitro, whereas 5,6-monoepoxyretinoic acid was inactive. 9. 9. The role of vitamins A and K on the lysosomal membrane structure is discussed.

Q-Band beam wave-guide

Consideration is given to a 25-foot long Q-band (8 mm) confocal, zoned dielectric lens beam waveguide. Numerical expressions for the axial and radial fields are presented. The experimental set-up consisted of uniformly spaced zoned dielectric lenses, a transmitting horn and a receiving horn. It was found that: (1) the wave beam is reiterated when confocal, zoned dielectric lenses act as phase transformers in place of smooth surfaced transformers in beam waveguides; (2) the axial field is oscillatory near the source and the oscillation persists for about 25 cm from the source; (3) the oscillation disappears after one lens is used; (4) higher order modes with higher attenuation rates die out faster than fundamental modes; (5) phase transformers do not alter beam modes; (6) without any lens the beam cross-section broadens significantly in the Z-direction; (7) with one lens the beam exhibits the reiteration phenomenon; and (8) inserting a second lens on the axial and cross-sectional field distribution shows further the reiteration principle.

Differential reproductive success in Cassia fistula in different habitants-A case of pollinator limitations?

Differences in flower success patterns in two habitat types that differed drastically with respect to rainfall, tree density and species composition were studied at Mudumalai wildlife sanctuary, India. Observations on phenological patterns of two species, Cassia fistula and Gmelina arborea, were made from April 1988 through June 1990. Quantitative data on flower-fruit ratio, insect visitation rates, pollen grain per stigma and the number of fruits per tree were recorded. Data were also collected on the number of pollen deposited on the stigma after different types of bees visited the flower. The data suggested that only carpenter bees (Xylocopa spp) effect pollination in C. fistula. The differences in fruit-flower ratios were attributed to the differences in insect visitation rates to inflorescences between sites. The low pollen number per stigma and the resultant reduction in reproductive success in C. fistula are attributed to the competing species G. arborea receiving more visitations from pollinators in the wetter site. These results suggest that pollinator limitation is another constraint in reproductive success of plants.

Role of lipid peroxidation in impairment of mitochondrial function at complex I by methyl isocyanate treatment of rats in vivo

The subcutaneous administration of methyl isocyanate (MIC) in 1.0 LD50 dose in rats caused a significant effect on hepatic mitochondrial function only at complex I region of the respiratory chain. MIC administration at 1.0 LD50 dose also resulted in significant increases in malondialdehyde and ferrous ion concentration in liver mitochondria. It is suggested that the augmented lipid peroxidation in hepatic mitochondria, catalyzed by iron, possibly mobilized from intracellular stores leads to the inhibition of enzymes of mitochondrial respiration at complex I region, in vivo, in rats receiving a lethal dose of MIC subcutaneously.

Support vector machine for evaluating seismic-liquefaction potential using shear wave velocity

The use of the shear wave velocity data as a field index for evaluating the liquefaction potential of sands is receiving increased attention because both shear wave velocity and liquefaction resistance are similarly influenced by many of the same factors such as void ratio, state of stress, stress history and geologic age. In this paper, the potential of support vector machine (SVM) based classification approach has been used to assess the liquefaction potential from actual shear wave velocity data. In this approach, an approximate implementation of a structural risk minimization (SRM) induction principle is done, which aims at minimizing a bound on the generalization error of a model rather than minimizing only the mean square error over the data set. Here SVM has been used as a classification tool to predict liquefaction potential of a soil based on shear wave velocity. The dataset consists the information of soil characteristics such as effective vertical stress (sigma'(v0)), soil type, shear wave velocity (V-s) and earthquake parameters such as peak horizontal acceleration (a(max)) and earthquake magnitude (M). Out of the available 186 datasets, 130 are considered for training and remaining 56 are used for testing the model. The study indicated that SVM can successfully model the complex relationship between seismic parameters, soil parameters and the liquefaction potential. In the model based on soil characteristics, the input parameters used are sigma'(v0), soil type. V-s, a(max) and M. In the other model based on shear wave velocity alone uses V-s, a(max) and M as input parameters. In this paper, it has been demonstrated that Vs alone can be used to predict the liquefaction potential of a soil using a support vector machine model. (C) 2010 Elsevier B.V. All rights reserved.

Reproductive phenology of a tropical dry forest in Mudumalai, Southern India

1 Flowering and fruiting phenologies of a tropical dry forest in Mudumalai, southern India, were studied between April 1988 and August 1990. Two sites, a wetter site I receiving 1100mm and a drier site II receiving 600mm of rainfall annually, are compared. A total of 286 trees from 38 species at site I and 167 trees from 27 species at site II was marked for phenological observations. There were 11 species common to the two sites. Several hypotheses relating to the evolution of reproductive phenology are tested. 2 Frequency of species flowering attained a peak at site I during the dry season but at site II, where soil moisture may be limiting during the dry months, the peak was during the wet season. At both sites a majority of species flushed leaves and flowered simultaneously. Among various guilds, the bird-pollinated guild showed distinct dry season flowering, which may be related to better advertisement of large flowers to pollinators during the leafless dry phase. The wind-pollinated guild flowered mainly during the wet season, when wind speeds are highest and favourable for pollen transport. The insect-pollinated guild showed no seasonality in flowering in site I but a wet season flowering in site II. 3 Fruiting frequency attained a peak in site I during the late wet season extending into the early dry season; a time-lag correlation showed that fruiting followed rainfall with a lag of about two months. Site II showed a similar fruiting pattern but this was not statistically significant. The dispersal guilds (animal, wind, and explosive passively-dispersed) did not show any clear seasonality in fruiting, except for the animal-dispersed guild which showed wet season fruiting in site I. 4 Hurlbert's overlap index was also calculated in order to look at synchrony in flowering and fruiting irrespective of climatic (dry and wet month) seasonality. In general, overlap in flowering and fruiting guilds was high because of seasonal aggregation. Among the exceptions, at site II the wind-pollinated flowering guild did not show significant overlap between species although flowering aggregated in the wet season. This could be due to the need to avoid heterospecific pollen transfer. 5 Rarer species tended to flower earlier in the dry season and this again could be an adaptation to avoid the risk of heterospecific pollen transfer or competition for pollinators. The more abundant species flowered mainly during the wet season. Species which flower earlier have larger flowers and, having invested more energy in flowers, also have shorter flower to fruit durations.

Post-seizure EEG fractal dimension of first ECT predicts antidepressant response at two weeks

Background: Duration of seizure by itself is an insufficient criterion for a therapeutically adequate seizure in ECT. Therefore, measures of seizure EEG other than its duration need to be explored as indices of seizure adequacy and predictors of treatment response. We measured the EEG seizure using a geometrical method-fractal dimension (FD) and examined if this measure predicted remission. Methods: Data from an efficacy study on melancholic depressives (n = 40) is used for the present exploration. They received thrice or once weekly ECTs, each schedule at two energy levels - high or low energy level. FD was computed for early-, mid- and post-seizure phases of the ictal EEG. Average of the two channels was used for analysis. Results: Two-thirds of the patients (n = 25) were remitted at the end of 2 weeks. As expected, a significantly higher proportion of patients receiving thrice weekly ECT remitted than in patients receiving once weekly ECT. Smaller post-seizure FD at first ECT is the only variable which predicted remission status after six ECTs. within the once weekly ECT group too, smaller post-seizure FD was associated with remission status. Conclusions: Post-seizure FD is proposed as a novel measure of seizure adequacy and predictor of treatment response. Clinical implications: Seizure measures at first ECT may guide selection of ECT schedule to optimize ECT. Limitations: The study examined short term antidepressant effects only. The results may not be generalized to medication-resistant depressives. (C) 1999 Elsevier Science B.V. All rights reserved.

Residual strength and fatigue life assessment of composite patch repaired specimens

Design, analysis and technology for the integrity enhancement of damaged or underdesigned structures continues to be an engineering challenge. Bonded composite patch repairs to metallic structures is receiving increased attention in the recent years. It offers various advantages over rivetted doubler, particularly for airframe repairs. This paper presents an experimental investigation of residual strength and fatigue crack-growth life of an edge-cracked aluminium specimen repaired using glass epoxy composite patch. The investigation begins with the evaluation of three different surface treatments from bond strength viewpoint. A simple thumb rule formula is employed to estimate the patch size. Cracked and repaired specimens are tested under static and fatigue loading. The patch appears to restore the original strength of the undamaged specimen and enhance the fatigue crack growth life by an order of magnitude. (C) 1999 Elsevier Science Ltd. All rights reserved.

Analytical models for energy consumption in infrastructure WLAN STAs carrying TCP traffic

We develop analytical models for estimating the energy spent by stations (STAs) in infrastructure WLANs when performing TCP controlled file downloads. We focus on the energy spent in radio communication when the STAs are in the Continuously Active Mode (CAM), or in the static Power Save Mode (PSM). Our approach is to develop accurate models for obtaining the fraction of times the STA radios spend in idling, receiving and transmitting. We discuss two traffic models for each mode of operation: (i) each STA performs one large file download, and (ii) the STAs perform short file transfers. We evaluate the rate of STA energy expenditure with long file downloads, and show that static PSM is worse than just using CAM. For short file downloads we compute the number of file downloads that can be completed with given battery capacity, and show that PSM performs better than CAM for this case. We provide a validation of our analytical models using the NS-2 simulator.

The Effect of Evacuated Backside Cavity on the Dynamic Characteristics of a Capacitive Micromachined Ultrasonic Transducer

In this paper, we investigate the effect of vacuum sealing the backside cavity of a Capacitive Micromachined Ultrasonic Transducer (CMUT). The presence or absence of air inside the cavity has a marked effect upon the system parameters, such as the natural frequency, damping, and the pull-in voltage. The presence of vacuum inside the cavity of the device causes a reduction in the effective gap height which leads to a reduction in the pull-in voltage. We carry out ANSYS simulations to quantify this reduction. The presence of vacuum inside the cavity of the device causes stress stiffening of the membrane, which changes the natural frequency of the device. A prestressed modal analysis is carried out to determine the change in natural frequency due to stress stiffening. The equivalent circuit method is used to evaluate the performance of the device in the receiver mode. The lumped parameters of the device are obtained and an equivalent circuit model of the device is constructed to determine the open circuit receiving sensitivity of the device. The effect of air in the cavity is included by incorporating an equivalent compliance and an equivalent resistance in the equivalent circuit.