Conditions for combining gene therapy with bone marrow transplantation in murine Krabbe disease.

Introduction: Krabbe disease (KD) is an autosomal recessive lysosomal disorder caused by mutations in the galactocerebrosidase (GALC) gene. This results in defective myelination in the peripheral and central nervous systems due to low GALC activity. Treatment at this time is limited to hematopoietic stem cell transplantation (HSCT) in pre-symptomatic individuals. While this treatment extends the lives of treated individuals, most have difficulty walking by the end of the first decade due to peripheral neuropathy. Studies in the murine model of KD, twitcher (twi) combining bone marrow transplantation (BMT) with AAVrh10-mGALC showed a great extension of life from 40 days to about 400 days, with some living a full life time. Methods: In order to find the optimum conditions for dosing and timing of this combined treatment, twi mice were injected with five doses of AAVrh10-mGALC at different times after BMT. Survival, as well as GALC expression were monitored along with studies of sciatic nerve myelination and possible liver pathology. Results: Dosing had a pronounced effect on survival and measured GALC activity. There was window of time after BMT to inject the viral vector and see similar results, however delaying both the BMT and the viral injection shortened the lifespans of the treated mice. Lowering the viral dose too much decreased the correction of the sciatic nerve myelination. There was no evidence for hepatic neoplasia. Conclusion: These studies provide the conditions optimum for successfully treating the murine model of KD. There is some flexibility in dosing and timing to obtain a satisfactory outcome. These studies are critical to the planning of a human trial combining the "standard of care", HSCT, with a single iv injection of AAVrh10-GALC

An Investigating of the Impact of Bed Flume Discordance on the Weir-Gate Hydraulic Structure

Discordance and concordance play a significant role in the hydraulic response for the flume, open channel, hydraulic structure, and flow field measurement. Bed discordance and bed concordance are regarded as common problems in open channels. Discordance is the dominant one, which could have an effect on the hydraulic structure that is constructed inside the channel. This paper deals with the impact of bed flume discordance on hydraulic flow characteristics at the weir-gate downstream hydraulic regime. Four configurations with different lengths and heights of the bed flume discordance are adopted here to investigate the impact of these configurations on the hydraulic characteristics. In addition, one configuration of the bed flume concordance is adopted to compare with the other four configurations. At downstream, the average water depth becomes dimensionless by dividing by upstream water depth, vertical distance between weir and gate, length of downstream, length of concordance, and length of discordance in order to evaluate the inequality in the distribution of Froude number. On one hand, certain results appear strongly between Reynolds number and Froude number at downstream, actual discharge and flow velocity at downstream, flow area past the gate and Froude number at downstream. On the other hand, there was a complex dramatic relation between the weir-gate discharge coefficient and Froude number at downstream. Overall, the study shows that there is a good relationship between specific energy, water depth, and flow speed. Doi: 10.28991/HIJ-2022-03-03-09 Full Text: PD

Analysis of the hydraulic interference between the baffles and the composite hydraulic structure

The purpose of the present study is to examine the influence of baffles presence at downstream system on weir gate hydraulic response. Two baffles configuration (triangle and angle shapes) are installed in bed flume. Two different spacing are used between the baffles and two different directions for baffles are also adopted. The study tries to investigate the variation in upstream Froude number, downstream Froude number, Reynolds number, actual discharge, discharge coefficient, downstream average water depth and the hydraulic system efficiency which is expressed as function of downstream water depth. It has been shown that the number of baffles has a direct and significant impact on flow hydraulic characteristics of weir-gate structure regardless of the spacing between baffles and the direction of baffles related to flow. Baffles number and spacing have essential impact on the water flow velocity of system and this impact leads to increase the flow resistance. The results clarify that the upstream Froude number, downstream Froude number, Reynolds number, actual discharge and discharge coefficient are decreased with the increase in baffles number except the average downstream water depth which increases with increase in baffles number. The efficiency of hydraulic system gives a good indicator for using baffles with weir-gate structure. At the end this paper shows a fruitful result of efficiency. This experiment run condense on the baffle’s numbers and directions with respect to the water flow direction at the downstream regime. So, the rises in the water level relies on the numbers and directions of the baffles as compare to the case without using baffles at the flume downstream region. The actual discharge and weir-gate discharge coefficient are more sensitive to the increase in the baffles’ numbers and the baffles direction with respect to the water flow directio

Review of Hussain Sagar Lake Pollution, Hyderabad, India

Hussain sagar lake, a historical lake which was built in 1562 by Hussain Shaw Wali is situated in the heart of Hyderabad city, India. Earlier up to 1930's, it was the major water source to meet drinking and irrigation requirements for both twin cities of Hyderabad and Secunderabad. Now this lake turned to virtual garbage bin with no adequate treatment for wastewater loads originated from point and non point sources. Therefore the lake loses the capability of self purification system which was an important factor that depends on the maximum uptake of oxygen from the atmosphere. Multiple projects were undertaken by the concerned authorities for the improvement of Hussain sagar lake and its catchment area. Recently With referring to the Lake health status, In 2006, HMDA, a governing body set up by Andhra Pradesh Government, initiated “Hussainsagar Lake and Catchment Area Improvement project” and set up STPs and wastewater interception and diversion structures. It also installed fountains to aerate the lake to improve its water quality as well as to add beauty. But these measures are lying ineffective to manage wastewater loads. This paper discusses that the Hussain Sagar lake water body over decades, has been polluted adversely from discharging of organic and inorganic pollutants through open drains as well as point and non point sources and also presents various measures had taken to rejuvenate Hussain Sagar Lake to its past glory