DNA Damage Induction by Bilirubin Induced Oxidative Stress and Activation of DNA Repair Pathways by Bilirubin

“Kernicterus” due to hyperbilirubinemia is one of main cause of irreversible brain damage in low and middle income countries. Deaths due to “kernicterus” are ranked within the top 3 causes of neonatal death in African countries. Neonates experiencing permanent or temporary absence or reduced activity of Uridine diphosphate-glucuronosyl-transferase A1 (UGT1A1) enzyme present increased levels of total unconjugated bilirubin (UCB) in the blood. When the bilirubin binding capacity of serum albumin is saturated, this results in the increase in the free fraction of bilirubin (Bf). The excess of Bf is accumulated in lipid-rich tissues such as the brain, where it may reach toxic levels causing bilirubin-induced encephalopathy in jaundiced newborns and patients with Crigler-Najjar syndrome Type I, leading to kernicterus if not promptly treated. Bilirubin causes severe neurological dysfunction by affecting several different cellular pathways such as, induction of oxidative stress, endoplasmic reticulum (ER) stress, autophagy, neuroinflammation and DNA damage. The work done in this thesis focus on the DNA damaging effect of bilirubin on neuronal (SH SY 5Y) and non-neuronal (HeLa) cells and the effect of bilirubin on the different double stranded break (DSB) repair pathways was investigated using HeLa DR GFP and HeLa cell lines. Bilirubin exposure led to time-dependent increase in DNA damage in neuronal cells. Treatment with the anti-oxidant N-acetylcysteine (NAC) caused a dose-dependent decrease in DNA damage, suggesting a key role of oxidative stress in bilirubin-induced DNA damage. In the second part of this work, I studied the effect of bilirubin on different DSB repair pathways using HeLa cell lines. Treatment with bilirubin modulated Homologous Recombination (HR) in a time-dependent manner. In fact, treatment with different doses of bilirubin led to a dose-dependent increase in HR. Bilirubin-induced increase in HR was reversed by addition of NAC, suggesting the important role of oxidative stress in bilirubin-induced modulation of HR. DNA damage analysis after bilirubin treatment showed an increase in DNA damage in HeLa cells. Unexpectedly, bilirubin-induced DNA damage had no effect on the cell cycle profile. Similarly, exposure to bilirubin concentrations similar to those found in patients led to an increase in the Non-Homologous End Joining (NHEJ) pathway. These results suggest the general increase in DSB repair pathways by bilirubin

Classification and Segmentation of MRI Images of Brain Tumors Using Deep Learning and Hybrid Approach

Manual prediction of brain tumors is a time-consuming and subjective task, reliant on radiologists\u27 expertise, leading to potential inaccuracies. In response, this study proposes an automated solution utilizing a Convolutional Neural Network (CNN) for brain tumor classification, achieving an impressive accuracy of 98.89%. Following classification, a hybrid approach, integrating graph-based and threshold segmentation techniques, accurately locates the tumor region in magnetic resonance (MR) brain images across sagittal, coronal, and axial views. Comparative analysis with existing research papers validates the effectiveness of the proposed method, and similarity coefficients, including a Bfscore of 1 and a Jaccard similarity of 93.86%, attest to the high concordance between segmented images and ground truth

Giant cell tumor distal end radius: resection and reconstruction using proximal fibular graft

Giant cell tumour forms 4% of all primary tumors. GCT distal radius is very rare. Current study presents a case of a 27 year female who was managed by wide excision and reconstruction with ipsilateral fibula. At one year follow up, patient had excellent range of motion at wrist joint and hand

Functional characterization of L-tryptophan transport across mammalian cornea

In last few years transporter targeted drug delivery has drawn attention of research to identify and explore various nutrient transport systems including amino acid transporters for better drug delivery. The aim of present research work is to investigate the transport characteristics of L-tryptophan (L-try) across goat cornea. Transport of L-try was investigated using a glass diffusion cell for effect of concentration, pH, presence of other amino acids or metabolic inhibitor or dipeptide and tripeptide. The amount of L-try transported increased as the pH of L-try aqueous solution increased from 5 to 9. Inhibition was observed in L-try transport in absence of sodium ions where L-try solution was made isotonic with dextrose. Amino acids like L-histidine, L-arginine, L-lysine (cationic), L-glutamic acid, L-aspartic acid (anionic), glycine and L-proline (neutral) inhibited the L-try transport as compared to control (L-try alone). In presence of sodium azide and Ouabain the inhibition in L-try transport across goat cornea was observed while no marked inhibition was observed on L-try transport across goat cornea in presence of aspartame and glutathione. The L-try transport was favored up to concentration 1% w/v and at higher pH in presence of sodium ions through excised goat cornea. Functional presence of a sodium dependent L-try transport system as inhibited by ouabain having affinity to cationic and neutral amino acid is evident on goat cornea.Keywords: Cornea; Amino acid; Tryptophan; Transpor

Functional characterization of L-tryptophan transport across mammalian cornea

In last few years transporter targeted drug delivery has drawn attention of research to identify and explore various nutrient transport systems including amino acid transporters for better drug delivery. The aim of present research work is to investigate the transport characteristics of L-tryptophan (L-try) across goat cornea. Transport of L-try was investigated using a glass diffusion cell for effect of concentration, pH, presence of other amino acids or metabolic inhibitor or dipeptide and tripeptide. The amount of L-try transported increased as the pH of L-try aqueous solution increased from 5 to 9. Inhibition was observed in L-try transport in absence of sodium ions where L-try solution was made isotonic with dextrose. Amino acids like L-histidine, L-arginine, L-lysine (cationic), L-glutamic acid, L-aspartic acid (anionic), glycine and L-proline (neutral) inhibited the L-try transport as compared to control (L-try alone). In presence of sodium azide and Ouabain the inhibition in L-try transport across goat cornea was observed while no marked inhibition was observed on L-try transport across goat cornea in presence of aspartame and glutathione. The L-try transport was favored up to concentration 1% w/v and at higher pH in presence of sodium ions through excised goat cornea. Functional presence of a sodium dependent L-try transport system as inhibited by ouabain having affinity to cationic and neutral amino acid is evident on goat cornea.Keywords: Cornea; Amino acid; Tryptophan; Transpor

Designing of Real-time Communication Method to Monitor Water Quality using WSN Based on IOT

Data accuracy has always been the essential and foremost requirement of any communication. A Real-time Water quality-monitoring system (WQMS) needs high-level data accuracy to process the water perfectly for the desired usage in any specific purpose.  Exponential growth in man-made processes, human activities, Industrialization, and economic growth along with depleting safe water resources has made the water pollution issue a foremost threat to human survival and human civilisation as a whole. The Conventional WQMS lacks in providing data accuracy while testing and analysing the water samples at sites due to improper data transmission, human intervention, instrument node working and calibration issues. Therefore, monitoring the quality of the water is essential with a prime focus on data accuracy through proper testing, data analysis and data transmission methods to provide real-time data accuracy. In this research work, an IOT-based wireless sensor network (WSN) is proposed that uses mesh networking to connect the sensor nodes and message queuing telemetry transfer (MQTT) protocol to send the acquired data to a cloud server ADDA Fruit IO. ESP32 standalone microcontroller with in-built Wi-Fi is used as a transceiver on sensor nodes and master nodes. As far as sensor and master node power is concerned, a self-adapting power generation system is incorporated using solar power and water energy harvesting techniques. The sensor nodes are calibrated as per WHO standards using deionized water and buffer capsules. Five random samples are collected from river water, pond water, Borewell water, R.O water and Municipal committee water to analyse the proposed system’s accuracy. The accuracy test and analysis is done using statistical tools on water sample measurements by the proposed sensor node, and the same is compared with the actual certified instrument, hardware manual-based measurement, Laboratory value check and transmitted value on Cloud Server. The proposed WQMS is designed to measure various WQM parameters i.e. Total Dissolve Solid (TDS), pH, Temperature and turbidity and to ensure data accuracy

Reduced rating T-connected autotransformer based thirty-pulse AC-DC converter for vector controlled induction motor drives

The design and performance analysis of a reduced rating autotransformer based thirty-pulse AC-DC converter is carried out for feeding a vector controlled induction motor drive (VCIMD). The configuration of the proposed autotransformer consists of only two single phase transformers, with their windings connected in a T-shape, resulting in simplicity in design, manufacturing and in a reduction in magnetics rating. The design procedure of the autotransformer along with the newly designed interphase transformer is presented. The proposed configuration has flexibility in varying the transformer output voltage ratios as required. The design of the autotransformer can be modified for retrofit applications, where presently a 6-pulse diode bridge rectifier is used. The proposed thirty-pulse AC-DC converter is capable of suppressing less than 29th harmonics in the supply current. The power factor is also improved to near unity in the wide operating range of the drive. A comparison of different power quality indices at AC mains and DC bus is demonstrated in a conventional 6-pulse AC-DC converter and the proposed AC-DC converter feeding a VCIMD. A laboratory prototype of the proposed autotransformer based 30-pulse AC-DC converter was developed with test results validating the proposed design and system

An input current waveshaping AC-DC converter for rectifier loads

This paper presents the design and analysis of a new input AC current waveshaping AC-DC converter for cost effective harmonic mitigation under varying loads. The proposed converter consists of a delta-polygon connected autotransformer based twelve-pulse AC-DC converter and a small rating passive shunt filter tuned at 11th harmonic frequency. The proposed AC-DC converter eliminates the most dominant 5th, 7th and 11th harmonics and reduces higher order harmonics; thereby, resulting in an improved power quality at AC mains. Moreover, the design of the autotransformer is modified to make it suitable for retrofit applications, where presently a 6-pulse diode bridge rectifier is used. To validate the proposed approach, various power quality indices are presented under varying loads. Experimental results obtained on the developed converter are given to validate the model and design of the proposed converter