title: Novel sulfonamides for the treatment of breast and cervical cancers

authors: Buckley, Nathaniel Thomas

subjects: Sulfonamide

abstract: A series of novel sulfonamides were studied computationally to identify a potential mechanism of action for the treatment of breast and cervical cancers. Previous in vivo testing demonstrated varying degrees of effectiveness, with seven molecules showing the highest cytotoxicity. Computational calculations were chosen as the means for determining the drug target. Previous studies indicated β-Tubulin and Carbonic Anhydrase IX as the most likely proteins of interest, so these were selected for study.
The computational methodology selected for this study follows that of Krzywik et al.¹ For this, conventional docking studies were undertaken using Autodock Vina, followed by more accurate and computationally demanding molecular dynamics simulations using the MM/PBSA procedures in AMBER. Docking studies for the seven active compounds were performed using Vina, and showed promising results. The three most effective compounds (5AP, 6AP and 7BP) were then utilised in a series of MM/PBSA calculations to determine strength of interaction between the sulfonamides and drug targets.
The results of the AMBER calculations determined β-Tubulin to be the more likely drug target, although this result did show 6AP (the most effective in vivo molecule) to have the weakest binding, which was an unexpected result. A LIGPLOT study was done to determine a potential cause for this, showing a heavy emphasis on non-polar interactions between the drug molecules and proteins. Drug-like comparisons and pKa calculations were also performed, showing all three molecules to have very similar acidity and hydrogen bond capabilities, but suggesting lipophilicity and molecule size to be possible determining factors in the overall effect of the compounds. Transport across the cell membrane and through the cytoplasm were also suggested as potential reasons for the differing results, and further studies into these were suggested for possible confirmation.

text: Novel sulfonamides for the treatment of breast and cervical cancers A series of novel sulfonamides were studied computationally to identify a potential mechanism of action for the treatment of breast and cervical cancers. Previous in vivo testing demonstrated varying degrees of effectiveness, with seven molecules showing the highest cytotoxicity. Computational calculations were chosen as the means for determining the drug target. Previous studies indicated β-Tubulin and Carbonic Anhydrase IX as the most likely proteins of interest, so these were selected for study.
The computational methodology selected for this study follows that of Krzywik et al.¹ For this, conventional docking studies were undertaken using Autodock Vina, followed by more accurate and computationally demanding molecular dynamics simulations using the MM/PBSA procedures in AMBER. Docking studies for the seven active compounds were performed using Vina, and showed promising results. The three most effective compounds (5AP, 6AP and 7BP) were then utilised in a series of MM/PBSA calculations to determine strength of interaction between the sulfonamides and drug targets.
The results of the AMBER calculations determined β-Tubulin to be the more likely drug target, although this result did show 6AP (the most effective in vivo molecule) to have the weakest binding, which was an unexpected result. A LIGPLOT study was done to determine a potential cause for this, showing a heavy emphasis on non-polar interactions between the drug molecules and proteins. Drug-like comparisons and pKa calculations were also performed, showing all three molecules to have very similar acidity and hydrogen bond capabilities, but suggesting lipophilicity and molecule size to be possible determining factors in the overall effect of the compounds. Transport across the cell membrane and through the cytoplasm were also suggested as potential reasons for the differing results, and further studies into these were suggested for possible confirmation.

year: 2022

title: Supercapacitor-assisted LED (SCALED) technique for renewable energy systems: a very low frequency design approach with short-term DC-UPS capability eliminating battery banks

authors: Jayananda, Dilini

subjects: Science & Technology

abstract: The fluctuating nature of solar energy necessitates suitable energy storage systems. Compared to typical battery banks, supercapacitors offer longer cycle life eliminating the need to replace them regularly. However, compared to a typical maximum power point tracking controller, where the battery bank and resistive load fed by a switch-mode DC–DC converter allows impedance matching for maximum power transfer, a supercapacitor bank's significantly large capacitive load does not permit the typical impedance matching for maximum power transfer. This study compares the theoretical difference between battery versus supercapacitor energy storage, and highlights of the supercapacitor-assisted LED converter technique in achieving high-efficiency renewable energy-based DC-microgrid systems.

text: Supercapacitor-assisted LED (SCALED) technique for renewable energy systems: a very low frequency design approach with short-term DC-UPS capability eliminating battery banks The fluctuating nature of solar energy necessitates suitable energy storage systems. Compared to typical battery banks, supercapacitors offer longer cycle life eliminating the need to replace them regularly. However, compared to a typical maximum power point tracking controller, where the battery bank and resistive load fed by a switch-mode DC–DC converter allows impedance matching for maximum power transfer, a supercapacitor bank's significantly large capacitive load does not permit the typical impedance matching for maximum power transfer. This study compares the theoretical difference between battery versus supercapacitor energy storage, and highlights of the supercapacitor-assisted LED converter technique in achieving high-efficiency renewable energy-based DC-microgrid systems.

year: 2020

title: Review: Memoirs of Active Service

authors: Cheesman, Sue

subjects: Maaka Pepene

abstract: Ka maumahara tonu tatou ki a ratou - we will remember them…poignant last words…   bidding farewell to a generation of veterans moving on...leaving fragments  of memories and diaries for children/grandchildren to honour, celebrate and remember …black costumes billow, fold, swirl and wrap the dancers bodies…wide sweeping arm movements…jumps and turns…slides on all fours - provides the vehicle for five accomplished dancers to fill the space with fluidity and lyricism in this very moving finale, a lament set to Albinoni’s adagio - maybe old soldiers never die.

text: Review: Memoirs of Active Service Ka maumahara tonu tatou ki a ratou - we will remember them…poignant last words…   bidding farewell to a generation of veterans moving on...leaving fragments  of memories and diaries for children/grandchildren to honour, celebrate and remember …black costumes billow, fold, swirl and wrap the dancers bodies…wide sweeping arm movements…jumps and turns…slides on all fours - provides the vehicle for five accomplished dancers to fill the space with fluidity and lyricism in this very moving finale, a lament set to Albinoni’s adagio - maybe old soldiers never die.

year: 2007