Papers by Mohammad Ozair Sultan
Plastics are key resources in circular economy and recycling after the end of useful life with ec... more Plastics are key resources in circular economy and recycling after the end of useful life with economic value creation and minimal damage to environment is the key to their sustainable management. The project elucidates about the use of plastic in civil construction. The component used include everything from plastic screws and hanger to bigger plastic parts that are used in decoration, electric wiring, flooring, wall covering and waterproofing.There has been a considerable imbalance between the availability of conventional building materials and their demand in the recent past. On the other hand the laterite quarry waste is abundantly available and the disposal of waste plastics (PET, PP,etc.)is a biggest challenge, as repeated recycling of PET bottles pose a potential danger of being transformed to a carcinogenic material and only a small proportion of PET bottles are being recycled.The bricks manufactured possess the properties such as neat and even finishing, with negligible wat...
Chemotherapy: Open Access
In cancers, there exists a subpopulation of cells which are referred to as cancer stem cells (CSC... more In cancers, there exists a subpopulation of cells which are referred to as cancer stem cells (CSCs) or tumor initiating cells that have enhanced tumor-initiating capacity and metastatic potential, and drive tumor progression. Since the initial identification of acute myeloid leukemia CSCs in 1997, CSCs have been found in many types of cancer and have intrinsic resistance to the current chemotherapeutic strategies. With increased levels of detoxifying enzymes, enhanced DNA repair abilities, impressive efflux capacity, and a slower cell-cycle; CSCs present a formidable obstacle against effective chemotherapy. Several methods of specifically targeting CSCs have been developed in recent years, and these compounds have potential as adjuvant therapies. The following is a review of the mechanisms responsible for chemoresistance in CSCs, with an emphasis on potential strategies to overcome this resistance.
Carcinogenesis, Feb 19, 2016
The enhanced ability of cancer stem cells (CSCs) to give rise to new tumors suggests that these c... more The enhanced ability of cancer stem cells (CSCs) to give rise to new tumors suggests that these cells may also have an advantage in evading immune detection and elimination. This tumor-forming ability, combined with the known plasticity of the immune system, which can play both protumorigenic and antitumorigenic roles, has motivated investigations into the interaction between CSCs and the immune system. Herein, we review the interplay between host immunity and CSCs by examining the immune-related mechanisms that favor CSCs and the CSC-mediated expansion of protumorigenic immune cells. Furthermore, we discuss immune cells, such as natural killer cells, that preferentially target CSCs and the strategies used by CSCs to evade immune detection and destruction. An increased understanding of these interactions and the pathways that regulate them may allow us to harness immune system components to create new adjuvant therapies that eradicate CSCs and improve patient survival.
Molecular Oncology, 2016
Breast cancer stem cells (CSCs) can be identified by increased Aldefluor fluorescence caused by i... more Breast cancer stem cells (CSCs) can be identified by increased Aldefluor fluorescence caused by increased expression of aldehyde dehydrogenase 1A3 (ALDH1A3), as well as ALDH1A1 and ALDH2. In addition to being a CSC marker, ALDH1A3 regulates gene expression via retinoic acid (RA) signaling and plays a key role in the progression and chemotherapy resistance of cancer. Therefore, ALDH1A3 represents a druggable anti-cancer target of interest. Since to date, there are no characterized ALDH1A3 isoform inhibitors, drugs that were previously described as inhibiting the activity of other ALDH isoforms were tested for anti-ALDH1A3 activity. Twelve drugs (3-hydroxy-DL-kynurenine, benomyl, citral, chloral hydrate, cyanamide, daidzin, DEAB, disulfiram, gossypol, kynurenic acid, molinate, and pargyline) were compared for their efficacy in inducing apoptosis and reducing ALDH1A3, ALDH1A1 and ALDH2-associated Aldefluor fluorescence in breast cancer cells. Citral was identified as the best inhibitor of ALDH1A3, reducing the Aldefluor fluorescence in breast cancer cell lines and in a patient-derived tumor xenograft. Nanoparticle encapsulated citral specifically reduced the enhanced tumor growth of MDA-MB-231 cells overexpressing ALDH1A3. To determine the potential mechanisms of citral-mediated tumor growth inhibition, we performed cell proliferation, clonogenic, and gene expression assays. Citral reduced ALDH1A3-mediated colony formation and expression of ALDH1A3-inducible genes. In conclusion, citral is an effective ALDH1A3 inhibitor and is able to block ALDH1A3mediated breast tumor growth, potentially via blocking its colony forming and gene expression regulation activity. The promise of ALDH1A3 inhibitors as adjuvant therapies for patients with tumors that have a large population of high-ALDH1A3 CSCs is discussed.
We present a machine learning framework for modeling protein dynamics. Our approach uses L1-regul... more We present a machine learning framework for modeling protein dynamics. Our approach uses L1-regularized, reversible hidden Markov models to understand large protein datasets generated via molecular dynamics simulations. Our model is motivated by three design principles: (1) the requirement of massive scalability; (2) the need to adhere to relevant physical law; and (3) the necessity of providing accessible interpretations, critical for both cellular biology and rational drug design. We present an EM algorithm for learning and introduce a model selection criteria based on the physical notion of convergence in relaxation timescales. We contrast our model with standard methods in biophysics and demonstrate improved robustness. We implement our algorithm on GPUs and apply the method to two large protein simulation datasets generated respectively on the NCSA Bluewaters supercomputer and the Folding@Home distributed computing network. Our analysis identifies the conformational dynamics of the ubiquitin protein critical to cellular signaling, and elucidates the stepwise activation mechanism of the c-Src kinase protein.
Oncotarget, Jan 6, 2016
Breast cancer subtyping, based on the expression of hormone receptors and other genes, can determ... more Breast cancer subtyping, based on the expression of hormone receptors and other genes, can determine patient prognosis and potential options for targeted therapy. Among breast cancer subtypes, tumors of basal-like and claudin-low subtypes are typically associated with worse patient outcomes, are primarily classified as triple-negative breast cancers (TNBC), and cannot be treated with existing hormone-receptor-targeted therapies. Understanding the molecular basis of these subtypes will lead to the development of more effective treatment options for TNBC. In this study, we focus on retinoic acid receptor responder 1 (RARRES1) as a paradigm to determine if breast cancer subtype dictates protein function and gene expression regulation. Patient tumor dataset analysis and gene expression studies of a 26 cell-line panel, representing the five breast cancer subtypes, demonstrate that RARRES1 expression is greatest in basal-like TNBCs. Cell proliferation and tumor growth assays reveal that R...
Deregulated signal transduction is a major facet of cancer development and progression. Herein, w... more Deregulated signal transduction is a major facet of cancer development and progression. Herein, we review the current paradigm for retinoic acid signaling, its role in cancer and potential therapeutic applications and challenges. Retinoic acid is used with remarkable success in the treatment of one of the most high-risk leukemias, acute promyelocytic leukemia; however, extending its use in the treatment of other cancers has had limited success at best. Functional studies provide clues for the poor performance of retinoic acid as a general cancer therapeutic, connecting retinoic acid signaling to both cell growth arrest and proliferation with tumor suppression and cancer progression consequences. The dualistic role of the retinoic acid signaling pathway in cancer is revealed in its gene transcription targets, cross-talk with other transcription factors, mediation of apoptotic pathways, and influence in the immune system. If the greatest potential benefit of retinoid-based cancer ther...
Biophysical Journal, 2014
We have carried out multiple 50 ns molecular dynamics simulations of explicitly solvated calmodul... more We have carried out multiple 50 ns molecular dynamics simulations of explicitly solvated calmodulin, starting from the calcium-bound (1cll) and apo (1cfd) structures. Simulations were performed using NAMD (University of Illinois) and the CHARMM27 force-field. Simulations suggest that Met oxidation alters the flexibility of calcium binding sites, the conformation of the linker helix connecting the lobes, and the relative orientation of the lobes. This work is a component of a larger study in which spectroscopic distance measurements and NMR experiments have been used to resolve the structural impact of site-specific CaM Met oxidation. We expect that our in silico results will bring atomic-level insight to spectroscopic measurements, and will be integral to creating a more complete model for oxidation-induced changes in CaM structural dynamics.
SAE Technical Paper Series, 1995
International Journal of Computer Applications, 2012
This paper presents a robust sliding-mode control technique to be applied to quaternion-based att... more This paper presents a robust sliding-mode control technique to be applied to quaternion-based attitude control for rest-to-rest maneuvers with external disturbances. A sliding mode controller has been designed to force the state variables of the closed loop system to converge to the desired values. A control strategy is designed based on a novel mathematical rule that computes the discontinuous feedback gains. The proposed approach is defined in such a way that the selected controller parameters can drive the state to hit the sliding surface fast and then keep the state sliding along the surface with less chattering and tracking error. Moreover, the control parameters are adjusted to avoid the body angular velocity reached the upper limit during the maneuver. A simulation model of the controlled spacecraft system was developed in MATLAB-SIMULINK software. The phase portraits and the state plots prove the control technique power. The "chattering" problem of the sliding mode control has been adopted using variable thickness boundary layer technique. The second method of Lyapunov is used to guarantee the system stability under the proposed control laws action. Simulations have been carried out to demonstrate and verify the developed controller performance.
Journal of Neurological Surgery Part B: Skull Base, 2014
Journal of Carcinogenesis & Mutagenesis, 2013
Deregulated signal transduction is a major facet of cancer development and progression. Herein, w... more Deregulated signal transduction is a major facet of cancer development and progression. Herein, we review the current paradigm for retinoic acid signaling, its role in cancer and potential therapeutic applications and challenges. Retinoic acid is used with remarkable success in the treatment of one of the most high-risk leukemias, acute promyelocytic leukemia; however, extending its use in the treatment of other cancers has had limited success at best. Functional studies provide clues for the poor performance of retinoic acid as a general cancer therapeutic, connecting retinoic acid signaling to both cell growth arrest and proliferation with tumor suppression and cancer progression consequences. The dualistic role of the retinoic acid signaling pathway in cancer is revealed in its gene transcription targets, cross-talk with other transcription factors, mediation of apoptotic pathways, and influence in the immune system. If the greatest potential benefit of retinoid-based cancer therapeutics is to be achieved, the many physiological roles of retinoic acid need to be considered.
ASME 2009 Summer Bioengineering Conference, Parts A and B, 2009
ABSTRACT Despite many advances in the treatment of cerebral aneurysms in the last few decades, no... more ABSTRACT Despite many advances in the treatment of cerebral aneurysms in the last few decades, none of the available methods provide an unequivocal solution for all aneurysm sizes and morphologies. The feasibility of successfully treating aneurysms solely by the placement of an intravascular flow-diverting mesh across the aneurysm neck was established more than a decade ago [1]. Flow diverters disrupt the momentum exchange between the parent artery and aneurysm and significantly reduce intraaneurysmal hydrodynamic vorticity and kinetic energy. The resultant flow stasis promotes thrombus formation within the aneurysm sac, which eventually matures into fibrotic tissue, leading to exclusion of the aneurysm from the circulation. With the increased use of stents in the intracranial circulation, cases where coiling is not feasible, or is staged as a secondary procedure, are providing clinical evidence of the successful treatment of aneurysms with stents alone [2,3]. Methodological evidence of the performance of appropriately designed flow diverters in treating cerebral aneurysms has recently become available in the literature [4,5].
The Journal of Physical Chemistry B, 2013
The supporting information index: S1. Parameters for calculating electrostatic energies S2. Input... more The supporting information index: S1. Parameters for calculating electrostatic energies S2. Input structure S3. Empirical method for assigning the partial charge distribution on the µ-oxo bridges S4. Calculated vs. experimental terminal water pK a s complexes in complexes 1-4. S5.Table 1. Comparison of calculated and experimental pK a s and E m s in complexes 5-8. Table 2. Predicted pK a s and E m s in complexes 5-8. Table 3. Predicted pK a s of complex 6 in ACN and water S6. The correlation between the atomic partial charges on the individual oxygen or nitrogen directly ligating the Mn ions and the E m and pK a shift in complexes 6-8. S7. The coupling between changes in E m and pH in coupled electron/proton transfer reactions. S8. The optimized structure and ESP (Electrostatic Potential) charges for all complexes S9. The references within Supplementary Information S1. Parameters for calculating electrostatic energies. The Poisson-Boltzmann solver DelPhi 1 is used to determine the electrostatic interactions between each pair of primitive objects in a microstate and the loss of solvation energy of each primitive object in the complex and isolated in water. DelPhi requires atomic coordinates, partial charges and radii. S8a-S8h gives this information for each cluster in a single redox and protonation state with deprotonated bridging oxygens and terminal waters. The net charge on each ligand is 0 for complexes 3-5 and-2 for complexes 2 and 6-8. The ligand atomic partial charges and positions are the same for all states of a complex. Mn can have charges +2, +3 or +4. The terminal hydroxyl group has a charge of-1.2 on the oxygen and 0.2 on the proton. The bridging hydroxyl has a charge of-1.7 on the oxygen and 0.7 on the proton. The desolvation energy (∆∆G solv,i) that determines the destabilization of a charged group when it is moved out of a high dielectric medium is the difference between the solvation energy for the fragment in the complex and when it is isolated in the appropriate solvent (water or ACN). 2,3 In solving the Poisson-Boltzmann equation, the internal dielectric constant of the complex is set to 4. This is chosen since the aim is to develop a method that can be used for clusters in proteins where the standard dielectric constant for cofactors is 4. 4 The external, solution dielectric constant is 80 for water and 40 for ACN. The probe radius for water or ACN solvent is 1.4 Å. The ion probe radius is 2.00 Å and the salt concentration is 0.15 mM. S2. Input structures Coordinates for complexes 3, 5 and 6 (Fig. 1) are obtained from the Cambridge Database (reference codes SAWYEU, 5 FIQFIU 6 and SOZMUP 7 , respectively). The structure of complex 4 is obtained from the published coordinates obtained by DFT. 8 For analysis of complexes 7 and 8, the chlorine and the NO 2 groups are added to the salpn ring of complex 6 at positions 3 and 5 using MacMolPlot. 9 The structures are optimized with DFT using the B3LYP 10-12 functional and LANL2DZ 13 basis sets for Mn and 6-31G* 14 for all other atoms. The terminal water pK a s are calculated for complexes 1-4 with their geometry optimized in the Mn oxidation state in which the pK a is measured (Table 1 main text). The geometries of complexes 3-8 are optimized considering the antiferromagnetic coupling between the di-Mn ions and generating the broken symmetry solution for the wavefunction with JAGUAR 15 or Gaussian09. 16 Optimization is carried out in both the Mn(IV,IV) and the Mn(III,IV) oxidation states. In the comparison of the structure dependence of the E m s and pK a s the ligand geometry is modified but the same ligand partial charges, optimized in the symmetric Mn(IV,IV) state are used for all calculations. The protons on the bridging oxygen are placed in the plane of the [Mn(µ-O) 2 Mn] core, bisecting the Mn-O-Mn angle using GaussView. 17 Protons are placed on terminal hydroxyo and waters within the MCCE program. 18 In addition the protons positions from the DFT optimization were added.
Proceedings of the National Academy of Sciences, 2012
Allostery is a fundamental property that allows the regulation of function and dynamic adaptabili... more Allostery is a fundamental property that allows the regulation of function and dynamic adaptability of enzymes and proteins. Gaining a detailed understanding of allosteric mechanisms would provide more precise control of enzyme function and roadmaps for the expansion of drug discovery beyond the active site responsible for catalytic activity. Here, we combine molecular dynamics (MD) simulations, nuclear magnetic resonance (NMR), and correlation analysis of protein motions based on network theory methods (i.e., the studies of graphs as See full research article on page E1428 of www.pnas.org.
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Papers by Mohammad Ozair Sultan