9 results on '"Iyer, Arvind"'
Search Results
2. Epistasis and evolutionary dependencies in human cancers.
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Mina, Marco, Iyer, Arvind, and Ciriello, Giovanni
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CANCER invasiveness , *GENOMICS , *BIOLOGY , *PHENOTYPES , *EPIGENETICS - Abstract
Cancer evolution is driven by the concerted action of multiple molecular alterations, which emerge and are selected during tumor progression. An alteration is selected when it provides an advantage to the tumor cell. However, the advantage provided by a specific alteration depends on the tumor lineage, cell epigenetic state, and presence of additional alterations. In this case, we say that an evolutionary dependency exists between an alteration and what influences its selection. Epistatic interactions between altered genes lead to evolutionary dependencies (EDs), by favoring or vetoing specific combinations of events. Large-scale cancer genomics studies have discovered examples of such dependencies, and showed that they influence tumor progression, disease phenotypes, and therapeutic response. In the past decade, several algorithmic approaches have been proposed to infer EDs from large-scale genomics datasets. These methods adopt diverse strategies to address common challenges and shed new light on cancer evolutionary trajectories. Here, we review these efforts starting from a simple conceptualization of the problem, presenting the tackled and still unmet needs in the field, and discussing the implications of EDs in cancer biology and precision oncology. [ABSTRACT FROM AUTHOR]
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- 2022
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3. Simulation of spatial high speed mixing layers using LES.
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Iyer, Arvind S. and Rajan, N.K.S.
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SIMULATION methods & models , *LARGE eddy simulation models , *SUPERSONIC aerodynamics , *STRAINS & stresses (Mechanics) , *VISCOSITY - Abstract
The present paper is concerned with the simulation of the spatial supersonic mixing layer using large eddy simulation, with PISO algorithm, using one equation eddy viscosity model for sub grid scale stress modelling, a fourth order spatial and a second order temporal scheme. The size of the domain is of a similar to that of experiments, and encompases the splitter plate effect. The calculations are ascertained to be grid independent for grid sizes of 1200 × 260 , 800 × 200 and 600 × 160 . The calculations are shown to match the experiments of Goebel and Dutton (1990) [1] and Papamoschou and Roshko (1988) [2] reasonably well, and are able to capture the effect of the reduced growth rate with increased M c within the tolerance of experiments. The simulations are used further to study the removal of velocity deficit and the attainment of self similarity with increasing M c . [ABSTRACT FROM AUTHOR]
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- 2015
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4. Erratum: Iyer, A., et al. Integrative Analysis and Machine Learning Based Characterization of Single Circulating Tumor Cells. J. Clin. Med. 2020, 9 , 1206.
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Iyer, Arvind, Gupta, Krishan, Sharma, Shreya, Hari, Kishore, Lee, Yi Fang, Ramalingam, Neevan, Yap, Yoon Sim, West, Jay, Bhagat, Ali Asgar, Subramani, Balaram Vishnu, Sabuwala, Burhanuddin, Zea Tan, Tuan, Thiery, Jean Paul, Jolly, Mohit Kumar, Ramalingam, Naveen, and Sengupta, Debarka
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MACHINE learning , *NUCLEIC acids , *SEARCH engines - Abstract
Integrative Analysis and Machine Learning Based Characterization of Single Circulating Tumor Cells. Conflicts of Interest The authors declare no conflict of interest. References 1 Iyer A., Gupta K., Sharma S., Hari K., Lee Y.F., Ramalingam N., Yap Y.S., West J., Bhagat A.A., Subramani B.V. Integrative Analysis and Machine Learning based Characterization of Single Circulating Tumor Cells. [Extracted from the article]
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- 2021
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5. Integrative Analysis and Machine Learning based Characterization of Single Circulating Tumor Cells.
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Iyer, Arvind, Gupta, Krishan, Sharma, Shreya, Hari, Kishore, Lee, Yi Fang, Ramalingam, Neevan, Yap, Yoon Sim, West, Jay, Bhagat, Ali Asgar, Subramani, Balaram Vishnu, Sabuwala, Burhanuddin, Tan, Tuan Zea, Thiery, Jean Paul, Jolly, Mohit Kumar, Ramalingam, Naveen, and Sengupta, Debarka
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MACHINE learning , *BLOOD cells , *BREAST cancer , *TRANSCRIPTOMES , *GENE expression - Abstract
We collated publicly available single-cell expression profiles of circulating tumor cells (CTCs) and showed that CTCs across cancers lie on a near-perfect continuum of epithelial to mesenchymal (EMT) transition. Integrative analysis of CTC transcriptomes also highlighted the inverse gene expression pattern between PD-L1 and MHC, which is implicated in cancer immunotherapy. We used the CTCs expression profiles in tandem with publicly available peripheral blood mononuclear cell (PBMC) transcriptomes to train a classifier that accurately recognizes CTCs of diverse phenotype. Further, we used this classifier to validate circulating breast tumor cells captured using a newly developed microfluidic system for label-free enrichment of CTCs. [ABSTRACT FROM AUTHOR]
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- 2020
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6. Viscous resistance in drop coalescence.
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Rahman, Md Mahmudur, Lee, Willis, Iyer, Arvind, and Williams, Stuart J.
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HYDRODYNAMICS , *NAVIER-Stokes equations , *FLUIDS , *COALESCENCE (Chemistry) , *ANISOTROPY - Abstract
Hydrodynamics of drop coalescence has been studied theoretically and numerically by solving the Navier Stokes equation considering a single fluid after the minimum bridge formation. Many experiments have been performed to document bridge growth over time with the use of high speed videography and electrical methods. However, internal fluid motion during coalescence has not been extensively studied, in part due to the spherical shape of the drops. This work observed overall fluid motion (except at the site of early coalescence) using particle image velocimetry for two-dimensional (sandwiched drop) coalescence. Fluid motion inside the bulk drops is inertial, and governing fluid flow in the bridge region is one dimensional. At the merging interface, incoming liquids join and coflow in the perpendicular direction. These observations were extended to a three-dimensional counterpart, and a scaling law was developed that was validated through experimentation. While flow in the bulk drops is inertial, the dominant resistance comes through a viscous effect in the merging interface region and at the lesser extent in the bridge region. Early dynamics of drop coalescence is dominated by the Ohnesorge number (Oh), and later dynamics are dependent on how drops are bounded. [ABSTRACT FROM AUTHOR]
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- 2019
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7. A combined experimental-computational approach uncovers a role for the Golgi matrix protein Giantin in breast cancer progression.
- Author
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Ghannoum, Salim, Fantini, Damiano, Zahoor, Muhammad, Reiterer, Veronika, Phuyal, Santosh, Leoncio Netto, Waldir, Sørensen, Øystein, Iyer, Arvind, Sengupta, Debarka, Prasmickaite, Lina, Mælandsmo, Gunhild Mari, Köhn-Luque, Alvaro, and Farhan, Hesso
- Abstract
Our understanding of how speed and persistence of cell migration affects the growth rate and size of tumors remains incomplete. To address this, we developed a mathematical model wherein cells migrate in two-dimensional space, divide, die or intravasate into the vasculature. Exploring a wide range of speed and persistence combinations, we find that tumor growth positively correlates with increasing speed and higher persistence. As a biologically relevant example, we focused on Golgi fragmentation, a phenomenon often linked to alterations of cell migration. Golgi fragmentation was induced by depletion of Giantin, a Golgi matrix protein, the downregulation of which correlates with poor patient survival. Applying the experimentally obtained migration and invasion traits of Giantin depleted breast cancer cells to our mathematical model, we predict that loss of Giantin increases the number of intravasating cells. This prediction was validated, by showing that circulating tumor cells express significantly less Giantin than primary tumor cells. Altogether, our computational model identifies cell migration traits that regulate tumor progression and uncovers a role of Giantin in breast cancer progression. Author summary: The Golgi is a specialised structure inside cells that functions as a factory where molecules necessary for diverse cell functions are modified and sorted for transport. One of the proteins that maintains the physical structure of the Golgi is called Giantin. We found that breast cancer patients whose tumors have lower Giantin die earlier compared to patients with higher Giantin tumors. To find an explanation, we induced Golgi fragmentation in breast cancer cells by depleting Giantin. Interestingly, we found that Giantin depletion alters the migratory and invasive properties of those cells. To understand the implications of altered migration and invasion, we run computer simulation of tumor growth and progression with and without Giantin depletion. Our simulations predicted that Giantin-depleted tumors, while smaller, are nevertheless capable of seeding more cells inside the circulatory system. This is a precondition for the formation of metastases in distant organs, which is the major factor that determines mortality in breast cancer patients. To validate our model prediction, we showed that breast cancer cells that have enter the circulatory system have lower Giantin that the tumors in the breast where the cancer was originated. In summary, our combination of modeling and experimental validation provides a possible explanation for poor survival of breast cancer patients with low Giantin levels. [ABSTRACT FROM AUTHOR]
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- 2023
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8. Persistent reduction in global longitudinal strain in the longer term after radiation therapy in patients with breast cancer.
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Trivedi, Siddharth J., Choudhary, Preeti, Lo, Queenie, Sritharan, Hari Prakash, Iyer, Arvind, Batumalai, Vikneswary, Delaney, Geoff P., and Thomas, Liza
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RADIOTHERAPY , *BREAST cancer patients , *BREAST cancer treatment , *VENTRICULAR ejection fraction - Abstract
Highlights • Global longitudinal strain remains significantly lower 12 months post radiotherapy. • Conventional indices such as left ventricular ejection fraction remain unchanged. • Findings maybe of specific relevance in patients receiving concurrent chemotherapy. • Longer term studies will determine association of reduced strain with outcomes. Abstract Background More than 80% of breast cancer patients receive radiotherapy (RT). However, RT can lead to cardiotoxicity, which usually develops insidiously over years, making diagnosis difficult. It is also unknown whether early identification of at-risk patients might improve long-term outcome. We have previously described subclinical alterations, detected by two-dimensional speckle tracking strain echocardiography, in left ventricular (LV) function immediately following RT in breast cancer. Hypothesis Subclinical myocardial alterations in LV function consequent to RT cardiotoxicity, observed early, persist at 12 months. Methods 40 chemotherapy naive women with left-sided breast cancer, treated with surgery and adjuvant breast RT, were prospectively recruited from two tertiary hospitals. Transthoracic echocardiography was performed at baseline (pre-RT), 6 weeks post-RT, and 12 months post-RT. Results An increase in LV end diastolic and end systolic volumes was seen from baseline, consistent with persistent LV remodelling; however, due to the increase in both systolic and diastolic volumes over time, no change in LV ejection fraction (EF) was observed. Global longitudinal strain (GLS) and S′ velocity remained significantly lower at 12 months post-RT. GLS dropped by >10% in 16 patients and by >20% in 4 patients compared to baseline. Conclusions Subclinical cardiac dysfunction using strain analysis, evident early, persists one year after RT, despite unchanged conventional indices such as LVEF. Persistent GLS reduction may be of particular importance in breast cancer patients receiving concomitant chemotherapy. Longer term prospective studies are required to determine if reductions in strain post-RT are associated with future adverse cardiovascular events. [ABSTRACT FROM AUTHOR]
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- 2019
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9. Better than the real thing: Eliciting fear with moving and static computer-generated stimuli
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Courtney, Christopher G., Dawson, Michael E., Schell, Anne M., Iyer, Arvind, and Parsons, Thomas D.
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VIRTUAL reality , *GALVANIC skin response , *EMOTIONS , *SELF-evaluation , *HEART beat , *ELECTRIC stimulation - Abstract
Abstract: As the popularity of virtual reality as an exposure therapy increases, it is important to validate the use of computer-generated stimuli in comparison to standardized images of “real” phobic objects, such as those of the International Affective Picture System (IAPS). The present study examined physiological and subjective measures of negative affect when viewing static IAPS images, static computer-generated images and moving videos of computer-generated images of feared stimuli and other negative stimuli which were not specifically feared. For example, a picture of a spider would be a “feared” stimulus for a spider fearful participant, whereas a picture of a snake would be categorized as a “negative” stimulus for that participant. Eighteen participants scoring high (high fear (HF) cohort) on questionnaires assessing specific fears of spiders or snakes and 20 participants scoring low (low fear (LF) cohort) on the questionnaires viewed the stimuli. The computer-generated videos elicited greater physiological (skin conductance and startle eyeblink potentiation) and self-report arousal responses than the IAPS images and the computer-generated static images. Computer-generated stills and IAPS images did not differ in eliciting emotional responses. Additionally, HF participants showed greater heart rate acceleration and larger skin conductance responses to their feared stimulus than to the negative stimulus, especially when viewing computer-generated moving videos. The results demonstrate the importance of motion in eliciting fear and the usefulness of computer-generated stimuli in the study of emotion. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
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