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604 results on '"Sivakumaran, P."'

1. Analysis of the navigation of magnetic microrobots through cerebral bifurcations

Author

Alves, Pedro G., Pinto, Maria, Moreira, Rosa, Sivakumaran, Derick, Landers, Fabian C., Guix, Maria, Nelson, Bradley J., Flouris, Andreas D., Pané, Salvador, Puigmartí-Luis, Josep, and Mayor, Tiago Sotto

Subjects
Mathematics - Numerical Analysis, Computer Science - Robotics, Electrical Engineering and Systems Science - Systems and Control, Physics - Biological Physics
Abstract

Local administration of thrombolytics in ischemic stroke could accelerate clot lysis and the ensuing reperfusion while minimizing the side effects of systemic administration. Medical microrobots could be injected into the bloodstream and magnetically navigated to the clot for administering the drugs directly to the target. The magnetic manipulation required to navigate medical microrobots will depend on various parameters such as the microrobots size, the blood velocity, and the imposed magnetic field gradients. Numerical simulation was used to study the motion of magnetically controlled microrobots flowing through representative cerebral bifurcations, for predicting the magnetic gradients required to navigate the microrobots from the injection point until the target location. Upon thorough validation of the model against several independent analytical and experimental results, the model was used to generate maps and a predictive equation providing quantitative information on the required magnetic gradients, for different scenarios. The developed maps and predictive equation are crucial to inform the design, operation and optimization of magnetic navigation systems for healthcare applications.

Published
2025

2. Clinically Ready Magnetic Microrobots for Targeted Therapies

Author

Landers, Fabian C., Hertle, Lukas, Pustovalov, Vitaly, Sivakumaran, Derick, Brinkmann, Oliver, Meiners, Kirstin, Theiler, Pascal, Gantenbein, Valentin, Veciana, Andrea, Mattmann, Michael, Riss, Silas, Gervasoni, Simone, Chautems, Christophe, Ye, Hao, Sevim, Semih, Flouris, Andreas D., Puigmartí-Luis, Josep, Mayor, Tiago Sotto, Alves, Pedro, Lühmann, Tessa, Chen, Xiangzhong, Ochsenbein, Nicole, Moehrlen, Ueli, Gruber, Philipp, Weisskopf, Miriam, Boehler, Quentin, Pané, Salvador, and Nelson, Bradley J.

Subjects
Computer Science - Robotics, Condensed Matter - Materials Science, Electrical Engineering and Systems Science - Systems and Control, Physics - Applied Physics, Physics - Biological Physics, Physics - Medical Physics
Abstract

Systemic drug administration often causes off-target effects limiting the efficacy of advanced therapies. Targeted drug delivery approaches increase local drug concentrations at the diseased site while minimizing systemic drug exposure. We present a magnetically guided microrobotic drug delivery system capable of precise navigation under physiological conditions. This platform integrates a clinical electromagnetic navigation system, a custom-designed release catheter, and a dissolvable capsule for accurate therapeutic delivery. In vitro tests showed precise navigation in human vasculature models, and in vivo experiments confirmed tracking under fluoroscopy and successful navigation in large animal models. The microrobot balances magnetic material concentration, contrast agent loading, and therapeutic drug capacity, enabling effective hosting of therapeutics despite the integration complexity of its components, offering a promising solution for precise targeted drug delivery.

Published
2025

3. Harmonizing tau positron emission tomography in Alzheimer's disease: The CenTauR scale and the joint propagation model

Author

Leuzy, Antoine, Raket, Lars Lau, Villemagne, Victor L, Klein, Gregory, Tonietto, Matteo, Olafson, Emily, Baker, Suzanne, Saad, Ziad S, Bullich, Santiago, Lopresti, Brian, Bohorquez, Sandra Sanabria, Boada, Mercè, Betthauser, Tobey J, Charil, Arnaud, Collins, Emily C, Collins, Jessica A, Cullen, Nicholas, Gunn, Roger N, Higuchi, Makoto, Hostetler, Eric, Hutchison, R Matthew, Iaccarino, Leonardo, Insel, Philip S, Irizarry, Michael C, Jack, Clifford R, Jagust, William J, Johnson, Keith A, Johnson, Sterling C, Karten, Yashmin, Marquié, Marta, Mathotaarachchi, Sulantha, Mintun, Mark A, Ossenkoppele, Rik, Pappas, Ioannis, Petersen, Ronald C, Rabinovici, Gil D, Rosa‐Neto, Pedro, Schwarz, Christopher G, Smith, Ruben, Stephens, Andrew W, Whittington, Alex, Carrillo, Maria C, Pontecorvo, Michael J, Haeberlein, Samantha Budd, Dunn, Billy, Kolb, Hartmuth C, Sivakumaran, Sudhir, Rowe, Christopher C, Hansson, Oskar, and Doré, Vincent

Subjects
Biological Psychology, Psychology, Biomedical Imaging, Neurodegenerative, Alzheimer's Disease, Brain Disorders, Dementia, Neurosciences, Acquired Cognitive Impairment, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Bioengineering, Aging, Neurological, Alzheimer Disease, Humans, Positron-Emission Tomography, tau Proteins, Brain, Male, Female, Aged, Cohort Studies, Radiopharmaceuticals, Models, Statistical, [F-18]Flortaucipir, [F-18]RO948, [F-18]MK-6240, [F-18]GTP1, [F-18]PI-2620, Alzheimer's disease, C-Path, CenTauR, Centiloid, CPAD, head-to-head, Imaging, PET, standardization, tau, C‐Path, [18F]Flortaucipir, [18F]GTP1, [18F]MK‐6240, [18F]PI‐2620, [18F]RO948, head‐to‐head, Clinical Sciences, Geriatrics, Clinical sciences, Biological psychology
Abstract

IntroductionTau-positron emission tomography (PET) outcome data of patients with Alzheimer's disease (AD) cannot currently be meaningfully compared or combined when different tracers are used due to differences in tracer properties, instrumentation, and methods of analysis.MethodsUsing head-to-head data from five cohorts with tau PET radiotracers designed to target tau deposition in AD, we tested a joint propagation model (JPM) to harmonize quantification (units termed "CenTauR" [CTR]). JPM is a statistical model that simultaneously models the relationships between head-to-head and anchor point data. JPM was compared to a linear regression approach analogous to the one used in the amyloid PET Centiloid scale.ResultsA strong linear relationship was observed between CTR values across brain regions. Using the JPM approach, CTR estimates were similar to, but more accurate than, those derived using the linear regression approach.DiscussionPreliminary findings using the JPM support the development and adoption of a universal scale for tau-PET quantification.HighlightsTested a novel joint propagation model (JPM) to harmonize quantification of tau PET. Units of common scale are termed "CenTauRs". Tested a Centiloid-like linear regression approach. Using five cohorts with head-to-head tau PET, JPM outperformed linearregressionbased approach. Strong linear relationship was observed between CenTauRs values across brain regions.

Published
2024

4. Distance Antimagic Labeling of Zero-Divisor Graphs

Author

Sivakumaran, V., Sankar, K., and Prabhu, S.

Subjects
Mathematics - Combinatorics, 05C78
Abstract

In this paper, we prove that for all $m\geq 1$ and $n=1$, the graph $ m\Gamma(\mathbb{Z}_9)+n\Gamma(\mathbb{Z}_4)$, for all $n\geq 1$, and $m=1$, the graph $m\overline{\Gamma(\mathbb{Z}_6)}+n\Gamma(\mathbb{Z}_9)$, for all $m\geq1$, $[m\Gamma(\mathbb{Z}_9)+\Gamma(\mathbb{Z}_4)]\times \Gamma(\mathbb{Z}_9)$, for all prime $m\geq3$, $\Gamma(\mathbb{Z}_6)\times\Gamma(\mathbb{Z}_{2m})$ and $\Gamma(\mathbb{Z}_6)\times\Gamma(\mathbb{Z}_{m^2})$ are all admit distance antimagic labeling.

Published
2024

5. Identifying the primary tumour in patients with cancer of unknown primary (CUP) using [18F]FDG PET/CT: a systematic review and individual patient data meta-analysis

Author

Willemse, Jeroen R. J., Lambregts, Doenja M. J., Balduzzi, Sara, Schats, Winnie, Snaebjornsson, Petur, Marchetti, Serena, Vollebergh, Marieke A., van Golen, Larissa W., Cheung, Zing, Vogel, Wouter V., Bodalal, Zuhir, Rostami, Sajjad, Gerke, Oke, Sivakumaran, Tharani, Beets-Tan, Regina G.H., and Lahaye, Max J.

Published
2024
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9. Two-trace two-dimensional correlation spectra (2T2D-COS) analysis using FTIR spectra to monitor the immune response by COVID-19

Author

Karthikeyan, Sivakumaran, Vazquez-Zapien, Gustavo J., Martinez-Cuazitl, Adriana, Delgado-Macuil, Raul J., Rivera-Alatorre, Daniel E., Garibay-Gonzalez, Francisco, Delgado-Gonzalez, Josemaria, Valencia-Trujillo, Daniel, Guerrero-Ruiz, Melissa, Atriano-Colorado, Consuelo, Lopez-Reyes, Alberto, Lopez-Mezquita, Dante J., and Mata-Miranda, Monica M.

Published
2024
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11. Important Factors in Measuring Learners' Satisfaction and Continuance Intention in Open And Distance Learning (ODL) Institutions

Author

Masrani, Saiful Ahmad, Mohd Amin, Mohd Rushidi, Sivakumaran, Vinesh Maran, and Piaralal, Shishi Kumar

Abstract

Purpose: The aim of this study is to explore and establish the relationships between justice dimensions, expectation-confirmation model (ECM) and continuance intention and also to examine the mediating effect of learners' satisfaction and perceived usefulness toward continuance intentions of the university learning management system (LMS) within open and distance learning (ODL) context. Design/methodology/approach: A cross-sectional research design was used, and the data were collected from a sample of 366 respondents utilizing the online survey questionnaire approach. Hypotheses were tested using the partial least square (PLS) SEM technique. Findings: The findings reveal that justice dimensions (distributive, procedural, interpersonal and informational justice) have a significant relationship with learners' satisfaction. Performance confirmation have significant relationship with learners' satisfaction and perceived usefulness. Perceived usefulness has a direct significant relationship toward learners' satisfaction, and learners' satisfaction has a direct significant relationship toward continuance intention. For mediation analysis, learners' satisfaction was found to have a mediation effect in the relationship between the justice dimensions and continuance intention. Learners' satisfaction was also found to have a mediation effect on the relationship between performance conformation and continuance intention. However, learners' satisfaction was found not to have a mediation effect on the relationship between perceived usefulness and continuance intention, and perceived usefulness does not have a mediation effect in the relationship of performance confirmation and learners' satisfaction. Originality/value: This study advances knowledge and provides valuable insights to practitioners and academic scholars to have a better understanding of the effective attributes of the university LMS, and also to maximize the revenues and the sustainability of the institutions in long term, especially in the 21st century.

Published
2023
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13. argXtract: Deriving IoT Security Configurations via Automated Static Analysis of Stripped ARM Binaries

Author

Sivakumaran, Pallavi and Blasco, Jorge

Subjects
Computer Science - Cryptography and Security
Abstract

Recent high-profile attacks on the Internet of Things (IoT) have brought to the forefront the vulnerability of "smart" devices, and have resulted in numerous IoT-focused security analyses. Many of the attacks had weak device configuration as the root cause. One potential source of rich and definitive information about the configuration of an IoT device is the device's firmware. However, firmware analysis is complex and automated firmware analyses have thus far been confined to devices with more traditional operating systems such as Linux or VxWorks. Most IoT peripherals, due to lacking traditional operating systems and implementing a wide variety of communication technologies, have only been the subject of smaller-scale analyses. Peripheral firmware analysis is further complicated by the fact that such firmware files are predominantly available as stripped binaries, without the ELF headers and symbol tables that would simplify reverse engineering. In this paper, we present argXtract, an open-source automated static analysis tool, which extracts security-relevant configuration information from stripped IoT peripheral firmware. Specifically, we focus on binaries that target the ARM Cortex-M architecture, due to its growing popularity among IoT peripherals. argXtract overcomes the challenges associated with stripped Cortex-M analysis and is able to retrieve arguments to security-relevant supervisor and function calls, enabling automated bulk analysis of firmware files. We demonstrate this via three real-world case studies. The largest case study covers a dataset of 243 Bluetooth Low Energy binaries targeting Nordic Semiconductor chipsets, while the other two focus on Nordic ANT and STMicroelectronics BlueNRG binaries. The results reveal widespread lack of security and privacy controls in IoT, such as minimal or no protection for data, fixed passkeys and trackable device addresses.

Published
2021

16. CRISPR screens identify gene targets at breast cancer risk loci

Author

Tuano, Natasha K., Beesley, Jonathan, Manning, Murray, Shi, Wei, Perlaza-Jimenez, Laura, Malaver-Ortega, Luis F., Paynter, Jacob M., Black, Debra, Civitarese, Andrew, McCue, Karen, Hatzipantelis, Aaron, Hillman, Kristine, Kaufmann, Susanne, Sivakumaran, Haran, Polo, Jose M., Reddel, Roger R., Band, Vimla, French, Juliet D., Edwards, Stacey L., Powell, David R., Chenevix-Trench, Georgia, and Rosenbluh, Joseph

Published
2023
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20. A Study of the Feasibility of Co-located App Attacks against BLE and a Large-Scale Analysis of the Current Application-Layer Security Landscape

Author

Sivakumaran, Pallavi and Blasco, Jorge

Subjects
Computer Science - Cryptography and Security
Abstract

Bluetooth Low Energy (BLE) is a fast-growing wireless technology with a large number of potential use cases, particularly in the IoT domain. Increasingly, these use cases require the storage of sensitive user data or critical device controls on the BLE device, as well as the access of this data by an augmentative mobile application. Uncontrolled access to such data could violate user privacy, cause a device to malfunction, or even endanger lives. The BLE standard provides security mechanisms such as pairing and bonding to protect sensitive data such that only authenticated devices can access it. In this paper we show how unauthorized co-located Android applications can access pairing-protected BLE data, without the user's knowledge. We discuss mitigation strategies in terms of the various stakeholders involved in this ecosystem, and argue that at present, the only possible option for securing BLE data is for BLE developers to implement remedial measures in the form of application-layer security between the BLE device and the Android application. We introduce BLECryptracer, a tool for identifying the presence of such application-layer security, and present the results of a large-scale static analysis over 18,900+ BLE-enabled Android applications. Our findings indicate that over 45% of these applications do not implement measures to protect BLE data, and that cryptography is sometimes applied incorrectly in those that do. This implies that a potentially large number of corresponding BLE peripheral devices are vulnerable to unauthorized data access., Comment: The % Downloads line graph (Fig-7) in v2 of this paper is inaccurate, as we do not have install counts per version of an application. It has been removed in this version [v3] of the paper

Published
2018

21. Review: the development of neural stem cell biology and technology in regenerative medicine

Author

Shanmuganathan, Divyanjali and Sivakumaran, Nivethika

Subjects
Quantitative Biology - Neurons and Cognition, Quantitative Biology - Tissues and Organs
Abstract

In the middle of the last century, it has been known that neural stem cells (NSCs) play a key role in regenerative medicine to cure the neurodegenerative disease. This review article covers about the introduction to neural stem cell biology and the isolation, differentiation and transplantation methods/techniques of neural stem cells. The neural stem cells can be transplanted into the human brain in the future to replace the damaged and dead neurons. The highly limited access to embryonic stem cells and ethical issues have escalated the search for other NSC sources. The developing technologies are indicating that it can be achieved before the end of this century. In addition, the differentiation and the maturation of NSCs can artificially accelerate by modern methods., Comment: 15 pages

Published
2018

22. A comprehensive review of Chronic Kidney Disease of Unknown Etiology

Author

Fernando, Adoni and Sivakumaran, Nivethika

Subjects
Quantitative Biology - Quantitative Methods, Quantitative Biology - Tissues and Organs
Abstract

This review was written to provide a comprehensive summary of the suggested etiologies of Chronic Kidney Disease of Unknown Etiology (CKDu) in Sri Lanka. In this review, Chronic Kidney Disease (CKD) is explained in detail and its known etiologies are discussed. CKDu is defined and its epidemiology is discussed, with the compilation of statistic from over 15 research papers through the years 2000 to present., Comment: 11 pages

Published
2018

23. Umbilical Cord Blood Banking and its Therapeutic Uses

Author

Sivakumaran, Nivethika, Rathnayaka, Imesha Rashmini, Shabbir, Rashida, Wimalsinghe, Sasini Sandareka, Jayakody, J. A. Sumalimina, Chandrasekaran, Mahisha, Mawatha, and Lanka, Sri

Subjects
Quantitative Biology - Cell Behavior, Quantitative Biology - Tissues and Organs
Abstract

Umbilical cord blood (UBC) can be viewed as the most promising source of stem cells, in which collection cost is minimal and its benefits are immense. The cord blood is used to treat malignant and nonmalignant diseases; this is due to its progenitor characteristics know as stem cells.Its properties of being, immunologically immature and high plasticity has made it superior to other sources of stem cells. The stem cells collected from cord blood have neutral differentiation capabilities which allow medical professionals to produce functional neural cells from these stem cells.Cord Blood Banking (CBB) is the storing of the umbilical cord blood which is collected immediately after the delivery of the baby. Great care and concern are needed for proper storage of these progenitor cells, hence cord blood banks come into the play, they are of 3 types which are: public, private and direct donation banks.Clinical trials are still at its very early stages having abundances to still be uncovered but results were obtained have demonstrated high potential and more scope towards effective development therapies and treatments for rare disorders.

Published
2018

27. Correction: A 32 kb Critical Region Excluding Y402H in CFH Mediates Risk for Age-Related Macular Degeneration

Author

Sivakumaran, Theru A, Igo, Robert P, Kidd, Jeffrey M, Itsara, Andy, Kopplin, Laura J, Chen, Wei, Hagstrom, Stephanie A, Peachey, Neal S, Francis, Peter J, Klein, Michael L, Chew, Emily Y, Ramprasad, Vedam L, Tay, Wan-Ting, Mitchell, Paul, Seielstad, Mark, Stambolian, Dwight E, Edwards, Albert O, Lee, Kristine E, Leontiev, Dmitry V, Jun, Gyungah, Wang, Yang, Tian, Liping, Qiu, Feiyou, Henning, Alice K, LaFramboise, Thomas, Sen, Parveen, Aarthi, Manoharan, George, Ronnie, Raman, Rajiv, Das, Manmath Kumar, Vijaya, Lingam, Kumaramanickavel, Govindasamy, Wong, Tien Y, Swaroop, Anand, Abecasis, Goncalo R, Klein, Ronald, Klein, Barbara EK, Nickerson, Deborah A, Eichler, Evan E, and Iyengar, Sudha K

Subjects
Biomedical and Clinical Sciences, Ophthalmology and Optometry, General Science & Technology
Abstract

[This corrects the article DOI: 10.1371/journal.pone.0025598.].

Published
2018

28. Breast cancer diagnosis by hybrid fuzzy CNN network

Author

Jacob, W. Stalin, Rosita, P. Jenifer Darling, Geetha, M. Sri, Jagadeesh, P., and Chandrasekaran, Sivakumaran

Abstract

Breast cancer is a common gynaecological ailment that affects women all over the world. Early identification of this disease has been shown to be extremely beneficial in terms of therapy. Mammographic pictures are analysed in this article utilising image processing methods and a pipeline structure to see whether they contain malignant tumours, which are subsequently categorised. The SVM classifier is used for classification, and it is fed by the characteristics that have been picked. It is supported by a number of kernel functions. This differs from standard machine learning classification and optimisation strategies, and it is shown in a unique manner. The outcomes of the actualised computer-aided diagnostic (CAD) learning process are analysed in order to determine whether or not it was successful. The BCDR-F03 dataset is evaluated, as well as the: 1) local mammographic dataset; 2) colony optimisation-based multi-layer perceptron (ACO-MLP) dataset.

Published
2025
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32. Inhibition of colony stimulating factor 1 receptor corrects maternal inflammation-induced microglial and synaptic dysfunction and behavioral abnormalities

Author

Ikezu, Seiko, Yeh, Hana, Delpech, Jean-Christophe, Woodbury, Maya E., Van Enoo, Alicia A., Ruan, Zhi, Sivakumaran, Sudhir, You, Yang, Holland, Carl, Guillamon-Vivancos, Teresa, Yoshii-Kitahara, Asuka, Botros, Mina B., Madore, Charlotte, Chao, Pin-Hao, Desani, Ankita, Manimaran, Solaiappan, Kalavai, Srinidhi Venkatesan, Johnson, W. Evan, Butovsky, Oleg, Medalla, Maria, Luebke, Jennifer I., and Ikezu, Tsuneya

Published
2021
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35. Evidence that the 5p12 Variant rs10941679 Confers Susceptibility to Estrogen-Receptor-Positive Breast Cancer through FGF10 and MRPS30 Regulation

Author

Ghoussaini, Maya, French, Juliet D, Michailidou, Kyriaki, Nord, Silje, Beesley, Jonathan, Canisus, Sander, Hillman, Kristine M, Kaufmann, Susanne, Sivakumaran, Haran, Marjaneh, Moradi, Lee, Jason S, Dennis, Joe, Bolla, Manjeet K, Wang, Qin, Dicks, Ed, Milne, Roger L, Hopper, John L, Southey, Melissa C, Schmidt, Marjanka K, Broeks, Annegien, Muir, Kenneth, Lophatananon, Artitaya, Fasching, Peter A, Beckmann, Matthias W, Fletcher, Olivia, Johnson, Nichola, Sawyer, Elinor J, Tomlinson, Ian, Burwinkel, Barbara, Marme, Frederik, Guénel, Pascal, Truong, Thérèse, Bojesen, Stig E, Flyger, Henrik, Benitez, Javier, González-Neira, Anna, Alonso, M Rosario, Pita, Guillermo, Neuhausen, Susan L, Anton-Culver, Hoda, Brenner, Hermann, Arndt, Volker, Meindl, Alfons, Schmutzler, Rita K, Brauch, Hiltrud, Hamann, Ute, Tessier, Daniel C, Vincent, Daniel, Nevanlinna, Heli, Khan, Sofia, Matsuo, Keitaro, Ito, Hidemi, Dörk, Thilo, Bogdanova, Natalia V, Lindblom, Annika, Margolin, Sara, Mannermaa, Arto, Kosma, Veli-Matti, Investigators, kConFab AOCS, Wu, Anna H, Van Den Berg, David, Lambrechts, Diether, Floris, Giuseppe, Chang-Claude, Jenny, Rudolph, Anja, Radice, Paolo, Barile, Monica, Couch, Fergus J, Hallberg, Emily, Giles, Graham G, Haiman, Christopher A, Le Marchand, Loic, Goldberg, Mark S, Teo, Soo H, Yip, Cheng Har, Borresen-Dale, Anne-Lise, Collaborators, NBCS, Zheng, Wei, Cai, Qiuyin, Winqvist, Robert, Pylkäs, Katri, Andrulis, Irene L, Devilee, Peter, Tollenaar, Rob AEM, García-Closas, Montserrat, Figueroa, Jonine, Hall, Per, Czene, Kamila, Brand, Judith S, Darabi, Hatef, Eriksson, Mikael, Hooning, Maartje J, Koppert, Linetta B, Li, Jingmei, Shu, Xiao-Ou, Zheng, Ying, Cox, Angela, Cross, Simon S, Shah, Mitul, and Rhenius, Valerie

Subjects
Prevention, Genetics, Cancer, Breast Cancer, Human Genome, 2.1 Biological and endogenous factors, Aetiology, Alleles, Breast Neoplasms, Case-Control Studies, Cell Line, Tumor, Chromosomes, Human, Pair 5, Enhancer Elements, Genetic, Fibroblast Growth Factor 10, Genetic Predisposition to Disease, Haplotypes, Humans, Polymorphism, Single Nucleotide, Promoter Regions, Genetic, Quantitative Trait Loci, Receptor, Fibroblast Growth Factor, Type 2, Receptors, Estrogen, kConFab/AOCS Investigators, NBCS Collaborators, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract

Genome-wide association studies (GWASs) have revealed increased breast cancer risk associated with multiple genetic variants at 5p12. Here, we report the fine mapping of this locus using data from 104,660 subjects from 50 case-control studies in the Breast Cancer Association Consortium (BCAC). With data for 3,365 genotyped and imputed SNPs across a 1 Mb region (positions 44,394,495-45,364,167; NCBI build 37), we found evidence for at least three independent signals: the strongest signal, consisting of a single SNP rs10941679, was associated with risk of estrogen-receptor-positive (ER+) breast cancer (per-g allele OR ER+ = 1.15; 95% CI 1.13-1.18; p = 8.35 × 10-30). After adjustment for rs10941679, we detected signal 2, consisting of 38 SNPs more strongly associated with ER-negative (ER-) breast cancer (lead SNP rs6864776: per-a allele OR ER- = 1.10; 95% CI 1.05-1.14; p conditional = 1.44 × 10-12), and a single signal 3 SNP (rs200229088: per-t allele OR ER+ = 1.12; 95% CI 1.09-1.15; p conditional = 1.12 × 10-05). Expression quantitative trait locus analysis in normal breast tissues and breast tumors showed that the g (risk) allele of rs10941679 was associated with increased expression of FGF10 and MRPS30. Functional assays demonstrated that SNP rs10941679 maps to an enhancer element that physically interacts with the FGF10 and MRPS30 promoter regions in breast cancer cell lines. FGF10 is an oncogene that binds to FGFR2 and is overexpressed in ∼10% of human breast cancers, whereas MRPS30 plays a key role in apoptosis. These data suggest that the strongest signal of association at 5p12 is mediated through coordinated activation of FGF10 and MRPS30, two candidate genes for breast cancer pathogenesis.

Published
2016

36. Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170.

Author

Dunning, Alison M, Michailidou, Kyriaki, Kuchenbaecker, Karoline B, Thompson, Deborah, French, Juliet D, Beesley, Jonathan, Healey, Catherine S, Kar, Siddhartha, Pooley, Karen A, Lopez-Knowles, Elena, Dicks, Ed, Barrowdale, Daniel, Sinnott-Armstrong, Nicholas A, Sallari, Richard C, Hillman, Kristine M, Kaufmann, Susanne, Sivakumaran, Haran, Moradi Marjaneh, Mahdi, Lee, Jason S, Hills, Margaret, Jarosz, Monika, Drury, Suzie, Canisius, Sander, Bolla, Manjeet K, Dennis, Joe, Wang, Qin, Hopper, John L, Southey, Melissa C, Broeks, Annegien, Schmidt, Marjanka K, Lophatananon, Artitaya, Muir, Kenneth, Beckmann, Matthias W, Fasching, Peter A, Dos-Santos-Silva, Isabel, Peto, Julian, Sawyer, Elinor J, Tomlinson, Ian, Burwinkel, Barbara, Marme, Frederik, Guénel, Pascal, Truong, Thérèse, Bojesen, Stig E, Flyger, Henrik, González-Neira, Anna, Perez, Jose IA, Anton-Culver, Hoda, Eunjung, Lee, Arndt, Volker, Brenner, Hermann, Meindl, Alfons, Schmutzler, Rita K, Brauch, Hiltrud, Hamann, Ute, Aittomäki, Kristiina, Blomqvist, Carl, Ito, Hidemi, Matsuo, Keitaro, Bogdanova, Natasha, Dörk, Thilo, Lindblom, Annika, Margolin, Sara, Kosma, Veli-Matti, Mannermaa, Arto, Tseng, Chiu-Chen, Wu, Anna H, Lambrechts, Diether, Wildiers, Hans, Chang-Claude, Jenny, Rudolph, Anja, Peterlongo, Paolo, Radice, Paolo, Olson, Janet E, Giles, Graham G, Milne, Roger L, Haiman, Christopher A, Henderson, Brian E, Goldberg, Mark S, Teo, Soo H, Yip, Cheng Har, Nord, Silje, Borresen-Dale, Anne-Lise, Kristensen, Vessela, Long, Jirong, Zheng, Wei, Pylkäs, Katri, Winqvist, Robert, Andrulis, Irene L, Knight, Julia A, Devilee, Peter, Seynaeve, Caroline, Figueroa, Jonine, Sherman, Mark E, Czene, Kamila, Darabi, Hatef, Hollestelle, Antoinette, van den Ouweland, Ans MW, Humphreys, Keith, Gao, Yu-Tang, and Shu, Xiao-Ou

Subjects
EMBRACE, GEMO Study Collaborators, HEBON, kConFab Investigators, Chromosomes, Human, Pair 6, Humans, Breast Neoplasms, Genetic Predisposition to Disease, Carrier Proteins, Cell Cycle Proteins, Estrogen Receptor alpha, Risk Factors, Gene Expression, Gene Expression Regulation, Neoplastic, Base Sequence, Protein Binding, Phenotype, Polymorphism, Single Nucleotide, Female, Genetic Association Studies, Cancer, Clinical Research, Breast Cancer, Genetics, Aetiology, 2.1 Biological and endogenous factors, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

We analyzed 3,872 common genetic variants across the ESR1 locus (encoding estrogen receptor α) in 118,816 subjects from three international consortia. We found evidence for at least five independent causal variants, each associated with different phenotype sets, including estrogen receptor (ER(+) or ER(-)) and human ERBB2 (HER2(+) or HER2(-)) tumor subtypes, mammographic density and tumor grade. The best candidate causal variants for ER(-) tumors lie in four separate enhancer elements, and their risk alleles reduce expression of ESR1, RMND1 and CCDC170, whereas the risk alleles of the strongest candidates for the remaining independent causal variant disrupt a silencer element and putatively increase ESR1 and RMND1 expression.

Published
2016

37. University-School Partnerships for Clinical Experiences: Design, Implementation, Assessment, and Data Collection

Author

Sivakumaran, Thillainatarajan, Holland, Glenda, Clark, Leonard, Heyning, Katharina, Wishart, William, and Flowers-Gibson, Beverly

Abstract

University teacher education programs establish partnerships with P-12 schools, in part to place their teacher education candidates in a learning environment that allows candidates to work with a diverse population of learners. The purpose of this study was to examine three universities in regard to the partnerships utilized for field and clinical preparation of teacher candidates. The study addressed the types of collaboration and partnerships that have been established between university teacher preparation programs and P-12 schools, the design and implementation of field experiences and clinical practices, teacher candidate evaluation, and the collection and dissemination of field and clinical data to stakeholders.

Published
2011

38. Overcoming Computer Anxiety: A Three-Step Process for Adult Learners

Author

Sivakumaran, Thillainatarajan and Lux, Allison C.

Abstract

Many adult learners returning to school later in life have discovered that technology is heavily embedded in the learning environment. Learning both course contents and technology in unison can be a daunting task for students who feel intimidated by technology. Computer anxiety is a term that describes resistance, fear or anxieties towards computers. Uncovering ways to not only help adult students dispel their computer anxiety, but also help students attain greater computer self-efficacy is a challenge for educators. This article proposes a three-step process for helping adult learners overcome that anxiety, purpose, positive environment, and provides support. Institutions of higher learning that employ this three-step process should be able to provide both a successful and meaningful experience for adult learners.

Published
2011

39. Germline polymorphisms in an enhancer of PSIP1 are associated with progression-free survival in epithelial ovarian cancer

Author

French, Juliet D, Johnatty, Sharon E, Lu, Yi, Beesley, Jonathan, Gao, Bo, Kalimutho, Murugan, Henderson, Michelle J, Russell, Amanda J, Kar, Siddhartha, Chen, Xiaoqing, Hillman, Kristine M, Kaufmann, Susanne, Sivakumaran, Haran, O’Reilly, Martin, Wang, Chen, Korbie, Darren J, Group, Australian Ovarian Cancer Study, Study, Australian Cancer, Lambrechts, Diether, Despierre, Evelyn, Van Nieuwenhuysen, Els, Lambrechts, Sandrina, Vergote, Ignace, Karlan, Beth, Lester, Jenny, Orsulic, Sandra, Walsh, Christine, Fasching, Peter A, Beckmann, Matthias W, Ekici, Arif B, Hein, Alexander, Matsuo, Keitaro, Hosono, Satoyo, Pisterer, Jacobus, Hillemanns, Peter, Nakanishi, Toru, Yatabe, Yasushi, Goodman, Marc T, Lurie, Galina, Matsuno, Rayna K, Thompson, Pamela J, Pejovic, Tanja, Bean, Yukie, Heitz, Florian, Harter, Philipp, du Bois, Andreas, Schwaab, Ira, Hogdall, Estrid, Kjaer, Susanne K, Jensen, Allan, Hogdall, Claus, Lundvall, Lene, Engelholm, Svend Aage, Brown, Bob, Flanagan, James M, Metcalf, Michelle D, Siddiqui, Nadeem, Sellers, Thomas, Fridley, Brooke, Cunningham, Julie, Schildkraut, Joellen M, Iversen, Ed, Weber, Rachel Palmieri, Brennan, Donal, Berchuck, Andrew, Pharoah, Paul, Harnett, Paul, Norris, Murray D, Haber, Michelle, Goode, Ellen L, Lee, Jason S, Khanna, Kum Kum, Meyer, Kerstin B, Chenevix-Trench, Georgia, deFazio, Anna, Edwards, Stacey L, MacGregor, Stuart, and Consortium, on behalf of the Ovarian Cancer Association

Subjects
Genetics, Rare Diseases, Human Genome, Ovarian Cancer, Cancer, Aetiology, 2.1 Biological and endogenous factors, Adaptor Proteins, Signal Transducing, Apoptosis, Biomarkers, Tumor, Cell Proliferation, Chromatin Immunoprecipitation, Cohort Studies, Cystadenocarcinoma, Serous, Electrophoretic Mobility Shift Assay, Enhancer Elements, Genetic, Fallopian Tube Neoplasms, Female, Follow-Up Studies, Germ-Line Mutation, Humans, Ovarian Neoplasms, Peritoneal Neoplasms, Polymorphism, Single Nucleotide, Prognosis, RNA, Messenger, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, Survival Rate, Transcription Factors, Tumor Cells, Cultured, epithelial ovarian cancer, progression free survival, genome-wide association study, PSIP1, chromosome conformation capture, Australian Ovarian Cancer Study Group, Australian Ovarian Cancer Study, Ovarian Cancer Association Consortium, Oncology and Carcinogenesis
Abstract

Women with epithelial ovarian cancer (EOC) are usually treated with platinum/taxane therapy after cytoreductive surgery but there is considerable inter-individual variation in response. To identify germline single-nucleotide polymorphisms (SNPs) that contribute to variations in individual responses to chemotherapy, we carried out a multi-phase genome-wide association study (GWAS) in 1,244 women diagnosed with serous EOC who were treated with the same first-line chemotherapy, carboplatin and paclitaxel. We identified two SNPs (rs7874043 and rs72700653) in TTC39B (best P=7x10-5, HR=1.90, for rs7874043) associated with progression-free survival (PFS). Functional analyses show that both SNPs lie in a putative regulatory element (PRE) that physically interacts with the promoters of PSIP1, CCDC171 and an alternative promoter of TTC39B. The C allele of rs7874043 is associated with poor PFS and showed increased binding of the Sp1 transcription factor, which is critical for chromatin interactions with PSIP1. Silencing of PSIP1 significantly impaired DNA damage-induced Rad51 nuclear foci and reduced cell viability in ovarian cancer lines. PSIP1 (PC4 and SFRS1 Interacting Protein 1) is known to protect cells from stress-induced apoptosis, and high expression is associated with poor PFS in EOC patients. We therefore suggest that the minor allele of rs7874043 confers poor PFS by increasing PSIP1 expression.

Published
2016

40. Systematic meta-analyses and field synopsis of genetic association studies in colorectal adenomas

Author

Montazeri, Zahra, Theodoratou, Evropi, Nyiraneza, Christine, Timofeeva, Maria, Chen, Wanjing, Svinti, Victoria, Sivakumaran, Shanya, Gresham, Gillian, Cubitt, Laura, Carvajal-Carmona, Luis, Bertagnolli, Monica M, Zauber, Ann G, Tomlinson, Ian, Farrington, Susan M, Dunlop, Malcolm G, Campbell, Harry, and Little, Julian

Subjects
Epidemiology, Health Sciences, Cancer, Colo-Rectal Cancer, Genetics, Human Genome, Digestive Diseases, Aetiology, 2.1 Biological and endogenous factors, Adenoma, Alleles, Arylamine N-Acetyltransferase, Bayes Theorem, Colorectal Neoplasms, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Isoenzymes, Methylenetetrahydrofolate Reductase (NADPH2), NAD(P)H Dehydrogenase (Quinone), Polymorphism, Single Nucleotide, Risk Factors, Tumor Suppressor Protein p53, Statistics, Public Health and Health Services, Public health
Abstract

BackgroundLow penetrance genetic variants, primarily single nucleotide polymorphisms, have substantial influence on colorectal cancer (CRC) susceptibility. Most CRCs develop from colorectal adenomas (CRA). Here we report the first comprehensive field synopsis that catalogues all genetic association studies on CRA, with a parallel online database [http://www.chs.med.ed.ac.uk/CRAgene/].MethodsWe performed a systematic review, reviewing 9750 titles, and then extracted data from 130 publications reporting on 181 polymorphisms in 74 genes. We conducted meta-analyses to derive summary effect estimates for 37 polymorphisms in 26 genes. We applied the Venice criteria and Bayesian False Discovery Probability (BFDP) to assess the levels of the credibility of associations.ResultsWe considered the association with the rs6983267 variant at 8q24 as 'highly credible', reaching genome-wide statistical significance in at least one meta-analysis model. We identified 'less credible' associations (higher heterogeneity, lower statistical power, BFDP > 0.02) with a further four variants of four independent genes: MTHFR c.677C>T p.A222V (rs1801133), TP53 c.215C>G p.R72P (rs1042522), NQO1 c.559C>T p.P187S (rs1800566), and NAT1 alleles imputed as fast acetylator genotypes. For the remaining 32 variants of 22 genes for which positive associations with CRA risk have been previously reported, the meta-analyses revealed no credible evidence to support these as true associations.ConclusionsThe limited number of credible associations between low penetrance genetic variants and CRA reflects the lower volume of evidence and associated lack of statistical power to detect associations of the magnitude typically observed for genetic variants and chronic diseases. The CRA gene database provides context for CRA genetic association data and will help inform future research directions.

Published
2016

41. Online Teaching Needs Assessment

Author

Holland, Glenda, Sivakumaran, Thillainatarajan, Dawson, Marcus Dewayne, Davis, Lucy, Choi, Yung Yu, and Absher, Ashley

Abstract

The study utilized a descriptive research approach to analyze the professional development needs of participants. Researchers for this study wanted to know the kinds of support and incentives that are being offered for faculty members who are teaching online courses, the kinds of professional development opportunities that are being offered, the topics faculty members are interested in learning more about, and their preferences for delivery methods of professional development sessions. A self-report survey was selected as the method of research. The population consisted of 40 faculty members who teach education-related courses at one southern university. Data were summarized utilizing descriptive statistics, specifically frequencies and percentages.

Published
2010

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