208 research outputs found
Mitochondrial Metabolism of Human Kidney Cancers
No full textThe general metadata -- e.g., title, author, abstract, subject headings, etc. -- is publicly available, but access to the submitted files is restricted to UT Southwestern campus access and/or authorized UT Southwestern users.Metabolism is often dysregulated in cancer. Pinpointing the exact metabolic requirements critical for cancer cell survival has been the subject of intense study for the last 100 years. However, very few metabolic targets have successfully translated to effective therapies for patients. Progress in clinical translation has been limited as the vast majority of cancer metabolism studies are currently conducted in preclinical models of cell culture and mice. How relevant these preclinical studies are to disease biology in humans is almost entirely unknown. I use a multidisciplinary approach to infuse 13C-labeled nutrients during surgical tumor resection in over 80 patients with kidney cancer. Labeling from [U-13C]glucose varies across cancer subtypes, indicating that the kidney environment alone cannot account for all metabolic reprogramming in these tumors. Compared to the adjacent kidney, clear cell renal cell carcinomas (ccRCC) display suppressed labelling of tricarboxylic acid (TCA) cycle intermediates in vivo and in organotypic slices cultured ex vivo, indicating that suppressed labeling is tissue intrinsic. Infusions of [1,2-13C]acetate and [U-13C]glutamine in patients, coupled with respiratory flux of mitochondria isolated from kidney and tumor tissue, reveal primary defects in mitochondrial function in human ccRCC. However, ccRCC metastases unexpectedly have enhanced labeling of TCA cycle intermediates compared to primary ccRCCs, indicating a divergent metabolic program during ccRCC metastasis in patients. In mice, stimulating respiration in ccRCC cells is sufficient to promote metastatic colonization. Altogether, these findings indicate that metabolic properties evolve during human kidney cancer progression, and suggest that mitochondrial respiration may be limiting for ccRCC metastasis but not for ccRCC growth at the site of origin
Merchants of Virtue
No full textMerchants of Virtue explores the question of what it meant to be Hindu in precolonial South Asia. Divya Cherian presents a fine-grained study of everyday life and local politics in the kingdom of Marwar in eighteenth-century western India to uncover how merchants enforced their caste ideals of vegetarianism and bodily austerity as universal markers of Hindu identity. Using legal strategies and alliances with elites, these merchants successfully remade the category of “Hindu,” setting it in contrast to “Untouchable” in a process that reconfigured Hinduism in caste terms. In a history pertinent to understanding India today, Cherian establishes the centrality of caste to the early-modern Hindu self and to its imagination of inadmissible others.
“A refreshingly different perspective on the history of caste and untouchability in India, enlarging the field of scholarship from its focus on the colonial era by telling us how precolonial configurations of power in the locality shaped the everyday experience of caste.” — GOPAL GURU, coauthor of The Cracked Mirror and Experience, Caste, and the Everyday Social
“This provocative and empirically rich study offers a plenitude of fascinating insights into aspects of western Indian history ca. 1800, from kingship and caste hierarchy to abortion and alcohol consumption. Particularly innovative is its focus on the critical role played by merchants in articulating social identities that became widespread in modern times.” — CYNTHIA TALBOT, author of The Last Hindu Emperor
“A pathbreaking book that explodes essentialist views of the construction of Hindu and Muslim identities in precolonial India. Divya Cherian provocatively argues that the category of ‘Hindu’ was the primary locus for a system of radical othering that excluded Untouchables (and Muslims as Untouchables) through mechanisms of state, law, and everyday life.” — CHRISTIAN LEE NOVETZKE, Professor of South Asian and Religious Studies, University of Washingto
Merchants of Virtue
No full textMerchants of Virtue explores the question of what it meant to be Hindu in precolonial South Asia. Divya Cherian presents a fine-grained study of everyday life and local politics in the kingdom of Marwar in eighteenth-century western India to uncover how merchants enforced their caste ideals of vegetarianism and bodily austerity as universal markers of Hindu identity. Using legal strategies and alliances with elites, these merchants successfully remade the category of “Hindu,” setting it in contrast to “Untouchable” in a process that reconfigured Hinduism in caste terms. In a history pertinent to understanding India today, Cherian establishes the centrality of caste to the early-modern Hindu self and to its imagination of inadmissible others.
“A refreshingly different perspective on the history of caste and untouchability in India, enlarging the field of scholarship from its focus on the colonial era by telling us how precolonial configurations of power in the locality shaped the everyday experience of caste.” — GOPAL GURU, coauthor of The Cracked Mirror and Experience, Caste, and the Everyday Social
“This provocative and empirically rich study offers a plenitude of fascinating insights into aspects of western Indian history ca. 1800, from kingship and caste hierarchy to abortion and alcohol consumption. Particularly innovative is its focus on the critical role played by merchants in articulating social identities that became widespread in modern times.” — CYNTHIA TALBOT, author of The Last Hindu Emperor
“A pathbreaking book that explodes essentialist views of the construction of Hindu and Muslim identities in precolonial India. Divya Cherian provocatively argues that the category of ‘Hindu’ was the primary locus for a system of radical othering that excluded Untouchables (and Muslims as Untouchables) through mechanisms of state, law, and everyday life.” — CHRISTIAN LEE NOVETZKE, Professor of South Asian and Religious Studies, University of Washingto
Improved collision detection in StarLogo Nova
No full textThesis: M. Eng., Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Science, 2015.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Cataloged from student-submitted PDF version of thesis.Includes bibliographical references (page 65).StarLogo Nova is blocks-based educational software that allows students to write and play their own 3D games online. It is the online version of StarLogo TNG. This thesis explores the problem of needing more accurate collision detection in StarLogo Nova while maintaining reasonable performance. Three new collision detection systems for StarLogo Nova are developed and evaluated. Compared to the spheres used to perform collision checks in the current system, the first new system, called the TightestFitCollider, introduces a variety of bounding spheres, bounding boxes, and bounding capsules as bounding structures that may fit the models in StarLogo Nova more closely. The second system, called the HierarchicalCollider, uses hierarchies of bounding boxes to perform even more precise collision detection than the TightestFitCollider. Finally, the third system combines the first two systems, so that the advantages of each can be used as appropriate. The three systems are evaluated for their accuracy and performance within the StarLogo Nova framework.by Divya Bajekal.M. Eng
Antiepileptic drugs for the primary and secondary prevention of seizures after subarachnoid haemorrhage
No full textBackground: subarachnoid haemorrhage may result in seizures both acutely and in the longer term. The use of antiepileptic drugs (AEDs) in the primary and secondary prevention of seizures after subarachnoid haemorrhage is uncertain, and there is currently no consensus on treatment.Objectives: to assess the effects of AEDs for the primary and secondary prevention of seizures after subarachnoid haemorrhage.Search methods: we searched the Cochrane Epilepsy Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 1) in The Cochrane Library, and MEDLINE (1946 to 12th March 2013). We checked the reference lists of articles retrieved from these searches.Selection criteria: we considered all randomised and quasi-randomised controlled trials in which patients were assigned to a treatment (one or more AEDs) or placebo.Data collection and analysis: two review authors (RM and JK) independently screened and assessed the methodological quality of the studies. If studies were included, one author extracted the data and the other checked it.Main results: no relevant studies were found.Authors' conclusions: there was no evidence to support or refute the use of antiepileptic drugs for the primary or secondary prevention of seizures related to subarachnoid haemorrhage. Well-designed randomised controlled trials are urgently needed to guide clinical practice
Magnetic resonance imaging of the cerebral metabolic rate of oxygen (CMRO₂)
No full textThesis (Ph. D.)--Harvard-MIT Division of Health Sciences and Technology, 2010.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Cataloged from student submitted PDF version of thesis.Includes bibliographical references (p. 120-128).Oxygen consumption is an essential process of the functioning brain. The rate at which the brain consumes oxygen is known as the cerebral metabolic rate of oxygen (CMRO₂). CMRO₂ is intimately related to brain health and function, and will change in settings of disease and functional activation. Accurate CMRO₂ measurement will enable detailed investigation of neuropathology and facilitate our understanding of the brain's underlying functional architecture. Despite the importance of CMRO₂ in both clinical and basic neuroscience settings, a robust CMRO₂ mapping technique amenable to functional and clinical MRI has not been established. To address this issue, a novel method called QUantitative Imaging of eXtraction of Oxygen and TIssue Consumption, or QUIXOTIC, is introduced. The key innovation in QUIXOTIC is the use of velocity-selective spin labeling to isolate MR signal exclusively from post-capillary venular blood on a voxel-by-voxel basis. This isolated signal can be related to venular oxygen saturation, oxygen extraction fraction, and ultimately CMRO₂. This thesis first explores fundamental theory behind the QUIXOTIC technique, including design of a novel MRI pulse sequence, explanation of the principal sequence parameters, and results from initial human experiences. A human trial follows, in which QUIXOTIC is used to measure cortical gray matter CMRO₂ in ten healthy volunteers.(cont.) QUIXOTIC-measured CMRO₂ is found to be within the expected physiological range and is comparable to values reported by other techniques. QUIXOTIC is then applied to evaluate CMRO₂ response to carbon-dioxide-induced hypercapnia in awake humans. In this study, CMRO₂ is observed to decrease in response to mild hypercapnia. Finally, pilot studies that show feasibility of QUIXOTIC-based functional MRI (fMRI) and so-called "turbo" QUIXOTIC are presented and discussed.by Divya Sanam Bolar.Ph.D
European Narratives on Remote Working and Coworking During the COVID-19 Pandemic
No full textThis open access book offers a multidisciplinary and comprehensive perspective regarding the immediate and long-term effects of the Covid-19 pandemic on coworking spaces in the European Region. The current pandemic has imposed several effects on work and spaces for work. Some are immediate effects and will last for a short time (such as the closing down of the space), some will last longer (namely, the reorganisation of the space to meet the physical distancing), and some will stay for a long time (remote working and hybrid working). Although the literature on coworking spaces and the effects of the pandemic is growing fast, empirical studies are yet limited. Within this context, this book seeks a twofold aim: (i) to contribute to the fast-growing literature on coworking space and their effects at different scales; (ii) to present a multidisciplinary perspective about the effects of the yet-lasting Corona-pandemic effects on the patterns of remote working and consequently on coworking spaces, as the most diffused form of new working spaces.History, Form & Aesthetic
Clinical trend discovery and analysis of Taiwanese health insurance claims data
No full textThesis: M. Eng., Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Science, 2016.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Cataloged from student-submitted PDF version of thesis.Includes bibliographical references (pages 61-62).Data-driven analysis can improve our understanding of medicine, and data from electronic health records and labs has been used successfully in predictive tasks. Less advanced analysis has been done on health insurance claims data, which can be rich and more structured but large in scale. Taiwan has had nationalized health insurance for twenty years; its National Health Research Institute Database (NHIRD) contains records of insurance claims, including medications, prescriptions, and treatment costs for both inpatient and outpatient visits, spanning sixteen years and a million patients. The NHIRD enables longitudinal studies of a patient's medical progression as well as aggregation and generalization to population-level insights. We conducted preliminary exploration of data trends in aggregate, such as diagnosis code frequency and average treatment cost over time. An infrastructure to perform large-scale queries and handle results was required to effectively use the NHIRD for research applications. After indexing database tables to improve query performance, we created a pipeline in Python to connect to and query the database, analyze data for hypothesis discovery and hypothesis testing, convert Taiwanese codes to international standards, and produce plots and graphs. This pipeline was used to examine drug side effects and comorbidities observed across a population, accounting for demographic variables. We also studied patient-specific longitudinal matrices of medical events, which were highly sparse. We attempted quantitative imputation methods to densify these matrices, but because the data was binary (indicating the presence of an event at a given time), categorical, and irregular, advanced imputation offered limited benefit. Nevertheless, we discovered interesting patterns in cohorts of diabetes patients treated with various classes of drugs. This information can be exploited in computational phenotyping and other learning methods, and combined with other data sources it could increase accuracy of clinical predictive tasks.by Divya P. Pillai.M. Eng
ASSESSMENT OF COMPLEX SKILLS IN COLLABORATIVE, ILL-STRUCTURED GAMES
No full textThis work is embargoed by the author and will not be publicly available until December 2025.Games offer a promising avenue for assessing authentic and complex learning that is increasingly sought in higher education. Collaborative, ill-structured games that simulate real-world problems are not compatible with traditional psychometric measurement approaches. There is no established framework for assessing collaborative, ill-structured games. In fact, assessment practice of games- and simulation-based learning more broadly is nascent. In spite of daunting challenges for valid and meaningful assessment of such activities, professional military education (PME) is rapidly expanding collaborative, ill-structured gaming in response to senior-level directives. PME’s concrete manifestation of the broader theoretical and methodological challenges of games-based assessment seen in higher education presents a unique opportunity to develop an assessment framework that can inform practice. Using an evidence-centered design (ECD) approach, this dissertation presents three studies which develop a validity argument, propose the Comprehensive Learning Assessment for Wargames (CLAW) framework, and then examine the relevance of, and evidentiary expectations for, that framework for assessing collaborative, ill-structured wargames in praxis. In toto, the CLAW provides a baseline for game designers to clearly specify their assessment claim(s) and identify the key evidence that they should consider to substantiate the interpretation and use of assessment evidence for their desired purpose(s). Although situated within PME, the framework has broader relevance as a model for assessment of collaborative, ill-structured games in other disciplines that are confronting similar challenges.2025-12-1
- …
