Novel mechanisms regulating inflammatory gene expression in adipocytes

Obesity and diabetes are major public health concerns worldwide that contribute to cardiovascular disease, hypertension, and stroke. Research over the last two decades has revealed an important role for adipose tissue (AT) in the regulation and control of whole-body metabolic homeostasis and that chronic AT inflammation is an important pathogenic mechanism that links obesity and diabetes. While it is now recognized that inflammation is increased in AT with obesity, studies are underway to identify key inflammatory mediators and their downstream pathways that contribute to adipocyte inflammation. Therefore, data presented in this dissertation demonstrate that three novel mechanisms that may mediate obesity-induced inflammation in adipocytes. Interleukin (IL)-12 family cytokines are heterodimeric proteins mostly expressed in classic immune cells and play critical roles in innate and adaptive immunity. However, recent evidence has shown that plasma levels of IL-12 family cytokines are elevated in obesity and diabetes, yet little has addressed a role for IL-12 family cytokines in adipocytes under any condition. Data presented in this dissertation demonstrate that various IL-12 family members are highly induced in AT under conditions of genetic and diet-induced obesity that is associated with increased inflammation and IR. Subsequently, we show that both preadipocytes (PAs) and adipocytes (ADs) secrete IL-27 in response to inflammatory stress and demonstrate a novel function of IL-27 in adipocytes that is dependent on environmental cues. While PAs and ADs both secrete IL-27 protein, divergent mRNA regulation of the IL-27 subunits (i.e., p28 and EBI3) was observed in response to tumor necrosis factor a (TNFa) in adipocytes. As our data indicated a role for epigenetic modifications in differential IL-27 mRNA expression, we further determined that histone deacetylases (HDACs) play a key role in TNFa-induced p28 gene expression. Thus, these data demonstrate that epigenetic modification of histones potentially regulates the divergent outcomes observed with p28 and EBI3 gene expression during inflammatory stress. While extensive studies have identified TNFa as a master cytokine involved in AT inflammation, questions regarding its inflammatory actions on gene expression remain unclear. Emerging evidence highlights an important role for the Golgi apparatus (GA) in TNFa-induced inflammation, in part, through TNF receptor (TNFR) storage and secretion to the cell-surface, thus allowing for TNFa signaling. Our findings demonstrate a critical role for the GA in TNFR cell-surface expression and TNFa signaling as well as suggest a novel mechanism for the GA in TNFa-induced inflammation that potentially involves Golgi-localized co-factor(s) necessary for transcriptional gene expression. Collectively, data presented in this dissertation provide seminal evidence for novel mechanisms regulating adipocyte inflammation, potentially linking obesity with metabolic diseases

Sculpture as systematic growth

The foundation of my work is built upon the idea that everything is comprised of constituent components in which all of the components serve a function in the creation of the integrated whole. This way of thinking is consistent with the principles of systems, however large or small, complex or simple. Every system has parameters that define and frame the behavior of its set of interacting and interdependent components. What I am interested in is not necessarily the final output of the system, but rather, the process in which the components interact within the parameters of the system and how the relationships of these interactions affect the outcome

User-centric secure cross-site interaction framework for online social networking services

Social networking service is one of major technological phenomena on Web 2.0. Hun- dreds of millions of users are posting message, photos, and videos on their profiles and interacting with other users, but the sharing and interaction are limited within the same social networking site. Although users can share some content on a social networking site with people outside of the social networking sites using a public references to their content, appropriate access control mechanisms are not supported. In this dissertation, we outline a cross-site interaction framework and identity mapping approaches that enable social net- work users to share their content across social networking sites. We propose a cross-site interaction framework x-mngr, allowing users to interact with others on other social net- working sites, with a cross-site access control policy. We also propose identity-mapping approaches that map user’s identities across social networking sites. The partial mapping approach based on a supervised learning mechanism which provides user’s identity map- ping based on a training set composed of a small subset of the profile mappings. We provide mechanisms to enable users to fuse identity-mapping decisions that are provided by their friends or others on the social network. Furthermore, we propose a Game With A Purpose (GWAP) approach that provides identity-mappings using a social network game. The proposed framework and game are implemented on real social networking sites such as Facebook and MySpace. The experiments are performed to evaluate the feasibility of our approaches. A user study is also performed and the result is included as part of our evaluation efforts for the proposed framework

The Heat is On: Exploring User Behaviour in a Multisensory Virtual Environment for Fire Evacuation

Understanding validity of user behaviour in Virtual Environments (VEs) is critical as they are increasingly being used for serious Health and Safety applications such as predicting human behaviour and training in hazardous situations. This paper presents a comparative study exploring user behaviour in VE-based fire evacuation and investigates whether this is affected by the addition of thermal and olfactory simulation. Participants (N=43) were exposed to a virtual fire in an office building. Quantitative and qualitative analyses of participant attitudes and behaviours found deviations from those we would expect in real life (e.g. pre-evacuation actions), but also valid behaviours like fire avoidance. Potentially important differences were found between multisensory and audiovisual-only conditions (e.g. perceived urgency). We conclude VEs have significant potential in safety-related applications, and that multimodality may afford additional uses in this context, but the identified limitations of behavioural validity must be carefully considered to avoid misapplication of the technology.Comment: CHI Conference on Human Factors in Computing System

Feasibility of Tomotherapy-Based Image-Guided Radiotherapy for Locally Advanced Oropharyngeal Cancer

PURPOSE: The study aims to assess the feasibility of tomotherapy-based image-guided (IGRT) radiotherapy for locally advanced oropharyngeal cancer. A retrospective review of 33 patients undergoing concurrent chemoradiation for locally advanced oropharyngeal cancers was conducted. Radiotherapy planning, treatment toxicity and loco-regional control were assessed. RESULTS: At a median follow-up of 32 months (6-47 months), no patient developed loco-regional recurrence. Two patients (6%) developed distant metastases. Grade 3-4 acute toxicity was respectively 72% and 25% for mucositis and gastrointestinal toxicity. Two patients (6%) had long-term dependence on tube feedings. Dose-volume histogram demonstrated excellent target volume coverage and low radiation dose to the organs at risk for complications. CONCLUSIONS AND CLINICAL RELEVANCE: IGRT provides excellent loco-regional control but acute toxicity remains significant and needs to be addressed in future prospective trials. The feasibility of Tomotherapy to decrease radiation dose to the normal tissues merits further investigations

Feasibility of image-guided radiotherapy based on helical tomotherapy to reduce contralateral parotid dose in head and neck cancer

Background To evaluate the feasibility of image-guided radiotherapy based on helical Tomotherapy to spare the contralateral parotid gland in head and neck cancer patients with unilateral or no neck node metastases. Methods A retrospective review of 52 patients undergoing radiotherapy for head and neck cancers with image guidance based on daily megavoltage CT imaging with helical tomotherapy was performed. Results Mean contralateral parotid dose and the volume of the contralateral parotid receiving 40 Gy or more were compared between radiotherapy plans with significant constraint (SC) of less than 20 Gy on parotid dose (23 patients) and the conventional constraint (CC) of 26 Gy (29 patients). All patients had PTV coverage of at least 95% to the contralateral elective neck nodes. Mean contralateral parotid dose was, respectively, 14.1 Gy and 24.7 Gy for the SC and CC plans (p < 0.0001). The volume of contralateral parotid receiving 40 Gy or more was respectively 5.3% and 18.2% (p < 0.0001) Conclusion Tomotherapy for head and neck cancer minimized radiotherapy dose to the contralateral parotid gland in patients undergoing elective node irradiation without sacrificing target coverage

Biophysical and electrochemical studies of protein-nucleic acid interactions

This review is devoted to biophysical and electrochemical methods used for studying protein-nucleic acid (NA) interactions. The importance of NA structure and protein-NA recognition for essential cellular processes, such as replication or transcription, is discussed to provide background for description of a range of biophysical chemistry methods that are applied to study a wide scope of protein-DNA and protein-RNA complexes. These techniques employ different detection principles with specific advantages and limitations and are often combined as mutually complementary approaches to provide a complete description of the interactions. Electrochemical methods have proven to be of great utility in such studies because they provide sensitive measurements and can be combined with other approaches that facilitate the protein-NA interactions. Recent applications of electrochemical methods in studies of protein-NA interactions are discussed in detail

Infant growth disparity in the Khanh Hoa province in Vietnam: a follow-up study

<p>Abstract</p> <p>Background</p> <p>Surveys in Vietnam have indicated that wasting and stunting have been prevalent among children, but the country is undergoing rapid socio-economic changes and little has been known about the relative situation in the different areas of the country. In 2006, the WHO introduced new growth standards applicable to all infant and child populations, which facilitates for improved assessments of the prevalence of growth impairment, independent of time, place and ethnicity. The aim of our study was to assess the growth of singleton infants delivered at term in three main birth clinics in the Khanh Hoa province in Vietnam by using the new WHO standards as reference, and the association between growth and some maternal, birth and health factors.</p> <p>Methods</p> <p>A cohort of 237 singleton infants born in the period May-July 2005 in three main delivery clinics in the Khanh Hoa province were observed prospectively. Their anthropometrical measures a year later were compared to the WHO sex-specific growth standards for weight-for-age, length-for-age, weight-for-length, and BMI-for-age. These measures were analysed as dependent outcomes using multiple linear regression models including the following independent factors: urban vs. rural birth, 1-minute Apgar score, weight and length at birth, duration of lactation, ever had diarrhoea, dengue fever, pneumonia or dysentery, and maternal age, height, gestational duration and parity.</p> <p>Results</p> <p>Compared to the standard distributions, 79% were below the median for weight-for-length; 18.0% were within the 5^thpercentile for length-for-age, 9.6% for weight-for-age, 20.3% for weight-for-length, and 19.8% for BMI. A lower length- and weight-for-age were statistically associated with being born rurally.</p> <p>Conclusions</p> <p>In this delivery-clinic based sample of children in the Khanh Hoa province in Vietnam, the proportions within the WHO-standard 5^thpercentiles for length-for-age, weight-for-length and BMI in late infancy were 3-4 times higher than expected, which indicate that deficient growth is prevalent. The infants born in a rural area had a lower weight- and length-for-age than their urban counterparts, independent of diarrhoea.</p