Qatar Foundation Annual Research Forum Volume 2011 Issue 1

From Orality to Image: Traditional Qatari Narratives and the Visual Media is a UREP project whose aim is to preserve and re-present traditional Qatari culture by adapting cross-generational oral narratives into text and graphic form. We are using traditional Qatari oral folk tales as the basis of a series of graphic stories. These graphic stories will be collected in an anthology targeted at all readers who are interested in Qatari culture in general, and young adult readers in particular. We believe that these stories, which are both informative and engaging, could be of valuable use in the classroom and beyond to educate young readers about traditional Qatari culture and lore, to promote literacy, and to instil an appreciation for reading and the visual arts.

The main aims are: To increase awareness of Qatari history, tradition and culture among the general reading public and particularly among young adults in Qatar and beyond; To increase reading among young adults who may be resistant to books and other materials that do not support their specific learning styles and/ or relate to their socio-cultural context; To provide opportunities for general and young adult readers to explore a text-based graphic medium to stimulate interest in reading, the visual arts, and Qatari culture; and To encourage bilingual literacy in Arabic and English by presenting versions of the graphic stories in both languages.

Overall, we regard our project as a way to help realize important national objectives and, moreover, that furthering these initiatives will in turn play a critical role in the development of a robust knowledge-based society in Qatar enriched by the contribution of the arts and humanities. The development of science and technology plays an important role in the growth of any modern society, including Qatar, but for a knowledge society to truly thrive, it must also develop artistic and humanistic values, including creativity, innovation, literacy, preservation of heritage and the fostering of cross-cultural dialogue and understanding.

The aim of this research is to identify some of the possible factors that lead to the uprising of the different Arab states, ultimately leading to what we know better as the “Arab Spring”. To be more precise, we shall see if the people were justified to revolt through their cause, and, if it was rightful, than we would witness the difference between a revolt and the right to revolt; the latter is based on anarchy whereas the former rests on a sense of duty. In order to do that, we shall embed ourselves in canonical western philosophy, as well as history, and apply the “philosophical triggers” on a case-by-case study of handpicked countries. Those countries will be Syria, Libya, Egypt, Tunisia, and Qatar. Furthermore, we shall isolate the various points of views extracted from contemporary authors and articles to see if a match can be established with the philosophers and their theories; used as our foundation of this research. The various theories accumulated from the contemporary authors will then be our dichotomy-meter, measuring to what scale the philosophical suggestions hold any truths as reason to these revolutionary uprising (economical, political, principle, rights, ethics…) When a match has been made we will try to understand why some countries were subject to these uprising and other countries in the region weren't. Our final step would be to foreshadow, in the best of our abilities and based on the research at hand, what the future might hold for these countries, which suffered a revolution. These “Blossoms of Revolution” would then reveal the fruits of their tumult, and they would help us in our last task. Finally, if the Holy Qu'ran, the Mandate of Heaven, and the Magna Carta count amongst their words those of a rightful uprising against oppressive rulers then, the Revolution would become a right, a safe-guard that transcends space and time, a tool passed down to use when the time for the generation in question has come, to restore balance between governed and governor.

Background: Harvard University Graduate School of Design has signed an agreement to lead a research project entitled Gulf Encyclopedia for Sustainable Urbanism (GESU). This holistic, multi-year, cross-disciplinary, cross-border study focusing on sustainable urbanism in the Gulf Region is sponsored by MSHEIREB, a subsidiary of Qatar Foundation, Qatar. The methodology will be based on a rigorous understanding of the past, present and future development trajectories in the region as well as on the most current knowledge of sustainability.

Objectives: Through a socio-cultural perspective, this research looks at the tribal migration patterns to and from Qatar and its affect on the concept of “fireeq”. The traditional culture of Qatar was largely based on this concept. It provided the social and physical fabric that bound the Qatari culture together. The research objective is to question and elucidate whether the concept of “fireeq” can be a culturally sustainable urban design model in contemporary times in Qatar.

Methods: Through a research survey of recorded oral histories and written historical accounts, an analysis will be made to determine the relevance of this concept in future residential and neighborhood planning studies for Qatar. This is part of a growing body of multi-disciplinary research to support and inform the goals of the Gulf Encyclopedia for Sustainable Urbanism.

Conclusions: Tribes first established their “fireeq” settlements in Qatar upon their physical attainment of land. In a socio-cultural context, the “fireeqs” were built and expanded as a means of survival; against the constant raids of other tribes; and as a manifestation of the tribal and family unity in a predominantly Muslim society. However, with the vast increase of migration of new families with varying value systems to Qatar in the 20th century and the ensuing life style changes came the act of co-modification of land. With the co-modification of land and transformations of socio-cultural customs and values, the actual applicability of the concept of the “fireeq” slowly began to fade. However, will some aspects of the “fireeq” concept evolve to be vitally effective and culturally important in the future well being and social patterns of Qatari communities' remains to be determined?

This thesis examines Qatar's mediation efforts in the Lebanese crisis of 2008 and how it succeeded in resolving the conflict. It explores the possibility of the emergence of a cross-cultural mediation model that may have relevant application to other Muslim countries. The study was informed by the wealth of Western and Islamic approaches to diplomacy. Qatar's mediation in the Lebanese conflict of 2008 demonstrated the use of tactics from both traditions.

The research found that both Islamic and western mediation models are compatible in important respects. The study suggests that building on the strengths of each approach leads to successful outcomes.

Qatar's mediation efforts in the Lebanese conflict employed largely western approaches in combination with Islamic principles and values. The experience has been identified as a new cross-cultural mediation model thvat may have a wider application in the region.

Epithelial Ovarian Carcinoma (EOC) is the sixth most common malignancy in women and the leading cause of death of gynecological cancer in the world. EOC has a predisposition to metastasis to the peritoneal cavity. A late stage peritoneal dissemination results in ascites and high mortality rates with an overall survival of 20 to 30 percent at 5 years after surgery.

While many studies in the literature address the issue of distant metastasis, the biology of peritoneal tumor spread in advanced ovarian cancer is not clear. Development of peritoneal carcinomatosis involves well-defined critical steps, including cell shedding and transport, interaction and adhesion to the mesothelial layer, and colonization of and proliferation into the sub-mesothelial microenvironment. It is now appreciated that there must be an initiation of a pre-metastatic niche within the target organ, one that facilitates the survival of tumor cells in a non-receptive organ. We think that a dual approach looking at oncogenomics and heterocellular interaction will allow us to better understand ovarian cancer metastasis biology and help design new therapeutic strategies. Oncogenomic approaches restricted to a given methodology may hinder mechanisms driving progression. We used a comprehensive approach utilizing integrated systems biology platforms to assess the genetic and genomic modifications within a tumor compared to the metastatic lesions. Using this approach we were able to demonstrate the implication of many pathways, in particular the Jak/Stat pathways in the occurrence of metastatic lesions. Moreover we were able to identify NOTCH3 as an amplified locus in primary and metastatic lesions and were able to demonstrate using a cell biology approach the role of the Notch pathway in chemo-resistance.

We will present evidence demonstrating our ability to integrate our oncogenomic approaches with our cell biology findings. Using a comprehensive multidisciplinary approach allowed us to identify some pathways implicated in the development of metastatic lesion in ovarian carcinomas. This will enable us to create new therapeutic strategies aiming at disrupting the interaction between the cancer cells and a permissive environment.

Obesity is a global epidemic and has been implicated as a risk factor for end-stage renal disease. In this study, we investigated the impact of obesity in the absence of hypertension, on renal lipid accumulation, oxidative stress, mitochondrial function, and endoplasmic reticulum (ER) stress, which could play a major role in the development of obesity-induced renal dysfunction. We compared two genetic mouse models of obesity which we have shown to be normotensive, the leptin-deficient ob/ob mice and a hyperleptinemic melanocortin 4 receptor knockout mice (LoxTB MC4R-/-), to lean wild type (WT) C57BL/6J mice and littermate controls (WT-LoxTB) from LoxTB MC4R-/-breeding colony respectively. We measured urinary albumin excretion, creatinine clearance, renal triglycerides, ATP levels, state-3 mitochondrial respiration, protein carbonylation (a marker of oxidative stress) and C/EBP homologous protein (CHOP) expression (a marker of ER stress) in these mice. Our results indicate that the ob/ob mice and LoxTB MC4R-/-mice exhibit significant albuminuria, increased creatinine clearance (693±61.1 vs. 534±31.5 and 752.3±50.6 vs. 488.9±81.2 μL/min) and renal triglyceride accumulation (8.1±0.8 vs. 4.8±0.2 and 3.9±0.5 vs. 2.2±0.3 mg triglyceride/g tissue) expressed as ob/ob vs. WT and LoxTB MC4R-/- vs. WT-LoxTB respectively. Despite significant decreases in renal ATP levels (6±0.3 vs. 7.9±0.4 and 5±0.2 vs. 8±1.1 pmol/mg) in both obese models, only the LoxTB MC4R-/-mice kidneys showed an impaired state-3 fatty acid oxidation, increased protein carbonylation and 3-fold induction of CHOP protein compared to WT-LoxTB control mice. Taken together, our data suggest that obesity in the absence of hypertension cause only mild renal dysfunction, and unveils the potential involvement of oxidative stress, impaired fatty acid oxidation and ER stress in obesity-induced renal injury associated with MC4R deficiency.

Imatinib is currently the standard drug used in the treatment of CML patients. However, imatinib is not curative since most patients who discontinue therapy will relapse. Interferon alpha (IFN) induces hematologic and cytogenetic remissions and interestingly, prior exposure to IFN allowed Imatinib discontinuation in some CML patients. Arsenic trioxide inhibits the proliferation of BCR-ABL-expressing cells.

We have investigated the effects of the combination arsenic/IFN on the proliferation of CML cell lines. We found that IFN alone had minimal effect. Arsenic alone significantly decreased their proliferation in a time and dose-dependent manner. Interestingly, the addition of IFN to arsenic was synergistic in AR230 and additive in K562. This synergistic effect between IFN and arsenic was accompanied by dose-dependent apoptosis as evidenced by annexin V staining, TUNEL positivity and caspase activation. Colony-forming assay was performed on bone marrow and CD34+ cells collected from CML patients. Interestingly, arsenic and IFN produced a synergistic decrease in myeloid colony formation, especially when compared to Imatinib.

Preliminary results of an in vivo study using the retroviral transduction CML mouse model showed prolonged survival of secondary recipients that received cells from primary leukemic mice treated with arsenic/IFN, as compared to those that received cells from untreated controls. These results suggest that arsenic and IFN synergize to inhibit proliferation, induce apoptosis and target dormant CML stem cells that are spared by Imatinib.

In addition to physical conditioning, successful sporting performance requires a level of perception coupled with efficiency and accuracy in movement. The FIFA World Cup is usually played during the summer months; therefore the aim of this study was to investigate the effects of heat exposure on cognitive performance.

Three experiments were performed in an environmental chamber under hot (HOT: 50°C, 30% rH) and control (CON: 24°C, 30% rH) conditions. Exposure time ranged from 15 minutes to 4.5 hours. Subjects performed simple and complex cognitive tasks under different levels of thermal strain. Neuromuscular assessments were performed to assess neural drive and muscular force production. Central (Tcore) and skin (Tskin) temperatures were recorded along with subjective measures of thermal comfort (TC) and thermal sensation (TS).

Hyperthermia had no impact upon attention tasks, however, impulsivity increased during sustained attention over prolonged periods. Significant increases in Tcore (>38.30°C) were associated with impaired complex cognitive task performance. The regular application of cold packs to the head limited the detrimental effects of hyperthermia upon short-term memory. However, rapid and substantial variations in Tskin of ∼3°C, independent of changes in Tcore, had similar detrimental effects upon cognitive task performance.

Results suggest that reductions in complex cognitive performance with heat exposure occur via a decrement in motor cortical excitability when Tcore increases to ∼38.3°C, but they also originate from an additional cognitive load imposed by thermal strain and the resulting allesthesial Tskin variations; with both these factors acting as competing variables to the cognitive processes.

The increase in Tcore with prolonged heat exposure impairs cognitive performance; however applying cold packs to the head can preserve these. Increases in Tskin during brief heat exposures appear to be a sufficient physiological response to alter the emotional state of individuals and impair effective decision-making. Hydration protocols and reducing exercise intensity and load can reduce the physiological strain. Strategies to minimise the ‘thermal shock’ of entering a warm environment should be developed to minimise the impact of subjective feelings of thermal discomfort upon cognitive performance.

Background: Cisplatin (cis-diamminedichloroplatinum (II), CDDP) is a highly effective antitumor drug. However, tumors can acquire resistance to CDDP. CDDP elevates the intracellular calcium concentration ([Ca²⁺]i), in various cell lines, leading to the activation of apoptotic pathways and cell death. Using cultured breast cancer (MCF-7) cells we: (1) investigated the effects of CDDP on [Ca²⁺]i, (2) compared these results to a cell line that has been desensitized to CDDP (“resistant”), (3) investigated the source of [Ca²⁺]i by modulating calcium channels and transport mechanisms, and (4) correlated these findings to cytotoxicity. Methods: Changes in the [Ca2+]i were recorded using fluorescence microscopy and Ca2+-binding fluorescent dye, Fluo-4AM. CDDP (1nM-10μM) was administered via a bath perfusion system to the sensitive and CDDP-”resistant” MCF-7 cells over a period of 1.5–2.5h. The [Ca²⁺]i modulators, (caffeine; 10mM, nimodipine; 10μM, ionomycin; 10μM, thapsigargin; 500nM, and 2-APB; 50μM) were administered. MTT assays and trypan blue cell viability tests were performed using CDDP at concentrations of 100pM, 1nM, 10nM, 100nM, 1μM, 10μM, 100μM, 1mM, and 10mM after 4, 8, and 24h of incubation. Results: CDDP induced a concentration-dependent increase of [Ca²⁺i. A concentration of CDDP 0.1μM triggered the largest elevation of [Ca²⁺]i with 120% increase (n=19). Induction of cytotoxicity was most likely directly correlated to the increase of [Ca²⁺]i, and was significantly lower in CDDP-”resistant” cells (P←0.05). Preapplication of the calcium channel blocker, nimodipine as well as the IP3 receptor blocker 2-APB significantly reduced this elevation (46.6%; n=26, 71.4%; n=52, increase, respectively) (p←0.05). Surprisingly, when [Ca²⁺]i was elevated due to the pre-application of caffeine, ionomycin or thapsigargin, the subsequent application of CDDP was also significantly reduced compared to control conditions (37.8%; n=15, 34.9%; n=32, 53.7%; n=21, increase, respectively) (p←0.05). Conclusion: CDDP concentration-dependently elevates [Ca²⁺]i by Ca²⁺ entry and Ca²⁺ release from the stores. These mechanisms, however, seem to be less effective in CDDP-”resistant” cells since they show increased restriction on Ca2+ elevation. The pre-elevation of [Ca²⁺]i, through releasing Ca²⁺ from the stores, reduces this elevation significantly. The exact mechanisms remain unclear and further investigations are required to determine the mechanisms and pathways that are involved in the disruption of [Ca²⁺]i.

Introduction: The application of therapeutic proteins and cytokines like Interleukin-2 (IL-2) for long-term, localized delivery has been hindered by a lack of a delivery device that releases active protein at a concentration within their therapeutic window. The purpose of this oral presentation is to report on the osmotic-driven, controlled-release from novel visible-light photocrosslinked biodegradable elastomeric devices recently designed in an attempt to overcome this limitation.

Materials and Methods: All chemicals were purchased from Sigma-Aldrich and used as received. Novel biodegradable and biocompatible poly (decaneco- tricarballylate) [PDET] elastomers were synthesized by polycondensation reaction between tricarballylic acid and alkylene diols, followed by acrylation and photo-curing. IL-2 loaded micro-cylinder and disk-shaped elastomeric devices were prepared by intimately mixing IL-2 lyophilized powder with the acrylated prepolymer prior to photocrosslinking. IL-2 release was analysed using IL-2 ELISA system and the in vitro bioactivity of released IL-2 was assessed using C57BL/6 mouse cytotoxic T lymphocyte. The influence of various parameters such as the elastomer crosslinking density, the volumetric drug loading percentage and the incorporation of osmotic excipients like trehalose on the release kinetics of the drug was also examined.

Results and discussion: The disk-shaped specimens showed faster IL-2 release profiles than microcylinders, with drug release proceeding via typical zero-order release kinetics. The increase in the device's surface area and the incorporation of trehalose in the loaded lyophilized mix increased the IL-2 release rate. As well, it was shown that the decrease in the degree of prepolymer acrylation of the prepared devices increased the IL-2 release rate. Cell based bioactivity assays showed that IL-2 released over a period of 28 days, retained more than 94% of its initial activity. These bioactivity results represent a highly significant improvement over the other previously published data provided with a quantitative analysis of the actual percentage of bioactive IL-2 released during the period of the release study.

Conclusion: The novel PDET elastomeric drug delivery systems demonstrated to be promising as protein drug delivery vehicles for localized and sustained IL-2 immunotherapy.

Acknowledgements: Work is supported by QNRF through the NPRP grant # 09-969-3-251 awarded to HM Younes.