Thyroid hormone metabolism in the hematopoietic system

Thesis (M.A.)--Boston UniversityThyroid hormones are iodinated compounds that are critical to differentiation, apoptosis, and cellular processes in virtually every vertebrate cell. The thyroid gland produces mostly thyroxine (T4) and also 3',3,5-triiodothyronine (T3). T4 acts as a "prehormone" and is converted in the periphery into the more physiologically active T3 via deiodination. Deiodination is also the process by which thyroid hormones are inactivated and thyroid hormone balance is maintained. Types 1 (Dl) and 2 (D2) deiodinase activate T4 into T3. Conversely, inactivation is accomplished by type 3 iodothyronine deiodinase (D3), which is the primary inactivator of both T4 and T3. D3 is highly expressed in fetal tissues and is re-expressed in adult tissues during pathophysiological states. This reactivated D3 leads to local inactivation of thyroid hormones, which is maladaptive in certain situations but may be adaptive in others. We hypothesize that D3 deficiency in hematopoietic cells will affect blood cell function and/or production during inflammatory stress, infection, and anemia. Methods: Human blood cell lines were stimulated with a tumor promoter and ionophore and assayed for deiodinase activity. Conditional knockout mice with blood-cell-specific D3 def1ciency were generated. Their complete blood counts and thyroid function tests were studied to determine the correlation between D3 and the hematopoietic system in both the well state and eventually stress states. Results: Dl, D2 and D3 were not stimulated by stressors in vitro. D3 was successfully knocked out of the hematopoietic system in mice. Blood-cell-specific D3 deficient mice had blood cell counts that were not significantly different from that of mice with a functional enzyme in the normal state (baseline). Mice of both genotypes were euthyroid in the normal state. Conclusion: D3 deficiency in the hematopoietic system was not sufficient to induce pancytopenia or thyroid hormone derangement in the normal state. Future studies will investigate the possible role of D1 and/or D2 in compensating for D3 deficiency. The development of a conditional D3 knockout in blood will provide a useful tool for studying the effect of D3 on blood function and/or development in inflammation, infection, and anemia in future studies

Design and Performance Analysis of a Non-Standard EPICS Fast Controller

The large scientific projects present new technological challenges, such as the distributed control over a communication network. In particular, the middleware EPICS is the most extended communication standard in particle accelerators. The integration of modern control architectures in these EPICS networks is becoming common, as for example for the PXI/PXIe and xTCA hardware alternatives. In this work, a different integration procedure for PXIe real time controllers from National Instruments is proposed, using LabVIEW as the design tool. This methodology is considered and its performance is analyzed by means of a set of laboratory experiments. This control architecture is proposed for achieving the implementation requirements of the fast controllers, which need an important amount of computational power and signal processing capability, with a tight real-time demand. The present work studies the advantages and drawbacks of this methodology and presents its comprehensive evaluation by means of a laboratory test bench, designed for the application of systematic tests. These tests compare the proposed fast controller performance with a similar system implemented using an standard EPICS IOC provided by the CODAC system.Comment: This is the extended version of the Conference Record presented in the IEEE Real-Time Conference 2014, Nara, Japan. This paper has been submitted to the IEEE Transactions on Nuclear Scienc

Ghosts of the past: The competing agendas of forensic work in identifying the missing across Bosnia and Herzegovina

International interventions in Bosnia and Herzegovina, that ultimately brought the war to a standstill, emphasised recovering and identifying the missing as chief among the goals of post-war repair and reconstruction, aiming to unite a heavily divided country. Still, local actors keep showing that unity is far from achieved and it is not a goal for all those involved. This paper examines the various actors that have taken up the task of locating and identifying the missing in order to examine their incentives as well as any competing agendas for participating in the process. These efforts cannot be understood without examining their impact both at the time and now, and we look at the biopolitics of the process and utilisation of the dead within. Due to the vastness and complexity of this process, instead of a conclusion, additional questions will be opened required for the process to keep moving forward