Mathematical modeling and simulation of thyroid homeostasis: Implications for the Allan-Herndon-Dudley syndrome

Introduction: A mathematical model of the pituitary-thyroid feedback loop is extended to deepen the understanding of the Allan-Herndon-Dudley syndrome (AHDS). The AHDS is characterized by unusual thyroid hormone concentrations and a mutation in the SLC16A2 gene encoding for the monocarboxylate transporter 8 (MCT8). This mutation leads to a loss of thyroid hormone transport activity. One hypothesis to explain the unusual hormone concentrations of AHDS patients is that due to the loss of thyroid hormone transport activity, thyroxine (T4) is partially retained in thyroid cells. Methods: This hypothesis is investigated by extending a mathematical model of the pituitary-thyroid feedback loop to include a model of the net effects of membrane transporters such that the thyroid hormone transport activity can be considered. A nonlinear modeling approach based on the Michaelis-Menten kinetics and its linear approximation are employed to consider the membrane transporters. The unknown parameters are estimated through a constrained parameter optimization. Results: In dynamic simulations, damaged membrane transporters result in a retention of T4 in thyroid cells and ultimately in the unusual hormone concentrations of AHDS patients. The Michaelis-Menten modeling approach and its linear approximation lead to similar results. Discussion: The results support the hypothesis that a partial retention of T4 in thyroid cells represents one mechanism responsible for the unusual hormone concentrations of AHDS patients. Moreover, our results suggest that the retention of T4 in thyroid cells could be the main reason for the unusual hormone concentrations of AHDS patients

USE of Mine Pool Water for Power Plant Cooling.

Water and energy production issues intersect in numerous ways. Water is produced along with oil and gas, water runs off of or accumulates in coal mines, and water is needed to operate steam electric power plants and hydropower generating facilities. However, water and energy are often not in the proper balance. For example, even if water is available in sufficient quantities, it may not have the physical and chemical characteristics suitable for energy or other uses. This report provides preliminary information about an opportunity to reuse an overabundant water source--ground water accumulated in underground coal mines--for cooling and process water in electric generating facilities. The report was funded by the U.S. Department of Energy's (DOE's) National Energy Technology Laboratory (NETL), which has implemented a water/energy research program (Feeley and Ramezan 2003). Among the topics studied under that program is the availability and use of ''non-traditional sources'' of water for use at power plants. This report supports NETL's water/energy research program

Policing the community together: the impact of technology on citizen engagement

Despite broad and often varied underlying definitions, a common theme throughout community and neighbourhood policing strategies establishes the need to target improvements in the relationship and level of engagement between the police and the communities they serve. Community policing approaches have long underpinned a desire to move away from reactive policing models towards those which establish a more proactive philosophy, responsive to the wants and needs of the community. The near ubiquitous proliferation of smartphones and other ICTs (Information and Communication Technologies) means they are often seen as a vector through which initiatives of all kinds can instil a culture of proactive engagement with their respective stakeholder communities. This paper builds upon existing research which suggests that technologies for crime prevention should be designed to support communications and problem-solving rather than used simply as a means to disseminate information, unpacking a number of the core concepts that are considered central to participation and effective engagement; social capital, public participation and social and digital inclusion. Moreover, examples of wider initiatives are comparatively discussed, not just those associated with community policing, which target the engagement of communities through the use of technology, and more specifically mobile applications, before reflecting on the empirical evidence and experiences gleaned through the EU H2020 funded ‘UNITY’ project, a project that sought to establish effective strategies for engagement between police and citizen communities

Preliminary technical and legal evaluation of disposing of nonhazardous oil field waste into salt caverns

Caverns can be readily formed in salt formations through solution mining. The caverns may be formed incidentally, as a result of salt recovery, or intentionally to create an underground chamber that can be used for storing hydrocarbon products or compressed air or disposing of wastes. The purpose of this report is to evaluate the feasibility, suitability, and legality of disposing of nonhazardous oil and gas exploration, development, and production wastes (hereafter referred to as oil field wastes, unless otherwise noted) in salt caverns. Chapter 2 provides background information on: types and locations of US subsurface salt deposits; basic solution mining techniques used to create caverns; and ways in which salt caverns are used. Later chapters provide discussion of: federal and state regulatory requirements concerning disposal of oil field waste, including which wastes are considered eligible for cavern disposal; waste streams that are considered to be oil field waste; and an evaluation of technical issues concerning the suitability of using salt caverns for disposing of oil field waste. Separate chapters present: types of oil field wastes suitable for cavern disposal; cavern design and location; disposal operations; and closure and remediation. This report does not suggest specific numerical limits for such factors or variables as distance to neighboring activities, depths for casings, pressure testing, or size and shape of cavern. The intent is to raise issues and general approaches that will contribute to the growing body of information on this subject

Mathematical modeling and simulation of thyroid homeostasis: Implications for the Allan-Herndon-Dudley syndrome

IntroductionA mathematical model of the pituitary-thyroid feedback loop is extended to deepen the understanding of the Allan-Herndon-Dudley syndrome (AHDS). The AHDS is characterized by unusual thyroid hormone concentrations and a mutation in the SLC16A2 gene encoding for the monocarboxylate transporter 8 (MCT8). This mutation leads to a loss of thyroid hormone transport activity. One hypothesis to explain the unusual hormone concentrations of AHDS patients is that due to the loss of thyroid hormone transport activity, thyroxine (T4) is partially retained in thyroid cells.MethodsThis hypothesis is investigated by extending a mathematical model of the pituitary-thyroid feedback loop to include a model of the net effects of membrane transporters such that the thyroid hormone transport activity can be considered. A nonlinear modeling approach based on the Michaelis-Menten kinetics and its linear approximation are employed to consider the membrane transporters. The unknown parameters are estimated through a constrained parameter optimization.ResultsIn dynamic simulations, damaged membrane transporters result in a retention of T4 in thyroid cells and ultimately in the unusual hormone concentrations of AHDS patients. The Michaelis-Menten modeling approach and its linear approximation lead to similar results.DiscussionThe results support the hypothesis that a partial retention of T4 in thyroid cells represents one mechanism responsible for the unusual hormone concentrations of AHDS patients. Moreover, our results suggest that the retention of T4 in thyroid cells could be the main reason for the unusual hormone concentrations of AHDS patients

Risk-shifting Through Issuer Liability and Corporate Monitoring

This article explores how issuer liability re-allocates fraud risk and how risk allocation may reduce the incidence of fraud. In the US, the apparent absence of individual liability of officeholders and insufficient monitoring by insurers under-mine the potential deterrent effect of securities litigation. The underlying reasons why both mechanisms remain ineffective are collective action problems under the prevailing dispersed ownership structure, which eliminates the incentives to moni-tor set by issuer liability. This article suggests that issuer liability could potentially have a stronger deterrent effect when it shifts risk to individuals or entities holding a larger financial stake. Thus, it would enlist large shareholders in monitoring in much of Europe. The same risk-shifting effect also has implications for the debate about the relationship between securities litigation and creditor interests. Credi-tors’ claims should not be given precedence over claims of defrauded investors (e.g., because of the capital maintenance principle), since bearing some of the fraud risk will more strongly incentivise large creditors, such as banks, to monitor the firm in jurisdictions where corporate debt is relatively concentrated

Examination of Late Palaeolithic archaeological sites in northern Europe for the preservation of cryptotephra layers

We report the first major study of cryptotephra (non-visible volcanic ash layers) on Late Palaeolithic archaeological sites in northern Europe. Examination of 34 sites dating from the Last Termination reveals seven with identifiable cryptotephra layers. Preservation is observed in minerogenic and organic deposits, although tephra is more common in organic sediments. Cryptotephra layers normally occur stratigraphically above or below the archaeology. Nearby off-site palaeoclimate archives (peat bogs and lakes <0.3 km distant) were better locations for detecting tephra. However in most cases the archaeology can only be correlated indirectly with such cryptotephras. Patterns affecting the presence/absence of cryptotephra include geographic position of sites relative to the emitting volcanic centre; the influence of past atmospherics on the quantity, direction and patterns of cryptotephra transport; the nature and timing of local site sedimentation; sampling considerations and subsequent taphonomic processes. Overall, while tephrostratigraphy has the potential to improve significantly the chronology of such sites many limiting factors currently impacts the successful application