Title VII of the Civil Rights Act of 1964 - Educational and Testing Requirements Invalid Unless Job-Related

The United States Supreme Court has held that an employer\u27s use of educational and testing requirements for screening job applicants violates Title VII of the Civil Rights Act of 1964 when the effect is to disqualify a disproportionate number of Negroes, and where there is no showing that either standard is significantly related to job performance. Griggs v. Duke Power Company, 401 U.S. 424 (1971)

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

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

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

Energy Penalty Analysis of Possible Cooling Water Intake Structure Requirements on Existing Coal-Fired Power Plants.

Section 316(b) of the Clean Water Act requires that cooling water intake structures must reflect the best technology available for minimizing adverse environmental impact. Many existing power plants in the United States utilize once-through cooling systems to condense steam. Once-through systems withdraw large volumes (often hundreds of millions of gallons per day) of water from surface water bodies. As the water is withdrawn, fish and other aquatic organisms can be trapped against the screens or other parts of the intake structure (impingement) or if small enough, can pass through the intake structure and be transported through the cooling system to the condenser (entrainment). Both of these processes can injure or kill the organisms. EPA adopted 316(b) regulations for new facilities (Phase I) on December 18, 2001. Under the final rule, most new facilities could be expected to install recirculating cooling systems, primarily wet cooling towers. The EPA Administrator signed proposed 316(b) regulations for existing facilities (Phase II) on February 28, 2002. The lead option in this proposal would allow most existing facilities to achieve compliance without requiring them to convert once-through cooling systems to recirculating systems. However, one of the alternate options being proposed would require recirculating cooling in selected plants. EPA is considering various options to determine best technology available. Among the options under consideration are wet-cooling towers and dry-cooling towers. Both types of towers are considered to be part of recirculating cooling systems, in which the cooling water is continuously recycled from the condenser, where it absorbs heat by cooling and condensing steam, to the tower, where it rejects heat to the atmosphere before returning to the condenser. Some water is lost to evaporation (wet tower only) and other water is removed from the recirculating system as a blow down stream to control the building up of suspended and dissolved solids. Makeup water is withdrawn, usually from surface water bodies, to replace the lost water. The volume of makeup water is many times smaller than the volume needed to operate a once-through system. Although neither the final new facility rule nor the proposed existing facility rule require dry cooling towers as the national best technology available, the environmental community and several States have supported the use of dry-cooling technology as the appropriate technology for addressing adverse environmental impacts. It is possible that the requirements included in the new facility rule and the ongoing push for dry cooling systems by some stakeholders may have a role in shaping the rule for existing facilities. The temperature of the cooling water entering the condenser affects the performance of the turbine--the cooler the temperature, the better the performance. This is because the cooling water temperature affects the level of vacuum at the discharge of the steam turbine. As cooling water temperatures decrease, a higher vacuum can be produced and additional energy can be extracted. On an annual average, once-through cooling water has a lower temperature than recirculated water from a cooling tower. By switching a once-through cooling system to a cooling tower, less energy can be generated by the power plant from the same amount of fuel. This reduction in energy output is known as the energy penalty. If a switch away from once-through cooling is broadly implemented through a final 316(b) rule or other regulatory initiatives, the energy penalty could result in adverse effects on energy supplies. Therefore, in accordance with the recommendations of the Report of the National Energy Policy Development Group (better known as the May 2001 National Energy Policy), the U.S. Department of Energy (DOE), through its Office of Fossil Energy, National Energy Technology Laboratory (NETL), and Argonne National Laboratory (ANL), has studied the energy penalty resulting from converting plants with once-through cooling to wet towers or indirect-dry towers. Five locations--Delaware River Basin (Philadelphia), Michigan/Great Lakes (Detroit), Ohio River Valley (Indianapolis), South (Atlanta), and Southwest (Yuma)--were modeled using an ASPEN simulator model. The model evaluated the performance and energy penalty for hypothetical 400-MW coal-fired plants that were retrofitted from using once-through cooling systems to wet- and dry-recirculating systems. The modeling was initially done to simulate the hottest time of the year using temperature input values that are exceeded only 1 percent of the time between June through September at each modeled location. These are the same temperature inputs commonly used by cooling tower designers to ensure that towers perform properly under most climatic conditions

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

Tspan8 is expressed in breast cancer and regulates E-cadherin/catenin signalling and metastasis accompanied by increased circulating extracellular vesicles

Tspan8 exhibits a functional role in many cancer types including pancreatic, colorectal, oesophagus carcinoma, and melanoma. We present a first study on the expression and function of Tspan8 in breast cancer. Tspan8 protein was present in the majority of human primary breast cancer lesions and metastases in the brain, bone, lung, and liver. In a syngeneic rat breast cancer model, Tspan8$^{+}$ tumours formed multiple liver and spleen metastases, while Tspan8$^{-}$ tumours exhibited a significantly diminished ability to metastasise, indicating a role of Tspan8 in metastases. Addressing the underlying molecular mechanisms, we discovered that Tspan8 can mediate up‐regulation of E‐cadherin and down‐regulation of Twist, p120‐catenin, and β‐catenin target genes accompanied by the change of cell phenotype, resembling the mesenchymal–epithelial transition. Furthermore, Tspan8$^{+}$ cells exhibited enhanced cell–cell adhesion, diminished motility, and decreased sensitivity to irradiation. As a regulator of the content and function of extracellular vesicles (EVs), Tspan8 mediated a several‐fold increase in EV number in cell culture and the circulation of tumour‐bearing animals. We observed increased protein levels of E‐cadherin and p120‐catenin in these EVs; furthermore, Tspan8 and p120‐catenin were co‐immunoprecipitated, indicating that they may interact with each other. Altogether, our findings show the presence of Tspan8 in breast cancer primary lesion and metastases and indicate its role as a regulator of cell behaviour and EV release in breast cancer