It is proposed that the multiple enhancer elements associated with locus control regions and super‐enhancers recruit RNA polymerase II and efficiently assemble elongation competent transcription complexes that are transferred to target genes by transcription termination and transient looping mechanisms. It is well established that transcription complexes are recruited not only to promoters but also to enhancers, where they generate enhancer RNAs. Transcription at enhancers is unstable and frequently aborted. Furthermore, the Integrator and WD‐domain containing protein 82 mediate transcription termination at (...) enhancers. Abortion and termination of transcription at the multiple enhancers of locus control regions and super‐enhancers provide a large pool of elongation competent transcription complexes. These are efficiently captured by strong basal promoter elements at target genes during transient looping interactions. -/- . (shrink)

When George Bernard Shaw described Dartington Hall as a ‘salon in the countryside’, he was referring to the maelstrom of ideas, conversations, and experimentation around psychology, mysticism, and spirituality within the estate's larger ethos of community living and rural reform. Disenchanted with the effects of industrialization and the ravages of the First World War, American railway heiress Dorothy Whitney Elmhirst and her second husband, Leonard Elmhirst, purchased the extensive Devonshire estate in 1925 and began to encourage regular visits and social (...) and spiritual advice from prominent British interwar intellectuals such as Aldous Huxley and Gerald Heard. As the estate's activities expanded during the 1930s, Dorothy enlisted the help of visiting American constitutional psychologist William Sheldon to assess and advise upon the well-being of children attending Dartington's experimental school. Sheldon's ‘Promethean Psychology’ and ‘Somatotyping’ body classification system offered the Dartington group, a social, spiritual, and ‘scientific’ alternative to Freudian understandings of the mind. Visitors such as Huxley, decades later, relied on Sheldon's somatotyping system to fashion a utopian education in Pala (in his last novel, Island) where the population might live in nonmaterialistic cooperative harmony. Dartington's attraction to the use of Sheldon's Promethean psychology in supporting a utopian view of progressive education was as short-lived as were Pala's utopian ambitions decades later. In years to come, however, elements of Sheldon's views continued to find an audience among physical educators and sports scientists, who saw in somatotypes a useful guide for assessing talent identification and future sporting success. (shrink)

Recent scholarship on sati has stressed the fact that the ‘problem’ of sati is that the problem extends far beyond and begins far before the act itself. One of the things that lies prior to and post the act is language, yet sati is an act that stands in a curious relationship to language. I will examine the relationship between the physical act of sati and the language that surrounds it: the ‘story’ prior to the act which gives the act (...) its meaning; the act itself which stands in an ironic relationship to the story –I will argue that the act is in fact possible only because it displaces the original story, so that every act of becoming sati presents itself not as a radical act in experience, but as an ‘acting out’ of the original story. It is in this acting out of a displaced story, that the boundary between the physical act and language becomes obscured and the body doing the act begins to occupy a liminal position, as it itself begins to function as a language – a language, which in its aspect of an ‘acting out’ obscures its own act. Lastly, I will consider the implications of the symbolic language of sati for the contemporary woman. (shrink)

Purpose: Studies of reactive and proactive modes of inhibitory control tend to show age-related declines and are accompanied by abnormalities in the prefrontal cortex. We explored which mode of inhibitory control would be more amenable to change and accrue greater benefits following engagement in a 4-week theater acting intervention in older adults. These gains were evaluated by performance on the AX-CPT task. We hypothesized that an increase in proactive control would relate to an increase in AY errors and a decrease (...) in BX errors. In contrast, an increase in reactive control would be associated with a decrease in AY errors, no change in AY reaction time, and an increase in BX response time. Further, we posited that an increase in behavioral proactive control would accompany greater cue versus probe activity for previously identified regions in the prefrontal cortex. In contrast, an increase in behavioral reactive control would be accompanied by greater probe activation in these identified brain areas.Materials and Methods: The participants were 179 community-dwelling adults aged 60–89 years who were on average, college-educated. Participants were pseudo-randomly assigned to either an active-experiencing acting intervention condition or the active control condition ; participant assignment was subject to time of enrollment. Participants in both groups were trained by theater-actor researchers with expertise in acting interventions. In contrast to the active control participants who attended a course on theater acting, the acting-intervention group was required to consistently deploy proactive and reactive control mechanisms. Both groups met two times/week for 75-min for 4 weeks. Participant brain-behavioral performance on the AX-CPT task was evaluated prior to and after this four-week period.Results: No intervention effects were found in favor of proactive control. Behavioral evidence in favor of reactive control was weak. Brain-related benefits to reactive control was illustrated by greater probe-activation in Brodmann areas 6 and 8, relative to controls and pre-intervention.Conclusion: We found some evidence for improvements in reactive control via brain measures, attributed to engagement in the acting intervention. (shrink)

The article focuses on issues relating to occupational exposures of researchers and lab workers, and exposures of bystanders such as health care workers and family members during HSR using nanomaterials. Such third-party exposures give rise to unique challenges relating to oversight as well as exposures to worker groups not previously studied. Given the current state of knowledge regarding health risks from such exposures, a more precautionary approach to oversight seems advisable.

Nanomedicine is a rapidly growing field in the academic as well as commercial arena. While some had predicted nanomedicine sales to reach $20.1 billion in 2011, the actual growth was much more rapid, with the global nanomedicine market being valued at $53 billion in 2009, and forecast to increase at an annual growth rate of 13.5% to reach more than $100 billion in 2014. In 2006, more than 130 nanotechnology-based drugs and delivery systems had entered preclinical, clinical, or commercial development. (...) The European Medicines Agency reviewed 18 marketing authorization applications for nanomedicines in 2010. In 2011, 22 drugs that had been approved by the FDA, and 87 Phase I and Phase II clinical trials were listed in the U.S. National Institutes of Health data base, www.clinicaltrials.gov. Although the fastest growing areas of nanomedicine are applications in medical imaging and diagnosis using contrast-enhancing agents, most nanomedicine research and commercialization is in the area of cancer drug therapy, including nano gold shells. (shrink)

Nanomedicine is yielding new and improved treatments and diagnostics for a range of diseases and disorders. Nanomedicine applications incorporate materials and components with nanoscale dimensions where novel physiochemical properties emerge as a result of size-dependent phenomena and high surface-to-mass ratio. Nanotherapeutics and in vivo nanodiagnostics are a subset of nanomedicine products that enter the human body. These include drugs, biological products, implantable medical devices, and combination products that are designed to function in the body in ways unachievable at larger scales. (...) Nanotherapeutics andin vivonanodiagnostics incorporate materials that are engineered at the nanoscale to express novel properties that are medicinally useful. These nanomedicine applications can also contain nanomaterials that are biologically active, producing interactions that depend on biological triggers. Examples include nanoscale formulations of insoluble drugs to improve bioavailability and pharmacokinetics, drugs encapsulated in hollow nanoparticles with the ability to target and cross cellular and tissue membranes and to release their payload at a specific time or location, imaging agents that demonstrate novel optical properties to aid in locating micrometastases, and antimicrobial and drug-eluting components or coatings of implantable medical devices such as stents. (shrink)

The OSHA system for oversight of chemicals in the workplace was evaluated to derive lessons for oversight of nanotechnology. Criteria relating to the development, attributes, evolution, and outcomes of the system were used for evaluation that was based upon quantitative expert elicitation and historical literature analysis. The oversight system had inadequate resources in terms of finances, expertise, and personnel, and insufficient incentive for compliance. The system showed a lack of flexibility in novel situations. There were minimal requirements on companies for (...) data on health and safety of their products. These factors have a strong influence on public confidence and health and safety. The oversight system also scored low on attributes such as public input, transparency, empirical basis, conflict of interest, and informed consent. The experts in our sample tend to believe that the current oversight system for chemicals in the workplace is neither adequate nor effective. It is very likely that the performance of the OSHA oversight system for nanomaterials will be equally inadequate. (shrink)

Nanotechnology is a collection of different technologies and approaches dealing with manipulating matter with dimensions on the nanometer scale. The growth of nanotechnology has been rapid in recent years and encompasses a range of industries including pharmaceuticals, chemicals, robotics, medicine, agriculture, electronics, national defense, fiber optics, and energy. Nanoparticles with shapes, morphologies, and chemical compositions engineered for specific functions and applications are now common. While estimates of the numbers of new types of nanoparticles being produced in academic and industrial labs (...) that combine these different characteristics are uncertain, it is likely that they run into the hundreds. (shrink)

The emergence of nanotechnology, and specifically nanobiotechnology, raises major oversight challenges. In the United States, government, industry, and researchers are debating what oversight approaches are most appropriate. Among the federal agencies already embroiled in discussion of oversight approaches are the Food and Drug Administration , Environmental Protection Agency , Department of Agriculture , Occupational Safety and Health Administration , and National Institutes of Health . All can learn from assessment of the successes and failures of past oversight efforts aimed at (...) emerging technologies. This article reports on work funded by the National Science Foundation aimed at learning the lessons of past oversight efforts. The article offers insights that emerge from comparing five oversight case studies that examine oversight of genetically engineered organisms in the food supply, pharmaceuticals, medical devices, chemicals in the workplace, and gene therapy. Using quantitative and qualitative analysis, the authors present a new way of evaluating oversight. (shrink)