Noncooperatively Optimized Tolerance: Decentralized Strategic Optimization in Complex Systems

We introduce noncooperatively optimized tolerance (NOT), a generalization of highly optimized tolerance (HOT) that involves strategic (game theoretic) interactions between parties in a complex system. We illustrate our model in the forest fire (percolation) framework. As the number of players increases, our model retains features of HOT, such as robustness, high yield combined with high density, and self-dissimilar landscapes, but also develops features of self-organized criticality (SOC) when the number of players is large enough. For example, the forest landscape becomes increasingly homogeneous and protection from adverse events (lightning strikes) becomes less closely correlated with the spatial distribution of these events. While HOT is a special case of our model, the resemblance to SOC is only partial; for example, the distribution of cascades, while becoming increasingly heavy-tailed as the number of players increases, also deviates more significantly from a power law in this regime. Surprisingly, the system retains considerable robustness even as it becomes fractured, due in part to emergent cooperation between neighboring players. At the same time, increasing homogeneity promotes resilience against changes in the lightning distribution, giving rise to intermediate regimes where the system is robust to a particular distribution of adverse events, yet not very fragile to changes

Ferroxitosis: a cell death from modulation of oxidative phosphorylation and PKM2-dependent glycolysis in melanoma

Reliance on glycolysis is a characteristic of malignancy, yet the development of resistance to BRAF inhibitors in melanoma is associated with gain of mitochondrial function. Concurrent attenuation of oxidative phosphorylation and HIF-1α/PKM2-dependent glycolysis promotes a non-apoptotic, iron- and oxygen-dependent cell death that we term ferroxitosis. The redox cycling agent menadione causes a robust increase in oxygen consumption, accompanied by significant loss of intracellular ATP and rapid cell death. Conversely, either hypoxic adaptation or iron chelation prevents menadione-induced ferroxitosis. Ectopic expression of K213Q HIF-1α mutant blunts the effects of menadione. However, knockdown of HIF-1α or PKM2 restores menadione-induced cytotoxicity in hypoxia. Similarly, exposure of melanoma cells to shikonin, a menadione analog and a potential PKM2 inhibitor, is sufficient to induce ferroxitosis under hypoxic conditions. Collectively, our findings reveal that ferroxitosis curtails metabolic plasticity in melanoma

The 25th Anniversary of the Baby Doe Rules: Perspectives from the Fields of Law, Health Care, Ethics, and Disability Policy

A highly publicized and controversial case involving the withholding of medical treatment from a “Baby Doe” with Down syndrome gave rise in 1984 to the federal law known as the Baby Doe Rules, which went into effect the following year. The law conditions the grant of federal funds for any state’s child protective services program on the state’s assurance that it can respond to reports of medical neglect, which may include the withholding of medical treatment from disabled infants with life-threatening conditions. Leading scholars and practitioners from the fields of health care, law, ethics, and disability policy who are experts in the field of neonatal medicine and decision-making involving very premature and other medically at-risk infants gathered to provide thoughtful commentary and debate on the occasion of the 25th Anniversary of the Baby Doe Rules. The Georgia State University Law Review will publish a symposium volume on the topic in Fall 2009

The 25th Anniversary of the Baby Doe Rules: Perspectives from the Fields of Law, Health Care, Ethics, and Disability Policy

A highly publicized and controversial case involving the withholding of medical treatment from a “Baby Doe” with Down syndrome gave rise in 1984 to the federal law known as the Baby Doe Rules, which went into effect the following year. The law conditions the grant of federal funds for any state’s child protective services program on the state’s assurance that it can respond to reports of medical neglect, which may include the withholding of medical treatment from disabled infants with life-threatening conditions. Leading scholars and practitioners from the fields of health care, law, ethics, and disability policy who are experts in the field of neonatal medicine and decision-making involving very premature and other medically at-risk infants gathered to provide thoughtful commentary and debate on the occasion of the 25th Anniversary of the Baby Doe Rules. The Georgia State University Law Review will publish a symposium volume on the topic in Fall 2009

National culture as a driver of pro-environmental attitudes and behavioural intentions in tourism

Voluntary changes in consumer behaviour hold significant potential to mitigate the growing environmental repercussions of tourism. Such behavioural changes can occur due to positive behavioural intentions that are in turn underpinned by pro-environmental consumer attitudes. To reinforce voluntary behavioural changes in tourism, it is paramount to understand the major drivers of pro-environmental consumer attitudes. Although national culture can influence pro-environmental attitudes of tourists, its role has been under-researched, especially in the context of emerging tourist markets. This study utilised the environment-orientated dimensions or value orientations of major cultural frameworks (Hofstede; Schwartz; Trompenaars and Hampden-Turner) to explore the effect of national culture on pro-environmental attitudes and behavioural intentions in a large-scale quantitative survey of Polish tourists. Correlation between the cultural background of tourists and their pro-environmental attitudes was established, thus highlighting the need for national culture to become an integral element of future scientific, policy-making and managerial discourse on the key drivers of more sustainable consumer behaviour in tourism

Role of intestinal P‐glycoprotein ( mdr1 ) in interpatient variation in the oral bioavailability of cyclosporine

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110064/1/cptclpt1997116.pd

Rapid climate-driven circulation changes threaten conservation of endangered north atlantic right whales

As climate trends accelerate, ecosystems will be pushed rapidly into new states, reducing the potential efficacy of conservation strategies based on historical patterns. In the Gulf of Maine, climate-driven changes have restructured the ecosystem rapidly over the past decade. Changes in the Atlantic meridional overturning circulation have altered deepwater dynamics, driving warming rates twice as high as the fastest surface rates. This has had implications for the copepod Calanus finmarchicus, a critical food supply for the endangered North Atlantic right whale (Eubalaena glacialis). The oceanographic changes have driven a deviation in the seasonal foraging patterns of E. glacialis upon which conservation strategies depend, making the whales more vulnerable to ship strikes and gear entanglements. The effects of rapid climate-driven changes on a species at risk undermine current management approaches.publishedVersio

Airborne differential absorption lidar system for measurements of atmospheric water vapor and aerosols

An airborne differential absorption lidar (DIAL) system has been developed at the NASA Langley Research Center for remote measurements of atmospheric water vapor (H2O) and aerosols. A solid-state alexandrite laser with a 1-pm linewidth and greater than 99.85% spectral purity was used as the on-line transmitter. Solid-state avalanche photodiode detector technology has replaced photomultiplier tubes in the receiver system, providing an average increase by a factor of 1.5-2.5 in the signal-to-noise ratio of the H2O measurement. By incorporating advanced diagnostic and data-acquisition instrumentation into other subsystems, we achieved additional improvements in system operational reliability and measurement accuracy. Laboratory spectroscopic measurements of H2O absorption-line parameters were performed to reduce the uncertainties in our knowledge of the absorption cross sections. Line-center H2O absorption cross sections were determined, with errors of 3-6%, for more than 120 lines in the 720-nm region. Flight tests of the system were conducted during 1989-1991 on the NASA Wallops Flight Facility Electra aircraft, and extensive intercomparison measurements were performed with dew-point hygrometers and H2O radiosondes. The H2O distributions measured with the DIAL system differed by less than 10% from the profiles determined with the in situ probes in a variety of atmospheric conditions

Performance/outcomes data and physician process challenges for practical big data efforts in radiation oncology

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146290/1/mp13136.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146290/2/mp13136_am.pd