A False Start in the Race Against Doping in Sport: Concerns With Cycling’s Biological Passport

Professional cycling has suffered from a number of doping scandals. The sport’s governing bodies have responded by implementing an aggressive new antidoping program known as the biological passport. Cycling’s biological passport marks a departure from traditional antidoping efforts, which have focused on directly detecting prohibited substances in a cyclist’s system. Instead, the biological passport tracks biological variables in a cyclist’s blood and urine over time, monitoring for fluctuations that are thought to indirectly reveal the effects of doping. Although this method of indirect detection is promising, it also raises serious legal and scientific concerns. Since its introduction, the cycling community has debated the reliability of indirect biological-passport evidence and the clarity, consistency, and transparency of its use in proving doping violations. Such uncertainty undermines the legitimacy of finding cyclists guilty of doping based on this indirect evidence alone. Antidoping authorities should address these important concerns before continuing to pursue doping sanctions against cyclists solely on the basis of their biological passports

Different reactions to adverse neighborhoods in games of cooperation

In social dilemmas, cooperation among randomly interacting individuals is often difficult to achieve. The situation changes if interactions take place in a network where the network structure jointly evolves with the behavioral strategies of the interacting individuals. In particular, cooperation can be stabilized if individuals tend to cut interaction links when facing adverse neighborhoods. Here we consider two different types of reaction to adverse neighborhoods, and all possible mixtures between these reactions. When faced with a gloomy outlook, players can either choose to cut and rewire some of their links to other individuals, or they can migrate to another location and establish new links in the new local neighborhood. We find that in general local rewiring is more favorable for the evolution of cooperation than emigration from adverse neighborhoods. Rewiring helps to maintain the diversity in the degree distribution of players and favors the spontaneous emergence of cooperative clusters. Both properties are known to favor the evolution of cooperation on networks. Interestingly, a mixture of migration and rewiring is even more favorable for the evolution of cooperation than rewiring on its own. While most models only consider a single type of reaction to adverse neighborhoods, the coexistence of several such reactions may actually be an optimal setting for the evolution of cooperation.Comment: 12 pages, 5 figures; accepted for publication in PLoS ON

Role of Chaperone Mediated Autophagy (CMA) in the Degradation of Misfolded N-CoR Protein in Non-Small Cell Lung Cancer (NSCLC) Cells

Nuclear receptor co-repressor (N-CoR) plays important role in transcriptional control mediated by several tumor suppressor proteins. Recently, we reported a role of misfolded-conformation dependent loss (MCDL) of N-CoR in the activation of oncogenic survival pathway in acute promyelocytic leukemia (APL). Since N-CoR plays important role in cellular homeostasis in various tissues, therefore, we hypothesized that an APL like MCDL of N-CoR might also be involved in other malignancy. Indeed, our initial screening of N-CoR status in various leukemia and solid tumor cells revealed an APL like MCDL of N-CoR in primary and secondary tumor cells derived from non-small cell lung cancer (NSCLC). The NSCLC cell specific N-CoR loss could be blocked by Kaletra, a clinical grade protease inhibitor and by genistein, an inhibitor of N-CoR misfolding previously characterized by us. The misfolded N-CoR presented in NSCLC cells was linked to the amplification of ER stress and was subjected to degradation by NSCLC cell specific aberrant protease activity. In NSCLC cells, misfolded N-CoR was found to be associated with Hsc70, a molecular chaperone involved in chaperone mediated autophagy (CMA). Genetic and chemical inhibition of Lamp2A, a rate limiting factor of CMA, significantly blocked the loss of N-CoR in NSCLC cells, suggesting a crucial role of CMA in N-CoR degradation. These findings identify an important role of CMA-induced degradation of misfolded N-CoR in the neutralization of ER stress and suggest a possible role of misfolded N-CoR protein in the activation of oncogenic survival pathway in NSCLC cells

Alpha particle losses from Tokamak Fusion Test Reactor deuterium–tritium plasmas

Because alpha particle losses can have a significant influence on tokamak reactor viability, the loss of deuterium–tritium alpha particles from the Tokamak Fusion Test Reactor (TFTR) [K. M. McGuire et al., Phys. Plasmas 2, 2176 (1995)] has been measured under a wide range of conditions. In TFTR, first orbit loss and stochastic toroidal field ripple diffusion are always present. Other losses can arise due to magnetohydrodynamic instabilities or due to waves in the ion cyclotron range of frequencies. No alpha particle losses have yet been seen due to collective instabilities driven by alphas. Ion Bernstein waves can drive large losses of fast ions from TFTR, and details of those losses support one element of the alpha energy channeling scenario. © 1996, American Institute of Physics. All rights reserved

Alpha particle losses from Tokamak Fusion Test Reactor deuterium–tritium plasmas

Because alpha particle losses can have a significant influence on tokamak reactor viability, the loss of deuterium–tritium alpha particles from the Tokamak Fusion Test Reactor (TFTR) [K. M. McGuire et al., Phys. Plasmas 2, 2176 (1995)] has been measured under a wide range of conditions. In TFTR, first orbit loss and stochastic toroidal field ripple diffusion are always present. Other losses can arise due to magnetohydrodynamic instabilities or due to waves in the ion cyclotron range of frequencies. No alpha particle losses have yet been seen due to collective instabilities driven by alphas. Ion Bernstein waves can drive large losses of fast ions from TFTR, and details of those losses support one element of the alpha energy channeling scenario. © 1996, American Institute of Physics. All rights reserved