PI3 Kinase Activation and Response to Trastuzumab Therapy: What's neu with Herceptin Resistance?

Trastuzumab is an established therapy for women with breast cancers that overexpress HER2. Despite its proven benefit in treating breast cancer, not all women derive benefit from this monoclonal antibody, and resistant disease can develop. In this issue of Cancer Cell, Berns et al. present evidence that activation of the PI3 kinase pathway, either via loss of the tumor suppressor PTEN or through oncogenic stimulation of PIK3CA, can mediate trastuzumab resistance. This study extends important work of others and forms the rationale for future investigations combining inhibitors of the PI3 kinase pathway in conjunction with trastuzumab therapy

Expand Paid Family and Medical Leave

This policy action statement was developed by members of the network engaged in the Grand Challenge to Advance Long and Productive Lives. The Grand Challenges initiative’s policy action statements present proposals emerging from Social Innovation for America’s Renewal, a policy conference organized by the Center for Social Development at Washington University in collaboration with theAmerican Academy of Social Work & Social Welfare, which is leading the Grand Challenges for Social Work initiative to champion social progress through a national agenda powered by science

Controllability of Linear and Nonlinear Control Systems related through Simulation Relations

For nonlinear input-disturbance systems that are connected by a simulation relation, we examine to what extent they share certain controllability properties. Specifically our main objective is to determine the conditions under which the following holds: given two control systems $F$ and $\tilde{F}$ where $F$ is simulated by $\tilde{F}$ and $F$ is completely controllable, we have that $\tilde{F}$ is also completely controllable. To this end, we show that under some additional conditions the property of complete controllability is preserved for pointwise graph simulation relations and compact graph simulation relations. Next in an attempt to prove a similar result between a nonlinear system and an almost linear system, but with the simulation relation submanifold being a regular level set of a particular map instead of a graph, we achieve the result of the simulating system $\tilde{F}$ being at most completely controllable modulo the kernel of a linear map. We show through an example that $\tilde{F}$ may fail to be completely controllable if it does not fulfill a certain compactness condition. By imposing this compactness condition along with other somewhat restrictive assumptions, we are able to prove a similar result for nonlinear control systems connected through a simulation relation submanifold in the form of a regular level set of a smooth mapping. We then illustrate the features of our final main result with an example

Novel Reproductive Behavior in an Asian Frog: Sex‐Reversed Inguinal Amplexus

Amphibians exhibit diverse reproductive behaviors, including nine documented types of amplexus, the behavior in which male and female frogs position themselves for courtship, oviposition, and fertilization. All known forms of amplexus involve the male on top of or in line horizontally (cloacal apposition) with the female. Here, we report a novel form of amplexus observed in Lau’s leaf litter toad (Leptobrachella laui; Megophryidae) in Hong Kong, China. Termed “sex‐reversed inguinal amplexus,” the female climbs on top of a male and the male transports the female to a concealed breeding site. We were unable to determine whether this was the amplectant position in which frogs engaged during oviposition or solely during courtship and prior to oviposition, but there are a number of possible evolutionary drivers that may have given rise to this behavior, including limiting suitable oviposition sites or strong competition for males among females. Further research will be necessary to understand the evolutionary origins of this novel reproductive behavior

The Impact of Computer Mediation on Group and Individual Preferences in Social Dilemmas

As sensitivity to social issues increases, corporations face a particularIy difficult challenge when confronted with trade-oEs between corporate self-interest and the public interest. The difficulty OE resolving sese socid d i l e m a s in groups is amplified by value conflicts across group members and also b y conflicts bciween an individual\u27s p e r s o d values and those of the corporation. This study investigates the impact of group suppol-\u27,s y s t e ~ (sGSS) on persuasive processes md fiecison outcomes associated with social dilerrunas. The theoretical foundafronfor the study is the literature on group gol&zation, in particular the theories of persuasive arguments and social comparison (Isen\u27ksg 1986)

"Cultural additivity" and how the values and norms of Confucianism, Buddhism, and Taoism co-exist, interact, and influence Vietnamese society: A Bayesian analysis of long-standing folktales, using R and Stan

Every year, the Vietnamese people reportedly burned about 50,000 tons of joss papers, which took the form of not only bank notes, but iPhones, cars, clothes, even housekeepers, in hope of pleasing the dead. The practice was mistakenly attributed to traditional Buddhist teachings but originated in fact from China, which most Vietnamese were not aware of. In other aspects of life, there were many similar examples of Vietnamese so ready and comfortable with adding new norms, values, and beliefs, even contradictory ones, to their culture. This phenomenon, dubbed "cultural additivity", prompted us to study the co-existence, interaction, and influences among core values and norms of the Three Teachings--Confucianism, Buddhism, and Taoism--as shown through Vietnamese folktales. By applying Bayesian logistic regression, we evaluated the possibility of whether the key message of a story was dominated by a religion (dependent variables), as affected by the appearance of values and anti-values pertaining to the Three Teachings in the story (independent variables).Comment: 8 figures, 35 page

Effect of Salts on the Co-Fermentation of Glucose and Xylose by a Genetically Engineered Strain of Saccharomyces Cerevisiae.

Background A challenge currently facing the cellulosic biofuel industry is the efficient fermentation of both C5 and C6 sugars in the presence of inhibitors. To overcome this challenge, microorganisms that are capable of mixed-sugar fermentation need to be further developed for increased inhibitor tolerance. However, this requires an understanding of the physiological impact of inhibitors on the microorganism. This paper investigates the effect of salts on Saccharomyces cerevisiae 424A(LNH-ST), a yeast strain capable of effectively co-fermenting glucose and xylose. Results In this study, we show that salts can be significant inhibitors of S. cerevisiae. All 6 pairs of anions (chloride and sulfate) and cations (sodium, potassium, and ammonium) tested resulted in reduced cell growth rate, glucose consumption rate, and ethanol production rate. In addition, the data showed that the xylose consumption is more strongly affected by salts than glucose consumption at all concentrations. At a NaCl concentration of 0.5M, the xylose consumption rate was reduced by 64.5% compared to the control. A metabolomics study found a shift in metabolism to increased glycerol production during xylose fermentation when salt was present, which was confirmed by an increase in extracellular glycerol titers by 4 fold. There were significant differences between the different cations. The salts with potassium cations were the least inhibitory. Surprisingly, although salts of sulfate produced twice the concentration of cations as compared to salts of chloride, the degree of inhibition was the same with one exception. Potassium salts of sulfate were less inhibitory than potassium paired with chloride, suggesting that chloride is more inhibitory than sulfate. Conclusions When developing microorganisms and processes for cellulosic ethanol production, it is important to consider salt concentrations as it has a significant negative impact on yeast performance, especially with regards to xylose fermentation