[No abstract]

People find it easier to learn about topics that interest them, but little is known about the mechanisms by which intrinsic motivational states affect learning. We used functional magnetic resonance imaging to investigate how curiosity (intrinsic motivation to learn) influences memory. In both immediate and one-day-delayed memory tests, participants showed improved memory for information that they were curious about and for incidental material learned during states of high curiosity. Functional magnetic resonance imaging results revealed that activity in the midbrain and the nucleus accumbens was enhanced during states of high curiosity. Importantly, individual variability in curiosity-driven memory benefits for incidental material was supported by anticipatory activity in the midbrain and hippocampus and by functional connectivity between these regions. These findings suggest a link between the mechanisms supporting extrinsic reward motivation and intrinsic curiosity and highlight the importance of stimulating curiosity to create more effective learning experiences.

© 2015 Shiboski et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credite

Recently, we have shown that small molecule dCK inhibitors in combination with pharmacological perturbations of de novo dNTP biosynthetic pathways could eliminate acute lymphoblastic leukemia cells in animal models. However, our previous lead compound had a short half-life in vivo. Therefore, we set out to develop dCK inhibitors with favorable pharmacokinetic properties. We delineated the sites of the inhibitor for modification, guided by crystal structures of dCK in complex with the lead compound and with derivatives. Crystal structure of the complex between dCK and the racemic mixture of our new lead compound indicated that the R-isomer is responsible for kinase inhibition. This was corroborated by kinetic analysis of the purified enantiomers, which showed that the R-isomer has >60-fold higher affinity than the S-isomer for dCK. This new lead compound has significantly improved metabolic stability, making it a prime candidate for dCK-inhibitor based therapies against hematological malignancies and, potentially, other cancers.

Objectives

There are some common occupational agents and exposure circumstances for which evidence of carcinogenicity is substantial but not yet conclusive for humans. Our objectives were to identify research gaps and needs for 20 agents prioritized for review based on evidence of widespread human exposures and potential carcinogenicity in animals or humans.

Data sources

For each chemical agent (or category of agents), a systematic review was conducted of new data published since the most recent pertinent International Agency for Research on Cancer (IARC) Monograph meeting on that agent.

Data extraction

Reviewers were charged with identifying data gaps and general and specific approaches to address them, focusing on research that would be important in resolving classification uncertainties. An expert meeting brought reviewers together to discuss each agent and the identified data gaps and approaches.

Data synthesis

Several overarching issues were identified that pertained to multiple agents; these included the importance of recognizing that carcinogenic agents can act through multiple toxicity pathways and mechanisms, including epigenetic mechanisms, oxidative stress, and immuno- and hormonal modulation.

Conclusions

Studies in occupational populations provide important opportunities to understand the mechanisms through which exogenous agents cause cancer and intervene to prevent human exposure and/or prevent or detect cancer among those already exposed. Scientific developments are likely to increase the challenges and complexities of carcinogen testing and evaluation in the future, and epidemiologic studies will be particularly critical to inform carcinogen classification and risk assessment processes.

A search is presented for the four-body decay B0 → ppp p in a sample of 471 million BB pairs collected with the BABAR detector, operated at the SLAC PEP-II asymmetric-energy e+e- collider. The center-ofmass energy is 10.58 GeV. From a fit to the distribution of the energy-substituted mass mES, the branching fraction B(B0 → ppp p) = (1.1 ± 0.5 ± 0.2) × 10-7 is extracted, where the first uncertainty is statistical and the second is systematic. The significance of the signal, including the systematic uncertainty, is 2.9 standard deviations. The upper limit on the branching fraction is determined to be 2.0 × 10-7 at 90% confidence level.