Results The continuous daily dosing regimen was predicted to result in the longest survival. TAD (24.5 months) and VAD (25.5 months) increased median overall survival as compared to a fixed dose schedule (19.9 and 21.5 months, respectively) and CAD (19.7 and 21.3 months, respectively), without markedly raising the risk of intolerable toxicities. Changes in neutrophil count and sVEGFR-3 were accurately forecasted in the majority of subjects (>65%), based on biweekly blood sampling. Conclusions Dose-adjustments based on the pharmacodynamic biomarkers neutrophil count and sVEGFR-3 can increase OS whilst retaining drug safety. Future efforts could explore the possibility of incorporating a model-based dose approach in clinical practice to increase dosing accuracy for these biomarkers.The intracellular environment is crowded and heterogeneous. Although the thermodynamic stability of nucleic acid duplexes is predictable in dilute solutions, methods of predicting such stability under specific intracellular conditions are not yet available. We recently showed that the nearest-neighbor model for self-complementary DNA is valid under molecular crowding condition of 40% polyethylene glycol with an average molecular weight of 200 (PEG 200) in 100 mM NaCl. Here, we determined nearest-neighbor parameters for DNA duplex formation under the same crowding condition to predict the thermodynamics of DNA duplexes in the intracellular environment. Preferential hydration of the nucleotides was found to be the key factor for nearest-neighbor parameters in the crowding condition. Idasanutlin in vitro The determined parameters were shown to predict the thermodynamic parameters (∆H°, ∆S°, and ∆G°37) and melting temperatures (T m) of the DNA duplexes in the crowding condition with significant accuracy. Moreover, we proposed a general method for predicting the stability of short DNA duplexes in different cosolutes based on the relationship between duplex stability and the water activity of the cosolute solution. The method described herein would be valuable for investigating biological processes that occur under specific intracellular crowded conditions and for the application of DNA-based biotechnologies in crowded environments.Global efforts for biodiversity protection and land use-based greenhouse gas mitigation call for increases in the effectiveness and efficiency of environmental conservation. Incentive-based policy instruments are key tools for meeting these goals, yet their effectiveness might be undermined by such factors as social norms regarding whether payments are considered fair. We investigated the causal link between equity and conservation effort with a randomized real-effort experiment in forest conservation with 443 land users near a tropical forest national park in the Vietnamese Central Annamites, a global biodiversity hotspot. The experiment introduced unjustified payment inequality based on luck, in contradiction of local fairness norms that were measured through responses to vignettes. Payment inequality was perceived as less fair than payment equality. In agreement with our preregistered hypotheses, participants who were disadvantaged by unequal payments exerted significantly less conservation effort than other participants receiving the same payment under an equal distribution. No effect was observed for participants advantaged by inequality. Thus, equity effects on effort can have consequences for the effectiveness and efficiency of incentive-based conservation instruments. Furthermore, we show that women exerted substantially more conservation effort than men, and that increasing payment size unexpectedly reduced effort. This emphasizes the need to consider social comparisons, local equity norms, and gender in environmental policies using monetary incentives to motivate behavioral change.Many attractive jobs in today’s world require people to take on new challenges and figure out how to master them. As with any challenging goal, this involves systematic strategy use. Here we ask Why are some people more likely to take a strategic stance toward their goals, and can this tendency be cultivated? To address these questions, we introduce the idea of a domain-general “strategic mindset.” This mindset involves asking oneself strategy-eliciting questions, such as “What can I do to help myself?”, “How else can I do this?”, or “Is there a way to do this even better?”, in the face of challenges or insufficient progress. In three studies (n = 864), people who scored higher on (or were primed with) a strategic mindset reported using more metacognitive strategies; in turn, they obtained higher college grade point averages (GPAs) (Study 1); reported greater progress toward their professional, educational, health, and fitness goals (Study 2); and responded to a challenging timed laboratory task by practicing it more and performing it faster (Study 3). We differentiated a strategic mindset from general self-efficacy, self-control, grit, and growth mindsets and showed that it explained unique variance in people’s use of metacognitive strategies. These findings suggest that being strategic entails more than just having specific metacognitive skills-it appears to also entail an orientation toward seeking and employing them.Einstein believed that mentors are especially influential in a protégé’s intellectual development, yet the link between mentorship and protégé success remains a mystery. We marshaled genealogical data on nearly 40,000 scientists who published 1,167,518 papers in biomedicine, chemistry, math, or physics between 1960 and 2017 to investigate the relationship between mentorship and protégé achievement. In our data, we find groupings of mentors with similar records and reputations who attracted protégés of similar talents and expected levels of professional success. However, each grouping has an exception One mentor has an additional hidden capability that can be mentored to their protégés. They display skill in creating and communicating prizewinning research. Because the mentor’s ability for creating and communicating celebrated research existed before the prize’s conferment, protégés of future prizewinning mentors can be uniquely exposed to mentorship for conducting celebrated research. Our models explain 34-44% of the variance in protégé success and reveals three main findings.