Short-lived p-nuclides in the early solar system and implications on the nucleosynthetic role of X-ray binaries

The data available for short-lived $p$-nuclides are used in an open nonlinear model of the chemical evolution of the Galaxy in order to discuss the origin of extinct radionuclides, the stellar sources of $p$-nuclides, and the chronology of solar system formation. It is concluded that the observed abundances of $^{97}$Tc, $^{98}$Tc, $^{92}$Nb, and $^{146}$Sm in the early solar system are consistent with nucleosynthesis in type II supernovae during continuous chemical evolution of the Galaxy and a subsequent short isolation of the presolar molecular cloud from fresh nucleosynthetic inputs. However, further work on supernova models is needed before $p$-radionuclides will comprise reliable cosmochronometers. Despite these limitations, we argue that niobium-92 can be used to test whether the {\it rp}-process contributed to the synthesis of light {\it p}-nuclides in the Mo-Ru region.Comment: 8 pages, 2 figures. Proceedings of the Nuclear Physics in Astrophysics Conference, Debrecen, Hungary, 2002, to appear in Nucl. Phys.

Fluctuating Environments, Sexual Selection and the Evolution of Flexible Mate Choice in Birds

Environmentally-induced fluctuation in the form and strength of natural selection can drive the evolution of morphology, physiology, and behavior. Here we test the idea that fluctuating climatic conditions may also influence the process of sexual selection by inducing unexpected reversals in the relative quality or sexual attractiveness of potential breeding partners. Although this phenomenon, known as ‘ecological cross-over’, has been documented in a variety of species, it remains unclear the extent to which it has driven the evolution of major interspecific differences in reproductive behavior. We show that after controlling for potentially influential life history and demographic variables, there are significant positive associations between the variability and predictability of annual climatic cycles and the prevalence of infidelity and divorce within populations of a taxonomically diverse array of socially monogamous birds. Our results are consistent with the hypothesis that environmental factors have shaped the evolution of reproductive flexibility and suggest that in the absence of severe time constraints, secondary mate choice behaviors can help prevent, correct, or minimize the negative consequences of ecological cross-overs. Our findings also illustrate how a basic evolutionary process like sexual selection is susceptible to the increasing variability and unpredictability of climatic conditions that is resulting from climate change

From molecular chaperones to membrane motors: through the lens of a mass spectrometrist

Twenty-five years ago, we obtained our first mass spectra of molecular chaperones in complex with protein ligands and entered a new field of gas-phase structural biology. It is perhaps now time to pause and reflect, and to ask how many of our initial structure predictions and models derived from mass spectrometry (MS) datasets were correct. With recent advances in structure determination, many of the most challenging complexes that we studied over the years have become tractable by other structural biology approaches enabling such comparisons to be made. Moreover, in the light of powerful new electron microscopy methods, what role is there now for MS? In considering these questions, I will give my personal view on progress and problems as well as my predictions for future directions

436 Immunotherapy Sensitization via Tumor Acidosis Mitigation by Esomeprazole Monitored with MRI

OBJECTIVES/GOALS: Acidity and the lactate-to-pyruvate ratio correlate with immunotherapy resistance. AcidoCEST MRI and hyperpolarized magnetic resonance spectroscopy (HP-MRS) measure extracellular pH and lactate-to-pyruvate ratio. We will establish a baseline for these biomarkers then observe changes after combination esomeprazole and immunotherapy. METHODS/STUDY POPULATION: We used multiple melanoma models created via serial in vivo passage under immunotherapeutic pressure (FVAX, CTLA-4, PD-1, PD-L1). We used four of these corresponding to 25%, 50%, 75% and 100% resistance (TMT, F2, F3, and F4, respectively). HP-MRS was performed two weeks post implantation in male BL6 mice with AcidoCEST MRI 2-3 days later. Tumors were implanted in additional mice and grown for 1 week. We used esomeprazole as a possible immunotherapy sensitizer. Esomeprazole (or PBS) alone and in combination with immune checkpoint blockade (ICB; αCTLA-4, αPD-1) was then conducted every 3 days for 3 doses. ICB was administered 3h after esomeprazole. AcidoCEST MRI was performed the day after the final dose of combination therapy and 3h after esomeprazole (or PBS) alone. HP-MRS was performed 2-3 days after acidoCEST MRI. RESULTS/ANTICIPATED RESULTS: There was a statistical increase in the lactate-to-pyruvate ratio of the F4 group compared with TMT, F2, and F3 groups (p < 0.05). The TMT, F2, and F3 groups did not differ significantly. The extracellular pH (pHe) of the TMT group was statistically lower than the F2 and F4 groups (p < 0.05). The pHe did not differ significantly between the TMT and F3 groups nor the F2, F3, and F4 groups. The lactate-to-pyruvate ratio and pHe after combination treatment with esomeprazole and ICB did not differ compared to PBS+ICB control. Treatment with esomeprazole alone generated higher lactate-to-pyruvate ratio compared with PBS alone. Tumor volume curves and survival curves of mice bearing F4 tumors treated with esomeprazole combination with ICB showed no difference compared with PBS+ICB, PBS alone, and esomeprazole alone. DISCUSSION/SIGNIFICANCE: We differentiated between the 100% and 25% resistant models with both pHe and lactate-to-pyruvate ratio, although the pHe was counterintuitive. Esomeprazole was ineffective, but other potential sensitizers exist. A non-invasive clinical imaging tool and sensitizer would permit more personalized treatment plans so treatment is more effective