Investigating the Lower Mass Gap with Low Mass X-ray Binary Population Synthesis

Mass measurements from low-mass black hole X-ray binaries (LMXBs) and radio pulsars have been used to identify a gap between the most massive neutron stars (NSs) and the least massive black holes (BHs). BH mass measurements in LMXBs are typically only possible for transient systems: outburst periods enable detection via all-sky X-ray monitors, while quiescent periods enable radial-velocity measurements of the low-mass donor. We quantitatively study selection biases due to the requirement of transient behavior for BH mass measurements. Using rapid population synthesis simulations (COSMIC), detailed binary stellar-evolution models (MESA), and the disk instability model of transient behavior, we demonstrate that transient-LMXB selection effects introduce observational biases, and can suppress mass-gap BHs in the observed sample. However, we find a population of transient LMXBs with mass-gap BHs form through accretion-induced collapse of a NS during the LMXB phase, which is inconsistent with observations. These results are robust against variations of binary evolution prescriptions. The significance of this accretion-induced collapse population depends upon the maximum NS birth mass $M_\mathrm{ NS, birth-max}$. To reflect the observed dearth of low-mass BHs, COSMIC and MESA models favor $M_\mathrm{ NS, birth-max} \lesssim2M_{\odot}$. In the absence of further observational biases against LMXBs with mass-gap BHs, our results indicate the need for additional physics connected to the modeling of LMXB formation and evolution.Comment: 21 pages, accepted to Ap

Pioglitazone Enhances the Beneficial Effects of Glucocorticoids in Experimental Nephrotic Syndrome

Glucocorticoids are the primary therapy for nephrotic syndrome (NS), but have serious side effects and are ineffective in ~20-50% of patients. Thiazolidinediones have recently been suggested to be renoprotective, and to modulate podocyte glucocorticoid-mediated nuclear receptor signaling. We hypothesized that thiazolidinediones could enhance glucocorticoid efficacy in NS. We found that puromycin aminonucleoside-induced proteinuria in rats was significantly reduced by both high-dose glucocorticoids (79%) and pioglitazone (61%), but not low-dose glucocorticoids (25%). Remarkably, pioglitazone + low-dose glucocorticoids also reduced proteinuria (63%) comparably to high-dose glucocorticoids, whereas pioglitazone + high-dose glucocorticoids reduced proteinuria to almost control levels (97%). Molecular analysis revealed that both glucocorticoids and pioglitazone enhanced glomerular synaptopodin and nephrin expression, and reduced COX-2 expression, after injury. Furthermore, the glomerular phosphorylation of glucocorticoid receptor and Akt, but not PPARγ, correlated with treatment-induced reductions in proteinuria. Notably, clinical translation of these findings to a child with refractory NS by the addition of pioglitazone to the treatment correlated with marked reductions in both proteinuria (80%) and overall immunosuppression (64%). These findings together suggest that repurposing pioglitazone could potentially enhance the proteinuria-reducing effects of glucocorticoids during NS treatment