SUMMARY Pancreatic ductal adenocarcinoma (PDAC) is characterized by extensive fibrosis and hypovascularization, resulting in significant intratumoral hypoxia (low oxygen) that contributes to its aggressiveness, therapeutic resistance, and high mortality. Despite oxygen being a fundamental requirement for many cellular and metabolic processes, and the severity of hypoxia in PDAC, the impact of oxygen deprivation on PDAC biology is poorly understood. Investigating how PDAC cells survive in the near absence of oxygen, we find that PDAC cell lines grow robustly in oxygen tensions down to 0.1%, maintaining mitochondrial morphology, membrane potential, and the oxidative metabolic activity required for the synthesis of key metabolites for proliferation. Disrupting electron transfer efficiency by targeting mitochondrial respiratory supercomplex assembly specifically affects hypoxic PDAC proliferation, metabolism, and in vivo tumor growth. Collectively, our results identify a mechanism that enables PDAC cells to thrive in severe, oxygen-limited microenvironments.

We propose a new approach for the estimation of defaults and other forms of exit of borrowers. Our approach is based on the ordered qualitative response model. We first show that any ordered qualitative response model is equivalent to the competing risks model -commonly employed in the estimation of corporate defaults and other forms of exit -in continuous-time. We then construct the continuous-time likelihood function of the models and further present its discrete-time simplification. Lastly, we compare and contrast the competing risks and ordered qualitative response models through numerical experiments in a two-state setting, and demonstrate that none of the alternatives necessarily dominates the others. Our results indicate that it may be worthwhile to estimate the models in continuous-time. Keywords: Banking, Risk Management, Finance, Econometrics, Financial EconometricsJel Classification: E50, G32, C58 Şirket Temerrütleri ve Diğer Türden Şirket Çıkışlarının Tahmini için Bir Sıralı Nitel Tepki Modelleme Yaklaşımı ÖzTemerrütler ve diğer türden şirket çıkışlarının tahmini için yeni bir yaklaşım öneriyoruz. Yaklaşımımız sıralı nitel tepki modeli üzerine kuruluyor. Önce, sıralı nitel tepki modelinin -şirket temerrütleri ve diğer türden şirket çıkışları tahmininde sıkça kullanılan -rakip riskler modeline sürekli zamanda denk olduğunu gösteriyoruz. Sonra, modellerin sürekli zaman olabilirlik fonksiyonunu kuruyor ve daha sonra, bu fonksiyonun basitleştirilmiş kesikli zaman şeklini sunuyoruz. Son olarak, iki durumlu bir uzayda yaptığımız sayısal deneylerle rakip riskler ve sıralı nitel tepki modellerini