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Abstract Forcespinning technique was used to fabricate sub-micron size polycaprolactone (PCL) fibers. Forcespinning method uses centrifugal forces for the generation of fibers unlike the electrospinning method which uses electrostatic force. PCL has been extensively used as scaffolds for cell regeneration, substrates for tissue engineering and in drug delivery systems. The aim of this study is to qualitatively analyze the force spun fiber mats and investigate the effect of the spinneret rotational speed on the fiber morphology, thermal and mechanical properties. The extracted fibers were characterized by scanning electron microscopy differential scanning calorimetry, tensile testing and dynamic mechanical analysis. The results showed that higher rotational speeds produced uniform fibers with less number of beads. The crystallinity of the fibers decreased with increase in rotational speeds. The Young’s modulus of the forcespun fibers was found to be in the range of 3.5 to 6 MPa. Storage and loss moduli decreased with the increase in the fiber diameter. The fibers collected at farther distance from spinneret exhibited optimal mechanical properties compared to the fibers collected at shorter distances. This study will aid in extracting fibers with uniform geometries and lower beads to achieve the desired nanofiber drug release properties. 

Inflammation and oxidative stress in pancreatic islets amplify the appearance of various posttranslational modifications to self-proteins. In this study, we identified a select group of carbonylated islet proteins arising before the onset of hyperglycemia in NOD mice. Of interest, we identified carbonyl modification of the prolyl-4-hydroxylase β subunit (P4Hb) that is responsible for proinsulin folding and trafficking as an autoantigen in both human and murine type 1 diabetes. We found that carbonylated P4Hb is amplified in stressed islets coincident with decreased glucose-stimulated insulin secretion and altered proinsulin-to-insulin ratios. Autoantibodies against P4Hb were detected in prediabetic NOD mice and in early human type 1 diabetes prior to the onset of anti-insulin autoimmunity. Moreover, we identify autoreactive CD4+ T-cell responses toward carbonyl-P4Hb epitopes in the circulation of patients with type 1 diabetes. Our studies provide mechanistic insight into the pathways of proinsulin metabolism and in creating autoantigenic forms of insulin in type 1 diabetes.