Anti-CKM monoclonal antibody, clone 1302 (1F2/1)

Diabetic ketoacidosis (DKA), a severe complication of diabetes mellitus with potentially fatal consequences, is characterized by hyperglycemia and metabolic acidosis due to the accumulation of ketone bodies, which requires people with diabetes to monitor both glucose and ketone bodies. However, despite major advances in diabetes management mainly since the emergence of new-generation continuous glucose monitoring (CGM) devices capable of in vivo monitoring of glucose directly in the interstitial fluid (ISF), the continuous monitoring of ketone bodies is yet to be addressed. Here, we present the first use of a real-time continuous ketone bodies monitoring (CKM) microneedle platform. The system is based on the electrochemical monitoring of beta-hydroxybutyrate (HB) as the dominant biomarker of ketone formation. Such real-time HB detection has been realized using the beta-hydroxybutyrate dehydrogenase (HBD) enzymatic reaction and by addressing the major challenges associated with the stable confinement of the enzyme/cofactor couple (HBD/NAD(+)) and with a stable and selective low-potential fouling-free anodic detection of NADH. The resulting CKM microneedle device displays an attractive analytical performance, with high sensitivity (with low detection limit, 50 mu M), high selectivity in the presence of potential interferences, along with good stability during prolonged operation in artificial ISF. The potential applicability of this microneedle sensor toward minimally invasive monitoring of ketone bodies has been demonstrated in a phantom gel skin-mimicking model. The ability to detect HB along with glucose and lactate on a single microneedle array has been demonstrated. These findings pave the way for CKM and for the simultaneous microneedle-based monitoring of multiple diabetes-related biomarkers toward a tight glycemic control.

Can the cosmological dynamics responsible for settling down the present values of the Cabibbo-Kobayashi-Maskawa matrix be related to electroweak symmetry breaking? If the Standard Model Yukawa couplings varied in the early universe and started with order one values before electroweak symmetry breaking, the CP violation associated with the CKM matrix could be the origin of the matter-antimatter asymmetry. The large effective Yukawa couplings which lead to the enhanced CP violation can also help in achieving a strong first-order electroweak phase transition. We study in detail the feasibility of this idea by implementing dynamical Yukawa couplings in the context of the Froggatt-Nielsen mechanism. We discuss two main realizations of such a mechanism, related phenomenology, cosmological and collider bounds, and provide an estimate of the baryonic yield. A generic prediction is that this scenario always features a new scalar field below the electroweak scale. We point out ways to get around this conclusion.