Glucokinase activators (GKAs) promise a new pharmacotherapy for diabetics

The glucose-phosphorylating enzyme glucokinase, a promising target for developing new antidiabetic agents, was identified through the combined efforts of basic research and human biochemical genetics. Allosteric glucokinase activators (GKAs) were discovered by high-throughput screening of a large compound library and first reported in 2003. GKAs stimulate insulin release and glucose metabolism in the liver thereby lowering blood sugar, and promising trials in humans demonstrate that they are highly effective in patients with type 2 diabetes mellitus. Many companies are now attempting to develop effective and safe GKAs for treating diabetics

Experimental Phase-Space Tomography of Semiconductor Laser Dynamics

© 2015 American Physical Society. We perform phase-space tomography of semiconductor laser dynamics by simultaneous experimental determination of optical intensity, frequency, and population inversion with high temporal resolution. We apply this technique to a laser with delayed feedback, serving as prominent example for high-dimensional chaotic dynamics and as model system for fundamental investigations of complex systems. Our approach allows us to explore so far unidentified trajectories in phase space and identify the underlying physical mechanism.This work was supported by Comunitat Autònoma de les Illes Balears via program Grups Competitius, FEDER and MINECO via project TRIPHOP (TEC2012-36335).Peer Reviewe

Autocorrelation properties of chaotic delay dynamical systems: A study on semiconductor lasers

We present a detailed experimental characterization of the autocorrelation properties of a delayed feedback semiconductor laser for different dynamical regimes. We show that in many cases the autocorrelation function of laser intensity dynamics can be approximated by the analytically derived autocorrelation function obtained from a linear stochastic model with delay. We extract a set of dynamic parameters from the fit with the analytic solutions and discuss the limits of validity of our approximation. The linear model captures multiple fundamental properties of delay systems, such as the shift and asymmetric broadening of the different delay echoes. Thus, our analysis provides significant additional insight into the relevant physical and dynamical properties of delayed feedback lasers

Deterministic and stochastic coarsening control in optically addressed spatial light modulators subject to optical feedback

Phase separation accompanied by domain growth and coarsening is a phenomenon common to a broad variety of dynamical systems. In this context, controlling such processes represents a relevant interdisciplinary problem. Through numerical modeling, we demonstrate two complementary approaches of coarsening control in bistable systems based on the example of a spatially extended model describing an optically addressed spatial light modulator with two-color illumination subject to optical feedback. The first method implies varying system parameters such that the system evolves as the pitchfork or saddle-node normal forms. The second method leverages noise, whose intensity serves as an additional system control parameter. Both deterministic and stochastic schemes allow us to control the direction and speed of the fronts separating spatial domains. The considered stochastic control represents a particular case of noise-sustained front propagation in bistable systems and involves the properties of the optical system under study. In contrast, the proposed deterministic control technique can generally be applied to bistable systems of different natures

Strict Selection Alone of Patients Undergoing Liver Transplantation for Hilar Cholangiocarcinoma Is Associated with Improved Survival

Liver transplantation for hilar cholangiocarcinoma (hCCA) has regained attention since the Mayo Clinic reported their favorable results with the use of a neo-adjuvant chemoradiation protocol. However, debate remains whether the success of the protocol should be attributed to the neo-adjuvant therapy or to the strict selection criteria that are being applied. The aim of this study was to investigate the value of patient selection alone on the outcome of liver transplantation for hCCA. In this retrospective study, patients that were transplanted for hCCA between1990 and 2010 in Europe were identified using the European Liver Transplant Registry (ELTR). Twenty-one centers reported 173 patients (69%) of a total of 249 patients in the ELTR. Twenty-six patients were wrongly coded, resulting in a study group of 147 patients. We identified 28 patients (19%) who met the strict selection criteria of the Mayo Clinic protocol, but had not undergone neo-adjuvant chemoradiation therapy. Five–year survival in this subgroup was 59%, which is comparable to patients with pretreatment pathological confirmed hCCA that were transplanted after completion of the chemoradiation protocol at the Mayo Clinic. In conclusion, although the results should be cautiously interpreted, this study suggests that with strict selection alone, improved survival after transplantation can be achieved, approaching the Mayo Clinic experience

Strict Selection Alone of Patients Undergoing Liver Transplantation for Hilar Cholangiocarcinoma is Associated with Improved Survival

Liver transplantation for hilar cholangiocarcinoma (hCCA) has regained attention since the Mayo Clinic reported their favorable results with the use of a neo-adjuvant chemoradiation protocol. However, debate remains whether the success of the protocol should be attributed to the neo-adjuvant therapy or to the strict selection criteria that are being applied. The aim of this study was to investigate the value of patient selection alone on the outcome of liver transplantation for hCCA. In this retrospective study, patients that were transplanted for hCCA between 1990 and 2010 in Europe were identified using the European Liver Transplant Registry (ELTR). Twenty-one centers reported 173 patients (69%) of a total of 249 patients in the ELTR. Twenty-six patients were wrongly coded, resulting in a study group of 147 patients. We identified 28 patients (19%) who met the strict selection criteria of the Mayo Clinic protocol, but had not undergone neo-adjuvant chemoradiation therapy. Five-year survival in this subgroup was 59%, which is comparable to patients with pretreatment pathological confirmed hCCA that were transplanted after completion of the chemoradiation protocol at the Mayo Clinic. In conclusion, although the results should be cautiously interpreted, this study suggests that with strict selection alone, improved survival after transplantation can be achieved, approaching the Mayo Clinic experience

Glucose regulation in non-insulin-dependent diabetes mellitus: Interaction between pancreatic islets and the liver

The degree of fasting hyperglycemia in patients with non-insulin-dependent diabetes mellitus is dependent on the rate of hepatic glucose production. The basal rate of hepatic glucose production is increased in patients with non-insulin-dependent diabetes mellitus, and there is a positive correlation between hepatic glucose production and fasting glucose levels. Diminished secretion of insulin, impaired hepatic sensitivity to insulin's effects, or a combination of these factors could contribute to the elevated hepatic glucose production in patients with non-insulin-dependent diabetes mellitus. The relationship between insulin secretion and hepatic glucose production is regulated by a closed feedback loop operating between glucose levels and pancreatic beta cells. Although fasting insulin levels are usually comparable between patients with non-insulin-dependent diabetes mellitus and normal subjects, insulin secretion is markedly impaired in non-insulin-dependent diabetes mellitus in relation to the degree of hyperglycemia present. In fact, the degree of fasting hyperglycemia in a given patient with non-insulin-dependent diabetes mellitus is closely related to the degree of impaired pancreatic beta-cell responsiveness to glucose. Such findings suggest that impaired insulin secretion leads to increased hepatic glucose production, which raises the plasma glucose level. The resulting hyperglycemia helps to maintain relatively normal basal insulin output. Chronic sulfonylurea drug therapy of patients with non-insulin-dependent diabetes mellitus enhances pancreatic islet sensitivity to glucose, leading to increased insulin secretion, suppression of hepatic glucose production, and a decline in the steady-state fasting glucose level.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25595/1/0000139.pd

Introduction: Studying Successful Public Policy in the Nordic Countries

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