Functional Inactivation of Drosophila GCK Orthologs Causes Genomic Instability and Oxidative Stress in a Fly Model of MODY-2

Maturity-onset diabetes of the young (MODY) type 2 is caused by heterozygous inactivating mutations in the gene encoding glucokinase (GCK), a pivotal enzyme for glucose homeostasis. In the pancreas GCK regulates insulin secretion, while in the liver it promotes glucose utilization and storage. We showed that silencing the Drosophila GCK orthologs Hex-A and Hex-C results in a MODY-2-like hyperglycemia. Targeted knock-down revealed that Hex-A is expressed in insulin producing cells (IPCs) whereas Hex-C is specifically expressed in the fat body. We showed that Hex-A is essential for insulin secretion and it is required for Hex-C expression. Reduced levels of either Hex-A or Hex-C resulted in chromosome aberrations (CABs), together with an increased production of advanced glycation end-products (AGEs) and reactive oxygen species (ROS). This result suggests that CABs, in GCK depleted cells, are likely due to hyperglycemia, which produces oxidative stress through AGE metabolism. In agreement with this hypothesis, treating GCK-depleted larvae with the antioxidant vitamin B6 rescued CABs, whereas the treatment with a B6 inhibitor enhanced genomic instability. Although MODY-2 rarely produces complications, our data revealed the possibility that MODY-2 impacts genome integrity.     

A comparative analysis of methods for pruning decision trees

In this paper, we address the problem of retrospectively pruning decision trees induced from data, according to a top-down approach. This problem has received considerable attention in the areas of pattern recognition and machine learning, and many distinct methods have been proposed in literature. We make a comparative study of six well-known pruning methods with the aim of understanding their theoretical foundations, their computational complexity, and the strengths and weaknesses of their formulation. Comments on the characteristics of each method are empirically supported. In particular, a wide experimentation performed on several data sets leads us to opposite conclusions on the predictive accuracy of simplified trees from some drawn in the literature. We attribute this divergence to differences in experimental designs. Finally, we prove and make use of a property of the reduced error pruning method to obtain an objective evaluation of the tendency to overprune/underprune observed in each method     

Localized dissection of the abdominal aorta. Diagnosis and surgical treatment

Abdominal aortic dissection is a rare pathology. As far as we are concerned, only 59 cases have been reported in the English literature. In the last two years, two cases were treated at our Institution. Both were males, over 70 years of age. They were evaluated with ultrasonography, angiography (1 case) and Magnetic Resonance Imaging which showed localised dissection of the abdominal aorta with aneurysmal dilatation. They underwent surgical treatment with good results. At 1 and 2 years from operation both patients are alive and well. A postoperative ultrasonography didn't show any residual dissection.     

Resonant Quantum Phenomena for an rf-SQUID: Moderate Underdamped and Extreme Underdamped Limit

We study the resonant quantum behaviour of a macroscopic superconducting system interacting with an external field. First we consider the resonant tunneling assisted by microwave frequency in the moderate underdamped quantum regime. Then we consider the resonant process in the extreme underdamped limit. In both regimes we have investigated a small frequency range, where resonant phenomena take place. The transition probability W from the left to the right potential well has been numerically calculated for an rf-SQUID as function of the external flux φ _x for both regimes. Results indicate that, in a proper frequency and φ _x range, the transition probability W can present two or three resonant peaks, depending on the damping regime.