Mutations in Rab3a alter circadian period and homeostatic response to sleep loss in the mouse

Rab3a is the most abundant Rab (ras-associated binding) protein in the brain and has a regulatory role in synaptic vesicle trafficking. Mice with a targeted loss-of-function mutation in Rab3a have defects in Ca(2+)-dependent synaptic transmission: the number of vesicles released in response to an action potential is greater than in wildtype mice, resulting in greater synaptic depression and the abolishment of CA3 mossy-fiber long term potentiation. The effect of these changes on behavior is unknown. In a screen for mouse mutants with abnormal rest-activity and sleep patterns, we identified a semidominant mutation, called earlybird, that shortens the circadian period of locomotor activity. Sequence analysis of Rab3a identified a point mutation in the conserved amino acid (Asp77Gly) within the GTP-binding domain of this protein in earlybird mutants, resulting in significantly reduced levels of Rab3a protein. Phenotypic assessment of earlybird mice and a null allele of Rab3a revealed anomalies in circadian period and sleep homeostasis, providing evidence that Rab3a-mediated synaptic transmission is involved in these behaviors.     

Disruption of fragmented parent bodies as the origin of asteroid families

Asteroid families are groups of small bodies that share certain orbit and spectral properties. More than 20 families have now been identified, each believed to have resulted from the collisional break-up of a large parent body in a regime where gravity controls the outcome of the collision more than the material strength of the rock. The size and velocity distributions of the family members provide important constraints for testing our understanding of the break-up process, but erosion and dynamical diffusion of the orbits over time can erase the original signature of the collision. The recently identified young Karin family provides a unique opportunity to study a collisional outcome almost unaffected by orbit evolution. Here we report numerical simulations modelling classes of collisions that reproduce the main characteristics of the Karin family. The sensitivity of the outcome of the collision to the internal structure of the parent body allows us to show that the family must have originated from the break-up of a pre-fragmented parent body, and that all large family members formed by the gravitational reaccumulation of smaller bodies. We argue that most of the identified asteroid families are likely to have had a similar history.     

Microfluidic systems: high radial acceleration in microvortices

Microfluidic systems can conveniently be used for rapid analysis of biological samples. Here we describe a single re-circulating flow, or microvortex, that can generate a maximum fluid rotational velocity of up to 12 m s(-1) and a corresponding radial acceleration in excess of 10(6)g. Such microvortices may be exploited in centrifugal microdevices to investigate the effects of high radial acceleration on biological and chemical processes.     

An epi-allelic series of p53 hypomorphs created by stable RNAi produces distinct tumor phenotypes in vivo

The application of RNA interference (RNAi) to mammalian systems has the potential to revolutionize genetics and produce novel therapies. Here we investigate whether RNAi applied to a well-characterized gene can stably suppress gene expression in hematopoietic stem cells and produce detectable phenotypes in mice. Deletion of the Trp53 tumor suppressor gene greatly accelerates Myc-induced lymphomagenesis, resulting in highly disseminated disease. To determine whether RNAi suppression of Trp53 could produce a similar phenotype, we introduced several Trp53 short hairpin RNAs (shRNAs) into hematopoietic stem cells derived from E(mu)-Myc transgenic mice, and monitored tumor onset and overall pathology in lethally irradiated recipients. Different Trp53 shRNAs produced distinct phenotypes in vivo, ranging from benign lymphoid hyperplasias to highly disseminated lymphomas that paralleled Trp53-/- lymphomagenesis in the E(mu)-Myc mouse. In all cases, the severity and type of disease correlated with the extent to which specific shRNAs inhibited p53 activity. Therefore, RNAi can stably suppress gene expression in stem cells and reconstituted organs derived from those cells. In addition, intrinsic differences between individual shRNA expression vectors targeting the same gene can be used to create an 'epi-allelic series' for dissecting gene function in vivo.     

A multiple intelligent agent system for credit risk prediction via an optimization of localized generalization error with diversity

Company bankruptcies cost billions of dollars in losses to banks each year. Thus credit risk prediction is a critical part of a bank＇s loan approval decision process. Traditional financial models for credit risk prediction are no longer adequate for describing today＇s complex relationship between the financial health and potential bankruptcy of a company. In this work, a multiple classifier system （embedded in a multiple intelligent agent system） is proposed to predict the financial health of a company. In our model, each individual agent （classifier） makes a prediction on the likelihood of credit risk based on only partial information of the company. Each of the agents is an expert, but has limited knowledge （represented by features） about the company. The decisions of all agents are combined together to form a final credit risk prediction. Experiments show that our model out-performs other existing methods using the benchmarking Compustat American Corporations dataset.     

Recent Advances in the Development of Polymer-supported Phosphines

1 Introduction Recent years have seen a growing use of polymer-supported reagents by organic chemists in traditional solution-phase synthesis.Of the many reagents supported by polymers available, variations of triphenylphosphine are among the most broadly used. This is because triphenylphosphine is not only a reagent in a wide range of organic reactions~([1]), but it also serves as a ligand in many organometallic reagents~([2]).Most importantly, polymer-supported triphenylphosphine affords the…