Novel gene function revealed by mouse mutagenesis screens for models of age-related disease

Determining the genetic bases of age-related disease remains a major challenge requiring a spectrum of approaches from human and clinical genetics to the utilization of model organism studies. Here we report a large-scale genetic screen in mice employing a phenotype-driven discovery platform to identify mutations resulting in age-related disease, both late-onset and progressive. We have utilized N-ethyl-N-nitrosourea mutagenesis to generate pedigrees of mutagenized mice that were subject to recurrent screens for mutant phenotypes as the mice aged. In total, we identify 105 distinct mutant lines from 157 pedigrees analysed, out of which 27 are late-onset phenotypes across a range of physiological systems. Using whole-genome sequencing we uncover the underlying genes for 44 of these mutant phenotypes, including 12 late-onset phenotypes. These genes reveal a number of novel pathways involved with age-related disease. We illustrate our findings by the recovery and characterization of a novel mouse model of age-related hearing loss

Differences in pre-sleep activity and sleep location are associated with variability in daytime/nighttime sleep electrophysiology in the domestic dog

The domestic dog (Canis familiaris) is a promising animal model. Yet, the canine neuroscience literature is predominantly comprised of studies wherein (semi-)invasive methods and intensive training are used to study awake dog behavior. Given prior findings with humans and/or dogs, our goal was to assess, in 16 family dogs (1.5–7 years old; 10 males; 10 different breeds) the effects of pre-sleep activity and timing and location of sleep on sleep electrophysiology. All three factors had a main and/or interactive effect on sleep macrostructure. Following an active day, dogs slept more, were more likely to have an earlier drowsiness and NREM, and spent less time in drowsiness and more time in NREM and REM. Activity also had location- and time of day-specific effects. Time of day had main effects; at nighttime, dogs slept more and spent less time in drowsiness and awake after first drowsiness, and more time in NREM and in REM. Location had a main effect; when not at home, REM sleep following a first NREM was less likely. Findings are consistent with and extend prior human and dog data and have implications for the dog as an animal model and for informing future comparative research on sleep

Air Traffic Control

Abstract : The report covers the development of improved surveillance and communication subsystems to meet the demands of the automated NAS/ARTS Air Traffic Control system. Field measurements of the beacon interference environment were completed and studies to upgrade sensor efficiency were intensified. Effort toward the development of a discrete address interrogator with a data link was concentrated upon the core problem of designing the signaling waveforms for both up and down links of the system. Particular attention is being given to system performance in the interference and multipath environment, as well as to system and equipment compatibility with ATCRBS. The project to develop an airborne situation display of NAS/ARTS data has reached the stage for definition of an experimental system. The computer simulated cockpit display has evoked enthusiastic response from experienced pilots and traffic controllers. Preliminary work on the laser beam warning system for Logan Airport was completed with successful demonstration of the prototype hardware in the Laboratory. Document type: Repor

Transaction mechanisms for distributed programming environments

Considerable research effort in the software engineering domain has been focused on the development of more advanced programming environments. A key aspect in this development is distribution. Distributed computer systems have the potential for high reliability. This is primarily because resources can be provided redundantly at different sites. However, the possibility of partial system failure and the high level of parallel activity in distributed systems make it difficult to realize this potential. In an attempt to simplify the treatment of these problems in distributed database systems, the notion of atomic transactions was introduced. The transaction concept is equally applicable to the area of distributed programming environments. However, traditional database transaction mechanisms are not efficient or flexible enought to meet the requirements of distributed programming environments. This paper presents a survey of transaction techniques and discusses the application of the transaction model to distributed programming environments