Time-Restricted Feeding Improves Circadian Dysfunction as well as Motor Symptoms in the Q175 Mouse Model of Huntington's Disease.

Huntington's disease (HD) patients suffer from a progressive neurodegeneration that results in cognitive, psychiatric, cardiovascular, and motor dysfunction. Disturbances in sleep/wake cycles are common among HD patients with reports of delayed sleep onset, frequent bedtime awakenings, and fatigue during the day. The heterozygous Q175 mouse model of HD has been shown to phenocopy many HD core symptoms including circadian dysfunctions. Because circadian dysfunction manifests early in the disease in both patients and mouse models, we sought to determine if early intervention that improve circadian rhythmicity can benefit HD and delay disease progression. We determined the effects of time-restricted feeding (TRF) on the Q175 mouse model. At six months of age, the animals were divided into two groups: ad libitum (ad lib) and TRF. The TRF-treated Q175 mice were exposed to a 6-h feeding/18-h fasting regimen that was designed to be aligned with the middle of the time when mice are normally active. After three months of treatment (when mice reached the early disease stage), the TRF-treated Q175 mice showed improvements in their locomotor activity rhythm and sleep awakening time. Furthermore, we found improved heart rate variability (HRV), suggesting that their autonomic nervous system dysfunction was improved. Importantly, treated Q175 mice exhibited improved motor performance compared to untreated Q175 controls, and the motor improvements were correlated with improved circadian output. Finally, we found that the expression of several HD-relevant markers was restored to WT levels in the striatum of the treated mice using NanoString gene expression assays

Requirements engineering: a review and research agenda

This paper reviews the area of requirements engineering. It outlines the key concerns to which attention should be devoted by both practitioners, who wish to "reengineer" their development processes, and academics, seeking intellectual challenges. It presents an assessment of the state-of-the-art and draws conclusions in the form of a research agenda

Pulsar-wind nebulae and magnetar outflows: observations at radio, X-ray, and gamma-ray wavelengths

We review observations of several classes of neutron-star-powered outflows: pulsar-wind nebulae (PWNe) inside shell supernova remnants (SNRs), PWNe interacting directly with interstellar medium (ISM), and magnetar-powered outflows. We describe radio, X-ray, and gamma-ray observations of PWNe, focusing first on integrated spectral-energy distributions (SEDs) and global spectral properties. High-resolution X-ray imaging of PWNe shows a bewildering array of morphologies, with jets, trails, and other structures. Several of the 23 so far identified magnetars show evidence for continuous or sporadic emission of material, sometimes associated with giant flares, and a few possible "magnetar-wind nebulae" have been recently identified.Comment: 61 pages, 44 figures (reduced in quality for size reasons). Published in Space Science Reviews, "Jets and Winds in Pulsar Wind Nebulae, Gamma-ray Bursts and Blazars: Physics of Extreme Energy Release

Herculin, a Fourth Member of the MyoD Family of Myogenic Regulatory Genes

We have identified and cloned herculin, a fourth mouse muscle regulatory gene. Comparison of its DNA and deduced amino acid sequences with those of the three known myogenic genes (MyoD, myogenin, and Myf-5) reveals scattered short spans with similarity to one or more of these genes and a long span with strong similarity to all three. This long span includes a sequence motif that is also present in proteins of the myc, achaete-scute, and immunoglobulin enhancer-binding families. The herculin gene is physically linked to the Myf-5 gene on the chromosome; only 8.5 kilobases separate their translational start sites. A putative 27-kDa protein is encoded by three exons contained within a 1.7-kilobase fragment of the herculin gene. When expressed under the control of the simian virus 40 early promoter, transfected herculin renders murine NIH 3T3 and C3H/10T1/2 fibroblasts myogenic. In doing so, it also activates expression of myogenin, MyoD, and endogenous herculin in NIH 3T3 recipients. In adult mice, herculin is expressed in skeletal muscle but is absent from smooth muscle, cardiac muscle, and all nonmuscle tissues assayed. Direct comparison of the four known myogenic regulators in adult muscle showed that herculin is expressed at a significantly higher level than is any of the others. This quantitative dominance suggests an important role in the establishment or maintenance of adult skeletal muscle

Measurement of \cal{B}(D^+ --> mu^+ nu) and the Pseudoscalar Decay Constant fD+f_{D^+}

In 60 pb-1 of data taken on the psi(3770) resonance with the CLEO-c detector, we find 8 D+ to mu+ nu event candidates that are mostly signal, containing only 1 estimated background. Using this statistically compelling sample, we measure preliminary values of B(D+ to mu+ nu) = (3.5 +- 1.4 +- 0.6)*10^{-4}, and determine f_{D+} =(201+- 41+- 17) MeV.Comment: 17 pages postscript, also available through http://www.lns.cornell.edu/public/CONF/2004/, Presented at ICHEP Aug 16-22,2004, Beijing, Chin

Evidence for B^(*)_s bar{B}^(*)_s Production at the Upsilon(5S)

Using data collected by the CLEO III detector at CESR, we started a series of investigations on the Upsilon(5S) resonance decay properties. The data sample used for this analysis consists of 0.42 fb-1 of data taken on the Upsilon(5S) resonance, 6.34 fb-1 of data collected on the Upsilon(4S) and 2.32 fb-1 of data taken in the continuum below the Upsilon(4S). B_s mesons are expected to decay predominantly into D_s meson, while the lighter B mesons decay into D_s only about 10% of the time. We exploit this difference to make a preliminary model dependent estimate of the ratio of B_s(*) anti-B_s(*) to the total b anti-b quark pair production at the Upsilon(5S) energy to be (21 +- 3 +- 9)%.Comment: 17 pages postscript,also available through http://www.lns.cornell.edu/public/CONF/2004/, Presented at ICHEP Aug 16-22,2004, Beijing, Chin