Conjunction of factors triggering waves of seasonal influenza

Using several longitudinal datasets describing putative factors affecting influenza incidence and clinical data on the disease and health status of over 150 million human subjects observed over a decade, we investigated the source and the mechanistic triggers of influenza epidemics. We conclude that the initiation of a pan-continental influenza wave emerges from the simultaneous realization of a complex set of conditions. The strongest predictor groups are as follows, ranked by importance: (1) the host population’s socio- and ethno-demographic properties; (2) weather variables pertaining to specific humidity, temperature, and solar radiation; (3) the virus’ antigenic drift over time; (4) the host population’€™s land-based travel habits, and; (5) recent spatio-temporal dynamics, as reflected in the influenza wave auto-correlation. The models we infer are demonstrably predictive (area under the Receiver Operating Characteristic curve 80%) when tested with out-of-sample data, opening the door to the potential formulation of new population-level intervention and mitigation policies

Mini-mast CSI testbed user's guide

The Mini-Mast testbed is a 20 m generic truss highly representative of future deployable trusses for space applications. It is fully instrumented for system identification and active vibrations control experiments and is used as a ground testbed at NASA-Langley. The facility has actuators and feedback sensors linked via fiber optic cables to the Advanced Real Time Simulation (ARTS) system, where user defined control laws are incorporated into generic controls software. The object of the facility is to conduct comprehensive active vibration control experiments on a dynamically realistic large space structure. A primary goal is to understand the practical effects of simplifying theoretical assumptions. This User's Guide describes the hardware and its primary components, the dynamic characteristics of the test article, the control law implementation process, and the necessary safeguards employed to protect the test article. Suggestions for a strawman controls experiment are also included

BAX Is Required for Neuronal Death after Trophic Factor Deprivation and during Development

AbstractMembers of the BCL2-related family of proteins either promote or repress programmed cell death. BAX, a death-promoting member, heterodimerizes with multiple death-repressing molecules, suggesting that it could prove critical to cell death. We tested whether Bax is required for neuronal death by trophic factor deprivation and during development. Neonatal sympathetic neurons and facial motor neurons from Bax-deficient mice survived nerve growth factor deprivation and disconnection from their targets by axotomy, respectively. These salvaged neurons displayed remarkable soma atrophy and reduced elaboration of neurites; yet they responded to readdition of trophic factor with soma hypertrophy and enhanced neurite outgrowth. Bax-deficient superior cervical ganglia and facial nuclei possessed increased numbers of neurons. Our observations demonstrate that trophic factor deprivation–induced death of sympathetic and motor neurons depends on Bax

Langley's CSI evolutionary model: Phase O

A testbed for the development of Controls Structures Interaction (CSI) technology to improve space science platform pointing is described. The evolutionary nature of the testbed will permit the study of global line-of-sight pointing in phases 0 and 1, whereas, multipayload pointing systems will be studied beginning with phase 2. The design, capabilities, and typical dynamic behavior of the phase 0 version of the CSI evolutionary model (CEM) is documented for investigator both internal and external to NASA. The model description includes line-of-sight pointing measurement, testbed structure, actuators, sensors, and real time computers, as well as finite element and state space models of major components

Influence of photoperiod and running wheel access on the entrainment of split circadian rhythms in hamsters

BACKGROUND: In the laboratory, behavioral and physiological states of nocturnal rodents alternate, with a period near 24 h, between those appropriate for the night (e.g., elevated wheel-running activity and high melatonin secretion) and for the day (e.g., rest and low melatonin secretion). Under appropriate 24 h light:dark:light:dark conditions, however, rodents may be readily induced to express bimodal rest/activity cycles that reflect a global temporal reorganization of the central neural pacemaker in the hypothalamus. We examine here how the relative length of the light and dark phases of the environmental cycle influences this rhythm splitting and the necessity of a running wheel for expression of this entrainment condition. RESULTS: Rhythm splitting was observed in wheel-running and general locomotion of Siberian and Syrian hamsters. The latter also manifest split rhythms in body temperature. Access to a running wheel was necessary neither for the induction nor maintenance of this entrainment pattern. While rhythms were only transiently split in many animals with two 5 h nights, the incidence of splitting was greater with twice daily nights of shorter duration. Removal of running wheels altered the body temperature rhythm but did not eliminate its clear bimodality. CONCLUSION: The expression of entrained, split circadian rhythms exhibits no strict dependence on access to a running wheel, but can be facilitated by manipulation of ambient lighting conditions. These circadian entrainment patterns may be of therapeutic value to human shift-workers and others facing chronobiological challenges

Weak evidence of bright light effects on human LH and FSH

<p>Abstract</p> <p>Background</p> <p>Most mammals are seasonal breeders whose gonads grow to anticipate reproduction in the spring and summer. As day length increases, secretion increases for two gonadotropins, luteinizing hormone (LH) and follicle stimulating hormone (FSH). This response is largely controlled by light. Light effects on gonadotropins are mediated through effects on the suprachiasmatic nucleus and responses of the circadian system. There is some evidence that seasonal breeding in humans is regulated by similar mechanisms, and that light stimulates LH secretion, but primate responses seem complex.</p> <p>Methods</p> <p>To gain further information on effects of bright light on LH and FSH secretion in humans, we analyzed urine samples collected in three experiments conducted for other goals. First, volunteers ages 18-30 years and 60-75 commenced an ultra-short 90-min sleep-wake cycle, during which they were exposed to 3000 lux light for 3 hours at balanced times of day, repeated for 3 days. Urine samples were assayed to explore any LH phase response curve. Second, depressed participants 60-79 years of age were treated with bright light or dim placebo light for 28 days, with measurements of urinary LH and FSH before and after treatment. Third, women of ages 20-45 years with premenstrual dysphoric disorder (PMDD) were treated to one 3-hour exposure of morning light, measuring LH and FSH in urine before and after the treatments.</p> <p>Results</p> <p>Two of the three studies showed significant increases in LH after light treatment, and FSH also tended to increase, but there were no significant contrasts with parallel placebo treatments and no significant time-of-day treatment effects.</p> <p>Conclusions</p> <p>These results gave some support for the hypothesis that bright light may augment LH secretion. Longer-duration studies may be needed to clarify the effects of light on human LH and FSH.</p

Rapid phase adjustment of melatonin and core body temperature rhythms following a 6-h advance of the light/dark cycle in the horse

<p>Abstract</p> <p>Background</p> <p>Rapid displacement across multiple time zones results in a conflict between the new cycle of light and dark and the previously entrained program of the internal circadian clock, a phenomenon known as jet lag. In humans, jet lag is often characterized by malaise, appetite loss, fatigue, disturbed sleep and performance deficit, the consequences of which are of particular concern to athletes hoping to perform optimally at an international destination. As a species renowned for its capacity for athletic performance, the consequences of jet lag are also relevant for the horse. However, the duration and severity of jet lag related circadian disruption is presently unknown in this species. We investigated the rates of re-entrainment of serum melatonin and core body temperature (BT) rhythms following an abrupt 6-h phase advance of the LD cycle in the horse.</p> <p>Methods</p> <p>Six healthy, 2 yr old mares entrained to a 12 h light/12 h dark (LD 12:12) natural photoperiod were housed in a light-proofed barn under a lighting schedule that mimicked the external LD cycle. Following baseline sampling on Day 0, an advance shift of the LD cycle was accomplished by ending the subsequent dark period 6 h early. Blood sampling for serum melatonin analysis and BT readings were taken at 3-h intervals for 24 h on alternate days for 11 days. Disturbances to the subsequent melatonin and BT 24-h rhythms were assessed using repeated measures ANOVA and analysis of Cosine curve fitting parameters.</p> <p>Results</p> <p>We demonstrate that the equine melatonin rhythm re-entrains rapidly to a 6-h phase advance of an LD12:12 photocycle. The phase shift in melatonin was fully complete on the first day of the new schedule and rhythm phase and waveform were stable thereafter. In comparison, the advance in the BT rhythm was achieved by the third day, however BT rhythm waveform, especially its mesor, was altered for many days following the LD shift.</p> <p>Conclusion</p> <p>Aside from the temperature rhythm disruption, rapid resynchronization of the melatonin rhythm suggests that the central circadian pacemaker of the horse may possess a particularly robust entrainment response. The consequences for athletic performance remain unknown.</p

Optical Propagation and Communication

Contains an introduction and reports on three research projects.Maryland Procurement Office Contract MDA 904-93-C4169Maryland Procurement Office Contract MDA 903-94-C6071U.S. Air Force - Office of Scientific Research Grant F49620-93-1-0604MIT Lincoln Laboratory Advanced Concepts Program Contract CX-16335U.S. Army Research Office Grant DAAH04-93-G-0399U.S. Army Research Office Grant DAAH04-93-G-018

Opposing brain differences in 16p11.2 deletion and duplication carriers

Deletions and duplications of the recurrent ∼600 kb chromosomal BP4–BP5 region of 16p11.2 are associated with a broad variety of neurodevelopmental outcomes including autism spectrum disorder. A clue to the pathogenesis of the copy number variant (CNV)'s effect on the brain is that the deletion is associated with a head size increase, whereas the duplication is associated with a decrease. Here we analyzed brain structure in a clinically ascertained group of human deletion (N = 25) and duplication (N = 17) carriers from the Simons Variation in Individuals Project compared with age-matched controls (N = 29 and 33, respectively). Multiple brain measures showed increased size in deletion carriers and reduced size in duplication carriers. The effects spanned global measures of intracranial volume, brain size, compartmental measures of gray matter and white matter, subcortical structures, and the cerebellum. Quantitatively, the largest effect was on the thalamus, but the collective results suggest a pervasive rather than a selective effect on the brain. Detailed analysis of cortical gray matter revealed that cortical surface area displays a strong dose-dependent effect of CNV (deletion > control > duplication), whereas average cortical thickness is less affected. These results suggest that the CNV may exert its opposing influences through mechanisms that influence early stages of embryonic brain development

Restricted Expression of G86R Cu/Zn Superoxide Dismutase in Astrocytes Results in Astrocytosis But Does Not Cause Motoneuron Degeneration

Evidence garnered from both human autopsy studies and genetic animal models has suggested a potential role for astrocytes in the pathogenesis of amyotrophic lateral sclerosis (ALS). Currently, mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1) represent the only known cause of motoneuron loss in the disease, producing 21q linked familial ALS (FALS). To determine whether astrocytic dysfunction has a primary role in familial ALS, we have generated multiple lines of transgenic mice expressing G86R mutant SOD1 restricted to astrocytes. In GFAP-m SOD1 mice, astrocytes exhibit significant hypertrophy and increased GFAP reactivity as the animals mature. However, GFAP-mutant SOD1 transgenic mice develop normally and do not experience spontaneous motor deficits with increasing age. Histological examination of spinal cord in aged GFAP-mSOD1 mice reveals normal motoneuron and microglial morphology. These results indicate that 21q linked FALS is not a primary disorder of astrocytes, and that expression of mutant SOD1 restricted to astrocytes is not sufficient to cause motoneuron degeneratio