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PubMed2002

An infrared system for monitoring Drosophila motility during microgravity.

Presently, the precise mechanisms of the aging process are unknown. Examination and comprehension of the aging process in other species could lead to significant advances in the understanding of human aging. Drosophila melanogaster (fruit fly), commonly used for aging studies, is a widely studied organism in terms of behavior, development, and genetics. Previous microgravity experiments have shown a significant decrease in the life span of young male Drosophila after microgravity exposure. This decrease in lifespan may be related to locomotor activity, a convenient measure of overall physiological performance. This study describes the design and performance of a Drosophila Infrared Motility Monitoring System (DIMMS). The DIMMS uses a unique design of two infrared (IR) beams per fly to measure the locomotor activity of 240 flies. Locomotor activity is measured in terms of number of IR crossings per unit time, instantaneous velocity, and continuous velocity. Ground-based results using the DIMMS equipment agree well with previous values for Drosophila locomotor velocity. DIMMS is an improvement over equipment previously used due to its ability to continuously monitor locomotor activity throughout short-duration microgravity exposure. DIMMS is also lightweight, compact, and power efficient. DIMMS has been flight tested onboard NASA's KC-135 reduced gravity research aircraft and a Nike-Orion sounding rocket.

Aging↗
PubMed2001

Efficient hemodynamic event detection utilizing relational databases and wavelet analysis.

Development of a temporal query framework for time-oriented medical databases has hitherto been a challenging problem. We describe a novel method for the detection of hemodynamic events in multiparameter trends utilizing wavelet coefficients in a MySQL relational database. Storage of the wavelet coefficients allowed for a compact representation of the trends, and provided robust descriptors for the dynamics of the parameter time series. A data model was developed to allow for simplified queries along several dimensions and time scales. Of particular importance, the data model and wavelet framework allowed for queries to be processed with minimal table-join operations. A web-based search engine was developed to allow for user-defined queries. Typical queries required between 0.01 and 0.02 seconds, with at least two orders of magnitude improvement in speed over conventional queries. This powerful and innovative structure will facilitate research on large-scale time-oriented medical databases.

Algorithms↗
PubMed2002

MIMIC II: a massive temporal ICU patient database to support research in intelligent patient monitoring.

Development and evaluation of Intensive Care Unit (ICU) decision-support systems would be greatly facilitated by the availability of a large-scale ICU patient database. Following our previous efforts with the MIMIC (Multi-parameter Intelligent Monitoring for Intensive Care) Database, we have leveraged advances in networking and storage technologies to develop a far more massive temporal database, MIMIC II. MIMIC II is an ongoing effort: data is continuously and prospectively archived from all ICU patients in our hospital. MIMIC II now consists of over 800 ICU patient records including over 120 gigabytes of data and is growing. A customized archiving system was used to store continuously up to four waveforms and 30 different parameters from ICU patient monitors. An integrated user-friendly relational database was developed for browsing of patients' clinical information (lab results, fluid balance, medications, nurses' progress notes). Based upon its unprecedented size and scope, MIMIC II will prove to be an important resource for intelligent patient monitoring research, and will support efforts in medical data mining and knowledge-discovery.

Artificial Intelligence↗
PubMed2002

Mechanisms of microgravity induced orthostatic intolerance: implications for effective countermeasures.

The development of orthostatic hypotension and instability immediately after return from spaceflight has been a significant operational problem to astronauts for more than four decades. Significant reductions in stroke volume and peripheral vascular resistance contribute to ineffective maintenance of systemic arterial blood pressure during standing after spaceflight despite compensatory elevations in heart rate. The primary mechanism underlying reduced stroke volume appears to be a reduction in preload associated with reduced circulating blood volume, although cardiac atrophy might also contribute. Space flight and ground based experiments have demonstrated that an inability to provide adequate peripheral vasoconstriction in astronauts that become presyncopal may be associated with several mechanisms including reduced sympathetic nerve activity, arterial smooth muscle atrophy and/or hyporeactivity, hypersensitivity of beta-adrenergic receptors, etc. In addition, an inability to provide adequate tachycardia in presyncopal subjects may be associated with reduced carotid-cardiac baroreflex sensitivity. Based on the current knowledge and understanding of cardiovascular mechanisms that are altered during exposure to microgravity, a major focus of future research should be directed to the systematic evaluation of potential countermeasures that specifically target and restore the function of these mechanisms. Based on a preliminary systematic evaluation presented in this review, acute physical exercise designed to elicit maximal effort, G-suit inflation, artificial gravity, and specific pharmacological interventions, alone or in combination, have shown promise as successful countermeasures that provide protection against post-flight orthostatic intolerance.

Aerospace Medicine↗
PubMed2002

Effects of spaceflight, simulated spaceflight and countermeasures on single muscle fiber physiology.

Since the first human flew in space in 1961, there has been extensive scientific interest in the responses of the human body and how it adapts to this unique environment. From the available data, it appears that all major systems in the human body undergo an adaptive change while in a microgravity environment. In particular the human muscle system appears to undergo loss of muscle mass and strength which greatly influences the maximal work capacity of the muscle. Recently, our research group has been involved in a series of whole muscle and cellular studies during periods of short duration space flight, bed rest, and unilateral lower limb suspension (ULLS) in an attempt to elucidate the changes that are occurring in the whole muscle and single muscle fiber contractile properties with unloading. In addition, various countermeasure activities for skeletal muscle have been part of the space flights and ground-based studies. The intention of this paper will be to briefly review our findings in whole muscle, cellular, and countermeasure effectiveness with human muscle.

NASA Discipline Musculoskeletal↗
PubMed2000

Genetic dissection of cardiac growth control pathways.

Cardiac muscle cells exhibit two related but distinct modes of growth that are highly regulated during development and disease. Cardiac myocytes rapidly proliferate during fetal life but exit the cell cycle irreversibly soon after birth, following which the predominant form of growth shifts from hyperplastic to hypertrophic. Much research has focused on identifying the candidate mitogens, hypertrophic agonists, and signaling pathways that mediate these processes in isolated cells. What drives the proliferative growth of embryonic myocardium in vivo and the mechanisms by which adult cardiac myocytes hypertrophy in vivo are less clear. Efforts to answer these questions have benefited from rapid progress made in techniques to manipulate the murine genome. Complementary technologies for gain- and loss-of-function now permit a mutational analysis of these growth control pathways in vivo in the intact heart. These studies have confirmed the importance of suspected pathways, have implicated unexpected pathways as well, and have led to new paradigms for the control of cardiac growth.

Animals↗
PubMed2004

Heavy particle irradiation, neurochemistry and behavior: thresholds, dose-response curves and recovery of function.

Exposure to heavy particles can affect the functioning of the central nervous system (CNS), particularly the dopaminergic system. In turn, the radiation-induced disruption of dopaminergic function affects a variety of behaviors that are dependent upon the integrity of this system, including motor behavior (upper body strength), amphetamine (dopamine)-mediated taste aversion learning, and operant conditioning (fixed-ratio bar pressing). Although the relationships between heavy particle irradiation and the effects of exposure depend, to some extent, upon the specific behavioral or neurochemical endpoint under consideration, a review of the available research leads to the hypothesis that the endpoints mediated by the CNS have certain characteristics in common. These include: (1) a threshold, below which there is no apparent effect; (2) the lack of a dose-response relationship, or an extremely steep dose-response curve, depending on the particular endpoint; and (3) the absence of recovery of function, such that the heavy particle-induced behavioral and neural changes are present when tested up to one year following exposure. The current report reviews the data relevant to the degree to which these characteristics are common to neurochemical and behavioral endpoints that are mediated by the effects of exposure to heavy particles on CNS activity.

Amphetamine↗
PubMedDate not supplied

Social roles and the evolution of networks in extreme and isolated environments.

This article reports on the evolution of network structure as it relates to formal and informal social roles in well-bounded, isolated groups. Research was conducted at the Amundsen-Scott South Pole Station. Data were collected on crewmembers' networks of social interaction over each of three winter-over periods, when the station is completely isolated. In addition, data were collected on the informal roles played by crewmembers (e.g., instrumental leadership, expressive leadership). The study found that globally coherent networks in winter-over groups were associated with group consensus on the presence of critically important informal social roles (e.g., expressive leadership) where global coherence is the extent to which a network forms a single group composed of a unitary core and periphery as opposed to being factionalized into two or more subgroups. Conversely, the evolution of multiple subgroups was associated with the absence of consensus on critical informal social roles, above all the critically important role of instrumental leader.

Adaptation, Psychological↗
PubMed2000

Sleep and mood during a winter in Antarctica.

Seasonal variations in sleep characteristics and their association with changes in mood were examined in 91 American men and women who spent the 1991 austral winter at three different research stations in Antarctica. Measures of total hours of sleep over a 24-hr period, duration of longest (i.e., "nighttime") sleep event, number of sleep events, time of sleep onset, and quality of sleep remained unchanged over the course of the austral winter (March through October). However, exposure to total darkness based on station latitude was significantly associated with total hours of sleep, duration of longest sleep event, time of sleep onset, and quality of sleep. Reported vigor the previous month was a significant independent predictor of changes in all five sleep measures; previous month's measures of all six POMS subscales were significant independent predictors of sleep quality. Sleep characteristics were significant independent predictors of vigor and confusion the following month; total sleep, longest sleep event, sleep onset and sleep quality were significant independent predictors of tension-anxiety and depression. Changes in mood during the austral winter are preceded by changes in sleep characteristics, but prolonged exposure to the photo-periodicity characteristic of the high latitudes appears to be associated with improved sleep. In turn, mood changes appear to affect certain sleep characteristics, especially sleep quality.

Adult↗
PubMed2004

The effects of proton exposure on neurochemistry and behavior.

Future space missions will involve long-term travel beyond the magnetic field of the Earth, where astronauts will be exposed to radiation hazards such as those that arise from galactic cosmic rays. Galactic cosmic rays are composed of protons, alpha particles, and particles of high energy and charge (HZE particles). Research by our group has shown that exposure to HZE particles, primarily 600 MeV/n and 1 GeV/n 56Fe, can produce significant alterations in brain neurochemistry and behavior. However, given that protons can make up a significant portion of the radiation spectrum, it is important to study their effects on neural functioning and on related performance. Therefore, these studies examined the effects of exposure to proton irradiation on neurochemical and behavioral endpoints, including dopaminergic functioning, amphetamine-induced conditioned taste aversion learning, and spatial learning and memory as measured by the Morris water maze. Male Sprague-Dawley rats received a dose of 0, 1.5, 3.0 or 4.0 Gy of 250 MeV protons at Loma Linda University and were tested in the different behavioral tests at various times following exposure. Results showed that there was no effect of proton irradiation at any dose on any of the endpoints measured. Therefore, there is a contrast between the insignificant effects of high dose proton exposure and the dramatic effectiveness of low dose (<0.1 Gy) exposures to 56Fe particles on both neurochemical and behavioral endpoints.

Animals↗
PubMed2000

Simian virus 40, poliovirus vaccines, and human cancer: research progress versus media and public interests.

From 1955 through early 1963, millions of people were inadvertently exposed to simian virus 40 (SV40) as a contaminant of poliovirus vaccines; the virus had been present in the monkey kidney cultures used to prepare the vaccines and had escaped detection. SV40 was discovered in 1960 and subsequently eliminated from poliovirus vaccines. This article reviews current knowledge about SV40 and considers public responses to reports in the media. SV40 is a potent tumour virus with broad tissue tropism that induces tumours in rodents and transforms cultured cells from many species. It is also an important laboratory model for basic studies of molecular processes in eukaryotic cells and mechanisms of neoplastic transformation. SV40 neutralizing antibodies have been detected in individuals not exposed to contaminated poliovirus vaccines. There have been many reports of detection of SV40 DNA in human tumours, especially mesotheliomas, brain tumours and osteosarcomas; and DNA sequence analyses have ruled out the possibility that the viral DNA in tumours was due to laboratory contamination or that the virus had been misidentified. However, additional studies are necessary to prove that SV40 is the cause of certain human cancers. A recently published review article evaluated the status of the field and received much media attention. The public response emphasized that there is great interest in the possibility of health risks today from vaccinations received in the past.

Animals↗
PubMed1999

Wrist actigraphic measures of sleep in space.

STUDY OBJECTIVES: To determine whether wrist actigraphy is useful as a tool for space-based sleep research. Specifically, to determine whether bedtimes and waketimes can be identified from the actigraphic record, and whether actigraphic measures of sleep in space are related to polysomnographic (PSG) ones. DESIGN AND SETTING: Actigraphy, sleep diary, and Polysomnographic (PSG) measures of sleep were obtained from four subjects in two 72h measurement blocks occurring 2d and 12d into a 17d Space Shuttle mission in orbiting the earth in microgravity. PATIENTS: Four healthy male astronauts aged 38y - 47y. INTERVENTIONS: NA. MEASUREMENTS AND RESULTS: Sleep onset and offset at "night" could be quite clearly identified from the actigraphic record and were better estimated by actigraph than by diary. There was a high correlation between actigraphic and PSG estimates of sleep duration (r = 0.96) and sleep efficiency (r = 0.88), and a similarity in the mean estimates obtained. On a minute-by-minute basis, there was a good correlation between sleep stage and actigraphic movement counts, with a higher level of counts per minute recorded in epochs with lighter PSG sleep stages. There was also a high correlation (r = 0.90) between minutes of stage 0 (wake) occurring between bedtime and wake time, and number of non-zero actigraph epochs during the same interval. CONCLUSIONS: Actigraphy worked well in space both as a way of detecting bedtimes and waketimes, and as an indicant of sleep restlessness.

Adult↗
PubMed2004

The effects of heavy particle irradiation on exploration and response to environmental change.

Free radicals produced by exposure to heavy particles have been found to produce motor and cognitive behavioral toxicity effects in rats similar to those found during aging. The present research was designed to investigate the effects of exposure to 56Fe particles on the ability of male Sprague-Dawley rats to detect novel arrangements in a given environment. Using a test of spatial memory previously demonstrated to be sensitive to aging, open field activity and reaction to spatial and non-spatial changes were measured in a group that received a dose of 1.5 Gy (n=10) of 56Fe heavy particle radiation or in non-radiated controls (n=10). Animals irradiated with 1.5 Gy of 56Fe particles exhibited some age-like effects in rats tested, even though they were, for the most part, subtle. Animals took longer to enter, visited less and spent significantly less time in the middle and the center portions of the open field, independently of total frequency and duration of activity of both groups. Likewise, irradiated subjects spend significantly more time exploring novel objects placed in the open field than did controls. However, irradiated subjects did not vary from controls in their exploration patterns when objects in the open field were spatially rearranged. Thus, irradiation with a dose of 1.5 Gy of 56Fe high-energy particle radiation elicited age-like effects in general open field exploratory behavior, but did not elicit age-like effects during the spatial and non-spatial rearrangement tasks.

Aging↗
PubMed2000

Vascular mechanics of the coronary artery.

UNLABELLED: This paper describes our research into the vascular mechanics of the coronary artery and plaque. The three sections describe the determination of arterial mechanical properties using intravascular ultrasound (IVUS), a constitutive relation for the arterial wall, and finite element method (FEM) models of the arterial wall and atheroma. METHODS: Inflation testing of porcine left anterior descending coronary arteries was conducted. The changes in the vessel geometry were monitored using IVUS, and intracoronary pressure was recorded using a pressure transducer. The creep and quasistatic stress/strain responses were determined. A Standard Linear Solid (SLS) was modified to reproduce the non-linear elastic behavior of the arterial wall. This Standard Non-linear Solid (SNS) was implemented into an axisymetric thick-walled cylinder numerical model. Finite element analysis models were created for five age groups and four levels of stenosis using the Pathobiological Determinants of Atherosclerosis Youth (PDAY) database. RESULTS: The arteries exhibited non-linear elastic behavior. The total tissue creep strain was epsilon creep = 0.082 +/- 0.018 mm/mm. The numerical model could reproduce both the non-linearity of the porcine data and time dependent behavior of the arterial wall found in the literature with a correlation coefficient of 0.985. Increasing age had a strong positive correlation with the shoulder stress level, (r = 0.95). The 30% stenosis had the highest shoulder stress due to the combination of a fully formed lipid pool and a thin cap. CONCLUSIONS: Studying the solid mechanics of the arterial wall and the atheroma provide important insights into the mechanisms involved in plaque rupture.

Animals↗
PubMed2000

Viral carcinogenesis: revelation of molecular mechanisms and etiology of human disease.

The RNA and DNA tumor viruses have made fundamental contributions to two major areas of cancer research. Viruses were vital, first, to the discovery and analysis of cellular growth control pathways and the synthesis of current concepts of cancer biology and, second, to the recognition of the etiology of some human cancers. Transforming retroviruses carry oncogenes derived from cellular genes that are involved in mitogenic signalling and growth control. DNA tumor viruses encode oncogenes of viral origin that are essential for viral replication and cell transformation; viral oncoproteins complex with cellular proteins to stimulate cell cycle progression and led to the discovery of tumor suppressors. Viral systems support the concept that cancer development occurs by the accumulation of multiple cooperating events. Viruses are now accepted as bona fide etiologic factors of human cancer; these include hepatitis B virus, Epstein-Barr virus, human papillomaviruses, human T-cell leukemia virus type I and hepatitis C virus, plus several candidate human cancer viruses. It is estimated that 15% of all human tumors worldwide are caused by viruses. The infectious nature of viruses distinguishes them from all other cancer-causing factors; tumor viruses establish long-term persistent infections in humans, with cancer an accidental side effect of viral replication strategies. Viruses are usually not complete carcinogens, and the known human cancer viruses display different roles in transformation. Many years may pass between initial infection and tumor appearance and most infected individuals do not develop cancer, although immunocompromised individuals are at elevated risk of viral-associated cancers. Variable factors that influence viral carcinogenesis are reviewed, including possible synergy between viruses and environmental cofactors. The difficulties in establishing an etiologic role for a virus in human cancer are discussed, as well as the different approaches that proved viral links to cancer. Future directions for tumor virus studies are considered.

Cell Transformation, Viral↗
PubMed2000

The sleep of healthy people--a diary study.

To provide baseline data for various research studies at the University of Pittsburgh over a 10-year period, 266 healthy subjects (144 male, 122 female, aged 20-50 years) meeting certain criteria each completed a 14-night sleep diary. For each night, the diary allowed the subjective measurement of bedtime, wake time, time in bed (TIB), sleep efficiency, number of minutes of wake after sleep onset (WASO), alertness on awakening, and percentage of morning needing an alarm (or a person functioning as one). Weeknight versus weekend night differences in TIB (TIBdiff), weekday altertness, and reliance on alarms were examined as possible indicators of sleep debt. In addition, general descriptive data were tabulated. On average, bedtimes were at 23:48 and wake times at 07:23, yielding a mean TIB of 7 hours 35 minutes. As expected, bedtimes and wake times were later on weekend nights than on weeknights. Bedtimes were 26 minutes later, wake times 53 minutes later, yielding a mean weekend TIB increase of 27 minutes. Overall, subjects perceived their sleep latency to be 10.5 minutes, reported an average of one awakening during the night (with an average of 6.4 minutes of WASO), had a diary sleep efficiency of 96.3%, and awoke with an alterness rating of 69.5%. These variables differed little between weeknight and weekend nights. Subjects used an alarm (or a person functioning as an alarm) on 60.9% nights overall, 68.3% on weeknights, 42.5% on weekends. When TIBdiff was used as an estimate of sleep debt (comparing subjects with TIBdiff > 75 minutes with those with a TIBdiff < 30 minutes), the group with more "catch-up sleep" on weekends had shorter weeknight TIB durations (by about 24 minutes) and relied more on an alarm for weekday waking (by about 22%), indicating the possible utility of these variables as sleep debt indices.

Adult↗
PubMed2000

Myotonic dystrophy protein kinase (DMPK) induces actin cytoskeletal reorganization and apoptotic-like blebbing in lens cells.

DMPK, the product of the DM locus, is a member of the same family of serine-threonine protein kinases as the Rho-associated enzymes. In DM, membrane inclusions accumulate in lens fiber cells producing cataracts. Overexpression of DMPK in cultured lens epithelial cells led to apoptotic-like blebbing of the plasma membrane and reorganization of the actin cytoskeleton. Enzymatically active DMPK was necessary for both effects; inactive mutant DMPK protein did not produce either effect. Active RhoA but not constitutive GDP-state mutant protein produced similar effects as DMPK. The similar actions of DMPK and RhoA suggest that they may function in the same regulatory network. The observed effects of DMPK may be relevant to the removal of membrane organelles during normal lens differentiation and the retention of intracellular membranes in DM lenses.

Actins↗
PubMed2000

A simulator for evaluating methods for the detection of lesion-deficit associations.

Although much has been learned about the functional organization of the human brain through lesion-deficit analysis, the variety of statistical and image-processing methods developed for this purpose precludes a closed-form analysis of the statistical power of these systems. Therefore, we developed a lesion-deficit simulator (LDS), which generates artificial subjects, each of which consists of a set of functional deficits, and a brain image with lesions; the deficits and lesions conform to predefined distributions. We used probability distributions to model the number, sizes, and spatial distribution of lesions, to model the structure-function associations, and to model registration error. We used the LDS to evaluate, as examples, the effects of the complexities and strengths of lesion-deficit associations, and of registration error, on the power of lesion-deficit analysis. We measured the numbers of recovered associations from these simulated data, as a function of the number of subjects analyzed, the strengths and number of associations in the statistical model, the number of structures associated with a particular function, and the prior probabilities of structures being abnormal. The number of subjects required to recover the simulated lesion-deficit associations was found to have an inverse relationship to the strength of associations, and to the smallest probability in the structure-function model. The number of structures associated with a particular function (i.e., the complexity of associations) had a much greater effect on the performance of the analysis method than did the total number of associations. We also found that registration error of 5 mm or less reduces the number of associations discovered by approximately 13% compared to perfect registration. The LDS provides a flexible framework for evaluating many aspects of lesion-deficit analysis.

Brain↗