1,233 research outputs found

    Geometric properties of a prestressed segmented spherical shell

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    Design and construction of plastic model of prestressed segmented spherical shel

    Development of a HgCdTe photomixer and impedance matched GaAs FET amplifier

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    A research program for the development of a 10.6 micron HgCdTe photodiode/GaAs field effect transistor amplifier package for use at cryogenic temperatures (77k). The photodiode/amplifier module achieved a noise equivalent power per unit bandwidth of 5.7 times 10 to the 20th power W/Hz at 2.0 GHz. The heterodyne sensitivity of the HgCdTe photodiode was improved by designing and building a low noise GaAs field effect transistor amplifier operating at 77K. The Johnson noise of the amplifier was reduced at 77K, and thus resulted in an increased photodiode heterodyne sensitivity

    Computational modelling of the regulation of Insulin signalling by oxidative stress

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    BACKGROUND: Existing models of insulin signalling focus on short term dynamics, rather than the longer term dynamics necessary to understand many physiologically relevant behaviours. We have developed a model of insulin signalling in rodent adipocytes that includes both transcriptional feedback through the Forkhead box type O (FOXO) transcription factor, and interaction with oxidative stress, in addition to the core pathway. In the model Reactive Oxygen Species are both generated endogenously and can be applied externally. They regulate signalling though inhibition of phosphatases and induction of the activity of Stress Activated Protein Kinases, which themselves modulate feedbacks to insulin signalling and FOXO. RESULTS: Insulin and oxidative stress combined produce a lower degree of activation of insulin signalling than insulin alone. Fasting (nutrient withdrawal) and weak oxidative stress upregulate antioxidant defences while stronger oxidative stress leads to a short term activation of insulin signalling but if prolonged can have other effects including degradation of the insulin receptor substrate (IRS1) and FOXO. At high insulin the protective effect of moderate oxidative stress may disappear. CONCLUSION: Our model is consistent with a wide range of experimental data, some of which is difficult to explain. Oxidative stress can have effects that are both up- and down-regulatory on insulin signalling. Our model therefore shows the complexity of the interaction between the two pathways and highlights the need for such integrated computational models to give insight into the dysregulation of insulin signalling along with more data at the individual level. A complete SBML model file can be downloaded from BIOMODELS (https://www.ebi.ac.uk/biomodels-main) with unique identifier MODEL1212210000. Other files and scripts are available as additional files with this journal article and can be downloaded from https://github.com/graham1034/Smith2012_insulin_signalling

    Rat mammary carcinogenesis following neutron- or X-radiation

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    Female 61 to 63 - day - old Sprague-Dawley rats were exposed once to a single dose of either 0.43 - MeV neutrons or 250 - kVX - rays . For neutrons 23 rats were exposed in plastic tubes rotated around and 31 c m from a water-cooled tritium impregnated target bombarded with 2.45 - MeV protons from a V a n de Graaff generator. The mean kerma was measured at the rat location by integrating the response of a rat - sized homogeneous tissue equivalent ionization chamber of minimum mass. The ratio between absorbed dose and kerma is under investigation and is anticipated to be approximately 0.7. A compensated GM gamma-ray dosimeter indicated that the gamma - ray doses were 3.5% of the total dose. All rats were examined weekly for the presence of breast tumours and these were removed, fixed, stained and verified histologically as mammary neoplasms. At 10 months after exposure 98<7ο of the rats were a live . The neutron kerma, the per cent of rats with mammary neoplasia, and the number of rats were, respectively: 0.125 rads, 8.2°}o, 182; 0.5 rads, 9.0^0, 89; 2 rads, 20. 6,68; and 8 rads, 31.1%, 45. The X - ray results were: 30 R, 1.4% 95; 60 R, 27. l°Io, 48; and 90 R, 35.4%, 48. A 3. O^o incidence was found in 167 control rats. At 10 months after exposure the mammary neoplastic response after 8 rads of neutrons corresponds approximately to that after 60 - 90 R of X - rays . Similarly, the response after 2 rads of neutrons was intermediate between 30 and 60 R of X - rays and the response after 0 . 125 and 0.5 rads of neutrons was similar to that after 30 R of X - rays . This demonstrates that the RBE for 0.43 - MeV neutrons is much lower at high doses than at low doses. Determination of the confidence limits for the dose-RBE dependence and dose-incidence relationship will be determined as additional data are collected

    Estrogen Modulation of VTA Dopamine Neuron Physiology and Behavioral Responsivity to Variable Social Stressors

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    The behavioral output of different animals, or even the same animal in different contexts, is remarkably variable in response to the same external stimulus. This behavioral diversity is due to the complex integration of external and internal stimuli, through both neuronal and hormonal signals that selects the best behavioral response. By their nature as long-distance signaling molecules, hormones play a critical role in communicating information about internal states across the organism. Many hormones produced in the periphery target the central nervous system to modulate animal behavior, selecting for behaviors that are appropriate over behaviors that are maladaptive in that specific situation. These hormones generally communicate the internal state of the organism, such as reproductive status, or stress. Sex steroid hormones are a diverse class of hormones that include estrogens, progestogens, and androgens. These hormones are released from the gonads and act on the brain to control a range of behaviors s involved in reproduction. Decades of research demonstrate both short- and long-term actions of these signaling molecules that directly affect the physiology of neurons in various regions of the brain. In addition to brain regions controlling behaviors involved in reproduction, these changes have also been found in regions important for controlling non-reproductive behaviors, such as memory, cognition, and motivation. Estrogens are a class of steroid hormones that activate estrogen receptors (ERs) and have a strong influence on neuronal activity throughout the brain and periphery. While estrogens are typically associated with the female reproductive cycle, more than 50 years of research shows that ERs are expressed throughout the brain in both sexes and modulate behavior and cognition not typically associated with reproductive behavior, such as memory and motivation. Moreover, estrogen signaling has a role in modulating motivation and mood in humans, non-human primates, and rodents, indicating a conserved role for estrogen signaling across species. The ventral tegmental area (VTA) is a dopaminergic nucleus in the midbrain that is associated with motivation is also highly conserved across species. Shifting of motivation through modulation of the dopaminergic hub of the brain is important for behavioral plasticity that determines an appropriate behavioral response based on the external and internal environment. Motivation refers to the drive to perform a behavior to obtain a goal (Simpson and Balsam, 2016). Strong primary motivations include obtaining food and shelter, finding a mate to reproduce, or avoiding dangerous situations. Motivated behaviors are triggered by an external event, such as a reward or a cue paired a reward. The behavioral response to a motivating cue is also modified by an internal state. Classic in vivo recordings of dopamine neurons in the VTA show increases in firing rate in response to both rewarding and aversive external stimuli. These responses are not limited to the reward or aversive stimuli, but also with neutral stimuli that have been paired with the reward or punishment. Research has revealed that the reward system, including the VTA, is modulated by estrogen signaling. However, much of the research in this area focuses on the effects of estrous cycle and estrogen signaling in regions that receive projections from the VTA, such as the striatum, the hippocampus, and the prefrontal cortex, while little research exists examining the role of estrogen in directly modulating the physiology of dopamine neurons in the VTA. Motivation is a component of mood, and a change in motivation to obtain reward is a hallmark of mood disorders such as depression. Women are up to twice as likely to be diagnosed with major depressive disorder (MDD) than men (Noble, 2005). In many women, changes in the menstrual cycle can lead to changes in mood and motivation. Several depressive disorders and modifiers of MDD in the Diagnostic and Statistical Manual V (DSM-V) are associated with fluctuations in hormones. These include premenstrual dysphoric disorder (PMDD), postpartum depression, and mood changes during perimenopause. Moreover, depression treated with medication can lead to changes in menstrual cycle length and regularity, suggesting an interaction between mood and hormone fluctuations (Rowland et al., 2002). Additionally, rodent models of stress susceptibility provide evidence that the dopaminergic response to stress is sex- and hormone dependent. In this dissertation, I will present experimental evidence that estrogen signaling in the VTA is an important modulator of dopamine neuron physiology, which leads to differences in the behavioral response to stress in female mice. I show that the physiology of dopamine neurons in the VTA of female mice changes across the estrous cycle. These changes are at least partially caused by changes in estrogen signaling, as shown by pharmacological manipulation of estrogen signaling in in vitro slice preparation. Moreover, estrogen signaling in the VTA is involved in the behavioral response to stress, as pharmacological manipulation of estrogen signaling in intact female mice changes the behavioral response to stress

    Taking the pulse of snowmelt: in situ sensors reveal seasonal, event and diurnal patterns of nitrate and dissolved organic matter variability in an upland forest stream

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    Highly resolved time series data are useful to accurately identify the timing, rate, and magnitude of solute transport in streams during hydrologically dynamic periods such as snowmelt. We used in situ optical sensors for nitrate (NO3 −) and chromophoric dissolved organic matter fluorescence (FDOM) to measure surface water concentrations at 30 min intervals over the snowmelt period (March 21–May 13, 2009) at a 40.5 hectare forested watershed at Sleepers River, Vermont. We also collected discrete samples for laboratory absorbance and fluorescence as well as δ18O–NO3 − isotopes to help interpret the drivers of variable NO3 − and FDOM concentrations measured in situ. In situ data revealed seasonal, event and diurnal patterns associated with hydrological and biogeochemical processes regulating stream NO3 − and FDOM concentrations. An observed decrease in NO3 − concentrations after peak snowmelt runoff and muted response to spring rainfall was consistent with the flushing of a limited supply of NO3 − (mainly from nitrification) from source areas in surficial soils. Stream FDOM concentrations were coupled with flow throughout the study period, suggesting a strong hydrologic control on DOM concentrations in the stream. However, higher FDOM concentrations per unit streamflow after snowmelt likely reflected a greater hydraulic connectivity of the stream to leachable DOM sources in upland soils. We also observed diurnal NO3 − variability of 1–2 μmol l−1 after snowpack ablation, presumably due to in-stream uptake prior to leafout. A comparison of NO3 − and dissolved organic carbon yields (DOC, measured by FDOM proxy) calculated from weekly discrete samples and in situ data sub-sampled daily resulted in small to moderate differences over the entire study period (−4 to 1% for NO3 − and −3 to −14% for DOC), but resulted in much larger differences for daily yields (−66 to +27% for NO3 − and −88 to +47% for DOC, respectively). Despite challenges inherent in in situ sensor deployments in harsh seasonal conditions, these data provide important insights into processes controlling NO3 − and FDOM in streams, and will be critical for evaluating the effects of climate change on snowmelt delivery to downstream ecosystems

    Measuring soil frost depth in forest ecosystems with ground penetrating radar

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    Soil frost depth in forest ecosystems can be variable and depends largely on early winter air temperaturesand the amount and timing of snowfall. A thorough evaluation of ecological responses to seasonallyfrozen ground is hampered by our inability to adequately characterize the frequency, depth, durationand intensity of soil frost events. We evaluated the use of ground penetrating radar to nondestructivelydelineate soil frost under field conditions in three forest ecosystems. Soil frost depth was monitoredperiodically using a 900 MHz antenna in South Burlington, Vermont (SB), Sleepers River Watershed,North Danville, Vermont (SR) and Hubbard Brook Experimental Forest, New Hampshire (HBEF) duringwinter 2011–2012 on plots with snow and cleared of snow. GPR-based estimates were compared to datafrom thermistors and frost tubes, which estimate soil frost depth with a color indicating solution. In theabsence of snow, frost was initially detected at a depth of 8–10 cm. Dry snow up to 35 cm deep, enhancednear-surface frost detection, raising the minimum frost detection depth to 4–5 cm. The most favorablesurface conditions for GPR detection were bare soil or shallow dry snow where frost had penetrated to theminimum detectable depth. Unfavorable conditions included: standing water on frozen soil, wet snow,thawed surface soils and deep snow pack. Both SB and SR were suitable for frost detection most of thewinter, while HBEF was not. Tree roots were detected as point reflections and were readily discriminatedfrom continuous frost reflections. The bias of GPR frost depth measurements relative to thermistors wassite dependent averaging 0.1 cm at SB and 1.1 cm at SR, and was not significantly different than zero. Whenseparated by snow manipulation treatment at SR, overestimation of soil frost depth (5.5 cm) occurredon plots cleared of snow and underestimation (−1.5 cm) occurred on plots with snow. Despite somelimitations posed by site and surface suitability, GPR could be useful for adding a spatial component topre-installed soil frost monitoring networks

    SafeCare®: Historical Perspective and Dynamic Development of an Evidence-Based Scaled-Up Model for the Prevention of Child Maltreatment

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    AbstractSafeCare is an evidence-based parent-training program that reduces child maltreatment, particularly neglect. The risk of child maltreatment, a public health issue affecting millions of U.S. children each year, can be markedly reduced by interventions such as SafeCare that deliver in-home services. Drawing from applied behavioral analysis roots, SafeCare focuses on providing parents with concrete skills in three areas: health, home safety, and parent-child/-infant interaction. This paper will include an overview of the SafeCare model, an historical perspective of its history and dynamic development, description of the theoretical underpinnings of the model, a description of the program targets and content by describing its modules and delivery, an overview of program outcomes, and data discussion of dissemination and implementation

    Phagocytes and the Lung

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72927/1/j.1749-6632.1997.tb46258.x.pd
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