Regulatory activity revealed by dynamic correlations in gene expression noise

Gene regulatory interactions are context dependent, active in some cellular states but not in others. Stochastic fluctuations, or 'noise', in gene expression propagate through active, but not inactive, regulatory links^(1,2). Thus, correlations in gene expression noise could provide a noninvasive means to probe the activity states of regulatory links. However, global, 'extrinsic', noise sources generate correlations even without direct regulatory links. Here we show that single-cell time-lapse microscopy, by revealing time lags due to regulation, can discriminate between active regulatory connections and extrinsic noise. We demonstrate this principle mathematically, using stochastic modeling, and experimentally, using simple synthetic gene circuits. We then use this approach to analyze dynamic noise correlations in the galactose metabolism genes of Escherichia coli. We find that the CRP-GalS-GalE feed-forward loop is inactive in standard conditions but can become active in a GalR mutant. These results show how noise can help analyze the context dependence of regulatory interactions in endogenous gene circuits

Frontal Metabolite Concentration Deficits in Opiate Dependence Relate to Substance Use, Cognition, and Self-Regulation.

ObjectiveProton magnetic resonance spectroscopy (1H MRS) in opiate dependence showed abnormalities in neuronal viability and glutamate concentration in the anterior cingulate cortex (ACC). Metabolite levels in dorsolateral prefrontal cortex (DLPFC) or orbitofrontal cortex (OFC) and their neuropsychological correlates have not been investigated in opiate dependence.MethodsSingle-volume proton MRS at 4 Tesla and neuropsychological testing were conducted in 21 opiate-dependent individuals (OD) on buprenorphine maintenance therapy. Results were compared to 28 controls (CON) and 35 alcohol-dependent individuals (ALC), commonly investigated treatment-seekers providing context for OD evaluation. Metabolite concentrations were measured from ACC, DLPFC, OFC and parieto-occipital cortical (POC) regions.ResultsCompared to CON, OD had lower concentrations of N-acetylaspartate (NAA), glutamate (Glu), creatine +phosphocreatine (Cr) and myo-Inositol (mI) in the DLPFC and lower NAA, Cr, and mI in the ACC. OD, ALC, and CON were equivalent on metabolite levels in the POC and γ-aminobutyric acid (GABA) concentration did not differ between groups in any region. In OD, prefrontal metabolite deficits in ACC Glu as well as DLPFC NAA and choline containing metabolites (Cho) correlated with poorer working memory, executive and visuospatial functioning; metabolite deficits in DLPFC Glu and ACC GABA and Cr correlated with substance use measures. In the OFC of OD, Glu and choline-containing metabolites were elevated and lower Cr concentration related to higher nonplanning impulsivity. Compared to 3 week abstinent ALC, OD had significant DLPFC metabolite deficits.ConclusionThe anterior frontal metabolite profile of OD differed significantly from that of CON and ALC. The frontal lobe metabolite abnormalities in OD and their neuropsychological correlates may play a role in treatment outcome and could be explored as specific targets for improved OD treatment

A COMPARISON OF RESISTED AND ASSISTED SPRINT TRAINING IN COLLEGIATE SPRINTERS

Sprint time (ST) is the product of stride length (SL) and stride rate (SR). Increases in either of these variables results in speed improvement. Purpose:  To compare resisted (RST) and assisted sprint training (AST) on sprint performance. Methods:  Twenty (10 male, 10 female) collegiate sprinters and hurdlers were randomly divided into two training groups: RST (age: 21.8±1.8yrs, height: 1.73±0.10m, mass: 69.5±12.8kg) and AST (age: 22.2±2.4yrs, height: 1.76±0.10m, mass: 69.1±9.9kg). Each group trained 3 days/week for 6 weeks. The RST group used a combination of weighted sled pulls, uphill sprinting and depth jumps. The AST group combined downhill running, towing, sprint ladders and single leg bounds. Prior to and following the training interventions SL and ST (10 meter sprint time) were recorded at sprint distances of 30m, 60m, and 120m during the last 10 meters of each sprint distance. Pre-post training ST and SL were compared within training groups at each sprint distance using paired t-tests. Additionally, a gain score was calculated by taking the difference between the post and pre test scores. The gain scores for SL and ST were compared between training groups via independent t-tests at each sprint distance. Results: For the RST 30m, ST (1.18±0.08s vs 1.14±0.08s, p<0.01) and SL (2.06±0.08m vs. 2.09±1.14m, p<0.01) were significantly improved. For the AST, 30m ST (1.19±0.08s vs. 1.18±0.08s, p<0.01) and SL (2.10±0.13m vs. 2.11±0.13, p=0.04) were significantly improved. No improvements in ST or SL were detected for either the RST or AST groups at the 60m sprint distance. For the RST 120m, ST (1.13±0.07s vs. 1.12±0.08s, p<0.01) was significantly improved. For the AST 120m, ST (1.12±0.07s vs. 1.11±0.07s, p<0.01) and SL (2.30±0.08 vs. 2.33±0.08, p<0.01) were significantly improved. At the 30M interval, the RST demonstrated significant improvements in SL and ST as compared to the AST (p<0.01). However, at the 120M interval, the AST demonstrated a significant improvement in SL as compared to the RST (p<0.01). Conclusion: Within the parameters of this study, RST and AST methods have proven effective at improving sprint performance. It appears that RST protocols may be of greatest benefit for improving sprint performance at shorter distances, while AST protocols may be of greater benefit at longer sprinting distances.  Article visualizations

Relationship between the Romberg Test and the Wii Basic Balance Test and Cognition in Athletes with Concussion

Background: Approximately 30% of individuals with a sport-related concussion present with postural instability. Multiple clinical balance tests exist to diagnose postural instability; yet little is known about the potential relationship between these type of postural assessments and cognition post-concussion. Aim: The purpose of the current study was to assess the relationship between the Romberg test, the Wii Fit basic balance test (WBBT), and the composite scores on the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) test in a sample of athletes with concussions. Methods: 55 post-concussed athletes (40 male) completed the Romberg Test (RT) (−/+), the WBBT, and ImPACT test. Wii Fit basic balance test performance was operationalized as the number of successfully completed trials (of 5 trials of increasing difficulty) within 30 seconds. Pearson’s and point-biserial correlations examined univariate associations among the variables. Results: The RT and WBBT were not significantly related (r = −0.029, p = 0.832). The RT weakly correlated with ImPACT impairment scores (r= 0.26, p= 0.041), whereas WBBT the number of trials did not (r = − 0.20, p = 0.155). Romberg Test scores were significantly correlated with ImPACT Visual Processing Speed Score (r = 0.27, p = 0.036) and Reaction Time score (r = 0.34, p = 0.006). In contrast, WBBT trials were significantly correlated with the ImPACT Visual Memory Score (r = − 0.41, p = 0.003). Conclusions: These results suggest that the WBBT and RT assess unique aspects of postural control. The RT may relate directly to single sensory cognitive and motor processing, while the WBBT may relate to multi-sensory visually driven cognitive and motor processing. Relevance for patients: Clinical balance tests could point to different cognitive impairments post-concussion

An Instrumental Approach to Full Employment: with Policy Implication

Dissertation advisor: Mathew Forstater.Includes bibliographic references (pages 221-235).Title from PDF of title page, viewed on December 13, 2010.Vita.Dissertation (Ph.D.)--College of Arts and Sciences. University of Missouri--Kansas City, 2010.The study proposes that in order to assure full employment, policy measures must address both Keynesian unemployment, and unemployment caused by structural and technological change. It is possible to attain full employment via expansionary fiscal policy advocated by Keynes. However given on-going technological change, it is not possible to maintain full employment with Keynesian policy alone. In order for any full employment policy to be effective it must address both of these issues. The purpose here is an investigation of the theory of unemployment from a Keynesian perspective and a structuralist perspective. I will make an argument that these are two sides of the same coin. Using an input-output framework it will be shown how the ELR program formally fits into the economy and addresses both types of unemployment. Furthermore, it will be shown that the ELR program works in conjunction with the private sector. The initial introduction of the ELR program causes an increase in the final demand for private sector goods and services, thus creating additional employment in the private sector. In order for the investigation of structural/technological unemployment, a structural framework of the ELR program is required. The dissertation will lay out a structural model of the economy with and without an ELR program. This then allows for an investigation of comparative benefits of such a program in addressing unemployment over current government policies. Simulations of model economy with and without the ELR program will be done to show that the ELR program stabilizes final demand. Additionally it will be seen that the ELR sector maintains full employment given structural and technological change.Abstract -- List of Illustrations -- List of Tables -- Post Keynesian Approaches to Economic Theory -- The Problem of Unemployment -- Heterodox Approaches to Production -- Employer of Last Resort: A Structural Approach -- Concluding Notes and Areas for Further Research -- Simulated Input Output Tables -- Reference List -- Vita

LUVMI: an innovative payload for the sampling of volatiles at the Lunar poles

The ISECG identifies one of the first exploration steps as in situ investigations of the moon or asteroids. Europe is developing payload concepts for drilling and sample analysis, a contribution to a 250kg rover as well as for sample return. To achieve these missions, ESA depends on international partnerships. Such missions will be seldom, expensive and the drill/sample site selected will be based on observations from orbit not calibrated with ground truth data. Many of the international science community’s objectives can be met at lower cost, or the chances of mission success improved and the quality of the science increased by making use of an innovative, low mass, mobile robotic payload following the LEAG recommendations. LUVMI provides a smart, low mass, innovative, modular mobile payload comprising surface and subsurface sensing with an in-situ sampling technology capable of depth-resolved extraction of volatiles, combined with a volatile analyser (mass spectrometer) capable of identifying the chemical composition of the most important volatiles. This will allow LUVMI to: traverse the lunar surface prospecting for volatiles; sample subsurface up to a depth of 10 cm (with a goal of 20 cm); extract water and other loosely bound volatiles; identify the chemical species extracted; access and sample permanently shadowed regions (PSR). The main innovation of LUVMI is to develop an in situ sampling technology capable of depth-resolved extraction of volatiles, and then to package within this tool, the analyser itself, so as to maximise transfer efficiency and minimise sample handling and its attendant mass requirements and risk of sample alteration. By building on national, EC and ESA funded research and developments, this project will develop to TRL6 instruments that together form a smart modular mobile payload that could be flight ready in 2020. The LUVMI sampling instrument will be tested in a highly representative environment including thermal, vacuum and regolith simulant and the integrated payload demonstrated in a representative environment

Work Measurement Decision Diagram Development and Application at NASA\u27s Kennedy Space Center

This paper presents a decision flow diagram developed at NASA\u27s Kennedy Space Center for the selection of the appropriate work measurement methodologies for Space Shuttle processing

Spatial epidemiological patterns suggest mechanisms of land-sea transmission for Sarcocystis neurona in a coastal marine mammal.

Sarcocystis neurona was recognised as an important cause of mortality in southern sea otters (Enhydra lutris nereis) after an outbreak in April 2004 and has since been detected in many marine mammal species in the Northeast Pacific Ocean. Risk of S. neurona exposure in sea otters is associated with consumption of clams and soft-sediment prey and is temporally associated with runoff events. We examined the spatial distribution of S. neurona exposure risk based on serum antibody testing and assessed risk factors for exposure in animals from California, Washington, British Columbia and Alaska. Significant spatial clustering of seropositive animals was observed in California and Washington, compared with British Columbia and Alaska. Adult males were at greatest risk for exposure to S. neurona, and there were strong associations with terrestrial features (wetlands, cropland, high human housing-unit density). In California, habitats containing soft sediment exhibited greater risk than hard substrate or kelp beds. Consuming a diet rich in clams was also associated with increased exposure risk. These findings suggest a transmission pathway analogous to that described for Toxoplasma gondii, with infectious stages traveling in freshwater runoff and being concentrated in particular locations by marine habitat features, ocean physical processes, and invertebrate bioconcentration