HOW POLICY DECISIONS ARE MADE IN CANADIAN AGRICULTURE

Agricultural and Food Policy,

Origin of broad polydispersion in functionalized dendrimers and its effects on cancer cell binding affinity

Nanoparticles with multiple ligands have been proposed for use in nanomedicine. The multiple targeting ligands on each nanoparticle can bind to several locations on a cell surface facilitating both drug targeting and uptake. Experiments show that the distribution of conjugated ligands is unexpectedly broad, and the desorption rate appears to depends exponentially upon the mean number of attached ligands. These two findings are explained with a model in which ligands conjugate to the nanoparticle with a positive cooperativity of $\approx 4kT$, and that nanoparticles bound to a surface by multiple bonds are permanently affixed. This drives new analysis of the data, which confirms that there is only one time constant for desorption, that of a nanoparticle bound to the surface by a single bond.Comment: 4 pages, with 6 figure

Exercise for Weight Loss: Further Evaluating Energy Compensation with Exercise

PURPOSE: This study assessed how individuals compensate for energy expended during a 12-wk aerobic exercise intervention, elucidating potential mechanisms and the role exercise dose plays in the compensatory response. PARTICIPANTS AND DESIGN: Three-arm, randomized controlled trial among sedentary adults age 18 to 40 yr, body mass index of 25 to 35. Groups included six exercise sessions per week, two sessions per week, and sedentary control. METHODS: Rate of exercise energy expenditure was calculated from a graded exercise test averaged across five heart rate zones. Energy compensation was calculated as the difference between expected weight loss (based on exercise energy expenditure) and changes in fat and fat-free mass (DXA). Resting energy expenditure was assessed via indirect calorimetry and concentrations of acylated ghrelin, leptin, insulin, and Glucagon-like peptide 1 (GLP-1) were assessed fasting and postprandial (six timepoints over 2 h). RESULTS: The 6-d·wk−1 group expended more energy (2753.5 kcal) and exercised longer (320.5 min) per week than the 2-d·wk−1 group (1490.7 kcal, 1888.8 min, P \u3c 0.05), resulting in greater fat loss compared with the 2-d or control groups (P \u3c 0.05). Exercise groups did not differ in the % or total kcal compensated. Greater decreases in area under the curve (AUC) for acylated ghrelin predicted greater fat loss, regardless of group, energy expended per week, exercise duration, or exercise intensity. Changes in leptin AUC was the only independent predictor for energy compensation, with a greater decrease in leptin AUC predicting less energy compensation. Exercise frequency, energy expended, duration, or intensity did not influence energy compensation. CONCLUSIONS: Leptin is an important factor in successful weight loss through exercise, with greater postprandial decreases promoting less compensation. Greater amounts of exercise do not influence the compensatory response to an exercise-induced energy deficit

Alterations in Cortical Sensorimotor Connectivity following Complete Cervical Spinal Cord Injury: A Prospective Resting-State fMRI Study

Functional magnetic resonance imaging (fMRI) studies have demonstrated alterations during task-induced brain activation in spinal cord injury (SCI) patients. The interruption to structural integrity of the spinal cord and the resultant disrupted flow of bidirectional communication between the brain and the spinal cord might contribute to the observed dynamic reorganization (neural plasticity). However, the effect of SCI on brain resting-state connectivity patterns remains unclear. We undertook a prospective resting-state fMRI (rs-fMRI) study to explore changes to cortical activation patterns following SCI. With institutional review board approval, rs-fMRI data was obtained in eleven patients with complete cervical SCI (\u3e2 years post injury) and nine age-matched controls. The data was processed using the Analysis of Functional Neuroimages software. Region of interest (ROI) based analysis was performed to study changes in the sensorimotor network using pre- and post-central gyri as seed regions. Two-sampled t-test was carried out to check for significant differences between the two groups. SCI patients showed decreased functional connectivity in motor and sensory cortical regions when compared to controls. The decrease was noted in ipsilateral, contralateral, and interhemispheric regions for left and right precentral ROIs. Additionally, the left postcentral ROI demonstrated increased connectivity with the thalamus bilaterally in SCI patients. Our results suggest that cortical activation patterns in the sensorimotor network undergo dynamic reorganization following SCI. The presence of these changes in chronic spinal cord injury patients is suggestive of the inherent neural plasticity within the central nervous system

Plasticization and antiplasticization of polymer melts diluted by low molar mass species

An analysis of glass formation for polymer melts that are diluted by structured molecular additives is derived by using the generalized entropy theory, which involves a combination of the Adam-Gibbs model and the direct computation of the configurational entropy based on a lattice model of polymer melts that includes monomer structural effects. Antiplasticization is accompanied by a "toughening" of the glass mixture relative to the pure polymer, and this effect is found to occur when the diluents are small species with strongly attractive interactions with the polymer matrix. Plasticization leads to a decreased glass transition temperature T_g and a "softening" of the fragile host polymer in the glass state. Plasticization is prompted by small additives with weakly attractive interactions with the polymer matrix. The shifts in T_g of polystyrene diluted by fully flexible short oligomers are evaluated from the computations, along with the relative changes in the isothermal compressibility at T_g to characterize the extent to which the additives act as antiplasticizers or plasticizers. The theory predicts that a decreased fragility can accompany both antiplasticization and plasticization of the glass by molecular additives. The general reduction in the T_g and fragility of polymers by these molecular additives is rationalized by analyzing the influence of the diluent's properties (cohesive energy, chain length, and stiffness) on glass formation in diluted polymer melts. The description of glass formation at fixed temperature that is induced upon change the fluid composition directly implies the Angell equation for the structural relaxation time as function of the polymer concentration, and the computed "zero mobility concentration" scales linearly with the inverse polymerization index N.Comment: 12 pages, 15 figure

Evaluation of Whole-Brain Resting-State Functional Connectivity in Spinal Cord Injury - A Large-Scale Network Analysis Using Network Based Statistic

Large-scale network analysis characterizes the brain as a complex network of nodes and edges to evaluate functional connectivity patterns. The utility of graph-based techniques has been demonstrated in an increasing number of restingstate functional MRI (rs-fMRI) studies in the normal and diseased brain. However, to our knowledge, graph theory has not been used to study the reorganization pattern of resting-state brain networks in patients with traumatic complete spinal cord injury (SCI). In the present analysis, we applied a graph-theoretical approach to explore changes to global brain network architecture as a result of SCI. Fifteen subjects with chronic (\u3e 2 years) complete (American Spinal Injury Association [ASIA] A) cervical SCI and 15 neurologically intact controls were scanned using rs-fMRI. The data were preprocessed followed by parcellation of the brain into 116 regions of interest (ROI) or nodes. The average time series was extracted at each node, and correlation analysis was performed between every pair of nodes. A functional connectivity matrix for each subject was then generated. Subsequently, the matrices were averaged across groups, and network changes were evaluated between groups using the network-based statistic (NBS) method. Our results showed decreased connectivity in a subnetwork of the whole brain in SCI compared with control subjects. Upon further examination, increased connectivity was observed in a subnetwork of the sensorimotor cortex and cerebellum network in SCI. In conclusion, our findings emphasize the applicability of NBS to study functional connectivity architecture in diseased brain states. Further, we show reorganization of large-scale resting-state brain networks in traumatic SCI, with potential prognostic and therapeutic implications

Three-kinase inhibitor combination recreates multipathway effects of a geldanamycin analogue on hepatocellular carcinoma cell death

Multitarget compounds that act on a diverse set of regulatory pathways are emerging as a therapeutic approach for a variety of cancers. Toward a more specified use of this approach, we hypothesize that the desired efficacy can be recreated in terms of a particular combination of relatively more specific (i.e., ostensibly single target) compounds. We test this hypothesis for the geldanamycin analogue 17-Allylamino-17-demethoxygeldanamycin (17AAG) in hepatocellular carcinoma cells, measuring critical phosphorylation levels that indicate the kinase pathway effects correlating with apoptotic responsiveness of the Hep3B cell line in contrast to the apoptotic resistance of the Huh7 cell line. A principal components analysis (PCA) constructed from time course measurements of seven phosphoprotein signaling levels identified modulation of the AKT, IκB kinase, and signal transducer and activator of transcription 3 pathways by 17AAG treatment as most important for distinguishing these cell-specific death responses. The analysis correctly suggested from 17AAG-induced effects on these phosphoprotein levels that the FOCUS cell line would show apoptotic responsiveness similarly to Hep3B. The PCA also guided the inhibition of three critical pathways and rendered Huh7 cells responsive to 17AAG. Strikingly, in all three hepatocellular carcinoma lines, the three-inhibitor combination alone exhibited similar or greater efficacy to 17AAG. We conclude that (a) the PCA captures and clusters the multipathway phosphoprotein time courses with respect to their 17AAG-induced apoptotic responsiveness and (b) we can recreate, in a more specified manner, the cellular responses of a prospective multitarget cancer therapeutic.National Institute of General Medical Sciences (U.S.). Cell Decision Processes CenterNational Cancer Institute (U.S.). Integrative Cancer Biology ProgramMassachusetts Institute of Technology. Presidential FellowshipNational Institutes of Health (U.S.

Cosmological implications of the Higgs mass measurement

We assume the validity of the Standard Model up to an arbitrary high-energy scale and discuss what information on the early stages of the Universe can be extracted from a measurement of the Higgs mass. For Mh < 130 GeV, the Higgs potential can develop an instability at large field values. From the absence of excessive thermal Higgs field fluctuations we derive a bound on the reheat temperature after inflation as a function of the Higgs and top masses. Then we discuss the interplay between the quantum Higgs fluctuations generated during the primordial stage of inflation and the cosmological perturbations, in the context of landscape scenarios in which the inflationary parameters scan. We show that, within the large-field models of inflation, it is highly improbable to obtain the observed cosmological perturbations in a Universe with a light Higgs. Moreover, independently of the inflationary model, the detection of primordial tensor perturbations through the B-mode of CMB polarization and the discovery of a light Higgs can simultaneously occur only with exponentially small probability, unless there is new physics beyond the Standard Model.Comment: 28 LaTeX pages, 6 figure

Evolution of brown carbon in wildfire plumes

Particulate brown carbon (BrC) in the atmosphere absorbs light at subvisible wavelengths and has poorly constrained but potentially large climate forcing impacts. BrC from biomass burning has virtually unknown lifecycle and atmospheric stability. Here, BrC emitted from intense wildfires was measured in plumes transported over 2 days from two main fires, during the 2013 NASA SEAC4RS mission. Concurrent measurements of organic aerosol (OA) and black carbon (BC) mass concentration, BC coating thickness, absorption Ångström exponent, and OA oxidation state reveal that the initial BrC emitted from the fires was largely unstable. Using back trajectories to estimate the transport time indicates that BrC aerosol light absorption decayed in the plumes with a half-life of 9 to 15 h, measured over day and night. Although most BrC was lost within a day, possibly through chemical loss and/or evaporation, the remaining persistent fraction likely determines the background BrC levels most relevant for climate forcing

N=1/2 quiver gauge theories from open strings with R-R fluxes

We consider a four dimensional N=1 gauge theory with bifundamental matter and a superpotential, defined on stacks of fractional branes. By turning on a flux for the R-R graviphoton field strength and computing open string amplitudes with insertions of R-R closed string vertices, we introduce a non-anticommutative deformation and obtain the N=1/2 version of the theory. We also comment on the appearance of a new structure in the effective Lagrangian.Comment: 30 pages, 5 figures, JHEP class (included); some comments and a reference adde