1,297 research outputs found
The emergence of modern statistics in agricultural science : Analysis of variance, experimental design and the reshaping of research at Rothamsted Experimental Station, 1919–1933
During the twentieth century statistical methods have transformed research in the experimental and social sciences. Qualitative evidence has largely been replaced by quantitative results and the tools of statistical inference have helped foster a new ideal of objectivity in scientific knowledge. The paper will investigate this transformation by considering the genesis of analysis of variance and experimental design, statistical methods nowadays taught in every elementary course of statistics for the experimental and social sciences. These methods were developed by the mathematician and geneticist R. A. Fisher during the 1920s, while he was working at Rothamsted Experimental Station, where agricultural research was in turn reshaped by Fisher’s methods. Analysis of variance and experimental design required new practices and instruments in field and laboratory research, and imposed a redistribution of expertise among statisticians, experimental scientists and the farm staff. On the other hand the use of statistical methods in agricultural science called for a systematization of information management and made computing an activity integral to the experimental research done at Rothamsted, permanently integrating the statisticians’ tools and expertise into the station research programme. Fisher’s statistical methods did not remain confined within agricultural research and by the end of the 1950s they had come to stay in psychology, sociology, education, chemistry, medicine, engineering, economics, quality control, just to mention a few of the disciplines which adopted them
Finite-Size Scaling of the Domain Wall Entropy Distributions for the 2D Ising Spin Glass
The statistics of domain walls for ground states of the 2D Ising spin glass
with +1 and -1 bonds are studied for square lattices with , and = 0.5, where is the fraction of negative bonds, using periodic
and/or antiperiodic boundary conditions. When is even, almost all domain
walls have energy = 0 or 4. When is odd, most domain walls have
= 2. The probability distribution of the entropy, , is found
to depend strongly on . When , the probability distribution
of is approximately exponential. The variance of this distribution
is proportional to , in agreement with the results of Saul and Kardar. For
the distribution of is not symmetric about zero. In
these cases the variance still appears to be linear in , but the average of
grows faster than . This suggests a one-parameter scaling
form for the -dependence of the distributions of for .Comment: 13 page
Effects of Phosphodiesterase 3A Modulation on Murine Cerebral Microhemorrhages
Background: Cerebral microbleeds (CMB) are MRI-demonstrable cerebral microhemorrhages (CMH) which commonly coexist with ischemic stroke. This creates a challenging therapeutic milieu, and a strategy that simultaneously protects the vessel wall and provides anti-thrombotic activity is an attractive potential approach. Phosphodiesterase 3A (PDE3A) inhibition is known to provide cerebral vessel wall protection combined with anti-thrombotic effects. As an initial step in the development of a therapy that simultaneously treats CMB and ischemic stroke, we hypothesized that inhibition of the PDE3A pathway is protective against CMH development.
Methods: The effect of PDE3A pathway inhibition was studied in the inflammation-induced and cerebral amyloid angiopathy (CAA)-associated mouse models of CMH. The PDE3A pathway was modulated using two approaches: genetic deletion of PDE3A and pharmacological inhibition of PDE3A by cilostazol. The effects of PDE3A pathway modulation on H&E- and Prussian blue (PB)-positive CMH development, BBB function (IgG, claudin-5, and fibrinogen), and neuroinflammation (ICAM-1, Iba-1, and GFAP) were investigated.
Results: Robust development of CMH in the inflammation-induced and CAA-associated spontaneous mouse models was observed. Inflammation-induced CMH were associated with markers of BBB dysfunction and inflammation, and CAA-associated spontaneous CMH were associated primarily with markers of neuroinflammation. Genetic deletion of the PDE3A gene did not alter BBB function, microglial activation, or CMH development, but significantly reduced endothelial and astrocyte activation in the inflammation-induced CMH mouse model. In the CAA-associated CMH mouse model, PDE3A modulation via pharmacological inhibition by cilostazol did not alter BBB function, neuroinflammation, or CMH development.
Conclusions: Modulation of the PDE3A pathway, either by genetic deletion or pharmacological inhibition, does not alter CMH development in an inflammation-induced or in a CAA-associated mouse model of CMH. The role of microglial activation and BBB injury in CMH development warrants further investigation
Protecting eyewitness evidence: Examining the efficacy of a self-administered interview tool
Given the crucial role of eyewitness evidence, statements should be obtained as soon as possible after an incident. This is not always achieved due to demands on police resources. Two studies trace the development of a new tool, the Self-Administered Interview (SAI), designed to elicit a comprehensive initial statement. In Study 1, SAI participants reported more correct details than participants who provided a free recall account, and performed at the same level as participants given a Cognitive Interview. In Study 2, participants viewed a simulated crime and half recorded their statement using the SAI. After a delay of 1 week, all participants completed a free recall test. SAI participants recalled more correct details in the delayed recall task than control participants
Aging Exacerbates Development of Cerebral Microbleeds in a Mouse Model
Background: Cerebral microhemorrhages (CMH) are commonly found in the aging brain. CMH are also the neuropathological substrate of cerebral microbleeds (CMB), demonstrated on brain MRI. Recent studies demonstrate the importance of systemic inflammation in CMH development, but the relationships among inflammation, aging, and CMH development are not well-defined. In the current study, we hypothesized that the pathogenesis of inflammation-induced CMH in mice differs by age.
Methods: We studied young (3 months, n = 20) and old (18 months, n = 25) C57BL/6 mice injected with low-dose lipopolysaccharide (LPS; 1 mg/kg, i.p.) or saline at 0, 6, and 24 h. Seven days after the first LPS/saline injection, brains were harvested, sectioned, and stained with hematoxylin and eosin (H&E) and Prussian blue (PB) to estimate acute/fresh and sub-acute CMH development, respectively. The relationships between microglial/macrophage activation (ionized calcium-binding adapter molecule-1), astrocyte activation (glial fibrillary acidic protein), blood-brain barrier (BBB) disruption (brain immunoglobulin G), aging, and CMH development were examined using immunohistochemistry.
Results: Aging alone did not increase spontaneous H&E-positive CMH development but significantly increased the number, size, and total area of LPS-induced H&E-positive CMH in mice. LPS- and saline-treated aged mice had significantly larger PB-positive CMH compared with young mice, but the total area of PB-positive CMH was increased only in LPS-treated aged mice. Aged mice had significantly increased microglial/macrophage activation, which correlated with H&E- and PB-positive CMH development. Aged mice treated with LPS had significantly increased astrocyte activation and BBB disruption compared with young LPS-treated mice.
Conclusions:
Aging makes the brain more susceptible to inflammation-induced CMH in mice, and this increase in CMH with aging is associated with microglial/macrophage activation
Sensitivity to grid resolution in the ability of a chemical transport model to simulate observed oxidant chemistry under high-isoprene conditions
Formation of ozone and organic aerosol in continental atmospheres depends on whether isoprene emitted by vegetation is oxidized by the high-NOx pathway (where peroxy radicals react with NO) or by low-NOx pathways (where peroxy radicals react by alternate channels, mostly with HO2). We used mixed layer observations from the SEAC4RS aircraft campaign over the Southeast US to test the ability of the GEOS-Chem chemical transport model at different grid resolutions (0.25°  ×  0.3125°, 2°  ×  2.5°, 4°  ×  5°) to simulate this chemistry under high-isoprene, variable-NOx conditions. Observations of isoprene and NOx over the Southeast US show a negative correlation, reflecting the spatial segregation of emissions; this negative correlation is captured in the model at 0.25°  ×  0.3125° resolution but not at coarser resolutions. As a result, less isoprene oxidation takes place by the high-NOx pathway in the model at 0.25°  ×  0.3125° resolution (54 %) than at coarser resolution (59 %). The cumulative probability distribution functions (CDFs) of NOx, isoprene, and ozone concentrations show little difference across model resolutions and good agreement with observations, while formaldehyde is overestimated at coarse resolution because excessive isoprene oxidation takes place by the high-NOx pathway with high formaldehyde yield. The good agreement of simulated and observed concentration variances implies that smaller-scale non-linearities (urban and power plant plumes) are not important on the regional scale. Correlations of simulated vs. observed concentrations do not improve with grid resolution because finer modes of variability are intrinsically more difficult to capture. Higher model resolution leads to decreased conversion of NOx to organic nitrates and increased conversion to nitric acid, with total reactive nitrogen oxides (NOy) changing little across model resolutions. Model concentrations in the lower free troposphere are also insensitive to grid resolution. The overall low sensitivity of modeled concentrations to grid resolution implies that coarse resolution is adequate when modeling continental boundary layer chemistry for global applications
Drought drove forest decline and dune building in eastern upper Michigan, USA, as the upper Great Lakes became closed basins
Current models of landscape response to Holocene climate change in midcontinent North America largely reconcile Earth orbital and atmospheric climate forcing with pollen-based forest histories on the east and eolian chronologies in Great Plains grasslands on the west. However, thousands of sand dunes spread across 12,000 km2 in eastern upper Michigan (EUM), more than 500 km east of the present forest-prairie ecotone, present a challenge to such models. We use 65 optically stimulated luminescence (OSL) ages on quartz sand deposited in silt caps (n = 8) and dunes (n = 57) to document eolian activity in EUM. Dune building was widespread ca. 10–8 ka, indicating a sharp, sustained decline in forest cover during that period. This decline was roughly coincident with hydrologic closure of the upper Great Lakes, but temporally inconsistent with most pollen-based models that imply canopy closure throughout the Holocene. Early Holocene forest openings are rarely recognized in pollen sums from EUM because faint signatures of non-arboreal pollen are largely obscured by abundant and highly mobile pine pollen. Early Holocene spikes in nonarboreal pollen are recorded in cores from small ponds, but suggest only a modest extent of forest openings. OSL dating of dune emplacement provides a direct, spatially explicit archive of greatly diminished forest cover during a very dry climate in eastern midcontinent North America ca. 10–8 ka
Random Field and Random Anisotropy Effects in Defect-Free Three-Dimensional XY Models
Monte Carlo simulations have been used to study a vortex-free XY ferromagnet
with a random field or a random anisotropy on simple cubic lattices. In the
random field case, which can be related to a charge-density wave pinned by
random point defects, it is found that long-range order is destroyed even for
weak randomness. In the random anisotropy case, which can be related to a
randomly pinned spin-density wave, the long-range order is not destroyed and
the correlation length is finite. In both cases there are many local minima of
the free energy separated by high entropy barriers. Our results for the random
field case are consistent with the existence of a Bragg glass phase of the type
discussed by Emig, Bogner and Nattermann.Comment: 10 pages, including 2 figures, extensively revise
Why do models overestimate surface ozone in the Southeast United States
Ozone pollution in the Southeast US involves complex chemistry driven by emissions of anthropogenic nitrogen oxide radicals (NOx  ≡  NO + NO2) and biogenic isoprene. Model estimates of surface ozone concentrations tend to be biased high in the region and this is of concern for designing effective emission control strategies to meet air quality standards. We use detailed chemical observations from the SEAC4RS aircraft campaign in August and September 2013, interpreted with the GEOS-Chem chemical transport model at 0.25°  ×  0.3125° horizontal resolution, to better understand the factors controlling surface ozone in the Southeast US. We find that the National Emission Inventory (NEI) for NOx from the US Environmental Protection Agency (EPA) is too high. This finding is based on SEAC4RS observations of NOx and its oxidation products, surface network observations of nitrate wet deposition fluxes, and OMI satellite observations of tropospheric NO2 columns. Our results indicate that NEI NOx emissions from mobile and industrial sources must be reduced by 30–60 %, dependent on the assumption of the contribution by soil NOx emissions. Upper-tropospheric NO2 from lightning makes a large contribution to satellite observations of tropospheric NO2 that must be accounted for when using these data to estimate surface NOx emissions. We find that only half of isoprene oxidation proceeds by the high-NOx pathway to produce ozone; this fraction is only moderately sensitive to changes in NOx emissions because isoprene and NOx emissions are spatially segregated. GEOS-Chem with reduced NOx emissions provides an unbiased simulation of ozone observations from the aircraft and reproduces the observed ozone production efficiency in the boundary layer as derived from a regression of ozone and NOx oxidation products. However, the model is still biased high by 6 ± 14 ppb relative to observed surface ozone in the Southeast US. Ozonesondes launched during midday hours show a 7 ppb ozone decrease from 1.5 km to the surface that GEOS-Chem does not capture. This bias may reflect a combination of excessive vertical mixing and net ozone production in the model boundary layer
A Murine Model of Inflammation-Induced Cerebral Microbleeds
Background: Cerebral microhemorrhages (CMH) are tiny deposits of blood degradation products in the brain and are pathological substrates of cerebral microbleeds. The existing CMH animal models are β-amyloid-, hypoxic brain injury-, or hypertension-induced. Recent evidence shows that CMH develop independently of hypoxic brain injury, hypertension, or amyloid deposition and CMH are associated with normal aging, sepsis, and neurodegenerative conditions. One common factor among the above pathologies is inflammation, and recent clinical studies show a link between systemic inflammation and CMH. Hence, we hypothesize that inflammation induces CMH development and thus, lipopolysaccharide (LPS)-induced CMH may be an appropriate model to study cerebral microbleeds.
Methods: Adult C57BL/6 mice were injected with LPS (3 or 1 mg/kg, i.p.) or saline at 0, 6, and 24 h. At 2 or 7 days after the first injection, brains were harvested. Hematoxylin and eosin (H&E) and Prussian blue (PB) were used to stain fresh (acute) hemorrhages and hemosiderin (sub-acute) hemorrhages, respectively. Brain tissue ICAM-1, IgG, Iba1, and GFAP immunohistochemistry were used to examine endothelium activation, blood-brain barrier (BBB) disruption, and neuroinflammation. MRI and fluorescence microscopy were used to further confirm CMH development in this model.
Results: LPS-treated mice developed H&E-positive (at 2 days) and PB-positive (at 7 days) CMH. No surface and negligible H&E-positive CMH were observed in saline-treated mice (n = 12). LPS (3 mg/kg; n = 10) produced significantly higher number, size, and area of H&E-positive CMH at 2 days. LPS (1 mg/kg; n = 9) produced robust development of PB-positive CMH at 7 days, with significantly higher number and area compared with saline (n = 9)-treated mice. CMH showed the highest distribution in the cerebellum followed by the sub-cortex and cortex. LPS-induced CMH were predominantly adjacent to cerebral capillaries, and CMH load was associated with indices of brain endothelium activation, BBB disruption, and neuroinflammation. Fluorescence microscopy confirmed the extravasation of red blood cells into the brain parenchyma, and MRI demonstrated the presence of cerebral microbleeds.
Conclusions: LPS produced rapid and robust development of H&E-positive (at 2 days) and PB-positive (at 7 days) CMH. The ease of development of both H&E- and PB-positive CMH makes the LPS-induced mouse model suitable to study inflammation-induced CMH
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