304 research outputs found
Impact of freight traffic on school walking decisions in urban environments
In light of the decline in social acceptance of walking and biking to school, there is a critical need to examine issues impacting school transportation decisions and to identify strategies to promote healthier behavior. In urban areas with high volume freight corridors, factors affecting school walking decisions can be complicated by increased truck and rail traffic. This paper presents findings from a study of urban neighborhoods in a major southeastern city, including those that are adjacent to freight corridors. Perceptions of neighborhood residents are compared in the context of existing infrastructure and network characteristics (urban vs. urban freight-centric). The results provide insight into factors influencing school transportation decisions in urban environments, and highlight discrepancies between perceptions and actual issues relevant to child pedestrian safety
The background in the neutrinoless double beta decay experiment GERDA
The GERmanium Detector Array (GERDA) experiment at the Gran Sasso underground
laboratory (LNGS) of INFN is searching for neutrinoless double beta decay of
76Ge. The signature of the signal is a monoenergetic peak at 2039 keV, the
Q-value of the decay, Q_bb. To avoid bias in the signal search, the present
analysis does not consider all those events, that fall in a 40 keV wide region
centered around Q_bb. The main parameters needed for the neutrinoless double
beta decay analysis are described. A background model was developed to describe
the observed energy spectrum. The model contains several contributions, that
are expected on the basis of material screening or that are established by the
observation of characteristic structures in the energy spectrum. The model
predicts a flat energy spectrum for the blinding window around Q_bb with a
background index ranging from 17.6 to 23.8*10^{-3} counts/(keV kg yr). A part
of the data not considered before has been used to test if the predictions of
the background model are consistent. The observed number of events in this
energy region is consistent with the background model. The background at Q-bb
is dominated by close sources, mainly due to 42K, 214Bi, 228Th, 60Co and alpha
emitting isotopes from the 226Ra decay chain. The individual fractions depend
on the assumed locations of the contaminants. It is shown, that after removal
of the known gamma peaks, the energy spectrum can be fitted in an energy range
of 200 kev around Q_bb with a constant background. This gives a background
index consistent with the full model and uncertainties of the same size
Oxidative stress and proinflammatory cytokines contribute to demyelination and axonal damage in a cerebellar culture model of neuroinflammation
Background: Demyelination and axonal damage are critical processes in the pathogenesis of multiple sclerosis (MS). Oxidative stress and pro-inflammatory cytokines elicited by inflammation mediates tissue damage. Methods/Principal Findings: To monitor the demyelination and axonal injury associated with microglia activation we employed a model using cerebellar organotypic cultures stimulated with lipopolysaccharide (LPS). Microglia activated by LPS released pro-inflammatory cytokines (IL-1β, IL-6 and TNFα), and increased the expression of inducible nitric oxide synthase (iNOS) and production of reactive oxygen species (ROS). This activation was associated with demyelination and axonal damage in cerebellar cultures. Axonal damage, as revealed by the presence of non-phosphorylated neurofilaments, mitochondrial accumulation in axonal spheroids, and axonal transection, was associated with stronger iNOS expression and concomitant increases in ROS. Moreover, we analyzed the contribution of pro-inflammatory cytokines and oxidative stress in demyelination and axonal degeneration using the iNOS inhibitor ethyl pyruvate, a free-scavenger and xanthine oxidase inhibitor allopurinol, as well as via blockage of pro-inflammatory cytokines using a Fc-TNFR1 construct. We found that blocking microglia activation with ethyl pyruvate or allopurinol significantly decreased axonal damage, and to a lesser extent, demyelination. Blocking TNFα significantly decreased demyelination but did not prevented axonal damage. Moreover, the most common therapy for MS, interferon-beta, was used as an example of an immunomodulator compound that can be tested in this model. In vitro, interferon-beta treatment decreased oxidative stress (iNOS and ROS levels) and the release of pro-inflammatory cytokines after LPS stimulation, reducing axonal damage. Conclusion: The model of neuroinflammation using cerebellar culture stimulated with endotoxin mimicked myelin and axonal damage mediated by the combination of oxidative stress and pro-inflammatory cytokines. This model may both facilitate understanding of the events involved in neuroinflammation and aid in the development of neuroprotective therapies for the treatment of MS and other neurodegenerative diseases
Status of the GERDA experiment
The study of neutrinoless double beta (0nbb) decay is the only one presently known approach to the fundamental question if the neutrino is a Majorana particle, i.e. its own anti-particle. The observation of 0nbb decay would prove that lepton number is not conserved, establish that neutrino has a Majorana component and, assuming that light neutrino is the dominating process, provide a method for the determination of its effective mass. GERDA is a new 0nbb decay experiment which is currently taking data at the Laboratori Nazionali del Gran Sasso (LNGS) of INFN in Italy. It implements a new shielding concept by operating bare diodes made from Ge with enriched 76Ge in high purity liquid argon supplemented by a water shield. The aim of GERDA is to verify or refute the recent claim of discovery, and, in a second phase, to achieve a two orders of magnitude lower background index than past experiments, to increase the sensitive mass and to collect an exposure of 100 kg yr. The paper will discuss design, physics reach, and status of data taking of GERDA.JRC.D.4-Standards for Nuclear Safety, Security and Safeguard
Price assymetry in the Dutch retail gasoline market
This paper analyses retail price adjustments in the Dutch gasoline market. We estimate an asymmetric error correction model on weekly price changes for the years 1996 to 2001. We construct five datasets, one for each working day. The conclusions on asymmetric pricing are shown to differ over these datasets, suggesting that the choice of the day for which prices are observed matters more than commonly believed. In our view, the insufficient robustness of outcomes might explain the mixed conclusions found in the literature. Using two approaches, we also show that the effect of asymmetry on Dutch consumer costs is negligible
The recognition of early developmental stages in haemopoiesis
Almost all tissues of multicellular organisms contain cells which
have the capacity to change their proliferative activity according to
the demand. Some tissues show little or no cellular turnover under
normal steady state conditions, but they can switch to a regeneration
process in response to perturbation (e.g., mechanical injury). In
other tissues, there is continuous cell production to compensate for
cell loss due to the continuous utilization of functional cells even
under normal conditions. Variation in demand is met by variation in
the rate of cell production. The cells which generate offspring
throughout life in the continuously renewing tissues are usually designated
as stem cells. Stem cells are capable of extensive proliferation
which results in new stem cells as well as differentiating cells.
The most extensively studied stem cell systems in vertebrates are
those of the epidermis, the intestinal epithelium, the testis and the
haemopoietic tissues. These systems are commonly used for investigations
on the mechanisms of cellular differentiation. In comparison to
differentiation processes during embryogenesis, the organization of
the stem cell systems in the adult is relatively simple. In adulthood,
differentiation is restricted to one or to a limited number of cell
types, while, in embryogenesis, differentiation into a large variety
of tissues takes plac
A Role for Protein Arginine Methyltransferase 7 in Repetitive and Mild Traumatic Brain Injury
Mild traumatic brain injury affects the largest proportion of individuals in the United States and world-wide. Pre-clinical studies of repetitive and mild traumatic brain injury (rmTBI) have been limited in their ability to recapitulate human pathology (i.e. diffuse rotational injury). We used the closed-head impact model of engineered rotation acceleration (CHIMERA) to simulate rotational injury observed in patients and to study the pathological outcomes post-rmTBI using C57BL/6J mice. Enhanced cytokine production was observed in both the cortex and hippocampus to suggest neuroinflammation. Furthermore, microglia were assessed via enhanced iba1 protein levels and morphological changes using immunofluorescence. In addition, LC/MS analyses revealed excess glutamate production, as well as diffuse axonal injury via Bielschowsky\u27s silver stain kit. Moreover, the heterogeneous nature of rmTBI has made it challenging to identify drug therapies that address rmTBI, therefore we sought to identify novel targets in the concurrent rmTBI pathology. The pathophysiological findings correlated with a time-dependent decrease in protein arginine methyltransferase 7 (PRMT7) protein expression and activity post-rmTBI along with dysregulation of PRMT upstream mediators s-adenosylmethionine and methionine adenosyltransferase 2 (MAT2) in vivo. In addition, inhibition of the upstream mediator MAT2A using the HT22 hippocampal neuronal cell line suggest a mechanistic role for PRMT7 via MAT2A in vitro. Collectively, we have identified PRMT7 as a novel target in rmTBI pathology in vivo and a mechanistic link between PRMT7 and upstream mediator MAT2A in vitro
PRMT7 Can Prevent Neurovascular Uncoupling, Blood-Brain Barrier Permeability, and Mitochondrial Dysfunction in Repetitive and Mild Traumatic Brain Injury
Mild traumatic brain injury (TBI) comprises the largest percentage of TBI-related injuries, with pathophysiological and functional deficits that persist in a subset of TBI patients. In our three-hit paradigm of repetitive and mild traumatic brain injury (rmTBI), we observed neurovascular uncoupling via decreased red blood cell velocity, microvessel diameter, and leukocyte rolling velocity 3 days post-rmTBI via intra-vital two-photon laser scanning microscopy. Furthermore, our data suggest increased blood-brain barrier (BBB) permeability (leakage), with corresponding decrease in junctional protein expression post-rmTBI. Mitochondrial oxygen consumption rates (measured via Seahorse XFe24) were also altered 3 days post-rmTBI, along with disrupted mitochondrial dynamics of fission and fusion. Overall, these pathophysiological findings correlated with decreased protein arginine methyltransferase 7 (PRMT7) protein levels and activity post-rmTBI. Here, we increased PRMT7 levels in vivo to assess the role of the neurovasculature and mitochondria post-rmTBI. In vivo overexpression of PRMT7 using a neuronal specific AAV vector led to restoration of neurovascular coupling, prevented BBB leakage, and promoted mitochondrial respiration, altogether to suggest a protective and functional role of PRMT7 in rmTBI
Effects of IFN-β1a and IFN-β1b treatment on the expression of cytokines, inducible NOS (NOS type II), and myelin proteins in animal model of multiple sclerosis
Searching for Solar KDAR with DUNE
The observation of 236 MeV muon neutrinos from kaon-decay-at-rest (KDAR) originating in the core of the Sun would provide a unique signature of dark matter annihilation. Since excellent angle and energy reconstruction are necessary to detect this monoenergetic, directional neutrino flux, DUNE with its vast volume and reconstruction capabilities, is a promising candidate for a KDAR neutrino search. In this work, we evaluate the proposed KDAR neutrino search strategies by realistically modeling both neutrino-nucleus interactions and the response of DUNE. We find that, although reconstruction of the neutrino energy and direction is difficult with current techniques in the relevant energy range, the superb energy resolution, angular resolution, and particle identification offered by DUNE can still permit great signal/background discrimination. Moreover, there are non-standard scenarios in which searches at DUNE for KDAR in the Sun can probe dark matter interactions
- …
