3,894 research outputs found
Chemotherapeutic agent 5-fluorouracil increases survival of SOD1 mouse model of ALS
Amyotrophic lateral sclerosis (ALS) is a lethal motor neuron disease with no cure. Currently there are only two ALS drugs approved by the FDA, both with a limited therapeutic effect. In the search for drug candidates for ALS, we studied the effect of known stem cell mobilizing agents (treatment) and antimetabolite 5-fluorouracil (5-FU) (anti-treatment) in SOD1G93A model of ALS. Surprisingly, we found that anti-cancer drug 5-FU increases lifespan, delays the disease onset and improves motor performance in ALS mice. Although we were not able to demonstrate the mechanistic basis of the beneficial 5-FU action in ALS mice, our findings suggest that 5-FU or similar drugs are possible drug candidates for the treatment of motor neuron diseases through drug repurposing
Phthalocyanine-nanocarbon ensembles: From discrete molecular and supramolecular systems to hybrid nanomaterials
This document is the Accepted Manuscript version of a Published Work that appeared in final form in Accounts of Chemical Research, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://dx.doi.org/10.1021/ar5004384Conspectus Phthalocyanines (Pcs) are macrocyclic and aromatic compounds that present unique electronic features such as high molar absorption coefficients, rich redox chemistry, and photoinduced energy/electron transfer abilities that can be modulated as a function of the electronic character of their counterparts in donor-acceptor (D-A) ensembles. In this context, carbon nanostructures such as fullerenes, carbon nanotubes (CNTs), and, more recently, graphene are among the most suitable Pc companions. Pc-C60 ensembles have been for a long time the main actors in this field, due to the commercial availability of C60 and the ell-established synthetic methods for its functionalization. As a result, many Pc-C60 architectures have been prepared, featuring different connectivities (covalent or supramolecular), intermolecular interactions (self-organized or molecularly dispersed species), and Pc HOMO/LUMO levels. All these elements provide a versatile toolbox for tuning the photophysical properties in terms of the type of process (photoinduced energy/electron transfer), the nature of the interactions beteen the electroactive units (through bond or space), and the kinetics of the formation/decay of the photogenerated species. Some recent trends in this field include the preparation of stimuli-responsive multicomponent systems ith tunable photophysical properties and highly ordered nanoarchitectures and surface-supported systems shoing high charge mobilities. A breakthrough in the Pc-nanocarbon field as the appearance of CNTs and graphene, hich opened a ne avenue for the preparation of intriguing photoresponsive hybrid ensembles shoing light-stimulated charge separation. The scarce solubility of these 1-D and 2-D nanocarbons, together ith their loer reactivity ith respect to C60 stemming from their less strained sp2 carbon netorks, has not meant an unsurmountable limitation for the preparation of variety of Pc-based hybrids. These systems, hich sho improved solubility and dispersibility features, bring together the unique electronic transport properties of CNTs and graphene ith the excellent light-harvesting and tunable redox properties of Pcs. A singular and distinctive feature of these Pc-CNT/graphene (single- or fe-layers) hybrid materials is the control of the direction of the photoinduced charge transfer as a result of the band-like electronic structure of these carbon nanoforms and the adjustable electronic levels of Pcs. Moreover, these conjugates present intensified light-harvesting capabilities resulting from the grafting of several chromophores on the same nanocarbon platform.In this Account, recent progress in the construction of covalent and supramolecular Pc-nanocarbon ensembles is summarized, ith a particular emphasis on their photoinduced behavior. e believe that the high degree of control achieved in the preparation of Pc-carbon nanostructures, together ith the increasing knoledge of the factors governing their photophysics, ill allo for the design of next-generation light-fueled electroactive systems. Possible implementation of these Pc-nanocarbons in high performance devices is envisioned, finally turning into reality much of the expectations generated by these materialsFinancial support from the Spanish MICINN (CTQ2011-24187/BQU), the Comunidad de Madrid (S2013/MIT-2841 FOTOCARBON) and the EU (“SO2S” FP7-PEOPLE-2012-ITN, no.: 316975) is acknowledge
Intensive care unit discharge to the ward with a tracheostomy cannula as a risk factor for mortality: A prospective, multicenter propensity analysis
To analyze the impact of decannulation before intensive care unit
discharge on ward survival in nonexperimental conditions. DESIGN: Prospective,
observational survey. SETTING: Thirty-one intensive care units throughout Spain.
PATIENTS: All patients admitted from March 1, 2008 to May 31, 2008.
INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: At intensive care unit
discharge, we recorded demographic variables, severity score, and intensive care
unit treatments, with special attention to tracheostomy. After intensive care
unit discharge, we recorded intensive care unit readmission and hospital
survival. STATISTICS: Multivariate analyses for ward mortality, with Cox
proportional hazard ratio adjusted for propensity score for intensive care unit
decannulation. We included 4,132 patients, 1,996 of whom needed mechanical
ventilation. Of these, 260 (13%) were tracheostomized and 59 (23%) died in the
intensive care unit. Of the 201 intensive care unit tracheostomized survivors, 60
were decannulated in the intensive care unit and 141 were discharged to the ward
with cannulae in place. Variables associated with intensive care unit
decannulation (non-neurologic disease [85% vs. 64%], vasoactive drugs [90% vs.
76%], parenteral nutrition [55% vs. 33%], acute renal failure [37% vs. 23%], and
good prognosis at intensive care unit discharge [40% vs. 18%]) were included in a
propensity score model for decannulation. Crude ward mortality was similar in
decannulated and nondecannulated patients (22% vs. 23%); however, after
adjustment for the propensity score and Sabadell Score, the presence of a
tracheostomy cannula was not associated with any survival disadvantage with an
odds ratio of 0.6 [0.3-1.2] (p=.1). CONCLUSION: In our multicenter setting,
intensive care unit discharge before decannulation is not a risk factor
Acute neuropsychological effects of MDMA and ethanol (co-)administration in healthy volunteers
Contains fulltext :
73592.pdf (publisher's version ) (Open Access)RATIONALE: In Western societies, a considerable percentage of young people expose themselves to 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy"). Commonly, ecstasy is used in combination with other substances, in particular alcohol (ethanol). MDMA induces both arousing as well as hallucinogenic effects, whereas ethanol is a general central nervous system depressant. OBJECTIVE: The aim of the present study is to assess the acute effects of single and co-administration of MDMA and ethanol on executive, memory, psychomotor, visuomotor, visuospatial and attention function, as well as on subjective experience. MATERIALS AND METHODS: We performed a four-way, double-blind, randomised, crossover, placebo-controlled study in 16 healthy volunteers (nine male, seven female) between the ages of 18-29. MDMA was given orally (100 mg) and blood alcohol concentration was maintained at 0.6 per thousand by an ethanol infusion regime. RESULTS: Co-administration of MDMA and ethanol was well tolerated and did not show greater impairment of performance compared to the single-drug conditions. Impaired memory function was consistently observed after all drug conditions, whereas impairment of psychomotor function and attention was less consistent across drug conditions. CONCLUSIONS: Co-administration of MDMA and ethanol did not exacerbate the effects of either drug alone. Although the impairment of performance by all drug conditions was relatively moderate, all induced significant impairment of cognitive function
Search for CP violation in D0 and D+ decays
A high statistics sample of photoproduced charm particles from the FOCUS
(E831) experiment at Fermilab has been used to search for CP violation in the
Cabibbo suppressed decay modes D+ to K-K+pi+, D0 to K-K+ and D0 to pi-pi+. We
have measured the following CP asymmetry parameters: A_CP(K-K+pi+) = +0.006 +/-
0.011 +/- 0.005, A_CP(K-K+) = -0.001 +/- 0.022 +/- 0.015 and A_CP(pi-pi+) =
+0.048 +/- 0.039 +/- 0.025 where the first error is statistical and the second
error is systematic. These asymmetries are consistent with zero with smaller
errors than previous measurements.Comment: 12 pages, 4 figure
Blood-brain barrier failure as a core mechanism in cerebral small vessel disease and dementia: evidence from a cohort study
Introduction: Small vessel disease (SVD) is a common contributor to dementia. Subtle blood-brain
barrier (BBB) leakage may be important in SVD-induced brain damage.
Methods: We assessed imaging, clinical variables, and cognition in patients with mild (i.e., nondisabling)
ischemic lacunar or cortical stroke. We analyzed BBB leakage, interstitial fluid, and white
matter integrity using multimodal tissue-specific spatial analysis around white matter hyperintensities
(WMH). We assessed predictors of 1 year cognition, recurrent stroke, and dependency.
Results: In 201 patients, median age 67 (range 34–97), BBB leakage, and interstitial fluid were
higher in WMH than normal-appearing white matter; leakage in normal-appearing white matter
increased with proximity to WMH (P , .0001), with WMH severity (P 5 .033), age (P 5 .03),
and hypertension (P , .0001). BBB leakage in WMH predicted declining cognition at 1 year.
Discussion: BBB leakage increases in normal-appearing white matter with WMH and predicts worsening
cognition. Interventions to reduce BBB leakage may prevent SVD-associated dementia
Search for the standard model Higgs boson in the H to ZZ to 2l 2nu channel in pp collisions at sqrt(s) = 7 TeV
A search for the standard model Higgs boson in the H to ZZ to 2l 2nu decay
channel, where l = e or mu, in pp collisions at a center-of-mass energy of 7
TeV is presented. The data were collected at the LHC, with the CMS detector,
and correspond to an integrated luminosity of 4.6 inverse femtobarns. No
significant excess is observed above the background expectation, and upper
limits are set on the Higgs boson production cross section. The presence of the
standard model Higgs boson with a mass in the 270-440 GeV range is excluded at
95% confidence level.Comment: Submitted to JHE
Single hadron response measurement and calorimeter jet energy scale uncertainty with the ATLAS detector at the LHC
The uncertainty on the calorimeter energy response to jets of particles is
derived for the ATLAS experiment at the Large Hadron Collider (LHC). First, the
calorimeter response to single isolated charged hadrons is measured and
compared to the Monte Carlo simulation using proton-proton collisions at
centre-of-mass energies of sqrt(s) = 900 GeV and 7 TeV collected during 2009
and 2010. Then, using the decay of K_s and Lambda particles, the calorimeter
response to specific types of particles (positively and negatively charged
pions, protons, and anti-protons) is measured and compared to the Monte Carlo
predictions. Finally, the jet energy scale uncertainty is determined by
propagating the response uncertainty for single charged and neutral particles
to jets. The response uncertainty is 2-5% for central isolated hadrons and 1-3%
for the final calorimeter jet energy scale.Comment: 24 pages plus author list (36 pages total), 23 figures, 1 table,
submitted to European Physical Journal
Search for anomalous t t-bar production in the highly-boosted all-hadronic final state
A search is presented for a massive particle, generically referred to as a
Z', decaying into a t t-bar pair. The search focuses on Z' resonances that are
sufficiently massive to produce highly Lorentz-boosted top quarks, which yield
collimated decay products that are partially or fully merged into single jets.
The analysis uses new methods to analyze jet substructure, providing
suppression of the non-top multijet backgrounds. The analysis is based on a
data sample of proton-proton collisions at a center-of-mass energy of 7 TeV,
corresponding to an integrated luminosity of 5 inverse femtobarns. Upper limits
in the range of 1 pb are set on the product of the production cross section and
branching fraction for a topcolor Z' modeled for several widths, as well as for
a Randall--Sundrum Kaluza--Klein gluon. In addition, the results constrain any
enhancement in t t-bar production beyond expectations of the standard model for
t t-bar invariant masses larger than 1 TeV.Comment: Submitted to the Journal of High Energy Physics; this version
includes a minor typo correction that will be submitted as an erratu
Search for New Physics with Jets and Missing Transverse Momentum in pp collisions at sqrt(s) = 7 TeV
A search for new physics is presented based on an event signature of at least
three jets accompanied by large missing transverse momentum, using a data
sample corresponding to an integrated luminosity of 36 inverse picobarns
collected in proton--proton collisions at sqrt(s)=7 TeV with the CMS detector
at the LHC. No excess of events is observed above the expected standard model
backgrounds, which are all estimated from the data. Exclusion limits are
presented for the constrained minimal supersymmetric extension of the standard
model. Cross section limits are also presented using simplified models with new
particles decaying to an undetected particle and one or two jets
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