Efficacy of N-acetyl cysteine in traumatic brain injury

In this study, using two different injury models in two different species, we found that early post-injury treatment with NAcetyl Cysteine (NAC) reversed the behavioral deficits associated with the TBI. These data suggest generalization of a protocol similar to our recent clinical trial with NAC in blast-induced mTBI in a battlefield setting [1], to mild concussion from blunt trauma. This study used both weight drop in mice and fluid percussion injury in rats. These were chosen to simulate either mild or moderate traumatic brain injury (TBI). For mice, we used novel object recognition and the Y maze. For rats, we used the Morris water maze. NAC was administered beginning 30-60 minutes after injury. Behavioral deficits due to injury in both species were significantly reversed by NAC treatment. We thus conclude NAC produces significant behavioral recovery after injury. Future preclinical studies are needed to define the mechanism of action, perhaps leading to more effective therapies in man

Chemical transformations in organic aerosol from biomass burning

International audienceFine aerosol particles were collected separately during daytime and nighttime at a tropical pasture site in Rondônia, Brazil, during the burning and dry-to-wet transition period in 2002. Total carbon (TC) and water-soluble organic carbon (WSOC) were measured by evolved gas analysis (EGA). Based on the thermochemical properties of the fine aerosol, the relative amounts of the low and higher molecular weight compounds were estimated. It was found that the thermally refractory (possibly higher molecular weight) compounds dominated the TC composition. Their contribution to TC was higher in the daytime samples than in the nighttime ones. The relative share of WSOC also showed a statistically significant diel variation and so did its refractory fraction. Anhydrosugars and phenolic acids were determined by GC-MS and their diel variation was studied. Based on the decrease of their relative concentrations between the biomass burning and transition periods and their distinctly different diel variations, we suggest that the phenolic acids may undergo chemical transformations in the aerosol phase, possibly towards more refractory compounds (humic-like substances, HULIS), as has been suggested previously. These conclusions are supported by the results of the thermally assisted hydrolysis and methylation gas chromatography-mass spectrometry of the same filter samples

Spectral light absorption by ambient aerosols influenced by biomass burning in the Amazon Basin. I: Comparison and field calibration of absorption measurement techniques

International audienceSpectral aerosol light absorption is an important parameter for the assessment of the radiation budget of the atmosphere. Although on-line measurement techniques for aerosol light absorption, such as the Aethalometer and the Particle Soot Absorption Photometer (PSAP), have been available for two decades, they are limited in accuracy and spectral resolution because of the need to deposit the aerosol on a filter substrate before measurement. Recently, a 7-wavelength (?) Aethalometer became commercially available, which covers the visible (VIS) to near-infrared (NIR) spectral range (?=450?950 nm), and laboratory calibration studies improved the degree of confidence in these measurement techniques. However, the applicability of the laboratory calibration factors to ambient conditions has not been investigated thoroughly yet. As part of the LBA-SMOCC (Large scale Biosphere atmosphere experiment in Amazonia ? SMOke aerosols, Clouds, rainfall and Climate) campaign from September to November 2002 in the Amazon basin we performed an extensive field calibration of a 1-? PSAP and a 7-? Aethalometer utilizing a photoacoustic spectrometer (PAS, 532 nm) as reference device. Especially during the dry period of the campaign, the aerosol population was dominated by pyrogenic emissions. The most pronounced artifact of integrating-plate type attenuation techniques (e.g. Aethalometer, PSAP) is due to multiple scattering effects within the filter matrix. For the PSAP, we essentially confirmed the laboratory calibration factor by Bond et al. (1999). On the other hand, for the Aethalometer we found a multiple scattering enhancement of 5.23 (or 4.55, if corrected for aerosol scattering), which is significantly larger than the factors previously reported (~2) for laboratory calibrations. While the exact reason for this discrepancy is unknown, the available data from the present and previous studies suggest aerosol mixing (internal versus external) as a likely cause. For Amazonian aerosol, we found no absorption enhancement due to hygroscopic particle growth in the relative humidity (RH) range between 40% and 80%. However, a substantial bias in PSAP sensitivity that correlated with both RH and temperature (T) was observed for 20%RH<30% and 24°

Local modes, phonons, and mass transport in solid 4^4He

We propose a model to treat the local motion of atoms in solid $^{4}$He as a local mode. In this model, the solid is assumed to be described by the Self Consistent Harmonic approximation, combined with an array of local modes. We show that in the bcc phase the atomic local motion is highly directional and correlated, while in the hcp phase there is no such correlation. The correlated motion in the bcc phase leads to a strong hybridization of the local modes with the T$_{1}(110)$ phonon branch, which becomes much softer than that obtained through a Self Consistent Harmonic calculation, in agreement with experiment. In addition we predict a high energy excitation branch which is important for self-diffusion. Both the hybridization and the presence of a high energy branch are a consequence of the correlation, and appear only in the bcc phase. We suggest that the local modes can play the role in mass transport usually attributed to point defects (vacancies). Our approach offers a more overall consistent picture than obtained using vacancies as the predominant point defect. In particular, we show that our approach resolves the long standing controversy regarding the contribution of point defects to the specific heat of solid $^{4}$He.Comment: 10 pages, 10 figure

Cerium Oxide Nanoparticles: Advances in Biodistribution, Toxicity, and Preclinical Exploration

Antioxidant nanoparticles have recently gained tremendous attention for their enormous potential in biomedicine. However, discrepant reports of either medical benefits or toxicity, and lack of reproducibility of many studies, generate uncertainties delaying their effective implementation. Herein, the case of cerium oxide is considered, a well‐known catalyst in the petrochemistry industry and one of the first antioxidant nanoparticles proposed for medicine. Like other nanoparticles, it is now described as a promising therapeutic alternative, now as threatening to health. Sources of these discrepancies and how this analysis helps to overcome contradictions found for other nanoparticles are summarized and discussed. For the context of this analysis, what has been reported in the liver is reviewed, where many diseases are related to oxidative stress. Since well‐dispersed nanoparticles passively accumulate in liver, it represents a major testing field for the study of new nanomedicines and their clinical translation. Even more, many contradictory works have reported in liver either cerium‐oxide‐associated toxicity or protection against oxidative stress and inflammation. Based on this, finally, the intention is to propose solutions to design improved nanoparticles that will work more precisely in medicine and safely in society

EGFRvIII upregulates DNA mismatch repair resulting in increased temozolomide sensitivity of MGMT promoter methylated glioblastoma

The oncogene epidermal growth factor receptor variant III (EGFRvIII) is frequently expressed in glioblastomas (GBM) but its impact on therapy response is still under controversial debate. Here we wanted to test if EGFRvIII influences the sensitivity towards the alkylating agent temozolomide (TMZ). Therefore, we retrospectively analyzed the survival of 336 GBM patients, demonstrating that under standard treatment, which includes TMZ, EGFRvIII expression is associated with prolonged survival, but only in patients with O6-methylguanine-DNA methyltransferase (MGMT) promoter methylated tumors. Using isogenic GBM cell lines with endogenous EGFRvIII expression we could demonstrate that EGFRvIII increases TMZ sensitivity and results in enhanced numbers of DNA double-strand breaks and a pronounced S/G2-phase arrest after TMZ treatment. We observed a higher expression of DNA mismatch repair (MMR) proteins in EGFRvIII+ cells and patient tumor samples, which was most pronounced for MSH2 and MSH6. EGFRvIII-specific knockdown reduced MMR protein expression thereby increasing TMZ resistance. Subsequent functional kinome profiling revealed an increased activation of p38- and ERK1/2-dependent signaling in EGFRvIII expressing cells, which regulates MMR protein expression downstream of EGFRvIII. In summary, our results demonstrate that the oncoprotein EGFRvIII sensitizes a fraction of GBM to current standard of care treatment through the upregulation of DNA MMR

\u3cem\u3eHerschel\u3c/em\u3e Observations of the Centaurus Oluster - the Dynamics of Cold Gas in a Cool Core

Brightest cluster galaxies (BCGs) in the cores of galaxy clusters have distinctly different properties from other low-redshift massive ellipticals. The majority of the BCGs in cool-core clusters show signs of active star formation. We present observations of NGC 4696, the BCG of the Centaurus galaxy cluster, at far-infrared (FIR) wavelengths with theHerschel space telescope. Using the PACS spectrometer, we detect the two strongest coolants of the interstellar medium, [C II] at 157.74 μm and [O I] at 63.18 μm, and in addition [N II] at 121.90 μm. The [C II] emission is extended over a region of 7 kpc with a similar spatial morphology and kinematics to the optical Hα emission. This has the profound implication that the optical hydrogen recombination line, Hα, the optical forbidden lines, [N II] λ6583 Å, the soft X-ray filaments and the FIR [C II] line all have the same energy source. We also detect dust emission using the PACS and SPIRE photometers at all six wavebands. We perform a detailed spectral energy distribution fitting using a two-component modified blackbody function and find a cold 19-K dust component with mass 1.6 × 106 M⊙ and a warm 46-K dust component with mass 4.0 × 103 M⊙. The total FIR luminosity between 8 and 1000 μm is 7.5 × 108 L⊙, which using Kennicutt relation yields a low star formation rate of 0.13 M⊙ yr−1. This value is consistent with values derived from other tracers, such as ultraviolet emission. Combining the spectroscopic and photometric results together with optical Hα, we model emitting clouds consisting of photodissociation regions adjacent to ionized regions. We show that in addition to old and young stellar populations, there is another source of energy, such as cosmic rays, shocks or reconnection diffusion, required to excite the Hα and [C II] filaments

Reliability of Bioelectrical Impedance Analysis for Estimating Whole‐Fish Energy Density and Percent Lipids

We evaluated bioelectrical impedance analysis (BIA) as a nonlethal means of predicting energy density and percent lipids for three fish species: Yellow perch Perca flavescens, walleye Sander vitreus, and lake whitefish Coregonus clupeaformis. Although models that combined BIA measures with fish wet mass provided strong predictions of total energy, total lipids, and total dry mass for whole fish, including BIA provided only slightly better predictions than using fish mass alone. Regression models that used BIA measures to directly predict the energy density or percent lipids of whole fish were generally better than those using body mass alone (based on Akaike’s information criterion). However, the goodness of fit of models that used BIA measures varied widely across species and at best explained only slightly more than one‐half the variation observed in fish energy density or percent lipids. Models that combined BIA measures with body mass for prediction had the strongest correlations between predicted and observed energy density or percent lipids for a validation group of fish, but there were significant biases in these predictions. For example, the models underestimated energy density and percent lipids for lipid‐rich fish and overestimated energy density and percent lipids for lipid‐poor fish. A comparison of observed versus predicted whole‐fish energy densities and percent lipids demonstrated that models that incorporated BIA measures had lower maximum percent error than models without BIA measures in them, although the errors for the BIA models were still generally high (energy density: 15‐18%; percent lipids: 82‐89%). Considerable work is still required before BIA can provide reliable predictions of whole‐fish energy density and percent lipids, including understanding how temperature, electrode placement, and the variation in lipid distribution within a fish affect BIA measures.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141722/1/tafs1519.pd

Bishops who live like princes: Bishop Tebartz-van Elst and the challenge of defining corruption

This article contributes to the debate on defining corruption. Rather than attempting to provide a definitive definition, it uses the case of Franz-Peter Tebartz-van Elst, a German bishop from the diocese of Limburg who stepped down in 2014, to illustrate that the disciplines of law, political science, economics, and anthropology all make important contributions to understanding what corruption is and how it should be conceptualized. Seen through these different lenses, the article argues, the case of “Bishop Bling” can be understood in strikingly different ways. This has ramifications not just for the case itself but also for how analysts understand corruption more broadly. Adopting an overtly interdisciplinary approach does not represent a way to “solve” the definitional dilemma, but it can help analysts understand more about corruption’s multiplicity