Correlation of cognitive status, MRI- and SPECT-imaging in CADASIL patients

Although there is evidence for correlations between disability and magnetic resonance imaging (MRI) total lesion volume in autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the significance of structural MRI abnormalities for cognitive dysfunction remains controversial. We performed detailed neuropsychological testing, high resolution MRI, and Tc-99m-ethyl cysteinate-dimer SPECT in three CADASIL patients. MR-images were rated independently by two investigators for the presence of white matter lesions, lacunar infarcts, microbleeds, and ventricular enlargement. Cortical atrophy was quantified by the use of automatic morphometric assessment of the cortical thickness. In addition, laboratory and patients' history data were collected in order to assess the individual vascular risk factor profile. The differences in cognitive performance between the three patients are neither explained by structural-, or functional neuroimaging, nor by the patient-specific vascular risk factor profiles. The neuroradiologically least affected patient met criteria for dementia, whereas the most severely affected patient was in the best clinical and cognitive state. Conventional structural and functional neuroimaging is important for the diagnosis of CADASIL, but it is no sufficient surrogate marker for the associated cognitive decline. Detailed neuropsychological assessment seems to be more useful, particularly with respect to the implementation of reliable outcome parameters in possible therapeutic trials

Update on a Pharmacokinetic-Centric Alternative Tier II Program for MMT—Part II: Physiologically Based Pharmacokinetic Modeling and Manganese Risk Assessment

Recently, a variety of physiologically based pharmacokinetic (PBPK) models have been developed for the essential element manganese. This paper reviews the development of PBPK models (e.g., adult, pregnant, lactating, and neonatal rats, nonhuman primates, and adult, pregnant, lactating, and neonatal humans) and relevant risk assessment applications. Each PBPK model incorporates critical features including dose-dependent saturable tissue capacities and asymmetrical diffusional flux of manganese into brain and other tissues. Varied influx and efflux diffusion rate and binding constants for different brain regions account for the differential increases in regional brain manganese concentrations observed experimentally. We also present novel PBPK simulations to predict manganese tissue concentrations in fetal, neonatal, pregnant, or aged individuals, as well as individuals with liver disease or chronic manganese inhalation. The results of these simulations could help guide risk assessors in the application of uncertainty factors as they establish exposure guidelines for the general public or workers

Immorality and Irrationality

Does immorality necessarily involve irrationality? The question is often taken to be among the deepest in moral philosophy. But apparently deep questions sometimes admit of deflationary answers. In this case we can make way for a deflationary answer by appealing to dualism about rationality, according to which there are two fundamentally distinct notions of rationality: structural rationality and substantive rationality. I have defended dualism elsewhere. Here, I’ll argue that it allows us to embrace a sensible – I will not say boring – moderate view about the relationship between immorality and irrationality: roughly, that immorality involves substantive irrationality, but not structural irrationality. I defend this moderate view, and argue that many of the arguments for less moderate views turn either on missing the distinction between substantive and structural rationality, or on misconstruing it

Causality in relativistic many body theory

The stability of the nuclear matter system with respect to density fluctuations is examined exploring in detail the pole structure of the electro-nuclear response functions. Making extensive use of the method of dispersion integrals we calculate the full polarization propagator not only for real energies in the spacelike and timelike regime but also in the whole complex energy plane. The latter proved to be necessary in order to identify unphysical causality violating poles which are the consequence of a neglection of vacuum polarization. On the contrary it is shown that Dirac sea effects stabilize the nuclear matter system shifting the unphysical pole from the upper energy plane back to the real axis. The exchange of strength between these real timelike collective excitations and the spacelike energy regime is shown to lead to a reduction of the quasielastic peak as it is seen in electron scattering experiments. Neglecting vacuum polarization one also obtains a reduction of the quasielastic peak but in this case the strength is partly shifted to the causality violating pole mentioned above which consequently cannot be considered as a physical reliable result. Our investigation of the response function in the energy region above the threshold of nucleon anti-nucleon production leads to another remarkable result. Treating the nucleons as point-like Dirac particles we show that for any isospin independent NN-interaction RPA-correlations provide a reduction of the production amplitude for $p\bar p$-pairs by a factor 2.Comment: 19 pages Latex including 12 postscript figure

Microbial community functioning during plant litter decomposition

International audienceAbstract Microbial life in soil is fueled by dissolved organic matter (DOM) that leaches from the litter layer. It is well known that decomposer communities adapt to the available litter source, but it remains unclear if they functionally compete or synergistically address different litter types. Therefore, we decomposed beech, oak, pine and grass litter from two geologically distinct sites in a lab-scale decomposition experiment. We performed a correlative network analysis on the results of direct infusion HR-MS DOM analysis and cross-validated functional predictions from 16S rRNA gene amplicon sequencing and with DOM and metaproteomic analyses. Here we show that many functions are redundantly distributed within decomposer communities and that their relative expression is rapidly optimized to address litter-specific properties. However, community changes are likely forced by antagonistic mechanisms as we identified several natural antibiotics in DOM. As a consequence, the decomposer community is specializing towards the litter source and the state of decomposition (community divergence) but showing similar litter metabolomes (metabolome convergence). Our multi-omics-based results highlight that DOM not only fuels microbial life, but it additionally holds meta-metabolomic information on the functioning of ecosystems

Polyatomic Molecular Structure Retrieval using Laser-Induced Electron Diffraction

Laser-induced electron diffraction is a developing dynamical imaging technique that is already able to probe molecular dynamics at few-femtosecond temporal resolutions and has the potential to reach the sub-femtosecond level. Here we provide the recipe for the extension of the technique to polyatomic molecules and we demonstrate the method by extracting the structure of aligned and anti-aligned acetylene (C₂H₂). We show that multiple bond lengths can be simultaneously imaged at high accuracy including elusive hydrogen containing bonds. Our results open the door to the investigation of larger complex molecules and the realization of a true molecular movie

The characterization of Vicker`s microhardness indentations and pile-up profiles as a strain-hardening microprobe

Microhardness measurements have long been used to examine strength properties and changes in strength properties in metals, for example, as induced by irradiation. Microhardness affords a relatively simple test that can be applied to very small volumes of material. Microhardness is nominally related to the flow stress of the material at a fixed level of plastic strain. Further, the geometry of the pile-up of material around the indentation is related to the strain-hardening behavior of a material; steeper pile-ups correspond to smaller strain-hardening rates. In this study the relationship between pile-up profiles and strain hardening is examined using both experimental and analytical methods. Vickers microhardness tests have been performed on a variety of metal alloys including low alloy, high Cr and austenitic stainless steels. The pile-up topology around the indentations has been quantified using confocal microscopy techniques. In addition, the indentation and pile-up geometry has been simulated using finite element method techniques. These results have been used to develop an improved quantification of the relationship between the pile-up geometry and the strain-hardening constitutive behavior of the test material

Polyatomic Molecular Structure Retrieval using Laser-Induced Electron Diffraction

Laser-induced electron diffraction is a developing dynamical imaging technique that is already able to probe molecular dynamics at few-femtosecond temporal resolutions and has the potential to reach the sub-femtosecond level. Here we provide the recipe for the extension of the technique to polyatomic molecules and we demonstrate the method by extracting the structure of aligned and anti-aligned acetylene (C₂H₂). We show that multiple bond lengths can be simultaneously imaged at high accuracy including elusive hydrogen containing bonds. Our results open the door to the investigation of larger complex molecules and the realization of a true molecular movie

Alterations in rhythmic and non-rhythmic resting-state EEG activity and their link to cognition in older age

While many structural and biochemical changes in the brain have been previously associated with aging, the findings concerning electrophysiological signatures, reflecting functional properties of neuronal networks, remain rather controversial. To try resolve this issue, we took advantage of a large population study (N=1703) and comprehensively investigated the association of multiple EEG biomarkers (power of alpha and theta oscillations, individual alpha peak frequency (IAF), the slope of 1/f power spectral decay), aging, and aging and cognitive performance. Cognitive performance was captured with three factors representing processing speed, episodic memory, and interference resolution. Our results show that not only did IAF decline with age but it was also associated with interference resolution over multiple cortical areas. To a weaker extent, 1/f slope of the PSD showed age-related reductions, mostly in frontal brain regions. Finally, alpha power was negatively associated with the speed of processing in the right frontal lobe, despite the absence of age-related alterations. Our results thus demonstrate that multiple electrophysiological features, as well as their interplay, should be considered when investigating the association between age, neuronal activity, and cognitive performance

Comparison of large-angle production of charged pions with incident protons on cylindrical long and short targets

The HARP collaboration has presented measurements of the double-differential pi+/pi- production cross-section in the range of momentum 100 MeV/c <= p 800 MeV/c and angle 0.35 rad <= theta <= 2.15 rad with proton beams hitting thin nuclear targets. In many applications the extrapolation to long targets is necessary. In this paper the analysis of data taken with long (one interaction length) solid cylindrical targets made of carbon, tantalum and lead is presented. The data were taken with the large acceptance HARP detector in the T9 beam line of the CERN PS. The secondary pions were produced by beams of protons with momenta 5 GeV/c, 8 GeV/c and 12 GeV/c. The tracking and identification of the produced particles were performed using a small-radius cylindrical time projection chamber (TPC) placed inside a solenoidal magnet. Incident protons were identified by an elaborate system of beam detectors. Results are obtained for the double-differential yields per target nucleon d2 sigma / dp dtheta. The measurements are compared with predictions of the MARS and GEANT4 Monte Carlo simulations.Comment: 43 pages, 20 figure