Impact of alpha-synuclein spreading on the nigrostriatal dopaminergic pathway depends on the onset of the pathology

Misfolded alpha-synuclein spreads along anatomically connected areas through the brain, prompting progressive neurodegeneration of the nigrostriatal pathway in Parkinson's disease. To investigate the impact of early stage seeding and spreading of misfolded alpha-synuclein along with the nigrostriatal pathway, we studied the pathophysiologic effect induced by a single acute alpha-synuclein preformed fibrils (PFFs) inoculation into the midbrain. Further, to model the progressive vulnerability that characterizes the dopamine (DA) neuron life span, we used two cohorts of mice with different ages: 2-month-old (young) and 5-month-old (adult) mice. Two months after a-synuclein PFFs injection, we found that striatal DA release decreased exclusively in adult mice. Adult DA neurons showed an increased level of pathology spreading along with the nigrostriatal pathway accompanied with a lower volume of alpha-synuclein deposition in the midbrain, impaired neurotransmission, rigid DA terminal composition, and less microglial reactivity compared with young neurons. Notably, preserved DA release and increased microglial coverage in the PFFs-seeded hemisphere coexist with decreased large-sized terminal density in young DA neurons. This suggests the presence of a targeted pruning mechanism that limits the detrimental effect of alpha-synuclein early spreading. This study suggests that the impact of the pathophysiology caused by misfolded alpha-synuclein spreading along the nigrostriatal pathway depends on the age of the DA network, reducing striatal DA release specifically in adult mice

In vivo imaging reveals reduced activity of neuronal circuits in a mouse tauopathy model

Pathological alterations of tau protein play a significant role in the emergence and progression of neurodegenerative disorders. Tauopathies are characterized by detachment of the tau protein from neuronal microtubules, and its subsequent aberrant hyperphosphorylation, aggregation and cellular distribution. The exact nature of tau protein species causing neuronal malfunction and degeneration is still unknown. In the present study, we used mice transgenic for human tau with the frontotemporal dementia with parkinsonism-associated P301S mutation. These mice are prone to develop fibrillar tau inclusions, especially in the spinal cord and brainstem. At the same time, cortical neurons are not as strongly affected by fibrillar tau forms, but rather by soluble tau forms. We took advantage of the possibility to induce formation of neurofibrillary tangles in a subset of these cortical neurons by local injection of preformed synthetic tau fibrils. By using chronic in vivo two-photon calcium imaging in awake mice, we were able for the first time to follow the activity of individual tangle-bearing neurons and compare it to the activity of tangle-free neurons over the disease course. Our results revealed strong reduction of calcium transient frequency in layer 2/3 cortical neurons of P301S mice, independent of neurofibrillary tangle presence. These results clearly point to the impairing role of soluble, mutated tau protein species present in the majority of the neurons investigated in this study

Calibration and instrumental line shape characterization of a set of portable FTIR spectrometers for detecting greenhouse gas emissions

A comprehensive calibration procedure for mobile, low-resolution, solar-absorption FTIR spectrometers, used for greenhouse gases observations, is developed. These instruments commend themselves for campaign use and deployment at remote sites. The instrumental line shape (ILS) of each spectrometer has been thoroughly characterized by analyzing the shape of H2O signatures in open path spectra. A setup for the external source is suggested and the invariance of derived ILS parameters with regard to chosen path length is demonstrated. The instrumental line shape characteristics of all spectrometers were found to be close to nominal. Side-by-side solar observations before and after a campaign, which involved shipping of all spectrometers to a selected target site and back, are applied for verifying the temporal invariability of instrumental characteristics and for deriving intercalibration factors for XCO2 and XCH4, which take into account residual differences of instrumental characteristics. An excellent level of agreement and stability was found between the different spectrometers: the uncorrected biases in XCO2 and XCH4 are smaller than 0.01 and 0.15 %, respectively, and the drifts are smaller than 0.005 and 0.035 %. As an additional sensitive demonstration of the instrumental performance we show the excellent agreement of ground pressure values obtained from the total column measurements of O2 and barometric records. We find a calibration factor of 0.9700 for the spectroscopic measurements in comparison to the barometric records and a very small scatter between the individual spectrometers (0.02 %). As a final calibration step, using a co-located TCCON (Total Carbon Column Observation Network) spectrometer as a reference, a common scaling factor has been derived for the XCO2 and XCH4 products, which ensures that the records are traceable to the WMO in situ scale. © Author(s) 2015

Mobile Communication Signatures of Unemployment

The mapping of populations socio-economic well-being is highly constrained by the logistics of censuses and surveys. Consequently, spatially detailed changes across scales of days, weeks, or months, or even year to year, are difficult to assess; thus the speed of which policies can be designed and evaluated is limited. However, recent studies have shown the value of mobile phone data as an enabling methodology for demographic modeling and measurement. In this work, we investigate whether indicators extracted from mobile phone usage can reveal information about the socio-economical status of microregions such as districts (i.e., average spatial resolution < 2.7km). For this we examine anonymized mobile phone metadata combined with beneficiaries records from unemployment benefit program. We find that aggregated activity, social, and mobility patterns strongly correlate with unemployment. Furthermore, we construct a simple model to produce accurate reconstruction of district level unemployment from their mobile communication patterns alone. Our results suggest that reliable and cost-effective economical indicators could be built based on passively collected and anonymized mobile phone data. With similar data being collected every day by telecommunication services across the world, survey-based methods of measuring community socioeconomic status could potentially be augmented or replaced by such passive sensing methods in the future

Maßnahmen zur Optimierung der Einsatztaktik bei Bränden in Räumen ohne direkten Zugang ins Freie - Teil I

Im Bericht werden zunächst die Grundlagen für Brände in Räumen ohne Zugang ins Freie, z.B. Keller-brände, dargestellt. Die Besonderheit liegt im begrenzten Angebot von Verbrennungsluft, so dass insbeson-dere auf die spezifischen Gefahren bei unterventilierten Bränden eingegangen wird. Im Anschluss wird die Einsatztaktik der Feuerwehr dargestellt, wobei insbesondere technische Hilfsmittel wie Mobiler Rauchverschluss und Taktische Ventilation näher beleuchtet werden. Weiterhin werden anlagentechnische Brandschutzmaßnahmen wie z.B. Löschanlagen, RWA, Sauerstoffre-duktionsanlagen mit ihren spezifischen Vor- und Nachteilen aufgeführ

Use of portable FTIR spectrometers for detecting greenhouse gas emissions of the megacity Berlin - Part 1: Instrumental line shape characterisation and calibration of a quintuple of spectrometers

Several low resolution spectrometers were used to investigate the CO2 and CH4 emissions of the megacity Berlin. Before and after the campaign the instruments were tested side-by-side. An excellent level of agreement and stability was found between the different spectrometers: the drifts in XCO2 and XCH4 are within 0.005 and 0.035%, respectively. The instrumental line shape characteristics of all spectrometers were found to be close to nominal. Cross-calibration factors for XCH4 and XCO2 were established for each spectrometer. An empirical airmass correction factor has been applied. As a last calibration step, using a co-located TCCON spectrometer as a reference, a common factor has been derived for the low-resolution campaign spectrometers, which ensures that the records are compatible to the WMO in-situ scale. Finally as a first result of the Berlin campaign we show the excellent agreement of ground pressure values obtained from total column measurements and in situ records

The Greenhouse Gas Climate Change Initiative (GHG-CCI): comparative validation of GHG-CCI SCIAMACHY/ENVISAT and TANSO-FTS/GOSAT CO₂ and CH₄ retrieval algorithm products with measurements from the TCCON

Column-averaged dry-air mole fractions of carbon dioxide and methane have been retrieved from spectra acquired by the TANSO-FTS (Thermal And Near-infrared Sensor for carbon Observations-Fourier Transform Spectrometer) and SCIAMACHY (Scanning Imaging Absorption Spectrometer for Atmospheric Cartography) instruments on board GOSAT (Greenhouse gases Observing SATellite) and ENVISAT (ENVIronmental SATellite), respectively, using a range of European retrieval algorithms. These retrievals have been compared with data from ground-based high-resolution Fourier transform spectrometers (FTSs) from the Total Carbon Column Observing Network (TCCON). The participating algorithms are the weighting function modified differential optical absorption spectroscopy (DOAS) algorithm (WFMD, University of Bremen), the Bremen optimal estimation DOAS algorithm (BESD, University of Bremen), the iterative maximum a posteriori DOAS (IMAP, Jet Propulsion Laboratory (JPL) and Netherlands Institute for Space Research algorithm (SRON)), the proxy and full-physics versions of SRON's RemoTeC algorithm (SRPR and SRFP, respectively) and the proxy and full-physics versions of the University of Leicester's adaptation of the OCO (Orbiting Carbon Observatory) algorithm (OCPR and OCFP, respectively). The goal of this algorithm inter-comparison was to identify strengths and weaknesses of the various so-called round- robin data sets generated with the various algorithms so as to determine which of the competing algorithms would proceed to the next round of the European Space Agency's (ESA) Greenhouse Gas Climate Change Initiative (GHG-CCI) project, which is the generation of the so-called Climate Research Data Package (CRDP), which is the first version of the Essential Climate Variable (ECV) "greenhouse gases" (GHGs). For XCO₂, all algorithms reach the precision requirements for inverse modelling (< 8 ppm), with only WFMD having a lower precision (4.7 ppm) than the other algorithm products (2.4–2.5 ppm). When looking at the seasonal relative accuracy (SRA, variability of the bias in space and time), none of the algorithms have reached the demanding < 0.5 ppm threshold. For XCH₄, the precision for both SCIAMACHY products (50.2 ppb for IMAP and 76.4 ppb for WFMD) fails to meet the < 34 ppb threshold for inverse modelling, but note that this work focusses on the period after the 2005 SCIAMACHY detector degradation. The GOSAT XCH₄ precision ranges between 18.1 and 14.0 ppb. Looking at the SRA, all GOSAT algorithm products reach the < 10 ppm threshold (values ranging between 5.4 and 6.2 ppb). For SCIAMACHY, IMAP and WFMD have a SRA of 17.2 and 10.5 ppb, respectively

Application of portable FTIR spectrometers for detecting greenhouse gas emissions of the major city Berlin

Five portable Bruker EM27/SUN FTIR (Fourier transform infrared) spectrometers have been used for the accurate and precise observation of column-averaged abundances of CO2 and CH4 around the major city Berlin. In the work by Frey et al. (2015), a calibration procedure is developed and applied to the set of spectrometers used for the Berlin campaign. Here, we describe the observational setup of the campaign and aspects of the data analysis, and we present the recorded time series of XCH4 and XCO2. We demonstrate that the CO2 emissions of Berlin can be clearly identified in the observations. A simple dispersion model is applied which indicates a total strength of the Berlin source of about 0.8 t CO2 s-1. In the Supplement of this work, we provide the measured data set and auxiliary data. We hope that the model community will exploit this unique data set for state-of-the art inversion studies of CO2 and CH4 sources in the Berlin area. © Author(s) 2015