From fix to fit into the autoptic human brains.

Formalin-fixed, paraffinembedded (FFPE) human brain tissues are very often stored in formalin for long time. Formalin fixation reduces immunostaining, and the DNA/RNA extraction from FFPE brain tissue becomes suboptimal. At present, there are different protocols of fixation and several procedures and kits to extract DNA/RNA from paraffin embedding tissue, but a gold standard protocol remains distant. In this study, we analyzed four types of fixation systems and compared histo and immuno-staining. Based on our results, we propose a modified method of combined fixation in formalin and formic acid for the autoptic adult brain to obtain easy, fast, safe and efficient immunolabelling of long-stored FFPE tissue. In particular, we have achieved an improved preservation of cellular morphology and obtained success in postmortem immunostaining for NeuN. This nuclear antigen is an important marker for mapping neurons, for example, to evaluate the histopathology of temporal lobe epilepsy or to draw the topography of cardiorespiratory brainstem nuclei in sudden infant death syndrome (SIDS). However, NeuN staining is frequently faint or lost in postmortem human brain tissues. In addition, we attained Fluoro Jade C staining, a marker of neurodegeneration, and immunofluorescent staining for stem cell antigens in the postnatal human brain, utilizing custom fit fixation procedures

Computing Macro-Effects and Welfare Costs of Temperature Volatility: A Structural Approach

We produce novel empirical evidence on the relevance of temperature volatility shocks for the dynamics of productivity, macroeconomic aggregates and asset prices. Using two centuries of UK temperature data, we document that the relationship between temperature volatility and the macroeconomy varies over time. First, the sign of the causality from temperature volatility to TFP growth is negative in the post-war period (i.e., 1950–2015) and positive before (i.e., 1800–1950). Second, over the pre-1950 (post-1950) period temperature volatility shocks positively (negatively) affect TFP growth. In the post-1950 period, temperature volatility shocks are also found to undermine equity valuations and other main macroeconomic aggregates. More importantly, temperature volatility shocks are priced in the cross section of returns and command a positive premium. We rationalize these findings within a production economy featuring long-run productivity and temperature volatility risk. In the model temperature volatility shocks generate non-negligible welfare costs. Such costs decrease (increase) when coupled with immediate technology adaptation (capital depreciation)

Analysis of vibrations recorded inside the cemetery area of Incisa, central Italy

Seismic stations are usually used to record seismic event and, therefore, they are recommended to be installed far from railways and traffic roads in order to avoid the superposition of ambient noise signals to those provoked by an earthquake. In this paper, instead, seismic stations, placed intentionally in areas near railway and traffic roads, are used to characterize the subsoil spectral properties and to assess the effect of vibrations due to trains and vehicles. A cemetery in the green countryside near Florence is chosen as a reference case study to deal with this topic. Most of the buildings in the cemetery area are affected by an extensive crack pattern. In January 2020 five seismic stations were installed in order to evaluate if the trains running in the tunnels of the regional and high-speed railway lines located below and in the vicinity of the cemetery and the vehicles traveling on the nearby A1 highway and regional road can produce vibrations in the ground that justify the observed damage pattern.Collected data are analyzed using the Nakamura technique in order to estimate the dynamic properties of the ground and compared to the limits provided by the current regulations. Furthermore, the trend of the Root Mean Square average over the entire recording period is computed as well.From the obtained results, it is possible to highlight that the average daily oscillation level increases from early morning until 7 p.m. and then it decreases, and also that the highest amplitudes of transients are concentrated in the late evening and during the night, when the background noise is lower.Furthermore, the computed values of the maximum and average amplitudes are lower than those that can cause damage to buildings as defined by the guidelines, the eigenfrequency of the ground falls in a range far from that ascribable to the cemetery buildings, so that the resonance effects can be excluded. In order to confirm these results, the amplitude of ground shaking due to recorded transients is compared to that produced by two earthquakes (a 3.4 Mw local earthquake at more than 100 km and a Mw 6.6 teleseism from Turkey) which occurred during the monitoring period. One can conclude that it seems unlikely that the shaking produced by nearby vehicles and trains could be responsible for the observed damage

Polarized Signaling via Purinoceptors in Normal and Cystic Fibrosis Airway Epithelia

Airway epithelia are confronted with distinct signals emanating from the luminal and/or serosal environments. This study tested whether airway epithelia exhibit polarized intracellular free calcium (Ca2+i) and anion secretory responses to 5′ triphosphate nucleotides (ATP/UTP), which may be released across both barriers of these epithelia. In both normal and cystic fibrosis (CF) airway epithelia, mucosal exposure to ATP/UTP increased Ca2+i and anion secretion, but both responses were greater in magnitude for CF epithelia. In CF epithelia, the mucosal nucleotide–induced response was mediated exclusively via Ca2+i interacting with a Ca2+-activated Cl− channel (CaCC). In normal airway epithelia (but not CF), nucleotides stimulated a component of anion secretion via a chelerythrine-sensitive, Ca2+-independent PKC activation of cystic fibrosis transmembrane conductance regulator. In normal and CF airway epithelia, serosally applied ATP or UTP were equally effective in mobilizing Ca2+i. However, serosally applied nucleotides failed to induce anion transport in CF epithelia, whereas a PKC-regulated anion secretory response was detected in normal airway epithelia. We conclude that (1) in normal nasal epithelium, apical/basolateral purinergic receptor activation by ATP/UTP regulates separate Ca2+-sensitive and Ca2+-insensitive (PKC-mediated) anion conductances; (2) in CF airway epithelia, the mucosal ATP/UTP-dependent anion secretory response is mediated exclusively via Ca2+i; and (3) Ca2+i regulation of the Ca2+-sensitive anion conductance (via CaCC) is compartmentalized in both CF and normal airway epithelia, with basolaterally released Ca2+i failing to activate CaCC in both epithelia

A convenient approach to characterizing model uncertainty with application to early dark energy solutions of the Hubble tension

Despite increasingly precise observations and sophisticated theoretical models, the discrepancy between measurements of H0 from the cosmic microwave background or from Baryon Acoustic Oscillations combined with Big-Bang Nucleosynthesis versus those from local distance ladder probes -- commonly known as the $H_0$ tension -- continues to perplex the scientific community. To address this tension, Early Dark Energy (EDE) models have been proposed as alternatives to $\Lambda$CDM, as they can change the observed sound horizon and the inferred Hubble constant from measurements based on this. In this paper, we investigate the use of Bayesian Model Averaging (BMA) to evaluate EDE as a solution to the H0 tension. BMA consists of assigning a prior to the model and deriving a posterior as for any other unknown parameter in a Bayesian analysis. BMA can be computationally challenging in that one must approximate the joint posterior of both model and parameters. Here we present a computational strategy for BMA that exploits existing MCMC software and combines model-specific posteriors post-hoc. In application to a comprehensive analysis of cosmological datasets, we quantify the impact of EDE on the H0 discrepancy. We find an EDE model probability of $\sim$90% whenever we include the H0 measurement from Type Ia Supernovae in the analysis, whereas the other data show a strong preference for the standard cosmological model. We finally present constraints on common parameters marginalized over both cosmological models. For reasonable priors on models with and without EDE, the H0 tension is reduced by at least 20%

Front-face fluorescence spectroscopy and chemometrics for quality control of cold-pressed rapeseed oil during storage

The aim of this study was to test the usability of fluorescence spectroscopy to evaluate the stability of cold-pressed rapeseed oil during storage. Freshly-pressed rapeseed oil was stored in colorless and green glass bottles exposed to light, and in darkness for a period of 6 months. The quality deterioration of oils was evaluated on the basis of several chemical parameters (peroxide value, acid value, K232 and K270, polar compounds, tocopherols, carotenoids, pheophytins, oxygen concentration) and fluorescence. Parallel factor analysis (PARAFAC) of oil excitation-emission matrices revealed the presence of four fluorophores that showed different evolution throughout the storage period. The fluorescence study provided direct information about tocopherol and pheophytin degradation and revealed formation of a new fluorescent product. Principal component analysis (PCA) performed on analytical and fluorescence data showed that oxidation was more advanced in samples exposed to light due to the photo-induced processes; only a very minor effect of the bottle color was observed. Multiple linear regression (MLR) and partial least squares regression (PLSR) on the PARAFAC scores revealed a quantitative relationship between fluorescence and some of the chemical parameters.Funding Agency Ministry of Science and Higher Education, Poland NN312428239 Poznan University of Economics and Businessinfo:eu-repo/semantics/publishedVersio

Polarized distribution of HCO3- transport in human normal and cystic fibrosis nasal epithelia

The polarized distribution of HCO3− transport was investigated in human nasal epithelial cells from normal and cystic fibrosis (CF) tissues. To test for HCO3− transport via conductive versus electroneutral Cl−/HCO3− exchange (anion exchange, AE) pathways, nasal cells were loaded with the pH probe 2′,7′-bis(carboxyethyl)-5(6)-carboxyfluorescein and mounted in a bilateral perfusion chamber. In normal, but not CF, epithelia, replacing mucosal Cl− with gluconate caused intracellular pH (pHi) to increase, and the initial rates (ΔpH min−1) of this increase were modestly augmented (∼26 %) when normal cells were pretreated with forskolin (10 μm). Recovery from this alkaline shift was dependent on mucosal Cl−, was insensitive to the AE inhibitor 4,4′-diisothiocyanatodihydrostilbene-2,2′-disulfonic acid (H2DIDS; 1.5 mm), but was sensitive to the cystic fibrosis transmembrane conductance regulator (CFTR) channel inhibitor diphenylamine-2-carboxylate (DPC; 100 μm). In contrast, removal of serosal Cl− caused pHi to alkalinize in both normal and CF epithelia. Recovery from this alkaline challenge was dependent on serosal Cl− and blocked by H2DIDS. Additional studies showed that serosally applied Ba2+ (5.0 mm) in normal, but not CF, cells induced influx of HCO3− across the apical membrane that was reversibly blocked by mucosal DPC. In a final series of studies, normal and CF cells acutely alkaline loaded by replacing bilateral Krebs bicarbonate Ringer (KBR) with Hepes-buffered Ringer solution exhibited basolateral, but not apical, recovery from an alkaline challenge that was dependent on Cl−, independent of Na+ and blocked by H2DIDS. We conclude that: (1) normal, but not CF, nasal epithelia have a constitutively active DPC-sensitive HCO3− influx/efflux pathway across the apical membrane of cells, consistent with the movement of HCO3− via CFTR; and (2) both normal and CF nasal epithelia have Na+-independent, H2DIDS-sensitive AE at their basolateral domain