Searches for light dark matter (DM) and studies of coherent elastic neutrino-nucleus scattering (CEvNS) imply the detection of nuclear recoils in the 100 eV range. However, an absolute energy ...calibration in this regime is still missing. The CRAB project proposes a method based on nuclear recoils induced by the emission of an MeV gamma following thermal neutron capture. A detailed feasibility study has shown that this method yields distinct nuclear recoil calibration peaks at 112 eV and 160 eV above background for tungsten. In the first phase, the CRAB project foresees to perform a nuclear recoil calibration of cryogenic CaWO
4
detectors read-out by TES, similar to the detectors used in CRESST and NUCLEUS. The low-power TRIGA reactor in Vienna provides a clean beam of thermal neutrons well suited for such a measurement. Newly developed and compact sub-keV calibration sources based on x-ray fluorescence (XRF) provide an absolute energy calibration during operation at the research reactor as well as in the DM/CEvNS experiments. In the second phase, additional tagging of the photons produced in the de-excitation process will allow extending the calibration method to even lower energies and to a wider range of detector materials, such as Ge. Combined with the XRF source, CRAB may allow measuring energy quenching in the sub-keV regime.
STUDY QUESTION
Are temporal trends and values of semen quality parameters in France identifiable in partners of totally infertile women?
SUMMARY ANSWER
Among a sample of 26 609 partners of totally ...infertile women undergoing an assisted reproductive technology (ART) procedures in the whole of France over a 17-year period, there was a continuous decrease in semen concentration of about 1.9% per year and a significant decrease in the percentage with morphologically normal forms but no global trend for motility.
WHAT IS KNOWN ALREADY
A global decrease in human sperm quality is still debated as geographical differences have been shown, and many criticisms have risen concerning studies with small and biased study populations or inappropriate statistical methodology. However, growing biological, toxicological, experimental and human exposure data support the endocrine disruptors' hypothesis assuming that fetal exposure to endocrine disruptors could impair reproductive outcomes.
STUDY DESIGN, SIZE, DURATION
This was a retrospective and descriptive study using data registered by Fivnat, the professional association in charge of statistics for ART in France during the 1989–2005 study period. Data were provided by 126 main ART centres over the whole metropolitan territory. The source population included 154 712 men, aged 18–70, who were partners of couples undergoing their first ART cycle and for whom semen quality indicators (concentration, total motility and percentage of morphologically normal forms), measured on fresh ejaculated semen, were available.
PARTICIPANTS/MATERIALS, SETTING, METHODS
The study population was 26 609 partners of women who had both tubes either absent or blocked. The temporal trends for each indicator of semen quality were modelled using a generalized additive model that allowed for nonlinear relationships between variables and were adjusted for season and age. In-depth sensitivity analyses included the reiteration of the analysis on data from a second spermiogram available for each man and on another subsample of men diagnosed as fertile. Variables such as centre, technique (standard in vitro fertilization or intra-cytoplasmic sperm injection) and an interaction factor between technique and time were also included in the model.
MAIN RESULTS AND THE ROLE OF CHANCE
There was a significant and continuous decrease in sperm concentration of 32.2% 26.3–36.3 during the study period. Projections indicate that concentration for a 35-year-old man went from an average of 73.6 million/ml 69.0–78.4 in 1989 to 49.9 million/ml 43.5–54.7 in 2005. A significant, but not quantifiable, decrease in the percentage of sperm with morphologically normal forms along the 17-year period was also observed. There was no global trend but a slight, significant increase in total motility between 1994 and 1998 was observed. The results were robust after sensitivity analysis.
LIMITATIONS, REASONS FOR CAUTION
Socioeconomic status could not be controlled for. Despite universal access to medical services in France, couples undergoing ART are expected to have a higher educational level on average compared with those of the general population. Therefore, the real values in the general population could be slightly lower than those presented and the decrease possibly stronger, as the population study is less likely to smoke or be overweight, two factors known to impair semen quality.
WIDER IMPLICATIONS OF THE FINDINGS
As the men were selected without a priori knowledge regarding their semen quality characteristics, the results are expected to be close to the values in the general French population. The very large sample size and the robustness of the results confer great statistical power and credibility to the results. To our knowledge, it is the first study concluding a severe and general decrease in sperm concentration and morphology at the scale of a whole country over a substantial period. This constitutes a serious public health warning. The link with the environment particularly needs to be determined.
STUDY FUNDING/COMPETING INTEREST(S)
No specific funding was sought for this study. The authors have no conflict of interest to declare.
The study has been authorized by the Commission Nationale de l'Informatique et des Libertés (CNIL), the national authority for the protection of personal data collected on individuals (authorization no DE-2010-063 dated 08/09/2010).
Although aesthetic benefits are a desirable effect of the treatment of skin aging, it is also important in controlling several skin diseases, mainly in aged people. The development of new ...dermocosmetics has rapidly increased due to consumers’ demand for non-invasive products with lower adverse effects than those currently available on the market. Natural compounds of plant origin and herbal-derived formulations have been popularized due to their various safe active products, which act through different mechanisms of action on several signaling pathways for skin aging. Based on this, the aim of the review was to identify the recent advances in herbal-derived product research, including herbal formulations and isolated compounds with skin anti-aging properties. The studies evaluated the biological effects of herbal-derived products in in vitro, ex vivo, and in vivo studies, highlighting the effects that were reported in clinical trials with available pharmacodynamics data that support their protective effects to treat, prevent, or control human skin aging. Thus, it was possible to identify that gallic and ferulic acids and herbal formulations containing Thymus vulgaris, Panax ginseng, Triticum aestivum, or Andrographis paniculata are the most promising natural products for the development of new dermocosmetics with skin anti-aging properties.
•We developed an algorithm to search for collapse pits in LROC NAC images.•We found ten pits in maria and highlands, typically 40–100m in diameter and depth.•We found over 200 pits in impact melt, ...which average 16m in diameter and 7m in depth.•Pits are often significantly younger than their host materials.•Some pits have confirmed overhangs, and may connect to larger sublunarean voids.
Lunar Reconnaissance Orbiter Camera images reveal the presence of steep-walled pits in mare basalt (n=8), impact melt deposits (n=221), and highland terrain (n=2). Pits represent evidence of subsurface voids of unknown extents. By analogy with terrestrial counterparts, the voids associated with mare pits may extend for hundreds of meters to kilometers in length, thereby providing extensive potential habitats and access to subsurface geology. Because of their small sizes relative to the local equilibrium crater diameters, the mare pits are likely to be post-flow features rather than volcanic skylights. The impact melt pits are indirect evidence both of extensive subsurface movement of impact melt and of exploitable sublunarean voids. Due to the small sizes of pits (mare, highland, and impact melt) and the absolute ages of their host materials, it is likely that most pits formed as secondary features.
The salient viscoelastic properties of aramid textile materials and methods of their study are described. Preliminary information about the viscoelasticity of the studied materials can be obtained ...from experimental tensile diagrams and, for a more detailed study of viscoelastic properties, mathematical modeling of relaxation or deformation processes is necessary.
FK506 binding protein 51 (FKBP51) is an Hsp90 co-chaperone and regulator of the glucocorticoid receptor, and consequently of stress physiology. Clinical studies suggest a genetic link between FKBP51 ...and antidepressant response in mood disorders; however, the underlying mechanisms remain elusive. The objective of this study was to elucidate the role of FKBP51 in the actions of antidepressants, with a particular focus on pathways of autophagy.
Established cell lines, primary neural cells, human blood cells of healthy individuals and patients with depression, and mice were treated with antidepressants. Mice were tested for several neuroendocrine and behavioral parameters. Protein interactions and autophagic pathway activity were mainly evaluated by co-immunoprecipitation and Western blots. We first show that the effects of acute antidepressant treatment on behavior are abolished in FKBP51 knockout (51KO) mice. Autophagic markers, such as the autophagy initiator Beclin1, were increased following acute antidepressant treatment in brains from wild-type, but not 51KO, animals. FKBP51 binds to Beclin1, changes decisive protein interactions and phosphorylation of Beclin1, and triggers autophagic pathways. Antidepressants and FKBP51 exhibited synergistic effects on these pathways. Using chronic social defeat as a depression-relevant stress model in combination with chronic paroxetine (PAR) treatment revealed that the stress response, as well as the effects of antidepressants on behavior and autophagic markers, depends on FKBP51. In human blood cells of healthy individuals, FKBP51 levels correlated with the potential of antidepressants to induce autophagic pathways. Importantly, the clinical antidepressant response of patients with depression (n = 51) could be predicted by the antidepressant response of autophagic markers in patient-derived peripheral blood lymphocytes cultivated and treated ex vivo (Beclin1/amitriptyline: r = 0.572, p = 0.003; Beclin1/PAR: r = 0.569, p = 0.004; Beclin1/fluoxetine: r = 0.454, p = 0.026; pAkt/amitriptyline: r = -0.416, p = 0.006; pAkt/PAR: r = -0.355, p = 0.021; LC3B-II/PAR: r = 0.453, p = 0.02), as well as by the lymphocytic expression levels of FKBP51 (r = 0.631, p<0.0001), pAkt (r = -0.515, p = 0.003), and Beclin1 (r = 0.521, p = 0.002) at admission. Limitations of the study include the use of male mice only and the relatively low number of patients for protein analyses.
To our knowledge, these findings provide the first evidence for the molecular mechanism of FKBP51 in priming autophagic pathways; this process is linked to the potency of at least some antidepressants. These newly discovered functions of FKBP51 also provide novel predictive markers for treatment outcome, consistent with physiological and potential clinical relevance. Please see later in the article for the Editors' Summary.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
The valorisation of waste or by-products in Portland clinker production is a promising alternative for developing sustainable cements. The complexity of the chemical reactions during ...clinkering demands an adequate dosing method that considers the effect of feedstock impurities to maximise the potential substitution of natural resources by waste or by-products, while guaranteeing the clinker reactivity requirements. This study proposes a raw meal proportioning methodology for optimising co-processing of natural feedstocks with alternative raw materials in clinker production, intending to reduce the content of natural raw materials needed, while promoting an optimal clinker reactivity. A thermodynamic modelling sequence was developed considering the variability of raw materials composition and heating temperatures. The model was then validated by comparing simulation outcomes with results reported in previous studies. An experimental case study was conducted for validation of the proposed method using a spent fluid catalytic cracking catalyst (SFCC), a by-product from the oil industry as an alternative alumina source during clinkering. The modelling simulations indicated that substitution of natural feedstocks by 15 wt% SFCC promotes the formation of reactive clinkers with more than 54% tricalcium silicate (C
3
S). Mixes with the potential to form the highest C
3
S were then produced, and heating microscopy fusibility testing was applied for evaluating the clinkers’ stability. The main factors governing the reactivity and stability of the clinker phases were the melt phase content, alumina modulus, and formation of C
3
S and dicalcium silicate (C
2
S). The self-pulverisation of clinker during cooling was observed in selected mixes, and it is potentially associated with high viscosity and low Fe content in the melt phase. The proposed framework enables optimisation of the dosing of raw meals containing alternative alumina-rich feedstocks for clinker production and allows a deeper interpretation of limited sets of empirical data.
Background In July 2006, a lasting and severe heat wave occurred in Western Europe. Since the 2003 heat wave, several preventive measures and an alert system aiming at reducing the risks related to ...high temperatures have been set up in France by the health authorities and institutions. In order to evaluate the effectiveness of those measures, the observed excess mortality during the 2006 heat wave was compared to the expected excess mortality. Methods A Poisson regression model relating the daily fluctuations in summer temperature and mortality in France from 1975 to 2003 was used to estimate the daily expected number of deaths over the period 2004–2006 as a function of the observed temperatures. Results During the 2006 heat wave (from 11 to 28 July), about 2065 excess deaths occurred in France. Considering the observed temperatures and with the hypothesis that heat-related mortality had not changed since 2003, 6452 excess deaths were predicted for the period. The observed mortality during the 2006 heat wave was thus markedly less than the expected mortality (∼4400 less deaths). Conclusions The excess mortality during the 2006 heat wave, which was markedly lower than that predicted by the model, may be interpreted as a decrease in the population's vulnerability to heat, together with, since 2003, increased awareness of the risk related to extreme temperatures, preventive measures and the set-up of the warning system.
It has been demonstrated that the neuropeptide oxytocin (OT) attenuates oxidative stress and inflammation in macrophages. In the current study, we examined the role of inflammation on the expression ...of the oxytocin receptor (OXTR). We hypothesized that OXTR expression is increased during the inflammation through a nuclear factor-κB (NF-κB)-mediated pathway, thus responding as an acute-phase protein. Inflammation was induced by treating macrophages (human primary, THP-1, and murine) with lipopolysaccharide (LPS) and monitored by expression of IL-6. Expression of OXTR and vasopressin receptors was assessed by qPCR, and OXTR expression was confirmed by immunoblotting. Inflammation upregulated OXTR transcription 10- to 250-fold relative to control in THP-1 and human primary macrophages and increased OXTR protein expression. In contrast, vasopressin receptor-2 mRNA expression was reduced following LPS treatment. Blocking NF-κB activation prevented the increase in OXTR transcription. OT treatment of control cells and LPS-treated cells increased ERK1/2 phosphorylation, demonstrating activation of the OXTR/G
signaling pathway. OT activation of OXTR reduced secretion of IL-6 in LPS-activated macrophages. Collectively, these findings suggest that OXTR is an acute-phase protein and that its increased expression is regulated by NF-κB and functions to attenuate cellular inflammatory responses in macrophages.
The influence of processing parameters and several combinations of natural as well as artificial aging on the mechanical properties of friction stir welded AA7075-T6 is analyzed in the present ...investigation. Different sets of welding parameters were employed to obtain joints characterized by different peak temperatures and thermal cycles. The joint obtained with the highest welding speed has guaranteed the best mechanical properties. The latter were shown to be strongly correlated to heat input, which influences both densities of dislocations in nugget zone grains and growth and dissolution of strengthening precipitates in the heat-affected zone that establish the mechanical characteristics of friction stir welds. On the other hand, artificial aging has drastically reduced the strain at break due to strain localization in the heat affected zones while it has proved its effectiveness in stabilizing the mechanical properties when exposed to further natural aging at room temperature.
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