Local interstellar spectra (LIS) of primary cosmic ray (CR) nuclei, such as helium, oxygen, and mostly primary carbon are derived for the rigidity range from 10 MV to ∼200 TV using the most recent ...experimental results combined with the state-of-the-art models for CR propagation in the Galaxy and in the heliosphere. Two propagation packages, GALPROP and HelMod, are combined into a single framework that is used to reproduce direct measurements of CR species at different modulation levels, and at both polarities of the solar magnetic field. The developed iterative maximum-likelihood method uses GALPROP-predicted LIS as input to HelMod, which provides the modulated spectra for specific time periods of the selected experiments for model-data comparison. The interstellar and heliospheric propagation parameters derived in this study are consistent with our prior analyses using the same methodology for propagation of CR protons, helium, antiprotons, and electrons. The resulting LIS accommodate a variety of measurements made in the local interstellar space (Voyager 1) and deep inside the heliosphere at low (ACE/CRIS, HEAO-3) and high energies (PAMELA, AMS-02).
Since its launch, the Alpha Magnetic Spectrometer-02 (AMS-02) has delivered outstanding quality measurements of the spectra of cosmic-ray (CR) species (
,
, and nuclei,
H-
O,
Ne,
Mg,
Si) which ...resulted in a number of breakthroughs. One of the latest long-awaited surprises is the spectrum of
Fe just published by AMS-02. Because of the large fragmentation cross section and large ionization energy losses, most of CR iron at low energies is local and may harbor some features associated with relatively recent supernova (SN) activity in the solar neighborhood. Our analysis of the new AMS-02 results, together with Voyager 1 and ACE-CRIS data, reveals an unexpected bump in the iron spectrum and in the Fe/He, Fe/O, and Fe/Si ratios at 1-2 GV, while a similar feature in the spectra of He, O, and Si and in their ratios is absent, hinting at a local source of low-energy CRs. The found excess extends the recent discoveries of radioactive
Fe deposits in terrestrial and lunar samples and in CRs. We provide an updated local interstellar spectrum (LIS) of iron in the energy range from 1 MeV nucleon
to ~10 TeV nucleon
. Our calculations employ the GALPROP-HELMOD framework, which has proved to be a reliable tool in deriving the LIS of CR
,
, and nuclei
⩽ 28.
Peripheral Nerve Injury (PNI) represents a major clinical and economic burden. Despite the ability of peripheral neurons to regenerate their axons after an injury, patients are often left with motor ...and/or sensory disability and may develop chronic pain. Successful regeneration and target organ reinnervation require comprehensive transcriptional changes in both injured neurons and support cells located at the site of injury. The expression of most of the genes required for axon growth and guidance and for synapsis formation is repressed by a single master transcriptional regulator, the Repressor Element 1 Silencing Transcription factor (REST). Sustained increase of REST levels after injury inhibits axon regeneration and leads to chronic pain. As targeting of transcription factors is challenging, we tested whether modulation of REST activity could be achieved through knockdown of carboxy-terminal domain small phosphatase 1 (CTDSP1), the enzyme that stabilizes REST by preventing its targeting to the proteasome. To test whether knockdown of CTDSP1 promotes neurotrophic factor expression in both support cells located at the site of injury and in peripheral neurons, we transfected mesenchymal progenitor cells (MPCs), a type of support cells that are present at high concentrations at the site of injury, and dorsal root ganglion (DRG) neurons with REST or CTDSP1 specific siRNA. We quantified neurotrophic factor expression by RT-qPCR and Western blot, and brain-derived neurotrophic factor (BDNF) release in the cell culture medium by ELISA, and we measured neurite outgrowth of DRG neurons in culture. Our results show that CTDSP1 knockdown promotes neurotrophic factor expression in both DRG neurons and the support cells MPCs, and promotes DRG neuron regeneration. Therapeutics targeting CTDSP1 activity may, therefore, represent a novel epigenetic strategy to promote peripheral nerve regeneration after PNI by promoting the regenerative program repressed by injury-induced increased levels of REST in both neurons and support cells.
The cosmic rays propagation inside the heliosphere is well described by a transport equation introduced by Parker in 1965. To solve this equation, several approaches were followed in the past. ...Recently, a Monte Carlo approach became widely used in force of its advantages with respect to other numerical methods. In this approach the transport equation is associated to a fully equivalent set of stochastic differential equations (SDE). This set is used to describe the stochastic path of quasi‐particle from a source, e.g., the interstellar space, to a specific target, e.g., a detector at Earth. We present a comparison of forward‐in‐time and backward‐in‐time methods to solve the cosmic rays transport equation in the heliosphere. The Parker equation and the related set of SDE in the several formulations are treated in this paper. For the sake of clarity, this work is focused on the one‐dimensional solutions. Results were compared with an alternative numerical solution, namely, Crank‐Nicolson method, specifically developed for the case under study. The methods presented are fully consistent each others for energy greater than 400 MeV. The comparison between stochastic integrations and Crank‐Nicolson allows us to estimate the systematic uncertainties of Monte Carlo methods. The forward‐in‐time stochastic integrations method showed a systematic uncertainty <5%, while backward‐in‐time stochastic integrations method showed a systematic uncertainty <1% in the studied energy range.
Key Points
Quantitative comparison of backward‐forward‐in‐time cosmic rays transport Monte Carlo methods
Estimation of systematic error of both methods for spectra at 1 AU for energies above 1 GV
Backward‐in‐time method is suited for predicting modulated spectra for high‐precision experiments
Abstract
Since its launch, the Alpha Magnetic Spectrometer–02 (AMS-02) has delivered outstanding quality measurements of the spectra of cosmic-ray (CR) species (
p
¯
,
e
±
) and nuclei (H–O, Ne, Mg, ...Si, Fe), which resulted in a number of breakthroughs. The most recent AMS-02 result is the measurement of the spectrum of CR fluorine up to ∼2 TV. Given its very low solar system abundance, fluorine in CRs is thought to be mostly secondary, produced in fragmentations of heavier species, predominantly Ne, Mg, and Si. Similar to the best-measured secondary-to-primary boron to carbon nuclei ratio that is widely used to study the origin and propagation of CR species, the precise fluorine data would allow the origin of Si-group nuclei to be studied independently. Meanwhile, the secondary origin of CR fluorine has never been tested in a wide energy range due to the lack of accurate CR data. In this paper, we use the first ever precise measurements of the fluorine spectrum by AMS-02 together with ACE-CRIS and Voyager 1 data to actually test this paradigm. Our detailed modeling shows an excess below 10 GV in the fluorine spectrum that may hint at a primary fluorine component. We also provide an updated local interstellar spectrum (LIS) of fluorine in the rigidity range from a few MV to ∼2 TV. Our calculations employ the self-consistent
GalProp
–
HelMod
framework that has proved to be a reliable tool in deriving the LIS of CR
p
¯
and
e
−
, and nuclei
Z
≤ 28.
Abstract
Since its launch, the Alpha Magnetic Spectrometer-02 (AMS-02) has delivered outstanding quality measurements of the spectra of cosmic-ray (CR) species,
p
¯
,
e
±
, and nuclei (H–Si, Fe), ...which resulted in a number of breakthroughs. The most recent AMS-02 result is the measurement of the spectra of CR sodium and aluminum up to ∼2 TV. Given their low solar system abundances, a significant fraction of each element is produced in fragmentations of heavier species, predominantly Ne, Mg, and Si. In this paper, we use precise measurements of the sodium and aluminum spectra by AMS-02 together with ACE-CRIS and Voyager 1 data to test their origin. We show that the sodium spectrum agrees well with the predictions made with the
GalProp
-
HelMod
framework, while the aluminum spectrum shows a significant excess in the rigidity range from 2–7 GV. In this context, we discuss the origin of other low-energy excesses in Li, F, and Fe found earlier. The observed excesses in Li, F, and Al appear to be consistent with the local Wolf-Rayet stars hypothesis, invoked to reproduce anomalous
22
Ne/
20
Ne,
12
C/
16
O, and
58
Fe/
56
Fe ratios in CRs, while excess in Fe is likely connected with a past supernova activity in the solar neighborhood. We also provide updated local interstellar spectra (LIS) of sodium and aluminum in the rigidity range from a few megavolts to ∼2 TV. Our calculations employ the self-consistent
GalProp
-
HelMod
framework, which has proved to be a reliable tool in deriving the LIS of CR
p
¯
,
e
−
, and nuclei
Z
≤ 28.
Context. Astrophysical polarized foregrounds represent the most critical challenge in cosmic microwave background (CMB) B -mode experiments, requiring multifrequency observations to constrain ...astrophysical foregrounds and isolate the CMB signal. However, recent observations indicate that foreground emission may be more complex than anticipated. Not properly accounting for these complexities during component separation can lead to a bias in the recovered tensor-to-scalar ratio. Aims. In this paper we investigate how the increased spectral resolution provided by band-splitting in bolometric interferometry (BI) through a technique called spectral imaging can help control the foreground contamination in the case of an unaccounted-for Galactic dust frequency de-correlation along the line of sight (LOS). Methods. We focused on the next-generation ground-based CMB experiment CMB-S4 and compared its anticipated sensitivity, frequency, and sky coverage with a hypothetical version of the same experiment based on BI (CMB-S4/BI). We performed a Monte Carlo analysis based on parametric component separation methods (FGBuster and Commander) and computed the likelihood of the recovered tensor-to-scalar ratio, r . Results. The main result is that spectral imaging allows us to detect systematic uncertainties on r from frequency de-correlation when this effect is not accounted for in the component separation. Conversely, an imager such as CMB-S4 would detect a biased value of r and would be unable to spot the presence of a systematic effect. We find a similar result in the reconstruction of the dust spectral index, and we show that with BI we can more precisely measure the dust spectral index when frequency de-correlation is present and not accounted for in the component separation. Conclusions. The in-band frequency resolution provided by BI allows us to identify dust LOS frequency de-correlation residuals where an imager with a similar level of performance would fail. This creates the possibility of exploiting this potential in the context of future CMB polarization experiments that will be challenged by complex foregrounds in their quest for B -mode detection.
Axonal protein synthesis is a complex process involving selective mRNA localization and translational regulation. In this study, using in situ hybridization and metabolic labeling, we show that the ...mRNAs encoding eukaryotic translation initiation factors eIF2B2 and eIF4G2 are present in the axons of rat sympathetic neurons and are locally translated. We also report that a noncoding microRNA, miR16, modulates the axonal expression of eIF2B2 and eIF4G2. Transfection of axons with precursor miR16 and anti-miR16 showed that local miR16 levels modulated axonal eIF2B2 and eIF4G2 mRNA and protein levels, as well as axon outgrowth. siRNA-mediated knock-down of axonal eIF2B2 and eIF4G2 mRNA also resulted in a significant decrease in axonal eIF2B2 and eIF4G2 protein. Moreover, results of metabolic labeling studies showed that downregulation of axonal eIF2B2 and eIF4G2 expression also inhibited local protein synthesis and axon growth. Together, these data provide evidence that miR16 mediates axonal growth, at least in part, by regulating the local protein synthesis of eukaryotic translation initiation factors eIF2B2 and eIF4G2 in the axon.
Mammalian ejaculated spermatozoa must undergo a series of changes in the female reproductive tract, collectively called capacitation, in order to fertilize the oocyte. We reported that fibronectin ...(Fn), a glycoprotein from the extracellular matrix, and anandamide (AEA), one of the major members of the endocannabinoid family, are present in the bovine oviductal fluid and regulate bull sperm function. Also, AEA induces bovine sperm capacitation, through CB1 and TRPV1 receptors.
In this work, we investigated if Fn induces bovine sperm capacitation thought the activation of the endocannabinoid system in this process. We incubated sperm with Fn (100 μg/ml) and/or capsazepine, a TRPV1 antagonist (0.1 μM) and some events related to sperm capacitation such as LPC-induced acrosome reaction, sperm-release from the oviduct, induction of PKA phosphorylated substrates (pPKAs) and protein tyrosine phosphorylation (pY) and nitric oxide (NO) production were assessed. Also, we studied the activity of fatty acid amide hydrolase (FAAH), the enzyme that degrades AEA. We found that Fn, via α5β1 integrin, induced capacitation-associated events. Also, Fn stimulated signaling pathways associated to capacitation as cAMP/PKA and NO/NO synthase. Moreover, Fn decreased the FAAH activity and this correlated with sperm capacitation. Capsazepine reversed fibronectin-induced capacitation, and pPKAs and NO levels. The incubation of spermatozoa with R-methanandamide (1.4 nM), a stable analogue of AEA, increased cAMP and pPKAs levels. The presence of H89 (50 μM) or KT5720 (100 nM) (PKA inhibitors) prevented AEA-induced capacitation. In addition, R-methanandamide and capsaicin (0.01 μM), a TRPV1 agonist, increased NO production via the PKA pathway. These results indicate that Fn, through α5β1, supports capacitation in bovine spermatozoa. This effect is dependent on the activation of TRPV1 through cAMP/PKA and NO signaling pathways. We propose that Fn could be considered as a new agent that promotes sperm capacitation in bull sperm. Our findings contribute to better understand the significance of Fn signaling in the capacitating events that lead to successful fertilization and embryo development in mammals including humans.
•Fibronectin through α5β1 integrin induces sperm capacitation in bull spermatozoa.•TRPV1 receptor is involved in fibronectin signaling pathway.•PKA phosphorylated substrates and nitric oxide levels are increased during fibronectin-induced sperm capacitation.
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