Polar and charged amino acids (AAs) are heavily expressed in non-collagenous proteins (NCPs), and are involved in hydroxyapatite (HA) mineralization in bone. Here, we review what is known on the ...effect of single AAs on HA precipitation. Negatively charged AAs, such as aspartic acid, glutamic acid (Glu) and phosphoserine are largely expressed in NCPs and play a critical role in controlling HA nucleation and growth. Positively charged ones such as arginine (Arg) or lysine (Lys) are heavily involved in HA nucleation within extracellular matrix proteins such as collagen. Glu, Arg and Lys intake can also increase bone mineral density by stimulating growth hormone production. In vitro studies suggest that the role of AAs in controlling HA precipitation is affected by their mobility. While dissolved AAs are able to inhibit HA precipitation and growth by chelating Ca2+ and PO43− ions or binding to nuclei of calcium phosphate and preventing their further growth, AAs bound to surfaces can promote HA precipitation by attracting Ca2+ and PO43− ions and increasing the local supersaturation. Overall, the effect of AAs on HA precipitation is worth being investigated more, especially under conditions closer to the physiological ones, where the presence of other factors such as collagen, mineralization inhibitors, and cells heavily influences HA precipitation. A deeper understanding of the role of AAs in HA mineralization will increase our fundamental knowledge related to bone formation, and could lead to new therapies to improve bone regeneration in damaged tissues or cure pathological diseases caused by excessive mineralization in tissues such as cartilage, blood vessels and cardiac valves.
Current Cherenkov telescopes have identified a population of ultra-high-frequency peaked BL Lac objects (UHBLs), also known as extreme blazars, that exhibit exceptionally hard TeV spectra, including ...1ES 0229+200, 1ES 0347−121, RGB J0710+591, 1ES 1101−232, and 1ES 1218+304. Although one-zone synchrotron-self-Compton (SSC) models have been generally successful in interpreting the high-energy emission observed in other BL Lac objects, they are problematic for UHBLs, necessitating very large Doppler factors and/or extremely high minimum Lorentz factors of the emitting leptonic population. In this context, we have investigated alternative scenarios where hadronic emission processes are important, using a newly developed (lepto-)hadronic numerical code to systematically explore the physical parameters of the emission region that reproduces the observed spectra while avoiding the extreme values encountered in pure SSC models. Assuming a fixed Doppler factor δ = 30, two principal parameter regimes are identified, where the high-energy emission is due to: (1) proton-synchrotron radiation, with magnetic fields B ∼ 1–100 G and maximum proton energies E
p; max ≲ 1019 eV; and (2) synchrotron emission from p–γ-induced cascades as well as SSC emission from primary leptons, with B ∼ 0.1–1 G and E
p; max ≲ 1017 eV. This can be realized with plausible, sub-Eddington values for the total (kinetic plus magnetic) power of the emitting plasma, in contrast to hadronic interpretations for other blazar classes that often warrant highly super-Eddington values.
ABSTRACT While active galactic nuclei with relativistic jets have long been prime candidates for the origin of extragalactic cosmic rays and neutrinos, the BL Lac object TXS 0506+056 is the first ...astrophysical source observed to be associated with some confidence (∼3σ) with a high-energy neutrino, IceCube-170922A, detected by the IceCube Observatory. The source was found to be active in high-energy γ-rays with Fermi-LAT and in very-high-energy γ-rays with the MAGIC telescopes. To consistently explain the observed neutrino and multiwavelength electromagnetic emission of TXS 0506+056, we investigate in detail single-zone models of leptohadronic emission, assuming cospatial acceleration of electrons and protons in the jet, and synchrotron photons from the electrons as targets for photohadronic neutrino production. The parameter space concerning the physical conditions of the emission region and particle populations is extensively explored for scenarios where the γ-rays are dominated by either (1) proton synchrotron emission or (2) synchrotron-self-Compton emission, with a subdominant but non-negligible contribution from photohadronic cascades in both cases. We find that the latter can be compatible with the neutrino observations, while the former is strongly disfavoured due to the insufficient neutrino production rate.
Context. The wealth of recent data from Imaging Air Cherenkov telescopes (IACTs), ultra-high energy cosmic-ray experiments and neutrino telescopes have fuelled a renewed interest in hadronic emission ...models for γ-loud blazars. Aims. We explore physically plausible solutions for a lepto-hadronic interpretation of the stationary emission from high-frequency peaked BL Lac objects (HBLs). The modelled spectral energy distributions are then searched for specific signatures at very high energies that could help to distinguish the hadronic origin of the emission from a standard leptonic scenario. Methods. By introducing a few basic constraints on parameters of the model, such as assuming the co-acceleration of electrons and protons, we significantly reduced the number of free parameters. We then systematically explored the parameter space of the size of the emission region and its magnetic field for two bright γ-loud HBLs, PKS 2155-304 and Mrk 421. For all solutions close to equipartition between the energy densities of protons and of the magnetic field, and with acceptable jet power and light-crossing timescales, we inspected the spectral hardening in the multi-TeV domain from proton-photon induced cascades and muon-synchrotron emission inside the source. Very-high-energy spectra simulated with the available instrument functions from the future Cherenkov Telescope Array (CTA) were evaluated for detectable features as a function of exposure time, source redshift, and flux level. Results. A range of hadronic scenarios are found to provide satisfactory solutions for the broad band emission of the sources under study. The TeV spectrum can be dominated either by proton-synchrotron emission or by muon-synchrotron emission. The solutions for HBLs cover a parameter space that is distinct from the one found for the most extreme BL Lac objects in an earlier study. Over a large range of model parameters, the spectral hardening due to internal synchrotron-pair cascades, the “cascade bump”, should be detectable for acceptable exposure times with the future CTA for a few nearby and bright HBLs.
Periodontal regeneration is still a challenge for periodontists and tissue engineers, as it requires the simultaneous restoration of different tissues—namely, cementum, gingiva, bone, and periodontal ...ligament (PDL). Here, we synthetized a chitosan (CH)–based trilayer porous scaffold to achieve periodontal regeneration driven by multitissue simultaneous healing. We produced 2 porous compartments for bone and gingiva regeneration by cross-linking with genipin either medium molecular weight (MMW) or low molecular weight (LMW) CH and freeze-drying the resulting scaffolds. We synthetized a third compartment for PDL regeneration by CH electrochemical deposition; this allowed us to produce highly oriented microchannels of about 450-µm diameter intended to drive PDL fiber growth toward the dental root. In vitro characterization showed rapid equilibrium water content for MMW-CH and LMW-CH compartments (equilibrium water content after 5 min >85%). The MMW-CH compartment degraded more slowly and provided significantly more resistance to compression (28% ± 1% of weight loss at 4 wk; compression modulus HA = 18 ± 6 kPa) than the LMW-CH compartment (34% ± 1%; 7.7 ± 0.8 kPa) as required to match the physiologic healing rates of bone and gingiva and their mechanical properties. More than 90% of all human primary periodontal cell populations tested on the corresponding compartment survived during cytocompatibility tests, showing active cell metabolism in the alkaline phosphatase and collagen deposition assays. In vivo tests showed high biocompatibility in wild-type mice, tissue ingrowth, and vascularization within the scaffold. Using the periodontal ectopic model in nude mice, we preseeded scaffold compartments with human gingival fibroblasts, osteoblasts, and PDL fibroblasts and found a dense mineralized matrix within the MMW-CH region, with weakly mineralized deposits at the dentin interface. Together, these results support this resorbable trilayer scaffold as a promising candidate for periodontal regeneration.
Magnesium is an attractive material for use in biodegradable implants due to its low density, non-toxicity and mechanical properties similar to those of human tissue such as bone. Its ...biocompatibility makes it amenable for use in a wide range of applications from bone to cardiovascular implants. Here we investigated the corrosion rate in simulated body fluid (SBF) of a series of Mg–Sr alloys, with Sr in the range of 0.3–2.5%, and found that the Mg–0.5 Sr alloy showed the slowest corrosion rate. The degradation rate from this alloy indicated that the daily Sr intake from a typical stent would be 0.01–0.02mgday−1, which is well below the maximum daily Sr intake levels of 4mgday−1. Indirect cytotoxicity assays using human umbilical vascular endothelial cells indicated that Mg–0.5 Sr extraction medium did not cause any toxicity or detrimental effect on the viability of the cells. Finally, a tubular Mg–0.5 Sr stent sample, along with a WE43 control stent, was implanted into the right and left dog femoral artery. No thrombosis effect was observed in the Mg–0.5 Sr stent after 3weeks of implantation while the WE43 stent thrombosed. X-ray diffraction demonstrated the formation of hydroxyapatite and Mg(OH)2 as a result of the degradation of Mg–0.5 Sr alloy after 3days in SBF. X-ray photoelectron spectroscopy further showed the possibility of the formation of a hydroxyapatite Sr-substituted layer that presents as a thin layer at the interface between the Mg–0.5 Sr alloy and the corrosion products. We believe that this interfacial layer stabilizes the surface of the Mg–0.5 Sr alloy, and slows down its degradation rate over time.
Non-collagenous proteins (NCPs) inhibit hydroxyapatite (HA; Ca5(PO4)3OH) formation in living organisms by binding to nascent nuclei of HA and preventing their further growth. Polar and charged amino ...acids (AAs) are highly expressed in NCPs, and the negatively charged ones, such as glutamic acid (Glu) and phosphoserine (P-Ser) seem to be mainly responsible for the inhibitory effect of NCPs. Despite the recognized importance of these AAs on the behaviour of NCPs, their specific effect on HA crystallization is still unclear, and controversial results have been reported concerning the efficacy of HA inhibition of positively versus negatively charged AAs. We focused on a positively charged (arginine, Arg) and a negatively charged (Glu) AA, and their combination in the same solution. We studied their inhibitory effect on HA nucleation and growth at physiological temperature and pH and we determined the mechanism by which they can affect HA crystallization. Our results showed a strong inhibitory effect of Arg on HA nucleation; however, Glu was more effective in inhibiting HA crystal growth during the growth stage. The combination of Glu and Arg was less effective in controlling HA nucleation, but it inhibited HA crystal growth. We attributed these differences to the stability of complexes formed between AAs and calcium and phosphate ions at the nucleation stage, and in bonding strength of AAs to HA crystal faces during the growth stage. The AAs also influenced the morphology of synthesized HA. Presence of either Arg or Glu resulted in the formation of spherulites consisting of preferentially oriented nanoplatelets orientation. This was attributed to kinetic factors favoring growth front nucleation (GFN) mechanism.
Context. The one-zone synchrotron-self-Compton (SSC) model aims to describe the spectral energy distribution (SED) of BL Lac objects via synchrotron emission by a non-thermal population of electrons ...and positrons in a single homogeneous emission region, partially upscattered to γ-rays by the particles themselves. Aims. The model is usually considered as degenerate, given that the number of free parameters is higher than the number of observables. It is thus common to model the SED by choosing a single set of values for the SSC model parameters that provide a good description of the data, without studying the entire parameter space. We present here a new numerical algorithm that permits us to find the complete set of solutions, using the information coming from the detection in the GeV and TeV energy bands. Methods. The algorithm is composed of three separate steps: we first prepared a grid of simulated SEDs and extracted from each SED the values of the observables; we then parametrized each observable as a function of the SSC parameters; we finally solved the system for a given set of observables. We iteratively solved the system to take into account uncertainties in the values of the observables, producing a family of solutions. Results. We present a first application of our algorithm to the typical high-frequency-peaked BL Lac object 1RXS J101015.9 - 311909, provide constraints on the SSC parameters, and discuss the result in terms of our understanding of the blazar emitting region.
Hydroxyapatite (HA, Ca5(PO4)3OH) is the main inorganic component of hard tissues, such as bone and dentine. HA nucleation involves a set of negatively charged phosphorylated proteins known as ...non-collagenous proteins (NCPs). These proteins attract Ca2+ and PO43− ions and increase the local supersaturation to a level required for HA precipitation. Polar and charged amino acids (AAs) are highly expressed in NCPs, and seem to be responsible for the mineralizing effect of NCPs; however, the individual effect of these AAs on HA mineralization is still unclear. In this work, we investigate the effect of a negatively charged (Glu) and positively charged (Arg) AA bound to carboxylated graphene oxide (CGO) on HA mineralization in simulated body fluids (SBF). Our results show that Arg induces HA precipitation faster and in larger amounts than Glu. We attribute this to the higher stability of the complexes formed between Arg and Ca2+ and PO43− ions, and also to the fact that Arg exposes both carboxyl and amino groups on the surface. These can electrostatically attract both Ca2+ and PO43− ions, thus increasing local supersaturation more than Glu, which exposes carboxyl groups only.
ABSTRACT The Galactic Center ridge has been observed extensively in the past by both GeV and TeV gamma-ray instruments revealing a wealth of structure, including a diffuse component and the point ...sources G0.9+0.1 (a composite supernova remnant) and Sgr A* (believed to be associated with the supermassive black hole located at the center of our Galaxy). Previous very high energy (VHE) gamma-ray observations with the H.E.S.S. experiment have also detected an extended TeV gamma-ray component along the Galactic plane in the >300 GeV gamma-ray regime. Here we report on observations of the Galactic Center ridge from 2010 to 2014 by the VERITAS telescope array in the >2 TeV energy range. From these observations we (1) provide improved measurements of the differential energy spectrum for Sgr A* in the >2 TeV gamma-ray regime, (2) provide a detection in the >2 TeV gamma-ray emission from the composite SNR G0.9+0.1 and an improved determination of its multi-TeV gamma-ray energy spectrum, and (3) report on the detection of VER J1746-289, a localized enhancement of >2 TeV gamma-ray emission along the Galactic plane.
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