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The High-energy Particle Detector (HEPD) on board the China Seismo-Electromagnetic Satellite (CSES-01)—launched on 2018 February 2—is a light and compact payload suitable for measuring electrons (3–100 MeV), protons (30–250 MeV), and light nuclei (up to a few hundreds of MeV). The Sun-synchronous orbit and large acceptance allow HEPD to measure cosmic-ray particles near the ±65° latitude limit for a fair amount of time per day. In this work, three semiannual galactic hydrogen energy spectra between ∼40 and 250 MeV are presented, including a comparison with theoretical spectra from HelMod, a 2D Monte Carlo model developed to simulate the solar modulation of cosmic rays throughout the heliosphere. To our knowledge, these are the first hydrogen energy spectra below 250 MeV measured at 1 au between 2018 and 2020.

In this paper we test the ability of Raman micro-spectroscopy and Raman mapping to investigate the status of cells grown in adhesion on different substrates. The spectra of immortalized SH-SY5Y cells, grown on silicon and on metallic substrates are compared with those obtained for the same type of cells adhering on organic polyaniline (PANI), a memristive substrate chosen to achieve a living bio-hybrid system. Raman spectra give information on the status of the single cell, its local biochemical composition, and on the modifications induced by the substrate interaction. The good agreement between Raman spectra collected from cells adhering on different substrates confirms that the PANI, besides allowing the cell growth, doesn't strongly affect the general biochemical properties of the cell. The investigation of the cellular state in a label free condition is challenging and the obtained results confirm the Raman ability to achieve this information.

Because of their hollow interior, transmembrane channels are capable of opening up pathways for ions across lipid membranes of living cells. Here, we demonstrate ion conduction induced by a single DNA duplex that lacks a hollow central channel. Decorated with six porpyrin-tags, our duplex is designed to span lipid membranes. Combining electrophysiology measurements with all-atom molecular dynamics simulations, we elucidate the microscopic conductance pathway. Ions flow at the DNA-lipid interface as the lipid head groups tilt toward the amphiphilic duplex forming a toroidal pore filled with water and ions. Ionic current traces produced by the DNA-lipid channel show well-defined insertion steps, closures, and gating similar to those observed for traditional protein channels or synthetic pores. Ionic conductances obtained through simulations and experiments are in excellent quantitative agreement. The conductance mechanism realized here with the smallest possible DNA-based ion channel offers a route to design a new class of synthetic ion channels with maximum simplicity.

In the present study, FTIR spectroscopy was used to monitor the freeze-thaw cycle of two cellular lines (HuDe and Jurkat) suspended in three different media: phosphate buffer solution (PBS); dimethylsulfoxide (DMSO)/PBS solution at 0.1 DMSO molar fraction; and CryoSure (0.1 DMSO molar fraction PBS solution+dextran 5% w/v) solution. The Trypan Blue test was also applied before freezing and after thawing each cell sample to estimate the recovery of membrane integrity after thermal treatment, and correlate this datum with spectroscopic results. By following the temperature evolution of two different spectral components (the libration and bending combination mode ?c(H2O) at 2000-2500cm-1, and the methylene symmetric stretching vibration ?sym(CH2) at about 2850cm-1) in the -120÷28°C range, we evidenced the main transition of lipid membrane in connection with cell dehydration, as induced by ice formation in the extracellular medium. In particular, in DMSO/PBS and CryoSure samples we observed a transition to a more rigid state of the lipid membrane together with an increased amount of non-freezable water in the extracellular medium; these results are connected to the role of DMSO as a cryoprotective agent irrespective of the nature of cell type.

A Late Quaternary continental succession in central Italy (Bagnoli, Valdelsa Basin) which includes terrigenous and carbonate (calcareous tufa and travertine) sediments was investigated with palynology, 14 C dating and stable isotopic techniques. Pollen analyses of 43 samples, including quantification by the Climate Amplitude Method, allowed the documentation of the main palaeoenvironmental, vegetational and climatic changes. Taphonomic biases related to the depositional settings are expressed by i ) the significant occurrence of Pinus related to the increase of riverine input/waterborne pollen components in the basal terrigenous strata and by ii ) the generally significant presence of herbs, testimony to the local pollen input and dominance of the airborne pollen component in calcareous tufa and travertine. 14 C dating on organic samples confirms the Late Quaternary age of the section and the pollen record supports evidence for the onset of carbonate deposition during the Late Glacial Interstadial (LGI), coincident with expansion of thermophilous tree taxa, especially deciduous oaks. Successive cool and dry climate events are attested by the contemporaneous decrease of broad leaved deciduous forest taxa and a rise in herbs. Major unconformities as well as erosional, non-depositional or dissolution events, which interrupt the carbonate deposition at different times in the sequence, are interpreted as a direct response to global climate change and associated to cooler events (i.e. GS-2, GS-1, colder episodes during the LGI). As a whole δ 13 C and δ 18 O records do not show any clear relationship to the pollen-derived climatic data or to the carbonate units; rather they reflect a mixing of superficial CO 2 and a deeper source, underlining the complex origin of the Bagnoli carbonates.

On 25 August 2018, a G3-class geomagnetic storm reached the Earth’s magnetosphere, causing a transient rearrangement of the charged particle environment around the planet, which was detected by the High-Energy Particle Detector (HEPD) on board the China Seismo-Electromagnetic Satellite (CSES-01). We found that the count rates of electrons in the MeV range were characterized by a depletion during the storm’s main phase and a clear enhancement during the recovery caused by large substorm activity, with the key role played by auroral processes mapped into the outer belt. A post-storm rate increase was localized at L-shells immediately above ∼3 and mostly driven by non-adiabatic local acceleration caused by possible resonant interaction with low-frequency magnetospheric waves.

Many potential therapeutic compounds for brain diseases fail to reach their molecular targets due to the impermeability of the blood-brain barrier, limiting their clinical development. Nanotechnology-based approaches might improve compounds pharmacokinetics by enhancing binding to the cerebrovascular endothelium and translocation into the brain. Adsorption of apolipoprotein E4 onto polysorbate 80-stabilized nanoparticles to produce a protein corona allows the specific targeting of cerebrovascular endothelium. This strategy increased nanoparticle translocation into brain parenchyma, and improved brain nanoparticle accumulation 3-fold compared to undecorated particles (119.8 vs 40.5 picomoles). Apolipoprotein decorated nanoparticles have high clinical translational potential and may improve the development of nanotechnology-based medicine for a variety of neurological diseases. (C) 2017 Elsevier Inc. All rights reserved.

On Earth, water plays an active role in cellular life, over several scales of distance and time. At a nanoscale, water drives macromolecular conformation through hydrophobic forces and at short times acts as a proton donor/acceptor providing charge carriers for signal transmission. At longer times and larger distances, water controls osmosis, transport, and protein mobility. Neutron diffraction experiments augmented by computer simulation, show that the three-dimensional shape of the hydration shell of carboxyl and carboxylate groups belonging to different molecules is characteristic of each molecule. Different hydration shells identify and distinguish specific sites with the same chemical structure. This experimental evidence suggests an active role of water also in controlling, modulating, and mediating chemical reactions involving carboxyl and carboxylate groups.

Purpose: Recently, it has been demonstrated that Raman spectroscopy is able to differentiate between healthy parathyroid tissues and parathyroid adenoma based on the basis of a specific molecular fingerprint. However, to our knowledge, no previous studies have been performed to evaluate the metabolic profile of parathyroid adenoma. Therefore, we designed a proof of concept study aimed to investigate the glucose/fatty acid metabolisms, in addition to the mitochondrial changes, in solitary parathyroid adenoma and in healthy parathyroid glands. Methods: Nine females with primary hyperparathyroidism due to a solitary parathyroid adenoma and formal surgical indication for parathyroidectomy have been enrolled. At the time of surgery, the removed specimens were immediately submitted unfixed and a tissue slice of about 0.5 cm in diameter was obtained from the nodular lesion. The expression of selected metabolic enzymes and proteins has been evaluated by western blot analysis, using human parathyroid whole tissue lysates as control. Results: Data obtained highlighted an increase, compared with the healthy group, of: (i) the glucose uptake by the GLUT-1 receptor and its phosphorylation by hexokinase II (HXKII); (ii) the expression of 3-phosphoglycerate dehydrogenase (3-PGDH) and glucose-6-phosphate dehydrogenase (G6PD); (iii) lipids biosynthesis; and (iv) cytochrome c expression. Conclusions: Our findings highlight for the first time the parathyroid adenoma metabolic hallmarks that could represent potential molecular targets usable for the development of new pharmacological treatments, allowing to reduce surgical parathyroidectomy.

The collection and storage of water-related matrices such as biofilm from collection to processing are critical for the detection of Legionella pneumophila by cultural and molecular tests. SRK™ is a liquid medium that acts both as an antimicrobial neutralizing agent and a transport medium for bacterial culture enumeration and is useful to maintain the stability of the sample from collection to analysis. The aims of this study were to evaluate Legionella pneumophila viability and bacterial nucleic acids’ stability in SRK™ medium over time at different storage conditions. Artificial bacterial inoculates with an approximate concentration of 104, 103 and 102 CFU/mL were made using Legionella pneumophila certified reference material suspended in SRK™ medium. Bacteria recovery was analyzed by cultural and molecular methods at time 0, 24 and 48 h at room temperature and at 0, 24, 48 and 72 h at 2–8 °C, respectively. SRK™ medium supported Legionella pneumophila culture viability with CFU counts within the expected range. The recovery after 72 h at 2–8 °C was 83–100% and 75–95% after 48 h at room temperature. Real-time PCR appropriately detected Legionella pneumophila DNA at each temperature condition, dilution and time point. Results demonstrated a good performance of SRK™ medium for the reliable recovery of environmental Legionella.

The tripeptide Glycyl-L-prolyl-glycinamide HCl (GPG-NH2) is chosen as a model system to investigate β -turns formation in aqueous solutions and the role of trehalose in preserving this motif in drought conditions. In this first study relatively dilute solutions are investigated. Neutron diffraction experiments show the presence of both direct and water mediated β -turns, the latter ones increasing in number when trehalose is added to the aqueous solution. The structure of the ternary (GPG-NH2/water/trehalose) solution demonstrates that trehalose confines water close to the β -turns, possibly preserving their hydration when water runs low, without directly interacting with GPG-NH2 via Hydrogen bonds. Further experiments at lower water content are needed to confirm this finding.

We study the synthesis and characterisation of an innovative TEOS-based composite coating, which could improve previous formulations used in the field of monument conservation. The proposed coating is composed by a tetraethoxyorthosilicate matrix (TEOS), containing an elasticiser (hydroxyl-terminated polydimethylsiloxane (PDMS-OH)) and a non-ionic surfactant (n-octylamine). The specific self-cleaning and antifouling properties are obtained by the addition of different kinds of nanofillers: the commercial TiO2 nanoparticles, plus two different silica nanocontainers, loaded with the commercial biocide 2-mercaptobenzothiazole. Through a multi-analytical approach, we evaluate the effect of the nanoparticles concentration on the coatings drying rate, on the variation of their visual aspect and textural properties. Our results show that the addition of the silica nanocontainers at 0.05% (w/v) in sol does not change the colour of the coating and reduces the formation of cracks after drying. Moreover, the coating charged with nanocontainers undergoes slower drying, thus improving its penetration into the pores of the treated surface. Further tests of photocatalytic and biocidal properties of this new product on different lithotypes and their potential interactions are in progress.

Mid-infrared signals in the 2–5 μm wavelength range have been transmitted through samples of polymer pipes, as commonly used in the water supply industry. It is shown that simple through-transmission images can be obtained using a broad spectrum source and a suitable camera. This leads to the possibility of tomography, where images are obtained as the measurement system is rotated with respect to the axis of the pipe. The unusual 3D geometry created by a source of finite size and the imaging plane of a camera, plus the fact that refraction at the pipe wall would cause significant ray bending, meant that the reconstruction of tomographic images had to be considered with some care. A result is shown for a thinning defect on the inner wall of a polymer water pipe, demonstrating that such changes can be reconstructed successfully.

In cultural heritage field, significant research efforts have been recently made to improve the efficacy of anti-vegetative treatments and to reduce the environmental impact caused by biocides high concentration. According to the pro-ecological approach, this work reports a novel approach based on the encapsulation/incorporation of environmentally-friendly biocides in different silica nanosystems in order to control the development of biological patinas on outdoor cultural heritage. Two different green biocides have been selected and tested in silica nanosystems: the zosteric acid sodium salt (ZS), a natural antifoulant compound produced by Zostera marina (eelgrass), and the usnic acid (UA), a secondary metabolite produced by some saxicolous lichens. ZS was previously successfully encapsulated but never entrapped in mesoporous silica; instead, UA is, for the first time, encapsulated and in situ entrapped into the silica nanosystems in order to control the release over time. Both silica nanosystems have been characterized as far as their dimensions and superficial properties and loading capability. The antifouling activity was assessed against microorganisms from biopatinas colonising the Aurelian Walls in Rome. Our results have shown that the two nanosystems have complementary properties, thus it is possible to tune the antifouling efficiency by combining the two in different proportions.

In this paper, two new reversed-phase (RP) HPLC-UV methods enabling the quantitative achiral and chiral analysis of ruxolitinib in commercial tablets (containing 20 mg of active pharmaceutical ingredient, API) and not commercially available galenic capsules (with 5 mg of API) are described. For the achiral method based on the use of a water/acetonitrile [70:30, v/v; with 0.1% (v) formic acid] eluent, a “research validation” study was performed mostly following the “International Council for Harmonization” guidelines. All the system suitability parameters were within the acceptance criteria: tailing factor, between 1.7 and 2.0; retention factor, 2.2; number of theoretical plates, >9000. The linearity curve showed R2 = 0.99 (Rxv2 = 0.99), while trueness (expressed as recovery) was between 96.3 and 106.3%. Coefficient of variations (CVs) (repeatability: CVw and intermediate precision: CVIP) did not exceed 1.3% and 2.9%, respectively. Moreover, the use of the enantiomeric Whelk-O1 chiral stationary phases operated under similar RP eluent conditions as for the achiral analyses, and the “inverted chirality columns approach (ICCA)” allowed us to establish that the enantiomeric purity of ruxolitinib is retained upon reformulation from tablets to capsules. The two developed methods can allow accurate determinations of ruxolitinib in drug formulations for medical use.

In the last years, significant research efforts have been devoted to the reduction of the environmental impact of biocides and to the improvement of their effectiveness over time against degradation of stone artifacts. This work reports the spectroscopic characterization of two silica nanosystems, with different geometry and structure, loaded with a biologically-active compound, the 2-mercaptobenzothiazole (MBT), for controlled antifouling release on the surface of outdoor stone artefacts. We have combined FT-IR spectroscopy in ATR mode and Raman spectroscopy to investigate the biocide loading mechanism in both nanosystems from the physical and chemical point of view. These techniques demonstrate that the geometry of confinement influences the loading of the nanoparticles and their interaction with the confining medium, with possible consequences in the biocide release rate. Moreover, we have seen that the biocide interacts with the surfactant (cetrimonium bromide, CTAB) and tends to dimerize.

Precise time-dependent measurements of the Z = 2 component in the cosmic radiation provide crucial information about the propagation of charged particles through the heliosphere. The PAMELA experiment, with its long flight duration (2006 June 15-2016 January 23) and the low energy threshold (80 MeV/n) is an ideal detector for cosmic-ray solar modulation studies. In this paper, the helium nuclei spectra measured by the PAMELA instrument from 2006 July to 2009 December over a Carrington rotation time basis are presented. A state-of-the-art three-dimensional model for cosmic-ray propagation inside the heliosphere was used to interpret the time-dependent measured fluxes. Proton-to-helium flux ratio time profiles at various rigidities are also presented in order to study any features that could result from the different masses and local interstellar spectra shapes.

Neutron diffraction experiments have been performed to investigate and compare the structure of the hydration shell of three monosaccharides, namely, fructose, glucose, and mannose. It is found that despite their differences with respect to many thermodynamical quantities, bioprotective properties against environmental stresses, and taste, the influence of these monosaccharides on the bulk water solvent structure is virtually identical. Conversely, these sugars interact with the neighboring water molecules by forming H bonds of different length and strength. Interestingly, the sweetness of these monosaccharides, along with that of the disaccharide trehalose, is correlated with the length of these H bonds. This suggests that the small differences in stereochemistry between the different sugars determine a relevant change in polarity, which has a fundamental impact on the behavior of these molecules in vivo.

Natural sugars combine energy supply and, except a few cases, a pleasant taste. On the other hand, exaggerated consumption may impact population health. This has busted the research for the synthesis of increasingly cheaper artificial sweeteners, with low energy content and intense taste. Here, we suggest that studies of the hydration properties of three disaccharides, namely, the natural sucrose and lactose and the artificial sucralose, may explain the difference by orders of magnitude among their sweetness. This is done by analyzing via Monte Carlo simulations the neutron diffraction differential cross sections of aqueous solutions of the three sugars and their isotopes. Our results show that the strength of the sugar–water hydrogen bond interaction is one of the factors influencing sweetness, another being the number of water molecules within the first neighboring shell of the sugar whether bonded or not.

Cancer remains one of the most important challenges in biomedical sciences. Chemotherapeutic agents are very potent molecules that exhibit a significant level of toxicity in numerous tissues of the body, particularly in those characterized by high proliferative activity, such as the bone marrow. The scenario is even more complex in the case of the central nervous system, and in particular brain tumors, where the blood brain barrier limits the efficacy of drug therapies. Integrins, transmembrane proteins widely expressed in different types of cancer (glioblastoma, melanoma, and breast cancer), regulate the angiogenic process and play a pivotal role in tumor growth and invasion. Here, we report a nanotechnology strategy based on the use of AuNPs decorated with an arginine-glycine-aspartic acid-like peptide for the diagnosis and treatment of cancer. Two hours after administration in mice, the accumulation of the peptide-decorated NPs in the subcutaneous tumor was ∼4-fold higher than that of uncoated particles and ∼1.4-fold higher than that of PEGylated particles. Also, in the case of the intracranial tumor model, interesting results were obtained. Indeed, 2 h after administration, the amount of peptide-decorated particles in the brain was 1.5-fold that of undecorated particles and 5-fold that of PEGylated particles. In conclusion, this preliminary study demonstrates the high potential of this carrier developed for diagnostic and therapeutic applications., SCOPUS: ar.j, info:eu-repo/semantics/published

Neutron diffraction with isotopic H/D substitution on water, augmented by Empirical Potential Structure Refinement has been applied to extract the hydration properties of the osmolyte zwitterionic ectoine at 1.5 M concentration. This has evidenced differences between the hydration of COO− and NH groups, both in terms of number of water molecules involved in the hydration shell and of three-dimensional symmetry. Signatures of ectoine–ectoine contacts, due to hydrogen bonds, have been found, as possible precursors of ectoine aggregation at higher concentrations. The influence of ectoine on the water structure is ascribed to the dipolar electric field generated by the exposed charges of ectoine.

Magnetic mesoporous silica (MS) nanocomposites provide the possibility of generating multi-functional objects for application in different technological areas. This paper focuses on the magnetic properties of nanocomposites constituted by spinel iron oxide nanoparticles (magnetic nanoparticles (MNPs), < D > ≈ 8-9 nm) embedded in an MS matrix. The mesoporous structure of the silica matrix and the presence of the nanoparticles inside clearly emerge from transmission electron microscopy (TEM) measurements. Low temperature (5 K) field-dependent magnetization measurements reveal saturation magnetization (MS ) close to bulk value (M S bulk ∼ 90 emu g-1) for both MNPs and MNP/MS nanocomposites, indicating that the presence of silica does not affect the magnetic features of the single MNPs. Moreover, the dependence of the remanent magnetization on field (i.e. δM plots) at low temperature has shown a small but evident decrease of interaction in an MNP/MS sample with respect to MNP samples A m2 Kg-1. Finally, a partial orientation of the easy axis is observed when the MNPs are embedded in the silica matrix.

EUSO-Balloon is a pathfinder mission for the Extreme Universe Space Observatory onboard the Japanese Experiment Module (JEM-EUSO). It was launched on the moonless night of the 25th of August 2014 from Timmins, Canada. The flight ended successfully after maintaining the target altitude of 38 km for five hours. One part of the mission was a 2.5 hour underflight using a helicopter equipped with three UV light sources (LED, xenon flasher and laser) to perform an inflight calibration and examine the detectors capability to measure tracks moving at the speed of light. We describe the helicopter laser system and details of the underflight as well as how the laser tracks were recorded and found in the data. These are the first recorded laser tracks measured from a fluorescence detector looking down on the atmosphere. Finally, we present a first reconstruction of the direction of the laser tracks relative to the detector., 0, SCOPUS: ar.j, info:eu-repo/semantics/published

The Mu2e experiment is constructing a calorimeter consisting of 1,348 undoped CsI crystals in two disks. Each crystal has a dimension of 34 x 34 x 200 mm, and is readout by a large area silicon PMT array. A series of technical specifications was defined according to physics requirements. Preproduction CsI crystals were procured from three firms: Amcrys, Saint-Gobain and Shanghai Institute of Ceramics. We report the quality assurance on crystal's scintillation properties and their radiation hardness against ionization dose and neutrons. With a fast decay time of 30 ns and a light output of more than 100 p.e./MeV measured with a bi-alkali PMT, undoped CsI crystals provide a cost-effective solution for the Mu2e experiment., Comment: 7 pages, 16 figures, published in IEEE TNS NS (2018)

Objectives: The development of inhaled products to treat or to prevent lung infection is a very active research field in drug delivery. The pulmonary route is extremely attractive but very challenging. This paper reports the study of excipient, capsule brand and device influence on the aerodynamic behavior of dry powder formulations to treat tuberculosis.Methods: A capreomycin hydrophobic salt was powdered using spray-drying and formulated using lactose (added after spray-drying, external excipient) or L-leucine (added before spray-drying, internal excipient). Aerosolization performances were investigated loading the formulations in 2 different capsule brands and aerosolizing them with 3 different devices.Results: Capreomycin oleate and capreomycin oleate/L-leucine powders were produced with a yield around 70%. Capreomycin oleate 'powder was composed of particles with an irregular surface. Particles of capreomycin oleate/L-leucine were roundish and wrinkled on the surface. Capreomycin oleate/L-leucine formulation gave the highest values of respirable fraction in all cases. Statistical analysis asserted the significant effect on the respirable fraction of the powder (p < 0.001), the capsule brand (p < 0.01) and the device (p < 0.05).Conclusions: The use of L-leucine as internal excipient allows one to avoid the use of lactose, obtaining a carrier-free formulation. Even though differences are not very large, to obtain the highest RFE, the best choice between capsule and device is Quali-V (R) and model 8. (C) 2015 Elsevier B.V. All rights reserved.

Cocoa seed polyphenols have demonstrated interesting beneficial effects in humans. Most polyphenols contained in fresh seeds are chemically modified during fermentation, drying, and cocoa powder or chocolate production. The improvement of these procedures to obtain a high-polyphenol-content cocoa is highly desirable. To this aim, a field investigation on the effect of fermentation and natural drying on fine flavor National cocoa (cacao Nacional) was performed. Cocoa seeds were fermented for 6 days and, every day, samples were sun-dried and analyzed for polyphenol content and antioxidant power. During the first 2 days of fermentation, Folin-Ciocalteu and FRAP tests evidenced a significant reduction of polyphenol content and antioxidant capacity, respectively. Changes during the following days of fermentation were less significant. Epicatechin, the most studied member of the catechin family, followed a similar pathway of degradation. Data confirmed the high impact of fermentation and drying on cocoa seed polyphenols. Fermentation and drying are, on the one hand, necessary to obtain cocoa flavor and palatability but, on the other hand, are responsible for greatly compromising polyphenol content. To obtain high-polyphenol-content cocoa, the existing fermentation, drying, and manufacturing protocols should be scientifically reviewed to understand and modify the critical steps.

In recent decades, tissue engineering strategies have been proposed for the treatment of musculoskeletal diseases and bone fractures to overcome the limitations of the traditional surgical approaches based on allografts and autografts. In this work we report the development of a composite porous poly(DL-lactide-co-glycolide) scaffold suitable for bone regeneration. Scaffolds were produced by thermal sintering of porous microparticles. Next, in order to improve cell adhesion to the scaffold and subsequent proliferation, the scaffolds were coated with the osteoconductive biopolymers chitosan and sodium alginate, in a process that exploited electrostatic interactions between the positively charged biopolymers and the negatively charged PLGA scaffold. The resulting scaffolds were characterized in terms of porosity, degradation rate, mechanical properties, biocompatibility and suitability for bone regeneration. They were found to have an overall porosity of approximate to 85% and a degradation half time of approximate to 2weeks, considered suitable to support de novo bone matrix deposition from mesenchymal stem cells. Histology confirmed the ability of the scaffold to sustain adipose-derived mesenchymal stem cell adhesion, infiltration, proliferation and osteo-differentiation. Histological staining of calcium and microanalysis confirmed the presence of calcium phosphate in the scaffold sections.

Precision measurements of the Z = 2 component in cosmic radiation provide crucial information about the origin and propagation of the second most abundant cosmic ray species in the Galaxy (9% of the total). These measurements, acquired with the PAMELA space experiment orbiting Earth, allow to study solar modulation in details. Helium modulation is compared to the modulation of protons to study possible dependencies on charge and mass. The time dependence of helium fluxes on a monthly basis measured by PAMELA has been studied for the period between July 2006 to January 2016 in the energy range from 800 MeV/n to ~ 20 GeV/n.

Sodium-ion batteries (SIBs) are considered a good choice for post-lithium devices. Transition metal sodium pyrophosphates are among the most interesting cathode materials for SIBs. Here we study the electrochemical properties of the system Na 2 Fe 1´x Mn x P 2 O 7 (x = 0, 0.25, 0.5, 0.75, 1). By means of cyclic voltammetry (CV) and galvanostatic experiments, we confirm that pure Fe and Fe-rich compounds are promising for application in sodium batteries, whereas Mn-rich samples are less satisfactory, at least in case of solid-state reaction recipes and standard slurry preparations. Proper carbon coating is likely needed to improve the electrochemical behavior of Mn-rich samples.

In the framework of the PAMELA experiment the features of the large-scale anisotropy have been measured within the energy range 1-20 TeV/n. The measurements were carried out with the use of the calorimeter on the base of the hypothesis about the existence of a dipole anisotropy. The amplitude and phase of the dipole were obtained. The results are in agreement with the ground-based observations.

Pyrophosphate-based materials, in particular Na2FeP2O7, constitute an interesting class of cathode compounds for rechargeable Na-ion batteries. In this work we investigate the effect of different synthetic procedures, namely: (i) glucose-assisted solid-state synthesis, and (ii) Pechini-based wet chemistry approach, on the electrochemical performances of Na2FeP2O7. Both the methods allow good specific gravimetric capacity during charge/discharge, with values close to the theoretical one at low current rates, good capacity retention and coulombic efficiency to be obtained. These results, which are better than those obtained from solid-state synthesis without added glucose, are quite independent on the different microstructures originating from the synthesis approaches, and can be attributed to the residuals of the organic fractions added during the synthesis. In addition we show that the glucose-assisted solid-state synthesis assures electrochemical stability even at relatively high currents rates (100 cycles at 1C rate).

The cosmic-ray lithium and beryllium ($^{6}$Li, $^{7}$Li, $^{7}$Be, $^{9}$Be, $^{10}$Be) isotopic composition has been measured with the satellite-borne experiment PAMELA, which was launched into low-Earth orbit on-board the Resurs-DK1 satellite on June 15th 2006. The rare lithium and beryllium isotopes in cosmic rays are believed to originate mainly from the interaction of high energy carbon, nitrogen and oxygen nuclei with the interstellar medium (ISM), but also on "tertiary" interactions in the ISM (i.e. produced by further fragmentation of secondary beryllium and boron). In this paper the isotopic ratios $^{7}$Li/$^{6}$Li and $^{7}$Be/($^{9}$Be + $^{10}$Be) measured between 150 and 1100 MeV/n using two different detector systems from July 2006 to September 2014 will be presented., 13 pages, 11 figures, accepted for publication in the Astrophysical Journal. arXiv admin note: text overlap with arXiv:1512.06535

An all-optical experimental technique aimed at measuring photoisomerization quantum yield (phi) of the all-trans protonated Schiff base of retinal in solution has been implemented. Upon the increase in the excitation wavelength from 400 to 540 nm a slight increase in phi from 0.16 +/- 0.03 to 0.20 +/- 0.02 is observed in the chromophore dissolved in methanol, whereas the phi value of the one dissolved in acetonitrile varies only from 0.22 +/- 0.03 (400 nm) to 0.23 +/- 0.04 (540 nm). The results suggest that dissipation of the excited-state vibrational energy excess, along with environment-induced modifications of the potential energy surfaces are necessary for an efficient retinal photoisomerization in both solvent and protein environment.

The available data on the energy spectra of electrons, protons, and helium nuclei in the high-energy region are fragmentary, a situation made worse by their scarcity. Due to limitations imposed on the use of the magnetic spectrometer in the PAMELA satellite experiment, the calorimeter must be used for measurements performed in the high-energy region. The processing of experimental data accumulated in more than eight years of measurements with the calorimeter, neutron detector, and scintillation counters allows the spectra of high-energy particles to be obtained, greatly expanding our understanding of the nature of primary cosmic rays.

Macromolecules, such as poly(lactide-co-glycolide), have nowadays a pivotal role in drug delivery technologies. To have a precise and predictable control of the drug release kinetics in a delivery system, polymer physico-chemical characteristics must be deeply investigated together with all the other components of the device, including the active pharmaceutical ingredient/s. In fact, drug-polymer interaction may result in drastic changes of polymer characteristics. Plasticization, by changing polymer mechanical properties and diffusion coefficients, may seriously compromise device performances.We investigated the possibility to hinder the plasticizing effect of ketoprofen on poly(lactide-co-glycolide) (PLGA) during microparticle preparation. To this aim, ketoprofen was included in beta-cyclodextrin and then encapsulated in PLGA.The formation of the inclusion complex was confirmed by X-ray and FT-IR data, and UV-Vis analysis showed that 85% of ketoprofen was included in the cyclodextrins. Molecular dynamics forecasted the enthalpy-driven formation of 4 inclusion complexes with hydrogen bonding playing an important role on their stability. PLGA microparticles were prepared using the solvent diffusion/evaporation method with encapsulation efficiency higher than 60%, without polymer plasticization.We proved that ketoprofen/beta-cyclodextrin inclusion complex allowed to hinder the plasticizing effect of ketoprofen on PLGA during microparticle preparation. The inclusion of ketoprofen within beta-cyclodextrin hindered its physical interaction with the polymer chains thus avoiding plasticization. (C) 2015 Elsevier B.V. All rights reserved.

The satellite-borne PAMELA experiment is aimed at precision measurements of the charged light component of the cosmic-ray spectrum, with a particular focus on antimatter. It consists of a magnetic spectrometer, a time-of-flight system, an electromagnetic calorimeter with a tail catcher scintillating layer, an anticoincidence system and a neutron detector. PAMELA has measured the absolute fluxes of boron and carbon and the B/C ratio, which plays a central role in galactic propagation studies in order to derive the injection spectra at sources from measurements at Earth. In this paper, the data analysis techniques and the final results are presented.

Purpose: The aim of this work was the investigation of the effects of preparation variables on drug content for the development of capreomycin sulfate (CS) liposomal formulations as potential aerosol antitubercular agents.Methods: Dipalmitoylphosphatidylcholine (DPPC), hydrogenated phosphaticlylcholine (HPC) and distearoylphosphatidylcholine (DSPC) were used for liposome preparation. A freeze-thawing method was chosen for CS encapsulation. Peptide entrapment, size and morphology were evaluated by UV spectrophotometry, photocorrelation spectroscopy (PCS) and transmission electron microscopy (TEM), respectively. A 2(3) full factorial protocol was designed to evaluate the conditions for CS encapsulation improvement.Results: Peptide content ranged between 1 and 8%. Vesicles showed a narrow size distribution, with average diameters around 1 mu m and a good morphology. A mathematical model was generated for each liposomal system and check point analyses revealed good agreement between experimental and predicted values. DPPC liposomes were found to provide the highest CS content.Conclusions: Peptide content was successfully increased by assessing formulation variable effects using a 23 factorial design that proved to be a time saving method helpful in developing new CS liposomal formulations for a possible application in aerosol antitubercular therapies. (c) 2005 Elsevier B.V. All rights reserved.

Purpose. The aim of the study is to optimize the intercalation conditions of ferulic acid (FERH), ail antioxidant Compound, into Mg-Al-hydrotalcite for a safe skin photoprotection.Methods. The intercalation products were prepared incubating hydrotalcite (HTlc) in aqueous solutions of FERH sodium salt at different temperatures over 4 and 8 days. Quantitative determination of intercalated FERH was performed by thermogravimetric analysis and morphology by scanning electron microscopy (SEM). FERH stability study was carried out at different pHs and temperatures. FERH was analyzed by reversed phase-high-performance liquid chromatography. Response surface methods (RSMs) were used to assess optimal intercalation conditions and FERH stability.Results. In all intercalation products, FERH content was found to be about 48%, w/w except when the intercalation process was carried out at 52 degrees C for 8 days and at 60 degrees C for both 4 and 8 days. which resulted to be 40.39, 39.99, and 34.99%. respectively. The RSM designs showed that intercalation improvement can be achieved by working at pH 6, at temperatures below 40 degrees C, and over 4 days of incubation.Conclusions. The optimal conditions for a proper FERH intercalation were assessed. The development of a new optimized protocol may improve HTlc-FER complex performances and safety by augmenting dosage and reducing the presence of harmful reactive species in the final formulation.

The purpose of this research was to encapsulate superoxide dismutase (SOD) and catalase (CAT) in biodegradable microspheres (MS) to obtain suitable sustained protein delivery. A modified water/oil/water double emulsion method was used for poly(D,L-lactide-co-glycolide) (PLGA) and poly(D,L-lactide) PLA MS preparation co-encapsulating mannitol, trehalose, and PEG400 for protein stabilization. Size, morphology, porosity, mass loss, mass balance, in vitro release and in vitro activity were assessed by using BCA protein assay, scanning electron microscopy, BET surface area, and particle-sizing techniques. In vitro activity retention within MS was evaluated by nicotinammide adenine dinucleotide oxidation and H2O2 consumption assays. SOD encapsulation efficiency resulted in 30% to 34% for PLA MS and up to 51% for PLGA MS, whereas CAT encapsulation was 34% and 45% for PLGA and PLA MS, respectively. All MS were spherical with a smooth surface and low porosity. Particle mean diameters ranged from 10 to 17 mum. CAT release was prolonged, but the results were incomplete for both PLA and PLGA MS, whereas SOD was completely released from PLGA MS in a sustained manner after 2 months. CAT results were less stable and showed a stronger interaction than SOD with the polymers. Mass loss and mass balance correlated well with the release profiles. SOD and CAT in vitro activity was preserved in all the preparations, and SOD was better stabilized in PLGA MS. PLGA MS can be useful for SOD delivery in its native form and is promising as a new depot system.

Background The great interest in the production of highly pure lactic acid enantiomers comes from the application of polylactic acid (PLA) for the production of biodegradable plastics. Yeasts can be considered as alternative cell factories to lactic acid bacteria for lactic acid production, despite not being natural producers, since they can better tolerate acidic environments. We have previously described metabolically engineered Saccharomyces cerevisiae strains producing high amounts of L-lactic acid (>60 g/L) at low pH. The high product concentration represents the major limiting step of the process, mainly because of its toxic effects. Therefore, our goal was the identification of novel targets for strain improvement possibly involved in the yeast response to lactic acid stress. Results The enzyme S-adenosylmethionine (SAM) synthetase catalyses the only known reaction leading to the biosynthesis of SAM, an important cellular cofactor. SAM is involved in phospholipid biosynthesis and hence in membrane remodelling during acid stress. Since only the enzyme isoform 2 seems to be responsive to membrane related signals (e.g. myo-inositol), Sam2p was tagged with GFP to analyse its abundance and cellular localization under different stress conditions. Western blot analyses showed that lactic acid exposure correlates with an increase in protein levels. The SAM2 gene was then overexpressed and deleted in laboratory strains. Remarkably, in the BY4741 strain its deletion conferred higher resistance to lactic acid, while its overexpression was detrimental. Therefore, SAM2 was deleted in a strain previously engineered and evolved for industrial lactic acid production and tolerance, resulting in higher production. Conclusions Here we demonstrated that the modulation of SAM2 can have different outcomes, from clear effects to no significant phenotypic responses, upon lactic acid stress in different genetic backgrounds, and that at least in one genetic background SAM2 deletion led to an industrially relevant increase in lactic acid production. Further work is needed to elucidate the molecular basis of these observations, which underline once more that strain robustness relies on complex cellular mechanisms, involving regulatory genes and proteins. Our data confirm cofactor engineering as an important tool for cell factory improvement. Electronic supplementary material The online version of this article (doi:10.1186/s12934-014-0147-7) contains supplementary material, which is available to authorized users.

PAMELA is a satellite borne experiment designed to study with great accuracy cosmic rays of galactic, solar, and trapped nature, with particular focus on the antimatter component. The detector consists of a permanent magnet spectrometer core to provide rigidity and charge sign information, a Time-of-Flight system for velocity and charge information, a Silicon-Tungsten calorimeter and a Neutron detector for lepton/hadron identification. The velocity and rigidity information allow the identification of different isotopes for Z=1 and Z=2 particles in the energy range 100 MeV/n to 1 GeV/n. In this work we will present the PAMELA results on the H and He isotope fluxes based on the data collected during the 23rd solar minimum from 2006 to 2007. Such fluxes carry relevant information helpful in constraining parameters in galactic cosmic rays propagation models complementary to those obtained from other secondary to primary measurements such as the boron-to-carbon ratio. �� 2013 Elsevier B.V.

This paper compares the catalytic behavior of several heterogeneous acid catalysts in the direct hydrolysis of an untreated softwood dust. Among the various catalysts investigated, some were characterized by a relatively high yield to monosaccharides, such as a Zirconium phosphate and the reference Amberlyst 15. Conversely, some catalyst types, i.e. Sn/W mixed oxide and Zirconia-grafted trifluoromethanesulfonic acid, were selective into glucose, since sugars derived from hemicellulose dissolution and hydrolysis were rapidly degraded. A detailed analysis of the reactivity of Zr/P/O was conducted, in the hydrolysis of both untreated and ball-milled microcrystalline cellulose; at 150 °C and 3 h reaction time, the catalyst gave high selectivity to glucose, with negligible formation of 5-hydroxymethylfurfural, and moderate cellulose conversion. After cellulose ball-milling, a notable increase in conversion was achieved, still with a high selectivity to glucose and very low formation of degradation compounds. The catalyst showed high affinity for β-1,4-glucans, as demonstrated by the activity in cellobiose hydrolysis into glucose.

The purpose of this study was to address the effect of feedstock properties and process variables on the characteristics of antitubercular drug–palladium (Pd) containing poly(lactic) acid (PLA) microparticles (MP) obtained by spray‐drying of noncolloidal particle dispersions in fast drying regime. Two different systems were compared: capreomycin–Pd (C–Pd) and ofloxacin–Pd (Ofx–Pd) dispersions in acetonitrile PLA solution. Particle size, dynamic light scattering, differential scanning calorimetry, SEM–energy dispersive X‐ray, and spectrophotometric methods were used for MP characterization. C–Pd‐loaded MP were optimized preliminarily by experimental design and compared with Ofx–Pd‐loaded MP investigated in our previous work. Morphology of feedstock particles had a dominant role in determining MP morphology. The Charlesworth and Marshall theory was used to explain such behavior. The smaller and homogeneous C–Pd microparticulates favored MP inflation and buckling by forming a thick and nonporous shell. A percolation effect was proposed for the larger and irregular Ofx–Pd particles that produced smaller MP with a more porous shell. Increasing feedstock concentration led to higher particle loss. A tentative descriptive scheme of MP formation according to feedstock particle arrangement was proposed. This work suggested that spray‐drying of drug dispersions should carefully consider the morphology of feedstock particles as a major parameter influencing final MP properties. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:1255–1268, 2014

Objectives The aim of this work was to characterize novel palladium (Pd) complexes with second-line antitubercular drugs, namely capreomycin (C), kanamycin (K) and ofloxacin (Ofx), and to address the in vitro extracellular and intracellular activity against Mycobacterium tuberculosis infection. Methods Synthesis reaction kinetics and complex properties were assessed. Kf was calculated from the transition state quasi-equilibrium approximation and Arrhenius plot. The complexes were characterized for qualitative solubility, stoichiometry, powder size and morphology, element analysis, and thermal behaviour. Structural analyses were performed by Fourier transform infrared spectroscopy and nuclear magnetic resonance. Activity was evaluated against H37Ra M. tuberculosis strain and in infected THP-1 cells, and compared with that of the parent drugs. Key findings The complexes showed log Kf of 6 for CPd and OfxPd, and 10 for KPd indicating good stability. Stoichiometry of 1 : 1, 2 : 3 and 1 : 3 resulted for OfxPd, KPd, and CPd. OfxPd structure matched that in literature, while K and C had more complex structures with possible multiple coexisting species. The complexes had extracellular activity comparable with drugs and an improved efficacy against intracellular infection of M. tuberculosis. Conclusions The novel anti-tuberculosis (TB) complexes had promising properties, and extracellular and intracellular activity, which makes them potential tools for intracellular targeting of pulmonary TB.

PAMELA has been orbiting the Earth for more than six years, gathering data on solar, galactic and trapped cosmic rays during the time of the last solar minimum. The apparatus comprises a time-of-flight system, a silicon-microstrip magnetic spectrometer, a silicon-tungsten electromagnetic calorimeter, an anticoincidence system, a shower tail catcher scintillator and a neutron detector. The combination of these devices allows charged particle and antiparticle identification over a wide energy range and with an unprecedented precision. The quasi-polar orbit of the instrument, with an inclination of 70 degrees, makes it possible to measure low energy particles starting from about 100 MeV/n. In this work we present the time and rigidity dependence of the galactic proton and helium fluxes over the first 4 years of operation during the A < 0 solar minimum of solar cycle 23.

The pulmonary route is one of the main strategies investigated to improve tuberculosis therapy. The aim of this study was to develop a simple and scalable method to produce capreomycin inhalable powders to use as supergeneric. In vitro antimycobacterial activity and in vivo acute toxicity were assessed using agar proportion susceptibility test on Mycobacterium tuberculosis and chicken chorioallantoic membrane assay, respectively. Capreomycin and three different hydrophobic counterions, namely oleate, linoleate, and linolenate, were combined in solution to obtain hydrophobic ion-pairs that were successively spray-dried. Ion-pairing efficiency was influenced by the spray-dryer employed to produce the powder. In the case of capreomycin oleate, both instruments, mini and nano spray-dryer, were suitable to maintain a high ion-paired content, while for capreomycin linoleate and linolenate, mini spray-dryer was the most appropriate instrument. The three formulations showed morphology and particle sizes potentially suitable for inhalation. Capreornycin oleate and linoleate showed the same efficacy of capreomycin sulfate against M. tuberculosis, while capreomycin linolenate showed a reduced efficacy, even though strain growth was inhibited at 10(-4) mycobacterial inoculum. In vivo acute toxicity studies evidenced the lowest toxic potential for capreomycin oleate when compared to the single components or the other two salts. Overall, capreomycin oleate seems to possess the most promising characteristics to be used as supergenerics in pulmonary tuberculosis treatment. (C) 2012 Elsevier B.V. All rights reserved.

Purpose: The aim of the work was to assess the long-term stability and the safety of lipid nanoparticles intended for brain drug delivery.Methods: Lipid nanoparticles, prepared by high pressure homogenization, were stored at room temperature and 4 degrees C and monitored for their mean hydrodynamic diameter and Gaussian distribution width over time. Cetylpalmitate and polysorbate (R) 80 chemical integrity were investigated by nuclear magnetic resonance on diagnostic signals. Nanoparticle toxicity was assessed in chicken embryos by chorioallantoic membrane assay and in rodents,by brain histological evaluation.Results: Data showed nanoparticle stability at 4 degrees C over a period of time of 4 years with only a limited particle size increase while at room temperature destabilization was observed after 9 months. Nuclear magnetic resonance investigation confirmed the absence (