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We present an extensive investigation using density functional theory (DFT) calculations on various model graphene oxide (GO) nanostructures interacting with chlorine monoxide ClO, aiming to understand the role of this highly oxidizing species in C-C bond breakage and the formation of significant holes on GO sheets. During its function, the myeloperoxidase (MPO) enzyme abundantly generates chlorine-oxygen-containing species and their presence has been identified as the cause of degradation in carbon nanotubes of diverse sizes, morphologies, and chemical compositions, both in in vivo and in vitro samples. Notably, Kurapati et al. (Small, 2015, 11, 3985-3994) demonstrated efficient degradation of single GO monolayers through MPO catalysis, though the exact degradation mechanism remains unclear. In our study, we discover that breaking C-C bonds in a single graphene oxide sheet is achievable through a simple mechanism involving the dissociation of two ClO molecules that are chemically attached as nearest neighbor species but bonded to opposite sides of the GO layer (up/down configuration). Two new carbonyl oxygens appear on the surface and the Cl atoms can be transferred to the carbon layer or as physisorbed species near the GO surface. Relatively small energy barriers are associated with these molecular events. Continuing this process on neighboring sites leads to the presence of larger holes on the GO surface, accompanied by an increase in carbonyl species on the carbon network, consistent with X-ray photoelectron spectroscopy measurements. Indeed, the distribution of oxygen functionalities is found to be crucial in defining the damage pattern induced in the carbon layer. We emphasize the important role played by the local charge distribution in the stability or instability of chemical bonds, as well as in the energy barriers and reaction pathways. Finally, we explore the possibility of achieving chlorination of GO following MPO exposure. The here-reported predictions could be the root cause of the experimentally observed low stability of individual GO sheets during the MPO catalytic cycle.
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We report a combined experimental and theoretical study dedicated to analyze the N 1s core-level binding energies (CLBE) in N-doped carbon nanotubes (N-CNTs). X-ray photoelectron spectroscopy (XPS) data are obtained from N-CNT samples synthesized using the chemical vapor deposition technique. Extensive density functional theory (DFT) calculations are performed on various model single- and double-walled N-CNTs where N 1s CLBEs are determined using Koopman's theorem. However, we also present additional calculations within the (Z + 1) approximation to analyze the role of final-state effects. From XPS data up to 2 at% of N content was found in our samples and the high resolution analysis of the N 1s line shows, according to previous experimental results, that N species exist in CNTs as graphitic, pyrrolic, pyridinic, and molecular configurations. However, peak decomposition is characterized by five broad Gaussian curves that overlap considerably among them, having different widths and heights, implying a more complex distribution of N atoms within the structures. DFT calculations performed on model N-CNTs reveal a strong dependence of N 1s CLBE values and their shifts on the local atomic environment. Different types of graphitic N cover an energy range of 3 eV, while various configurations for pyridinic, pyrrolic, and molecular species reveal a dispersion in their energy values of 5.7, 2.7, and 5.2 eV, respectively. The previous distributions of theoretical CLBEs also strongly overlap, implying that some peaks in the XPS spectra must be understood as composite signals where the signals of different N defects coexist. We find, in agreement with the experimental data, that freestanding molecular nitrogen and (weakly interacting) encapsulated N2 within the hollow core of model CNTs have very similar CLBEs. Furthermore, we predict that chemisorbed N2 on defective regions of the nanotube walls has N 1s binding energy values that are considerably larger when compared to encapsulated N2, thus making possible their identification. In contrast to previous reports, we find a nontrivial dependence between CLBEs and the local electronic occupation at N sites. The assignment of spectral details in the XPS data to well-defined N-defects on CNTs is not straightforward and needs to be more deeply analyzed.
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Mesenchymal stem cell (MSC)-based therapy is being increasingly considered a powerful opportunity for several disorders based on MSC immunoregulatory properties. Nonetheless, MSC are versatile and plastic cells that require an efficient control of their features and functions for their optimal use in clinic. Recently, we have shown that PPARß/δ is pivotal for MSC immunoregulatory and therapeutic functions. However, the role of PPARß/δ on MSC metabolic activity and the relevance of PPARß/δ metabolic control on MSC immunosuppressive properties have never been addressed. Here, we demonstrate that PPARß/δ deficiency forces MSC metabolic adaptation increasing their glycolytic activity required for their immunoregulatory functions on Th1 and Th17 cells. Additionally, we show that the inhibition of the mitochondrial production of ATP in MSC expressing PPARß/δ, promotes their metabolic switch towards aerobic glycolysis to stably enhance their immunosuppressive capacities significantly. Altogether, these data demonstrate that PPARß/δ governs the immunoregulatory potential of MSC by dictating their metabolic reprogramming and pave the way for enhancing MSC immunoregulatory properties and counteracting their versatility.
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Células-Tronco Mesenquimais/metabolismo , PPAR beta/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Animais , Células da Medula Óssea/citologia , Linfócitos T CD4-Positivos/citologia , Proliferação de Células , Inativação Gênica , Glicólise , Terapia de Imunossupressão , Camundongos , Oligomicinas/química , Células Th1/citologia , Células Th17/citologiaRESUMO
We present a combined experimental and theoretical study dedicated to analyze the variations in the surface chemistry of hydroxylated multiwalled carbon nanotubes (MWCNTs), so called nanotubols, when exposed to H2O2 at high temperatures. The formation, surface density, and distribution of oxygen-containing functional groups are studied by infrared (IR) and X-ray photoelectron spectroscopy (XPS), as well as density functional theory (DFT) calculations performed on model functionalized carbon nanotubes (CNTs). After H2O2 exposure, the initial composition of -OH, -C[double bond, length as m-dash]O, and -COOH substituents notably changes, with carbonyl -C[double bond, length as m-dash]O groups being the ones that show the most notable increase on the carbon surface. Our highly oxidized MWCNTs are partially soluble and form complex two-dimensional patterns at the air-water interface, as evidenced by Brewster angle microscopy. In a second step, these films can be transferred to solid substrates to form porous multilayered carbon nanostructures with complex morphologies. In particular, and for the first time, we report the synthesis of "stadium-like" configurations made of MWCNT units whose formation and stability are a direct consequence of the self-assembly process occurring at the air/water interface. DFT calculations suggest the formation of molecular islands of oxygen-containing functional groups on the CNT surface. In addition, nudged elastic band studies reveal that, for these adsorbed phases, the reaction between two neighboring OH groups to produce atomic oxygen and a physisorbed water molecule is characterized by energy barriers of â¼0.2 eV. These small values could be at the origin of the sizable increase in chemisorbed single-oxygen species determined by XPS data after H2O2 treatment at 60 °C. The simulation of the C 1s binding energies (BE) allows us to more clearly identify the different oxygen-containing functionalities as well as to reveal how the local atomic environment affects their characteristic BEs. Even if we were unable to polyhydroxylate our carbon nanotubes, we believe that H2O2-treated MWCNTs are interesting materials for more complex post-functionalization procedures that might lead to the fabrication of novel carbon nanostructures.
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We present a combined experimental and theoretical study dedicated to analyzing the structural stability and chemical reactivity of single walled carbon nanotubes (SWCNTs) in the presence of air and nitrogen atmospheres in the temperature interval of 300-1000 K. The temperature dependence of the radial breathing mode (RBM) region of the Raman spectra is irreversible in the presence of air, but it is reversible up to 1000 K in a nitrogen atmosphere. Our density functional theory (DFT) calculations reveal that irreversibility is due to partial degradation of SWCNTs produced by dissociative chemical adsorption of molecular oxygen on intrinsic defects of the nanotube surface. Oxygen partially opens the nanotubes forming semi-tubes with a non-uniform diameter distribution observed by Raman scattering. In contrast, heating CNTs in a nitrogen atmosphere seems to lead to the formation of nitrogen-doped SWCNTs. Our DFT calculations indicate that in general the most common types of nitrogen doping (e.g., pyridinic, pyrrolic, and substitutional) modify the location of the RBM frequency, leading also to frequency shifts and intensity changes of the surrounding modes. However, by performing a systematic comparison between calculated and measured spectra we have been able to infer the possible adsorbed configurations adopted by N species on the nanotube surface. Interestingly, by allowing previously nitrogen-exposed SWCNTs to interact with air at different temperatures (up to 1000 K) we note that the RBM region remains nearly unperturbed, defining thus our nitrogen-pretreated SWCNTs as more appropriate carbon nanostructures for high temperature applications in realistic environments. We believe that we have implemented a post-growth heat-treatment process that improves the stability of carbon nanotubes preserving their diameter and inducing a defect-healing process of the carbon wall.
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We present a combined experimental and theoretical study to analyze the structure, electronic properties, and aggregation behavior of hydroxylated multiwalled carbon nanotubes (OH-MWCNT). Our MWCNTs have average diameters of ~2 nm, lengths of approximately 100-300 nm, and a hydroxyl surface coverage θ~0.1. When deposited on the air/water interface the OH-MWCNTs are partially soluble and the floating units interact and link with each other forming extended foam-like carbon networks. Surface pressure-area isotherms of the nanotube films are performed using the Langmuir balance method at different equilibration times. The films are transferred into a mica substrate and atomic force microscopy images show that the foam like structure is preserved and reveals fine details of their microstructure. Density functional theory calculations performed on model hydroxylated carbon nanotubes show that low energy atomic configurations are found when the OH groups form molecular islands on the nanotube's surface. This patchy behavior for the OH species is expected to produce nanotubes having reduced wettabilities, in line with experimental observations. OH doping yields nanotubes having small HOMO-LUMO energy gaps and generates a nanotube â OH direction for the charge transfer leading to the existence of more hole carriers in the structures. Our synthesized OH-MWCNTs might have promising applications.
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Nanotubos de Carbono/química , Elétrons , Hidroxilação , Estrutura Molecular , Teoria QuânticaRESUMO
We present extensive pseudopotential density functional theory (DFT) calculations in order to analyze the structural properties and chemical reactivity of nitrogen molecules confined in spheroidal (C(82)) and tubelike (C(110)) carbon fullerene structures. For a small number of encapsulated nitrogens, the N(2) species exist in a nonbonded state within the cavities and form well defined molecular conformations such as linear chains, zigzag arrays, as well as both spheroidal and tubular configurations. However, with increasing the number of stored molecules, the interaction among the confined nitrogens as well as between the N(2) species and the fullerene wall is not always mainly repulsive. Actually, at high densities of the encapsulated gas, we found both adsorption of N(2) to the inner carbon surface together with the formation of (N(2))(m) molecular clusters. Total energy DFT calculations reveal that the shape of the interaction potential of a test molecule moving within the carbon cavities strongly varies with the number and proximity of the coadsorbed N(2) from being purely repulsive to having short-range attractive contributions close to the inner wall. In particular, the latter are always found when a group of closely spaced nitrogens is located near the carbon cage (a fact that will naturally occur at high densities of the encapsulated gas), inducing the formation of covalent bonds between the N(2) and the fullerene network. Interestingly, in some cases, the previous nitrogen adsorption to the inner surface is reversible by reducing the gas pressure. The calculated average density of states of our considered carbon compounds reveals the appearance of well defined features that clearly reflect the occurring structural changes and modifications in the adsorption properties in the systems. Our results clearly underline the crucial role played by confinement effects on the reactivity of our endohedral compounds, define this kind of materials as nonideal nanocontainers for high density nitrogen storage applications, and must be taken into account when analyzing the diffusion properties of the encapsulated species.
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Carbono/química , Fulerenos/química , Nitrogênio/química , Adsorção , Simulação por Computador , Gases/química , Modelos Químicos , Estrutura Molecular , Pressão , Propriedades de SuperfícieRESUMO
OBJECTIVES: To assess the effectiveness and tolerability of zoledronic acid in prostate cancer patients with bone metastases at the hormone-sensitive (HS) and hormone-independent (HI) stages. MATERIALS AND METHODS: A nationwide, observational, prospective, open and multi-centre trial was devised, with a total of 218 male patients diagnosed with prostate cancer at the HS stage (36%) or HI stage (64%) who were administered zoledronic acid (4 mg/IV/month for 6 months) in addition to their specific oncological treatment. Effectiveness was assessed by the following means: 1) Assessment of the improvement in pain and mobility; 2) Incidence and time to onset of skeletal-related events (SREs) and 3) Analysis of bone markers. Tolerability was assessed by means of registering the number and type of adverse effects. A satisfaction survey was carried out amongst the patients after the end of the trial. RESULTS: Out of the 218 patients, 170 (78%) were evaluable for effectiveness. A decrease in pain ratings at rest and during movement was observed in all patients, whether in the HS or HI groups (p < 0.0001). Improved mobility was observed likewise (p = 0.005), as was quality of life. The global incidence of skeletal events was 11.2%, with a time to onset of SREs of 10.7 months. There were no significant differences observed between HS vs. HI patients. Osteolysis markers (N-telopeptide) decreased significantly with the treatment across both the HS and HI groups. For safety reasons. 212 patients were evaluable (97.2%). The incidence of adverse drug reactions was 16% (34/212) and was found to be significantly higher in HS patients (22.4%) compared with HI patients (11.9%). Overall, the tolerability of zoledronic acid was good, with no significant morbidity in either group (HS and HI). 66% of the patients reported feeling satisfied or very satisfied. CONCLUSIONS: Zoledronic acid proved effective in the relief of pain, improving mobility and quality of life as well as reducing or delaying the occurrence of skeletal-related events in prostate cancer patients presenting metastatic bone disease, regardless of the phase, whether HS or HI, they found themselves in. Tolerability and patient satisfaction were rates as good.
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Conservadores da Densidade Óssea/uso terapêutico , Neoplasias Ósseas/complicações , Neoplasias Ósseas/secundário , Difosfonatos/uso terapêutico , Imidazóis/uso terapêutico , Dor/prevenção & controle , Neoplasias da Próstata/patologia , Idoso , Humanos , Masculino , Dor/etiologia , Estudos Prospectivos , Ácido ZoledrônicoRESUMO
The excitation spectra and the structural properties of highly hydroxylated C(60)(OH)(x) fullerenes (so-called fullerenols) are analyzed by comparing optical absorption experiments on dilute fullerenol-water solutions with semiempirical and density functional theory electronic structure calculations. The optical spectrum of fullerenol molecules with 24-28 OH attached to the carbon surface is characterized by the existence of broad bands with reduced intensities near the ultraviolet region (below approximately 500 nm) together with a complete absence of optical transitions in the visible part of the spectra, contrasting with the intense absorption observed in C(60) solutions. Our theoretical calculations of the absorption spectra, performed within the framework of the semiempirical Zerner intermediate neglect of diatomic differential overlap method [Reviews in Computational Chemistry II, edited by K. B. Lipkowitz and D. B. Boyd (VCH, Weinheim, 1991), Chap. 8, pp. 313-316] for various gas-phase-like C(60)(OH)(26) isomers, reveal that the excitation spectra of fullerenol molecules strongly depend on the degree of surface functionalization, the precise distribution of the OH groups on the carbon structure, and the presence of impurities in the samples. Interestingly, we have surprisingly found that low energy atomic configurations are obtained when the OH groups segregate on the C(60) surface forming molecular domains of different sizes. This patchy behavior for the hydroxyl molecules on the carbon surface leads in general to the formation of fullerene compounds with closed electronic shells, large highest occupied molecular orbital-lowest unoccupied molecular orbital energy gaps, and existence of an excitation spectrum that accounts for the main qualitative features observed in the experimental data.
RESUMO
The local and average orbital moments
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Antropologia , Cidades , Meio Ambiente , Expedições , Geografia , Pesquisadores , Ciência , Antropologia/educação , Antropologia/história , Cidades/economia , Cidades/etnologia , Cidades/história , Cidades/legislação & jurisprudência , Planejamento de Cidades/economia , Planejamento de Cidades/educação , Planejamento de Cidades/história , Expedições/economia , Expedições/história , Expedições/psicologia , Geografia/educação , Geografia/história , História do Século XVIII , História do Século XIX , História Natural/educação , História Natural/história , Disciplinas das Ciências Naturais/educação , Disciplinas das Ciências Naturais/história , Pesquisadores/educação , Pesquisadores/história , Pesquisadores/psicologia , Ciência/educação , Ciência/história , Viagem/economia , Viagem/história , Viagem/psicologia , Saúde da População Urbana/história , População Urbana/história , Venezuela/etnologiaRESUMO
Histidine residues have been shown to be critical for alpha-BgTx binding to the acetylcholine receptor (Lacorazza et al., 1992; Bouzat et al., 1993; Lacorazza et al., 1995). Receptor subunits from Discopyge tschudii were modified with diethylpyrocarbonate (DEP). DEP treatment produces a concentration-dependent decrease of [125I] alpha-BgTx binding to the alpha-subunit. The neurotoxin binding capacity was fully restored by adding the nucleophile hydroxylamine. By proteolytic mapping of the alpha-subunit with V8-protease, we determined that the binding capacity to the fragment alpha V8-19 decreased 80% by DEP treatment. In addition, the [125I] alpha-BgTx binding to the same fragment decreased by 70% when the subunits were reduced and affinity-alkylated. We report the N-terminal sequence of both subunits and V8-fragments (alpha V8-10, alpha V8-13, and alpha V8-18), which constitute a first contribution to the knowledge of the primary structure of the Discopyge tschudii receptor. We propose that the fragment alpha V8-19 contains one or more of the histidine residues involved in the alpha-BgTx binding and probably includes the Cys alpha 192-193 disulfide bond. Only two histidine residues are present in the extracellular sequence of Torpedo californica for such fragments: His alpha 186 and alpha 204.
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Bungarotoxinas/química , Histidina/análise , Fragmentos de Peptídeos/química , Receptores Colinérgicos/química , Sequência de Aminoácidos , Animais , Peixe Elétrico , Dados de Sequência Molecular , Homologia de Sequência de AminoácidosRESUMO
Microtubule protein preparations purified from rat brain were used to study the effect of polycations and polyanions on the release of the COOH-terminal tyrosine of the alpha-chain of tubulin catalyzed by tubulin carboxypeptidase. (1) Most of the polycations and polyanions tested, independently of the ionogenic group, inhibited the reaction in a concentration-dependent fashion. Under steady-state conditions, detyrosination of the microtubule pool was inhibited to the same degree as occurred with the non-assembled tubulin pool, except in the case of chondroitin sulphate. This compound inhibited detyrosination of the non-assembled tubulin pool, but not that of microtubules. (2) Heparin, the most potent inhibitor tested, produced the dissociation of the carboxypeptidase from microtubules. Many, but not all, of the other microtubule-associated polypeptides were also dissociated by heparin. (3) Polylysine counteracted the inhibitory and dissociating effects of heparin. (4) Heparin protected tubulin carboxypeptidase against inactivation. Our results and previous reports describing, in nervous tissue, the presence of proteoglycans, RNA and basic proteins that inhibit detyrosination, suggest that tubulin carboxypeptidase might be physiologically modulated by electrically charged macromolecules.