Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 54
Filtrar
1.
Proc Natl Acad Sci U S A ; 121(2): e2312880120, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38175867

RESUMO

We unveil the multifractal behavior of Ising spin glasses in their low-temperature phase. Using the Janus II custom-built supercomputer, the spin-glass correlation function is studied locally. Dramatic fluctuations are found when pairs of sites at the same distance are compared. The scaling of these fluctuations, as the spin-glass coherence length grows with time, is characterized through the computation of the singularity spectrum and its corresponding Legendre transform. A comparatively small number of site pairs controls the average correlation that governs the response to a magnetic field. We explain how this scenario of dramatic fluctuations (at length scales smaller than the coherence length) can be reconciled with the smooth, self-averaging behavior that has long been considered to describe spin-glass dynamics.

2.
PLoS Comput Biol ; 18(11): e1010713, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36395332

RESUMO

The relationship between interactions, flexibility and disorder in proteins has been explored from many angles over the years: folding upon binding, flexibility of the core relative to the periphery, entropy changes, etc. In this work, we provide statistical evidence for the involvement of highly mobile and disordered regions in complex assembly. We ordered the entire set of X-ray crystallographic structures in the Protein Data Bank into hierarchies of progressive interactions involving identical or very similar protein chains, yielding 40205 hierarchies of protein complexes with increasing numbers of partners. We then examine them as proxies for the assembly pathways. Using this database, we show that upon oligomerisation, the new interfaces tend to be observed at residues that were characterised as softly disordered (flexible, amorphous or missing residues) in the complexes preceding them in the hierarchy. We also rule out the possibility that this correlation is just a surface effect by restricting the analysis to residues on the surface of the complexes. Interestingly, we find that the location of soft disordered residues in the sequence changes as the number of partners increases. Our results show that there is a general mechanism for protein assembly that involves soft disorder and modulates the way protein complexes are assembled. This work highlights the difficulty of predicting the structure of large protein complexes from sequence and emphasises the importance of linking predictors of soft disorder to the next generation of predictors of complex structure. Finally, we investigate the relationship between the Alphafold2's confidence metric pLDDT for structure prediction in unbound versus bound structures, and soft disorder. We show a strong correlation between Alphafold2 low confidence residues and the union of all regions of soft disorder observed in the hierarchy. This paves the way for using the pLDDT metric as a proxy for predicting interfaces and assembly paths.


Assuntos
Processos Mentais , Bases de Dados de Proteínas , Cristalografia por Raios X , Entropia
3.
J Pediatr ; 241: 126-132.e3, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34571020

RESUMO

OBJECTIVES: To determine the time to reverse transcription-polymerase chain reaction (RT-PCR) negativity after the first positive RT-PCR test, factors associated with longer time to RT-PCR negativity, proportion of children seroconverting after proven severe acute respiratory syndrome coronavirus 2 infection, and factors associated with the lack of seroconversion. STUDY DESIGN: The Epidemiological Study of Coronavirus in Children of the Spanish Society of Pediatrics is a multicenter study conducted in Spanish children to assess the characteristics of coronavirus disease 2019. In a subset of patients, 3 serial RT-PCR tests on nasopharyngeal swab specimens were performed after the first RT-PCR test, and immunoglobulin G serology for severe acute respiratory syndrome coronavirus 2 antibodies was performed in the acute and follow-up (<14 and ≥14 days after diagnosis) phase. RESULTS: In total, 324 patients were included in the study. The median time to RT-PCR negativity was 17 days (IQR, 8-29 days), and 35% of patients remained positive more than 4 weeks after the first RT-PCR test. The probability of RT-PCR negativity did not differ across groups defined by sex, disease severity, immunosuppressive drugs, or clinical phenotype. Globally, 24% of children failed to seroconvert after infection. Seroconversion was associated with hospitalization, persistence of RT-PCR positivity, and days of fever. CONCLUSIONS: Time to RT-PCR negativity was long, regardless of the severity of symptoms or other patient features. This finding should be considered when interpreting RT-PCR results in a child with symptoms, especially those with mild symptoms. Seroprevalence and postimmunization studies should consider that 11 in 4 infected children fail to seroconvert.


Assuntos
Teste de Ácido Nucleico para COVID-19 , COVID-19/diagnóstico , COVID-19/imunologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Soroconversão , Adolescente , COVID-19/epidemiologia , Teste Sorológico para COVID-19 , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Estimativa de Kaplan-Meier , Masculino , Sistema de Registros , Estudos Soroepidemiológicos , Espanha/epidemiologia , Fatores de Tempo
4.
PLoS Comput Biol ; 17(1): e1008546, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33417598

RESUMO

The importance of unstructured biology has quickly grown during the last decades accompanying the explosion of the number of experimentally resolved protein structures. The idea that structural disorder might be a novel mechanism of protein interaction is widespread in the literature, although the number of statistically significant structural studies supporting this idea is surprisingly low. At variance with previous works, our conclusions rely exclusively on a large-scale analysis of all the 134337 X-ray crystallographic structures of the Protein Data Bank averaged over clusters of almost identical protein sequences. In this work, we explore the complexity of the organisation of all the interaction interfaces observed when a protein lies in alternative complexes, showing that interfaces progressively add up in a hierarchical way, which is reflected in a logarithmic law for the size of the union of the interface regions on the number of distinct interfaces. We further investigate the connection of this complexity with different measures of structural disorder: the standard missing residues and a new definition, called "soft disorder", that covers all the flexible and structurally amorphous residues of a protein. We show evidences that both the interaction interfaces and the soft disordered regions tend to involve roughly the same amino-acids of the protein, and preliminary results suggesting that soft disorder spots those surface regions where new interfaces are progressively accommodated by complex formation. In fact, our results suggest that structurally disordered regions not only carry crucial information about the location of alternative interfaces within complexes, but also about the order of the assembly. We verify these hypotheses in several examples, such as the DNA binding domains of P53 and P73, the C3 exoenzyme, and two known biological orders of assembly. We finally compare our measures of structural disorder with several disorder bioinformatics predictors, showing that these latter are optimised to predict the residues that are missing in all the alternative structures of a protein and they are not able to catch the progressive evolution of the disordered regions upon complex formation. Yet, the predicted residues, when not missing, tend to be characterised as soft disordered regions.


Assuntos
Biologia Computacional/métodos , Proteínas Intrinsicamente Desordenadas/química , Conformação Proteica , Sequência de Aminoácidos , Análise por Conglomerados , Cristalografia por Raios X , Bases de Dados de Proteínas , Proteínas Intrinsicamente Desordenadas/metabolismo , Ligação Proteica
5.
Proc Natl Acad Sci U S A ; 116(31): 15350-15355, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31311870

RESUMO

The Mpemba effect occurs when a hot system cools faster than an initially colder one, when both are refrigerated in the same thermal reservoir. Using the custom-built supercomputer Janus II, we study the Mpemba effect in spin glasses and show that it is a nonequilibrium process, governed by the coherence length ξ of the system. The effect occurs when the bath temperature lies in the glassy phase, but it is not necessary for the thermal protocol to cross the critical temperature. In fact, the Mpemba effect follows from a strong relationship between the internal energy and ξ that turns out to be a sure-tell sign of being in the glassy phase. Thus, the Mpemba effect presents itself as an intriguing avenue for the experimental study of the coherence length in supercooled liquids and other glass formers.

6.
BMC Pregnancy Childbirth ; 21(1): 326, 2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33902483

RESUMO

BACKGROUND: Knowledge about SARS-CoV-2 infection in pregnancy and newborns is scarce. The objective of this study is to analyse clinical and epidemiological characteristics of a cohort of women infected with SARS-CoV-2 during pregnancy and their newborns exposed to SARS-CoV-2 during gestation. METHODS: Multicentric observational study of Spanish hospitals from the GESNEO-COVD cohort, participants in RECLIP (Spanish Network of Paediatric Clinical Assays). Women with confirmed SARS-CoV-2 infection by PCR and/or serology during pregnancy, diagnosed and delivering during the period 15/03/2020-31/07/2020 were included. Epidemiological, clinical, and analytical data was collected. RESULTS: A total of 105 pregnant women with a median of 34.1 years old (IQR: 28.8-37.1) and 107 newborns were included. Globally, almost 65% of pregnant women had some COVID-19 symptoms and more than 43% were treated for SARS-COV-2. Overall, 30.8% of pregnant women had pneumonia and 5 (4.8%) women were admitted to the intensive care unit needing invasive mechanical ventilation. There was a rate of 36.2% of caesarean sections, which was associated with pneumonia during pregnancy (OR: 4.203, CI 95%: 1.473-11.995) and lower gestational age at delivery (OR: 0.724, CI 95%: 0.578-0.906). The prevalence of preterm birth was 20.6% and prematurity was associated with pneumonia during gestation (OR: 6.970, CI95%: 2.340-22.750) and having a positive SARS-CoV-2 PCR at delivery (OR: 6.520, CI95%: 1.840-31.790). All nasopharyngeal PCR in newborns were negative at birth and one positivized at 15 days of life. Two newborns died, one due to causes related to prematurity and another of unexpected sudden death during early skin-to-skin contact after delivery. CONCLUSIONS: Although vertical transmission has not been reported in this cohort, the prognosis of newborns could be worsened by SARS-CoV-2 infection during pregnancy as COVID-19 pneumonia increased the risk of caesarean section deliveries and preterm births.


Assuntos
COVID-19/epidemiologia , Portador Sadio/epidemiologia , Complicações Infecciosas na Gravidez/epidemiologia , Nascimento Prematuro/epidemiologia , Adulto , Antibacterianos/uso terapêutico , Antivirais/uso terapêutico , COVID-19/fisiopatologia , COVID-19/terapia , Teste de Ácido Nucleico para COVID-19 , Cesárea/estatística & dados numéricos , Estudos de Coortes , Comorbidade , Tosse/fisiopatologia , Diabetes Gestacional/epidemiologia , Dispneia/fisiopatologia , Feminino , Febre/fisiopatologia , Idade Gestacional , Humanos , Hipertensão/epidemiologia , Hipotireoidismo/epidemiologia , Fatores Imunológicos/uso terapêutico , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas , Unidades de Terapia Intensiva/estatística & dados numéricos , Pulmão/diagnóstico por imagem , Masculino , Obesidade Materna/epidemiologia , Pneumonia Viral/diagnóstico por imagem , Pneumonia Viral/fisiopatologia , Pneumonia Viral/terapia , Gravidez , Complicações na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/fisiopatologia , Complicações Infecciosas na Gravidez/terapia , Segundo Trimestre da Gravidez , Terceiro Trimestre da Gravidez , Radiografia Torácica , Respiração Artificial , Fatores de Risco , SARS-CoV-2 , Índice de Gravidade de Doença , Espanha/epidemiologia , Tratamento Farmacológico da COVID-19
7.
Chem Soc Rev ; 49(18): 6694-6732, 2020 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-32820300

RESUMO

Metal-organic frameworks (MOFs) are a class of porous crystalline materials showing great potential for applications such as catalysis, gas storage, molecular separations, energy storage and drug delivery. The properties that render them interesting stem from their structure (e.g. morphology, porosity or metal coordination and geometry). Thus, gaining a deeper understanding strongly relies on the availability and adequate use of advanced characterization tools, which can interrogate MOFs under realistic synthesis as well as catalysis (or sorption) conditions. Herein, we present an overview of the various characterization techniques specifically suitable for the study on the underlying chemistry of the formation mechanisms and adsorption properties of three archetypal MOFs, namely MIL-100, ZIF-8 and HKUST-1. A section on using MOFs as supports for metal atoms or complexes that can be used for catalysis on the robust Zr6 nodes of UiO-66 or NU-1000, and the characterization techniques used thereof, is presented as well. In addition, we discuss recent developments on the application of nano-spectroscopic characterization for MOF thin-films and explore the potential of MOFs as model systems in catalysis. The conclusions and outlook provide future research possibilities in the field of MOF characterization.

8.
Respir Res ; 21(Suppl 1): 102, 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32907566

RESUMO

BACKGROUND: Navafenterol (AZD8871) is a dual-pharmacology muscarinic antagonist ß2-agonist (MABA) molecule in development for the treatment of chronic obstructive pulmonary disease (COPD). The pharmacodynamics, safety and tolerability of single doses of navafenterol were investigated in patients with moderate to severe COPD. METHODS: This was a randomized, five-way complete cross-over study. Patients received single doses of navafenterol 400 µg, navafenterol 1800 µg and placebo (all double-blind) and indacaterol 150 µg and tiotropium 18 µg (both open-label active comparators). The primary pharmacodynamic endpoint was change from baseline in trough forced expiratory volume in 1 s (FEV1) on day 2. Safety and tolerability were monitored throughout. RESULTS: Thirty-eight patients were randomized and 28 (73.7%) completed the study. Navafenterol 400 µg and 1800 µg demonstrated statistically significant improvements vs placebo in change from baseline in trough FEV1 (least squares mean [95% confidence interval]: 0.111 [0.059, 0.163] L and 0.210 [0.156, 0.264] L, respectively, both P < .0001). The changes were significantly greater with navafenterol 1800 µg vs the active comparators (least squares mean treatment difference: 0.065-0.069 L, both P < .05). The frequency of treatment-emergent adverse events was similar for placebo and the active comparators (range 34.4-37.5%), slightly higher for navafenterol 400 µg (52.9%), and lowest for navafenterol 1800 µg (22.6%). CONCLUSIONS: Both doses of navafenterol demonstrated sustained bronchodilation over 24 h. Navafenterol was well tolerated and no safety concerns were raised. TRIAL REGISTRY: ClinicalTrials.gov ; No.: NCT02573155 ; URL: www.clinicaltrials.gov . Registered 9th October, 2015.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Broncoconstrição/efeitos dos fármacos , Broncodilatadores/administração & dosagem , Pulmão/efeitos dos fármacos , Antagonistas Muscarínicos/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Quinolinas/administração & dosagem , Triazóis/administração & dosagem , Administração por Inalação , Agonistas de Receptores Adrenérgicos beta 2/efeitos adversos , Agonistas de Receptores Adrenérgicos beta 2/farmacocinética , Idoso , Broncodilatadores/efeitos adversos , Broncodilatadores/farmacocinética , Estudos Cross-Over , Método Duplo-Cego , Inglaterra , Feminino , Volume Expiratório Forçado , Humanos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Antagonistas Muscarínicos/efeitos adversos , Antagonistas Muscarínicos/farmacocinética , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Quinolinas/efeitos adversos , Quinolinas/farmacocinética , Recuperação de Função Fisiológica , Resultado do Tratamento , Triazóis/efeitos adversos , Triazóis/farmacocinética , Capacidade Vital
9.
Respir Res ; 21(Suppl 1): 212, 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32907575

RESUMO

BACKGROUND: Navafenterol (AZD8871) is a novel, long-acting, dual-pharmacology (muscarinic receptor antagonist and ß2-adrenoceptor agonist) molecule in development for chronic obstructive pulmonary disease and asthma. METHODS: These two phase I, randomised, single-blind, multiple-ascending-dose studies evaluated inhaled navafenterol and placebo (3:1 ratio) in healthy, male, non-Japanese (study A; NCT02814656) and Japanese (study B; NCT03159442) volunteers. In each study, volunteers were dosed in three cohorts, allowing gradual dose escalation from 300 µg to 600 µg to 900 µg. The primary objective was to investigate the safety and tolerability of navafenterol at steady state. Pharmacokinetics were also assessed. RESULTS: Twenty-four volunteers completed each study (navafenterol, n = 6; placebo, n = 2 in each cohort). There were no deaths, serious adverse events (AEs) or treatment-emergent AEs (TEAEs) leading to discontinuation of navafenterol. The most frequent TEAEs were vessel puncture-site bruise (placebo, n = 2; navafenterol 900 µg; n = 3) in study A and diarrhoea (placebo, n = 1; navafenterol 300 µg, n = 2; navafenterol 900 µg, n = 3) in study B. No dose-response relationship was observed for TEAEs. There was a dose-dependent increase in mean heart rate on day 16 in both studies. The pharmacokinetics of navafenterol were similar between non-Japanese and Japanese volunteers. CONCLUSIONS: Multiple ascending doses of navafenterol were well-tolerated and the safety and pharmacokinetics of navafenterol were similar in non-Japanese and Japanese volunteers. The findings support navafenterol clinical development. TRIAL REGISTRATION: ClinicalTrials.gov ; Nos.: NCT02814656 and NCT03159442; URL: www.clinicaltrials.gov .


Assuntos
Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Broncodilatadores/administração & dosagem , Antagonistas Muscarínicos/administração & dosagem , Quinolinas/administração & dosagem , Triazóis/administração & dosagem , Administração por Inalação , Agonistas de Receptores Adrenérgicos beta 2/efeitos adversos , Agonistas de Receptores Adrenérgicos beta 2/farmacocinética , Adulto , Povo Asiático , Broncodilatadores/efeitos adversos , Broncodilatadores/farmacocinética , Voluntários Saudáveis , Humanos , Japão/etnologia , Londres , Masculino , Pessoa de Meia-Idade , Antagonistas Muscarínicos/efeitos adversos , Antagonistas Muscarínicos/farmacocinética , Quinolinas/efeitos adversos , Quinolinas/farmacocinética , Método Simples-Cego , Triazóis/efeitos adversos , Triazóis/farmacocinética
10.
Respir Res ; 21(Suppl 1): 211, 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32907576

RESUMO

BACKGROUND: Navafenterol (AZD8871) is an inhaled long-acting dual-pharmacology muscarinic antagonist/ß2-adrenoceptor agonist (MABA) in development for the treatment of obstructive airways diseases. The safety, tolerability, pharmacodynamics, and pharmacokinetics of navafenterol were investigated in patients with mild asthma. METHODS: This was a randomised, single-blind, placebo-controlled, single-ascending-dose study. Patients were randomly assigned to one of two cohorts which evaluated escalating doses of navafenterol (50-2100 µg) in an alternating manner over three treatment periods. The primary pharmacodynamic endpoint was the change from pre-dose baseline in trough forced expiratory volume in 1 s (FEV1) for each treatment period. RESULTS: Sixteen patients were randomised; 15 completed treatment. Data from all 16 patients were analysed. The maximum tolerated dose was not identified, and all doses of navafenterol were well tolerated. The most frequently reported treatment-emergent adverse events (TEAEs) were headache (n = 10, 62.5%) and nasopharyngitis (n = 7, 43.8%). No TEAEs were serious, fatal, or led to discontinuation, and no dose dependency was identified. Navafenterol demonstrated a dose-ordered bronchodilatory response with a rapid onset of action (within 5 min post-dose). Doses ≥200 µg resulted in improvements in trough FEV1 (mean change from baseline range 0.186-0.463 L) with sustained bronchodilation for 24-36 h. Plasma concentrations increased in a dose-proportional manner, peaking ~ 1 h post-dose, with a derived terminal elimination half-life of 15.96-23.10 h. CONCLUSIONS: In this study navafenterol was generally well tolerated with a rapid onset of action which was sustained over 36 h. TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT02573155.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Asma/tratamento farmacológico , Broncoconstrição/efeitos dos fármacos , Broncodilatadores/administração & dosagem , Pulmão/efeitos dos fármacos , Antagonistas Muscarínicos/administração & dosagem , Quinolinas/administração & dosagem , Triazóis/administração & dosagem , Administração por Inalação , Agonistas de Receptores Adrenérgicos beta 2/efeitos adversos , Agonistas de Receptores Adrenérgicos beta 2/farmacocinética , Adulto , Asma/diagnóstico , Asma/fisiopatologia , Broncodilatadores/efeitos adversos , Broncodilatadores/farmacocinética , Inglaterra , Feminino , Volume Expiratório Forçado , Humanos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Antagonistas Muscarínicos/efeitos adversos , Antagonistas Muscarínicos/farmacocinética , Quinolinas/efeitos adversos , Quinolinas/farmacocinética , Recuperação de Função Fisiológica , Índice de Gravidade de Doença , Método Simples-Cego , Resultado do Tratamento , Triazóis/efeitos adversos , Triazóis/farmacocinética
11.
Proc Natl Acad Sci U S A ; 114(8): 1838-1843, 2017 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-28174274

RESUMO

We have performed a very accurate computation of the nonequilibrium fluctuation-dissipation ratio for the 3D Edwards-Anderson Ising spin glass, by means of large-scale simulations on the special-purpose computers Janus and Janus II. This ratio (computed for finite times on very large, effectively infinite, systems) is compared with the equilibrium probability distribution of the spin overlap for finite sizes. Our main result is a quantitative statics-dynamics dictionary, which could allow the experimental exploration of important features of the spin-glass phase without requiring uncontrollable extrapolations to infinite times or system sizes.

12.
Proc Natl Acad Sci U S A ; 113(30): 8397-401, 2016 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-27402768

RESUMO

Low-temperature properties of crystalline solids can be understood using harmonic perturbations around a perfect lattice, as in Debye's theory. Low-temperature properties of amorphous solids, however, strongly depart from such descriptions, displaying enhanced transport, activated slow dynamics across energy barriers, excess vibrational modes with respect to Debye's theory (i.e., a boson peak), and complex irreversible responses to small mechanical deformations. These experimental observations indirectly suggest that the dynamics of amorphous solids becomes anomalous at low temperatures. Here, we present direct numerical evidence that vibrations change nature at a well-defined location deep inside the glass phase of a simple glass former. We provide a real-space description of this transition and of the rapidly growing time- and lengthscales that accompany it. Our results provide the seed for a universal understanding of low-temperature glass anomalies within the theoretical framework of the recently discovered Gardner phase transition.

13.
Chemistry ; 24(29): 7498-7506, 2018 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-29709084

RESUMO

Because of their high tunability and surface area, metal-organic frameworks (MOFs) show great promise as supports for metal nanoparticles. Depending on the synthesis route, MOFs may contain defects. Here, we show that highly crystalline MIL-100(Fe) and disordered Basolite® F300, with identical iron 1,3,5-benzenetricarboxylate composition, exhibit very divergent properties when used as a support for Pd nanoparticle deposition. While MIL-100(Fe) shows a regular MTN-zeotype crystal structure with two types of cages, Basolite® F300 lacks long-range order beyond 8 Šand has a single-pore system. The medium-range configurational linker-node disorder in Basolite® F300 results in a reduced number of Lewis acid sites, yielding more hydrophobic surface properties compared to hydrophilic MIL-100(Fe). The hydrophilic/hydrophobic nature of MIL-100(Fe) and Basolite® F300 impacts the amount of Pd and particle size distribution of Pd nanoparticles deposited during colloidal synthesis and dry impregnation methods, respectively. It is suggested that polar (apolar) solvents/precursors attractively interact with hydrophilic (hydrophobic) MOF surfaces, allowing tools at hand to increase the level of control over, for example, the nanoparticle size distribution.

14.
Soft Matter ; 14(25): 5222-5234, 2018 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-29892754

RESUMO

Motivated by the mean field prediction of a Gardner phase transition between a "normal glass" and a "marginally stable glass", we investigate the off-equilibrium dynamics of three-dimensional polydisperse hard spheres, used as a model for colloidal or granular glasses. Deep inside the glass phase, we find that a sharp crossover pressure PG separates two distinct dynamical regimes. For pressure P < PG, the glass behaves as a normal solid, displaying fast dynamics that quickly equilibrate within the glass free energy basin. For P > PG, instead, the dynamics become strongly anomalous, displaying very large equilibration timescales, aging, and a constantly increasing dynamical susceptibility. The crossover at PG is strongly reminiscent of the one observed in three-dimensional spin-glasses in an external field, suggesting that the two systems could be in the same universality class, consistent with theoretical expectations.

15.
Angew Chem Int Ed Engl ; 57(18): 5156-5160, 2018 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-29465815

RESUMO

Through IR microimaging the spatially and temporally resolved development of the CO2 concentration in a ZIF-8@6FDA-DAM mixed matrix membrane (MMM) was visualized during transient adsorption. By recording the evolution of the CO2 concentration, it is observed that the CO2 molecules propagate from the ZIF-8 filler, which acts as a transport "highway", towards the surrounding polymer. A high-CO2 -concentration layer is formed at the MOF/polymer interface, which becomes more pronounced at higher CO2 gas pressures. A microscopic explanation of the origins of this phenomenon is suggested by means of molecular modeling. By applying a computational methodology combining quantum and force-field based calculations, the formation of microvoids at the MOF/polymer interface is predicted. Grand canonical Monte Carlo simulations further demonstrate that CO2 tends to preferentially reside in these microvoids, which is expected to facilitate CO2 accumulation at the interface.

16.
J Chem Phys ; 147(8): 084704, 2017 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-28863547

RESUMO

We present a three-dimensional Ising model where lines of equal spins are frozen such that they form an ordered framework structure. The frame spins impose an external field on the rest of the spins (active spins). We demonstrate that this "porous Ising model" can be seen as a minimal model for condensation transitions of gas molecules in metal-organic frameworks. Using Monte Carlo simulation techniques, we compare the phase behavior of a porous Ising model with that of a particle-based model for the condensation of methane (CH4) in the isoreticular metal-organic framework IRMOF-16. For both models, we find a line of first-order phase transitions that end in a critical point. We show that the critical behavior in both cases belongs to the 3D Ising universality class, in contrast to other phase transitions in confinement such as capillary condensation.

17.
Adv Funct Mater ; 26(18): 3154-3163, 2016 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-29200991

RESUMO

Mixed-matrix membranes (MMMs) comprising NH2-MIL-53(Al) and Matrimid® or 6FDA-DAM have been investigated. The MOF loading has been varied between 5 and 20 wt%, while NH2-MIL-53(Al) with three different morphologies: nanoparticles, nanorods and microneedles have been dispersed in Matrimid®. The synthesized membranes have been tested in the separation of CO2 from CH4 in an equimolar mixture. At 3 bar and 298 K for 8 wt% MOF loading, incorporation of NH2-MIL-53(Al) nanoparticles leads to the largest improvement compared to nanorods and microneedles. The incorporation of the best performing filler, i.e. NH2-MIL-53(Al) nanoparticles, to the highly permeable 6FDA-DAM has a larger effect, and the CO2 permeability increased up to 85 % with slightly lower selectivities for 20 wt% MOF loading. Specifically, these membranes have a permeability of 660 Barrer with CO2/CH4 separation factor of 28, leading to a performance very close to the Robeson limit of 2008. Furthermore, a new non-destructive technique based on Raman spectroscopy mapping is introduced to assess the homogeneity of the filler dispersion in the polymer matrix. The MOF contribution can be calculated by modelling the spectra. The determined homogeneity of the MOF filler distribution in the polymer is confirmed by FIB-SEM analysis.

18.
Eur Respir J ; 48(4): 1030-1039, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27492833

RESUMO

The efficacy and safety of twice-daily aclidinium bromide/formoterol fumarate was compared with that of salmeterol/fluticasone propionate in patients with stable, moderate-to-severe chronic obstructive pulmonary disease (COPD).AFFIRM COPD (Aclidinium and Formoterol Findings in Respiratory Medicine COPD) was a 24-week, double-blind, double-dummy, active-controlled study. Patients were randomised (1:1) to aclidinium/formoterol 400/12 µg twice-daily via Genuair/Pressair or salmeterol/fluticasone 50/500 µg twice-daily via Accuhaler. The primary end-point was peak forced expiratory volume in 1 s (FEV1) at week 24. Other end-points included Transition Dyspnoea Index (TDI) focal score at week 24, TDI and St George's Respiratory Questionnaire (SGRQ) responders, COPD Assessment Test and SGRQ scores, assessment of COPD symptoms and exacerbations, use of reliever medication, and device preference. Adverse events were monitored throughout.In total, 933 patients were eligible (mean age 63.4 years, 65.1% male). Aclidinium/formoterol was superior to salmeterol/fluticasone in peak FEV1 and noninferior in TDI. Health status and reduction in exacerbation risk were similar in both groups. While both treatments were well tolerated, pneumonia occurred less frequently with aclidinium/formoterol than salmeterol/fluticasone.In stable COPD, aclidinium/formoterol significantly improved bronchodilation versus salmeterol/fluticasone, with equivalent benefits in symptom control and reduction in exacerbation risk. Both treatments were well tolerated and treatment-related adverse events were less common with aclidinium/formoterol.


Assuntos
Combinação Fluticasona-Salmeterol/administração & dosagem , Fumarato de Formoterol/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Tropanos/administração & dosagem , Adulto , Idoso , Broncodilatadores/farmacologia , Método Duplo-Cego , Feminino , Fluticasona/administração & dosagem , Volume Expiratório Forçado , Humanos , Masculino , Pessoa de Meia-Idade , Pneumologia , Xinafoato de Salmeterol/administração & dosagem , Fumar , Espirometria , Inquéritos e Questionários , Resultado do Tratamento
19.
Nat Mater ; 14(1): 48-55, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25362353

RESUMO

Composites incorporating two-dimensional nanostructures within polymeric matrices have potential as functional components for several technologies, including gas separation. Prospectively, employing metal-organic frameworks (MOFs) as versatile nanofillers would notably broaden the scope of functionalities. However, synthesizing MOFs in the form of freestanding nanosheets has proved challenging. We present a bottom-up synthesis strategy for dispersible copper 1,4-benzenedicarboxylate MOF lamellae of micrometre lateral dimensions and nanometre thickness. Incorporating MOF nanosheets into polymer matrices endows the resultant composites with outstanding CO2 separation performance from CO2/CH4 gas mixtures, together with an unusual and highly desired increase in the separation selectivity with pressure. As revealed by tomographic focused ion beam scanning electron microscopy, the unique separation behaviour stems from a superior occupation of the membrane cross-section by the MOF nanosheets as compared with isotropic crystals, which improves the efficiency of molecular discrimination and eliminates unselective permeation pathways. This approach opens the door to ultrathin MOF-polymer composites for various applications.

20.
Chemistry ; 22(41): 14467-70, 2016 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-27535016

RESUMO

Mixed-matrix membranes (MMMs) comprising Matrimid and a microporous azine-linked covalent organic frameworks (ACOF-1) were prepared and tested in the separation of CO2 from an equimolar CO2 /CH4 mixture. The COF-based MMMs show a more than doubling of the CO2 permeability upon 16 wt % ACOF-1 loading together with a slight increase in selectivity compared to the bare polymer. These results show the potential of COFs in the preparation of MMMs.

SELEÇÃO DE REFERÊNCIAS
Detalhe da pesquisa