Molecular dynamics in amorphous ergocalciferol

While developing new pharmaceutical products based on drug substances in their amorphous form, the molecular mobility of amorphous active ingredients have to be characterized in detail. The molecular mobility in the supercooled liquid and glassy states of ergocalciferol is studied using broadband dielectric spectroscopy over wide frequency and temperature ranges. Dielectric studies revealed a number of relaxation process of different molecular origi

Relaxation dynamics of amorphous dibucaine using dielectric studies

Using broadband dielectric spectroscopy the molecular mobility of dibucaine is investigated in the supercooled liquid and gassy states, over a wide temperature range for some test frequencies. Above the glass transition temperature T-g, the presence of structural alpha- relaxation peak was observed due to the cooperative motions of the molecule and upon cooling frozen kinetically to form the glass. The secondary relaxation process was perceivable below T-g due to localized motions. The peak loss frequency of alpha-relaxation process shows non-Arrhenius behavior and obeys Vogel-Fulcher-Tammann equation over the measured temperature range whereas the beta- process shows Arrhenius behavior

Coupling of Caged Molecule Dynamics to JG β-Relaxation: I

The paper (Sibik, J.; Elliott, S. R.; Zeitler, J. A. J. Phys. Chem. Lett. 2014, 5, 1968-1972) used terahertz time-domain spectroscopy (THz-TDS) to study the dynamics of the polyalcohols, glycerol, threitol, xylitol, and sorbitol, at temperatures from below to above the glass transition temperature Tg. On heating the glasses, they observed the dielectric losses, ε″(ν) at ν = 1 THz, increase monotonically with temperature and change dependence at two temperatures, first deep in the glassy state at TTHz = 0.65Tg and second at Tg. The effects at both temperatures are most prominent in sorbitol but become progressively weaker in the order of xylitol and threitol, and the sub-Tg change was not observed in glycerol. They suggested this feature originates from the high-frequency tail of the Johari-Goldstein (JG) β-relaxation, and the temperature region near 0.65Tg is the universal region for the secondary glass transition due to the JG β-relaxation. In this paper, we first use isothermal dielectric relaxation data at frequencies below 106 Hz to locate the "second glass transition" temperature Tβ at which the JG β-relaxation time βJG reaches 100 s. The value of Tβ is close to TTHz = 0.65Tg for sorbitol (0.63Tg) and xylitol (0.65Tg), but Tβ is 0.74Tg for threitol and 0.83Tg for glycerol. Notwithstanding, the larger values of Tβ of glycerol are consistent with the THz-TDS data. Next, we identify the dynamic process probed by THz-TDS as the caged molecule dynamics, showing up in susceptibility spectra as nearly constant loss (NCL). The caged molecule dynamics regime is terminated by the onset of the primitive relaxation of the coupling model, which is the precursor of the JG β-relaxation. From this relation, established is the connection of the magnitude and temperature dependence of the NCL and those of βJG. This connection explains the monotonic increase of NCL with temperature and change to a stronger dependence after crossing Tβ giving rise to the sub-Tg behavior of ε″(ν) observed in experiment. Beyond the polyalcohols, we present new dielectric relaxation measurements of flufenamic acid and recall dielectric, NMR, and calorimetric data of indomethacin. The data of these two pharmaceuticals enables us to determine the value of Tβ = 0.67Tg for flufenamic acid and Tβ = 0.58Tg or Tβ = 0.62Tg for indomethacin, which can be compared with experimental values of TTHz from THz-TDS measurements when they become available. We point out that the sub-Tg change of NCL at Tβ found by THz-TDS can be observed by other high frequency spectroscopy including neutron scattering, light scattering, Brillouin scattering, and inelastic X-ray scattering. An example from neutron scattering is cited. All the findings demonstrate the connection of all processes in the evolution of dynamics ending at the structural α-relaxation. © 2015 American Chemical Society

Revealing the rich dynamics of glass-forming systems by modification of composition and change of thermodynamic conditions

Secondary relaxations have been classified into two types, depending on whether they are related to the structural alpha-relaxation in properties or not. Those secondary relaxations that are related to the a-relaxation may have fundamental importance, and are called the Johari–Goldstein (JG) ß-relaxations. Two polar molecular glass-formers, one flexible and another rigid, dissolved in apolar host with higher glass transition temperature are studied by broadband dielectric spectroscopy at ambient and elevated pressure. The neat flexible glassformer diethylphthalate (DEP) has a resolved secondary relaxation which, unlike the a-relaxation, is insensitive to pressure and hence is not the JG ß-relaxation. In the solution, the JG ß-relaxation of DEP shows up in experiment and its relaxation time tß is pressure and temperature dependent like ta. The result supports the universal presence of the JG ß-relaxation in all glass-formers, and the separation between ta and tß is determined by intermolecular interaction. The rigid glass-former is cyano-benzene (CNBz) and its secondary relaxation involves the entire molecule is necessarily the JG ß-relaxation. The dielectric relaxation spectra obtained at a number of combinations of pressure and temperature at constant ta show not only unchanged is the frequency dispersion of the a-relaxation but also tß. The remarkable results indicate that the JG ß-relaxation bears a strong connection to the alpha-relaxation, and the two relaxations are inseparablewhen considering the dynamics of glass-forming systems. Experimentally, tau_alpha has been found to be a function of the product variables, T/rho^gamma, where rho is the density and gamma is a material constant. From the invariance of the ratio, tau_alphaa/tau_ß, to change of thermodynamic conditions seen in our experiment as well in other systems, it follows that tß is also a function of T/rho^gamma, with the same gamma at least approximately. Since the JG ß-relaxation is the precursor of the a-relaxation, causality implies that the T/rho^gamma-dependence originates from the JG ß-relaxation and is passed on to the alpha-relaxation

Reconstruction of fetal and infant anatomy using rapid prototyping of post-mortem MR images

OBJECTIVES: The recent decline in autopsy rates and lack of human anatomical material donated for research and training has resulted in issues for medical training in the United Kingdom. This study aims to examine the feasibility of making accurate three-dimensional (3D) models of the human body and visceral organs using post-mortem magnetic resonance (MR) imaging and rapid prototyping. METHODS: We performed post-mortem MR imaging using a 3D T2-weighted sequence in 11 fetuses and infants, before autopsy, using either a 1.5-T or 9.4-T MR scanner. Internal organs were reconstructed in silico and 3D models were created by rapid prototyping. RESULTS: The median gestation of fetuses was 20 (range 19-30) weeks and the median age of infants was 12 (range 8-16) weeks. Models created by rapid prototyping accurately depicted structural abnormalities and allowed clear visualisation of 3D relationships. CONCLUSIONS: Accurate 3D modelling of anatomical features from post-mortem imaging in fetuses and infants is feasible. These models could have a large number of medical applications, including improved parental counselling, invaluable teaching resources and significant medico-legal applications to demonstrate disease or injury, without the need to show actual autopsy photographs

Brain volume estimation from post-mortem newborn and fetal MRI

AbstractObjectiveMinimally invasive autopsy using post-mortem magnetic resonance imaging (MRI) is a valid alternative to conventional autopsy in fetuses and infants. Estimation of brain weight is an integral part of autopsy, but manual segmentation of organ volumes on MRI is labor intensive and prone to errors, therefore unsuitable for routine clinical practice. In this paper we aim to show that volumetric measurements of the post-mortem fetal and neonatal brain can be accurately estimated using semi-automatic techniques and a high correlation can be found with the weights measured from conventional autopsy results.MethodsThe brains of 17 newborn subjects, part of Magnetic Resonance Imaging Autopsy Study (MaRIAS), were segmented from post-mortem MR images into cerebrum, cerebellum and brainstem using a publicly available neonate brain atlas and semi-automatic segmentation algorithm. The results of the segmentation were averaged to create a new atlas, which was then used for the automated atlas-based segmentation of 17 MaRIAS fetus subjects. As validation, we manually segmented the MR images from 8 subjects of each cohort and compared them with the automatic ones. The semi-automatic estimation of cerebrum weight was compared with the results of the conventional autopsy.ResultsThe Dice overlaps between the manual and automatic segmentations are 0.991 and 0.992 for cerebrum, 0.873 and 0.888 for cerebellum and 0.819 and 0.815 for brainstem, for newborns and fetuses, respectively. Excellent agreement was obtained between the estimated MR weights and autopsy gold standard ones: mean absolute difference of 5 g and 2% maximum error for the fetus cohort and mean absolute difference of 20 g and 11% maximum error for the newborn one.ConclusionsThe high correlation between the obtained segmentation and autopsy weights strengthens the idea of using post-mortem MRI as an alternative for conventional autopsy of the brain

Diagnostic accuracy of post-mortem MRI for thoracic abnormalities in fetuses and children

OBJECTIVES: To compare the diagnostic accuracy of post-mortem magnetic resonance imaging (PMMR) specifically for non-cardiac thoracic pathology in fetuses and children, compared with conventional autopsy. METHODS: Institutional ethics approval and parental consent was obtained. A total of 400 unselected fetuses and children underwent PMMR before conventional autopsy, reported blinded to the other dataset. RESULTS: Of 400 non-cardiac thoracic abnormalities, 113 (28 %) were found at autopsy. Overall sensitivity and specificity (95 % confidence interval) of PMMR for any thoracic pathology was poor at 39.6 % (31.0, 48.9) and 85.5 % (80.7, 89.2) respectively, with positive predictive value (PPV) 53.7 % (42.9, 64.0) and negative predictive value (NPV) 77.0 % (71.8, 81.4). Overall agreement was 71.8 % (67.1, 76.2). PMMR was most sensitive at detecting anatomical abnormalities, including pleural effusions and lung or thoracic hypoplasia, but particularly poor at detecting infection. CONCLUSIONS: PMMR currently has relatively poor diagnostic detection rates for the commonest intra-thoracic pathologies identified at autopsy in fetuses and children, including respiratory tract infection and diffuse alveolar haemorrhage. The reasonable NPV suggests that normal thoracic appearances at PMMR exclude the majority of important thoracic lesions at autopsy, and so could be useful in the context of minimally invasive autopsy for detecting non-cardiac thoracic abnormalities. KEY POINTS: • PMMR has relatively poor diagnostic detection rates for common intrathoracic pathology • The moderate NPV suggests that normal PMMR appearances exclude most important abnormalities • Lung sampling at autopsy remains the "gold standard" for pulmonary pathology

A case study of polar cap sporadic-E layer associated with TEC variations

The Sporadic-E (Es) layer is an often-observed phenomenon at high latitudes; however, our understanding of the polar cap Es layer is severely limited due to the scarce number of measurements. Here, the first comprehensive study of the polar cap Es layer associated with Global Positioning System (GPS) Total Electron Content (TEC) variations and scintillations is presented with multiple measurements at Resolute, Canada (Canadian Advanced Digital Ionosonde (CADI), Northward-looking face of Resolute Incoherent-Scatter Radar (RISR-N), and GPS receiver). According to the joint observations, the polar cap Es layer is a thin patch structure with variously high electron density, which gradually develops into the lower E region (~100 km) and horizontally extends >200 km. Moreover, the TEC variations produced by the polar cap Es layer are pulse-like enhancements with a general amplitude of ~0.5 TECu and are followed by smaller but rapid TEC perturbations. Furthermore, the possible scintillation effects likely associated with the polar cap Es layer are also discussed. As a consequence, the results widely expand our understanding on the polar cap Es layer, in particular on TEC variations