Detection of the protein dimers, multiple monomeric states and hydrated forms of Plasmodium falciparum triosephosphate isomerase in the gas phase

Dimeric and monomeric forms of the enzyme triosephosphate isomerase (TIM) from Plasmodium falciparum (Pf) have been detected under conditions of nanoflow by electrospray mass spectrometry. The dimer (M = 55 663 Da) exhibits a narrow charge state distribution with intense peaks limited to values of 18(+) to 21(+), maximal intensity being observed for charge states 19(+) and 20(+). A monomeric species with a charge state distribution ranging from 11(+) to 16(+) is also observed, which may be assigned to folded dissociated subunits. Complete dimer dissociation results under normal electrospray condition. The effects of solution pH and source temperature have been investigated. The observation of four distinct charge state distributions which may be assigned to a dimer, folded monomer, partially folded monomer and unfolded monomer is reported. Circular dichromism and fluorescence studies of Pf TIM at low pH support the retention of substantial secondary and tertiary structures. Satellite peaks in mass spectra corresponding to hydrated species are also observed and isotope shift upon deuteration is demonstrated. The analysis of all available independent crystal structures of Pf TIM and TIMs from other organisms permits identification of structurally conserved water molecules. Hydration observed in the dimer and folded monomeric forms in the gas phase may correspond to these conserved sites.

Dipolar reorientation and phase-transition in mixed alkali-halide crystals

We show that the results of Lüty and Ortiz-Lopez relating the cyanide reorientation rates to the high-temperature phase diagrams of alkali-halide-alkali-cyanide mixed crystals can be understood within simple mean-field theory.

Electrochemical phase formation (ECPF): Nucleation growth vis-a-vis adsorption models

The nucleataon growth model of electrochemical phase formation is analysed for the hnear potential sweep input Apart from deducing diagnostic criteria and method~ of estimating model parameters, the predictions of the nucleation growth model are compared and contrasted with those of a sample adsorption model A dastlnCtlOn is made possible between adsorption and phase transition, which seems useful for understanding the nature of ECPF phenomena, especially underpotentlal deposition (UPD).

Realizing the 'hindered charge ordered phase' in nanoscale charge ordered manganites: magnetization, magneto-transport and EPR investigations

We report three prominent observations made on the nanoscale charge ordered ( CO) manganites RE(1-x)AE(x)MnO(3) (RE = Nd, Pr; AE = Ca; x = 0.5) probed by temperature dependent magnetization and magneto-transport, coupled with electron magnetic/paramagnetic resonance spectroscopy (EMR/EPR). First, evidence is presented to show that the predominant ground state magnetic phase in nanoscale CO manganites is ferromagnetic and it coexists with a residual anti-ferromagnetic phase. Secondly, the shallow minimum in the temperature dependence of the EPR linewidth shows the presence of a charge ordered phase in nanoscale manganites which was shown to be absent from the DC static magnetization and transport measurements. Thirdly, the EPR linewidth, reflective of spin dynamics, increases significantly with a decrease of particle size in CO manganites. We discuss the interesting observations made on various samples of different particle sizes and give possible explanations. We have shown that EMR spectroscopy is a highly useful technique to probe the 'hindered charge ordered phase' in nanoscale CO manganites, which is not possible by static DC magnetization and transport measurements.

Phase transitions and gravity

Einstein's gravitational field is non-minimally coupled to a self-interacting scalar field in the presence of radiation. Such a theory can give rise to a phase transition associated with a change of sign of the gravitational “constant”. In our approach, the criterion for stability is formulated in terms of an effective potential, the phase-transition takes place due to temperature dependence of the scalar self-interaction coupling constant.

DSC studies on the phase transformation of hydrazonium sulfate

The high temperature phase transformation of hydrazonium sulfate, N2H6SO4 has been studied using DSC. The enthalpy of phase transition is found to be 3.63 ± 0.1 kJ mole−1. The phase transition temperature is found to decrease with the increase of particle size. It appears that the strain energy and not surface energy, is responsible for the phase transformation. The molar volume of the salt increases during the transformation as found by the dilatometric experiment involving percentage of linear thermal expansion. On cooling, the transformation from the high temperature modification to orthorhombic form is incomplete and extends over a wide range of temperature.

From Polymorph Screening to Dissolution Testing - Solid Phase Analysis during Pharmaceutical Development and Manufacturing

Solid materials can exist in different physical structures without a change in chemical composition. This phenomenon, known as polymorphism, has several implications on pharmaceutical development and manufacturing. Various solid forms of a drug can possess different physical and chemical properties, which may affect processing characteristics and stability, as well as the performance of a drug in the human body. Therefore, knowledge and control of the solid forms is fundamental to maintain safety and high quality of pharmaceuticals. During manufacture, harsh conditions can give rise to unexpected solid phase transformations and therefore change the behavior of the drug. Traditionally, pharmaceutical production has relied on time-consuming off-line analysis of production batches and finished products. This has led to poor understanding of processes and drug products. Therefore, new powerful methods that enable real time monitoring of pharmaceuticals during manufacturing processes are greatly needed. The aim of this thesis was to apply spectroscopic techniques to solid phase analysis within different stages of drug development and manufacturing, and thus, provide a molecular level insight into the behavior of active pharmaceutical ingredients (APIs) during processing. Applications to polymorph screening and different unit operations were developed and studied. A new approach to dissolution testing, which involves simultaneous measurement of drug concentration in the dissolution medium and in-situ solid phase analysis of the dissolving sample, was introduced and studied. Solid phase analysis was successfully performed during different stages, enabling a molecular level insight into the occurring phenomena. Near-infrared (NIR) spectroscopy was utilized in screening of polymorphs and processing-induced transformations (PITs). Polymorph screening was also studied with NIR and Raman spectroscopy in tandem. Quantitative solid phase analysis during fluidized bed drying was performed with in-line NIR and Raman spectroscopy and partial least squares (PLS) regression, and different dehydration mechanisms were studied using in-situ spectroscopy and partial least squares discriminant analysis (PLS-DA). In-situ solid phase analysis with Raman spectroscopy during dissolution testing enabled analysis of dissolution as a whole, and provided a scientific explanation for changes in the dissolution rate. It was concluded that the methods applied and studied provide better process understanding and knowledge of the drug products, and therefore, a way to achieve better quality.

Phase transformations and metastable phase equilibria in Al-Ge alloy

In this paper the results of a detailed investigation on the metastable phase relations in undercooled as well as rapidly solidified Al---Ge alloys containing 2–50 at.% Ge are reported. Data obtained on the structure and morphology of phases enable us to arrive at the phase relations and transformation processes occurring in undercooled and rapidly quenched melts of this system. These results are explained with the help of a metastable phase diagram consisting of a peritectic and eutectic reaction involving metastable phases.

Raman scattering investigation of the phase transitions in (NH4)2ZnBr4

Results of Raman spectroscopic studies of (NH4)2ZnBr4 crystal in the spectral range from 20-250 cm-1 and over a range of temperature from 90K to 440K covering the low temperature ferroelectric and high temperature incommensurate phases are presented. The plots of the integrated areas and peak heights of the strong Raman lines versus temperature show anomalous behaviour near the two phase transitions.

Phase relations and dielectric properties of BaTi03 ceramics heavily substituted with neodymium

Investigations on the phase relations and dielectric properties of (1 -x)BaTiO3 + xNd2/3TiO 3 (BNT) ceramics sintered in air below 1650 K have been carried out. X-ray powder diffraction studies indicate apparent phase singularity for compositions with x < 0.3. Nd2Ti207 is detected at higher neodymium concentrations. The unit cell parameter changes continuously with neodymium content, and BaTiO3 is completely cubic at room temperature with x -- 0.0525, whereas electron diffraction studies indicate that the air-sintered BNT ceramics with x > 0.08 contain additional phases that are partly amorphous even to an electron beam. SEM observations reveal that BaTiO3 grains are mostly covered by a molten intergranular phase, and show the presence of randomly distributed Nd2Ti207 grains. Energy dispersive X-ray analysis shows the Ba-Nd-Ti ternary composition of the intergranular phase. Differential thermal analysis studies support the formation of a partial melt involving dissolution-precipitation of boundary layers of BaTiO3 grains. These complex phase relations are accounted for in terms of the phase instability of BaTiO3 with large cation-vacancy concentration as a result of heavy Nd 3+ substitution. The absence of structural intergrowth in (1 - x)BaTiO3 + xNd2/3TiO3 under oxidative conditions leads to a separation of phases wherein the new phases undergo melting and remain X-ray amorphous. BNT ceramics with 0.1 < x < 0.3 have ~eff >~ 104 with tan 6 < 0.1 and nearly flat temperature capacitance characteristics. The grain-size dependence of ee,, variations of ~eff and tan 6 with the measuring frequency, the non-ohmic resistivities, and the non-linear leakage currents at higher field-strengths which are accompanied by the decrease in eeff and rise in tan 3, are explained on the basis of an intergranular (internal boundary layer) dielectric characteristic of these ceramics.

Two-dimensional phase transitions at electrochemical interfaces

A two-state Ising model has been applied to the two-dimensional condensation of tymine at the mercury-water interface. The model predicts a quadratic dependence of the transition potential on temperature and on the logarithm of the adsorbate concentration. Both predictions have been confirmed experimentally.

Electronic-structures of h2o.bf3 and related n-v addition-compounds - a combined eels-ups study in vapor-phase

The detailed electronic structure of the n-v addition compound H2O·BF3 has been investigated for the first time by a combined use of electron energy loss spectroscopy (EELS) and UV photoelectron spectroscopy (UPS) augmented by MO calculations. The calculated molecular orbital energies of H2O·BF3 agree well with the UPS results and have been used to assign the electronic transitions obtained from EELS and to construct an orbital correlation diagram. The Journal of Chemical Physics is copyrighted by The American Institute of Physics.

Designs for phase I clinical trials with multiple courses of subjects at different doses

The goal of this article is to provide a new design framework and its corresponding estimation for phase I trials. Existing phase I designs assign each subject to one dose level based on responses from previous subjects. Yet it is possible that subjects with neither toxicity nor efficacy responses can be treated at higher dose levels, and their subsequent responses to higher doses will provide more information. In addition, for some trials, it might be possible to obtain multiple responses (repeated measures) from a subject at different dose levels. In this article, a nonparametric estimation method is developed for such studies. We also explore how the designs of multiple doses per subject can be implemented to improve design efficiency. The gain of efficiency from "single dose per subject" to "multiple doses per subject" is evaluated for several scenarios. Our numerical study shows that using "multiple doses per subject" and the proposed estimation method together increases the efficiency substantially.

EPR observation of phase transitions in calcium cadmium acetate hexahydrate: Using Mn2+ and Cu2+ ions as probe

Results of temperature dependence of EPR spectra of Mn2+ and Cu2+ ions doped calcium cadmium acetate hexahydrate (CaCd(CH3COO)4•6H2O) have been reported. The investigation has been carried out in the temperature range between room temperature ( 300 K) and liquid nitrogen temperature. A I-order phase transition at 146 ± 0.5 K has been confirmed. In addition a new II-order phase transition at 128 ± 1 K has been detected for the first time. There is evidence of large amplitude hindered rotations of CH3 groups which become frozen at 128 K. The incorporation of Cu2+ and Mn2+ probes at Ca2+ and Cd2+ sites respectively provide evidence that the phase transitions are caused by the molecular rearrangements of the common coordinating acetate groups between Ca2+ and Cd2+ sites. In contradiction to the previous reports of a change of symmetry from tetragonal to orthorhombic below 140 K, the symmetry of the host is concluded to remain tetragonal in all the three observed phases between room temperature and liquid nitrogen temperature.