Probing The effects of Experimental Conditions on the Character of Drug-Polymer Phase Diagrams Constructed Using Flory-Huggins Theory

Purpose: Amorphous drug-polymer solid dispersions have been found to result in improved drug dissolution rates when compared to their crystalline counterparts. However, when the drug exists in the amorphous form it will possess a higher Gibb’s free energy than its associated crystalline state and can recrystallize. Drug-polymer phase diagrams constructed through the application of the Flory Huggins (F-H) theory contain a wealth of information regarding thermodynamic and kinetic stability of the amorphous drug-polymer system. This study was aimed to evaluate the effects of various experimental conditions on the solubility and miscibility detections of drug-polymer binary system. Methods: Felodipine (FD)-Polyvinylpyrrolidone (PVP) K15 (PVPK15) and FD-Polyvinylpyrrolidone/vinyl acetate (PVP/VA64) were the selected systems for this research. Physical mixtures with different drug loadings were mixed and ball milled. These samples were then processed using Differential Scanning Calorimetry (DSC) and measurements of melting point (Tend) and glass transition (Tg) were detected using heating rates of 0.5, 1.0 and 5.0°C/min. Results: The melting point depression data was then used to calculate the F-H interaction parameter (χ) and extrapolated to lower temperatures to complete the liquid–solid transition curves. The theoretical binodal and spinodal curves were also constructed which were used to identify regions within the phase diagram. The effects of polymer selection, DSC heating rate, time above parent polymer Tg and polymer molecular weight were investigated by identifying amorphous drug miscibility limits at pharmaceutically relevant temperatures. Conclusion: The potential implications of these findings when applied to a non-ambient processing method such as Hot Melt Extrusion (HME) are also discussed.

The effect of clock jitter on the performance of continuous-time delta-sigma ADC for GNSS signals

Next generation Global Navigation Satellite System (GNSS) receivers will operate in multiple navigation bands. An efficient way to achieve this with lower power and cost is to employ BandPass Sampling (BPS); nevertheless, the sampling operation injects large amounts of jitter noise, which degrades the performance of the receiver. Continuous–Time (CT) Delta–Sigma (ΔΣ) modulators are capable of suppressing this noise but the impact of clock jitter at the output of the Digital– to–Analog Converter (DAC) in the feedback path of the modulator should be taken into account. This paper presents an analytical approach for describing clock jitter in GNSS receivers when a CT–ΔΣ modulator is utilized for Analog–to–Digital Conversion (ADC). The validity of the presented approach is verified through time–domain simulations using a behavioural model of the fourth–order CT–ΔΣ modulator with 1–bit NRZ DAC feedback pulse.

On the 'inherent' character of the right of states to self-defence

While there is no lack of studies on the use of armed force by states in self-defence, its qualification as an ‘inherent right’ in article 51 of the Charter of the United Nations has received little scholarly attention and has been too quickly dismissed as having no significance. The present article fills this gap in the literature. Its purpose is not to discuss the limits to which article 51 or customary international law submit the exercise of the right of self-defence by states, but to examine what its 'inherent’ character means and what legal consequences it entails. The article advances two main arguments. The first is that self-defence is a corollary of statehood as presently understood because it is essential to preserving its constitutive elements. The second argument is that the exercise of the right of self-defence must be distinguished from the right itself: it is only the former that may be delegated to other states or submitted to limitations under customary international law and treaty law. The right of self-defence, however, cannot be alienated and it takes precedence over other international obligations, although not over those specifically intended to limit the conduct of states in armed conflict or over non-derogable human rights provisions.

The Republic of México in 1876; a polítical and ethnographical division of the population, character, habits, costumes an vocations of its in habitans

UANL

Character and professionalism in the context of developing countries – the example of mercenaries

On pense souvent que le professionnalisme moderne exige qu’on regarde comme non relevante les traditions particulières ainsi que les liens avec familiaux, tribaux et religieux. Du point de vue du professionnalisme, ce qu’est important sont des règles internes à la profession et aussi les droits universels de l’homme vu comme individu abstrait. Dans une société où l’individualisme et le commerce deviennent omniprésents, les traditions éthiques et les identités narratives pourraient pourtant constituer un cadre de motivations clé pour l’intégrité éthique professionnelle. Je prendrai comme exemple la profession militaire et en particulier l’utilisation de mercenaires. En distinguant entre les compétences et les vertus je me demanderai si oui ou non il y a une relation nécessaire entre un bon soldat et le fait d’être un citoyen. Le fait d’être est compris ici comme catégorie morale qui occasionne un certain idéal de caractère et en particulier des vertus. Je conclus que l’action de contractualisation privée d’un soldat n’est pas en général moralement digne d’éloge et ne devrait pas être encouragée dans une société éthiquement orientée.

The Dalhousie Dentistry Story: A Case for Proportionality, Professionalism, and the Promotion of Moral Character

La tribune de l'éditeur / Editor's Soapbox

Pattern Analysis Techniques for the Recognition of Unconstrained Handwritten Malayalam Character Images

The objective of the study is to develop a hand written character recognition system that could recognisze all the characters in the mordern script of malayalam language at a high recognition rate

Theory for the change of bond character in divalent-metal clusters

To determine the size dependence of the bonding in divalent-metal clusters we use a many-electron Hamiltonian describing the interplay between van der Waals (vdW) and covalent interactions. Using a saddle-point slave-boson method and taking into account the size-dependent screening of charge fluctuations, we obtain for Hg_n a sharp transition from vdW to covalent bonding for increasing n. We show also, by solving the model Hamiltonian exactly, that for divalent metals vdW and covalent bonding coexist already in the dimers.

The timing of eukaryotic evolution: Does a relaxed molecular clock reconcile proteins and fossils?

The use of nucleotide and amino acid sequences allows improved understanding of the timing of evolutionary events of life on earth. Molecular estimates of divergence times are, however, controversial and are generally much more ancient than suggested by the fossil record. The limited number of genes and species explored and pervasive variations in evolutionary rates are the most likely sources of such discrepancies. Here we compared concatenated amino acid sequences of 129 proteins from 36 eukaryotes to determine the divergence times of several major clades, including animals, fungi, plants, and various protists. Due to significant variations in their evolutionary rates, and to handle the uncertainty of the fossil record, we used a Bayesian relaxed molecular clock simultaneously calibrated by six paleontological constraints. We show that, according to 95% credibility intervals, the eukaryotic kingdoms diversified 950-1,259 million years ago (Mya), animals diverged from choanoflagellates 761-957 Mya, and the debated age of the split between protostomes and deuterostomes occurred 642-761 Mya. The divergence times appeared to be robust with respect to prior assumptions and paleontological calibrations. Interestingly, these relaxed clock time estimates are much more recent than those obtained under the assumption of a global molecular clock, yet bilaterian diversification appears to be approximate to100 million years more ancient than the Cambrian boundary.

Characterisation of an amphioxus Fringe gene and the evolution of the vertebrate segmentation clock

In mouse and chick embryos, cyclic expression of lunatic fringe has an important role in the regulation of mesoderm segmentation. We have isolated a Fringe gene from the protochordate amphioxus. Amphioxus is the closest living relative of the vertebrates, and has mesoderm that is definitively segmented in a manner that is similar to, and probably homologous with, that of vertebrates. AmphiFringe is placed basal to vertebrate Fringe genes in molecular phylogenetic analyses, indicating that the duplications that formed radical-, manic- and lunatic fringe are specific to the vertebrate lineage. AmphiFringe expression was detected in the anterior neural plate of early neurulae, where it resolved into a series of segmental patches by the mid-neurulae stage. No AmphiFringe transcripts were detected in the mesoderm. Based on these observations, we propose a model depicting a successive recruitment of Fringe in the maintenance then regulation of segmentation during vertebrate evolution.

(Re)enchanting geography? The nature of being critical and the character of critique in human geography

Enchantment is a term frequently used by human geographers to express delight, wonder or that which cannot be simply explained. However, it is a concept that has yet to be subject to sustained critique, specifically how it can be used to progress geographic thought and praxis. This paper makes sense of, and space for, the unintelligibility of enchantment in order to encourage a less repressed, more cheerful way of engaging with the geographies of the world. We track back through our disciplinary heritage to explore how geographers have employed enchantment as a force through which the world inspires affective attachment. We review the terrain of the debate surrounding recent geographical engagements with enchantment, focusing on the nature of being critical and the character of critique in human geography, offering a new ‘enchanted’ stance to our geographical endeavours. We argue that the moment of enchantment has not passed with the current challenging climate; if anything, it is more pressing.