High speed DSC (hyper-DSC) as a tool to measure the solubility of a drug within a solid or semi-solid matrix

Conventional differential scanning calorimetry (DSC) techniques are commonly used to quantify the solubility of drugs within polymeric-controlled delivery systems. However, the nature of the DSC experiment, and in particular the relatively slow heating rates employed, limit its use to the measurement of drug solubility at the drug's melting temperature. Here, we describe the application of hyper-DSC (HDSC), a variant of DSC involving extremely rapid heating rates, to the calculation of the solubility of a model drug, metronidazole, in silicone elastomer, and demonstrate that the faster heating rates permit the solubility to be calculated under non-equilibrium conditions such that the solubility better approximates that at the temperature of use. At a heating rate of 400 degrees C/min (HDSC), metronidazole solubility was calculated to be 2.16 mg/g compared with 6.16 mg/g at 20 degrees C/min. (C) 2005 Elsevier B.V. All rights reserved.

Genome-wide profiling of methylation identifies novel targets with aberrant hyper-methylation and reduced expression in low-risk myelodysplastic syndromes

Gene expression profiling signatures may be used to classify the subtypes of Myelodysplastic syndrome (MDS) patients. However, there are few reports on the global methylation status in MDS. The integration of genome-wide epigenetic regulatory marks with gene expression levels would provide additional information regarding the biological differences between MDS and healthy controls. Gene expression and methylation status were measured using high-density microarrays. A total of 552 differentially methylated CpG loci were identified as being present in low-risk MDS; hypermethylated genes were more frequent than hypomethylated genes. In addition, mRNA expression profiling identified 1005 genes that significantly differed between low-risk MDS and the control group. Integrative analysis of the epigenetic and expression profiles revealed that 66.7% of the hypermethylated genes were underexpressed in low-risk MDS cases. Gene network analysis revealed molecular mechanisms associated with the low-risk MDS group, including altered apoptosis pathways. The two key apoptotic genes BCL2 and ETS1 were identified as silenced genes. In addition, the immune response and micro RNA biogenesis were affected by the hypermethylation and underexpression of IL27RA and DICER1. Our integrative analysis revealed that aberrant epigenetic regulation is a hallmark of low-risk MDS patients and could have a central role in these diseases.

Narrative on the Net:Bill and his hyper- lives, loves and texts

Narrative, by its very nature, is changing as a consequence of internet developments. Hypertexts are, for example, changing not just the way in which we disseminate information, but also the ways in which we write, speak and think. In this paper a narrative approach is taken to assess a case study of a person’s extensive home site on the web. Bill maintains an extensive web site documenting his life with Parkinson’s Disease, his love for running and all matters relating to the island of Montserrat in the Eastern Caribbean. Bill’s Parkinson’s Disease hypertext diary forms the focus of this case study of a life spent on-line. Though set up just as a diary about this progressively degenerative disease, because of its hypertextual qualities, this paper argues that it is through the diary that Bill comes to produce and sustain - to narrate - his identity. This paper thus contributes to the position that though hypertext encourages the construction of fragmented and false identity narratives, it is also a medium for sustaining linear and coherent representations of self-identity.

On the required shape corrections to the local density and generalized gradient approximations to the Kohn-Sham potentials for molecular response calculations of (hyper)polarizabilities and excitation energies

It is well known that shape corrections have to be applied to the local-density (LDA) and generalized gradient (GGA) approximations to the Kohn-Sham exchange-correlation potential in order to obtain reliable response properties in time dependent density functional theory calculations. Here we demonstrate that it is an oversimplified view that these shape corrections concern primarily the asymptotic part of the potential, and that they affect only Rydberg type transitions. The performance is assessed of two shape-corrected Kohn-Sham potentials, the gradient-regulated asymptotic connection procedure applied to the Becke-Perdew potential (BP-GRAC) and the statistical averaging of (model) orbital potentials (SAOP), versus LDA and GGA potentials, in molecular response calculations of the static average polarizability alpha, the Cauchy coefficient S-4, and the static average hyperpolarizability beta. The nature of the distortions of the LDA/GGA potentials is highlighted and it is shown that they introduce many spurious excited states at too low energy which may mix with valence excited states, resulting in wrong excited state compositions. They also lead to wrong oscillator strengths and thus to a wrong spectral structure of properties like the polarizability. LDA, Becke-Lee-Yang-Parr (BLYP), and Becke-Perdew (BP) characteristically underestimate contributions to alpha and S-4 from bound Rydberg-type states and overestimate those from the continuum. Cancellation of the errors in these contributions occasionally produces fortuitously good results. The distortions of the LDA, BLYP, and BP spectra are related to the deficiencies of the LDA/GGA potentials in both the bulk and outer molecular regions. In contrast, both SAOP and BP-GRAC potentials produce high quality polarizabilities for 21 molecules and also reliable Cauchy moments and hyperpolarizabilities for the selected molecules. The analysis for the N-2 molecule shows, that both SAOP and BP-GRAC yield reliable energies omega(i) and oscillator strengths f(i) of individual excitations, so that they reproduce well the spectral structure of alpha and S-4.(C) 2002 American Institute of Physics.

Exchange potential from the common energy denominator approximation for the Kohn-Sham Green's function: Application to (hyper)polarizabilities of molecular chains

An approximate Kohn-Sham (KS) exchange potential v(xsigma)(CEDA) is developed, based on the common energy denominator approximation (CEDA) for the static orbital Green's function, which preserves the essential structure of the density response function. v(xsigma)(CEDA) is an explicit functional of the occupied KS orbitals, which has the Slater v(Ssigma) and response v(respsigma)(CEDA) potentials as its components. The latter exhibits the characteristic step structure with "diagonal" contributions from the orbital densities \psi(isigma)\(2), as well as "off-diagonal" ones from the occupied-occupied orbital products psi(isigma)psi(j(not equal1)sigma). Comparison of the results of atomic and molecular ground-state CEDA calculations with those of the Krieger-Li-Iafrate (KLI), exact exchange (EXX), and Hartree-Fock (HF) methods show, that both KLI and CEDA potentials can be considered as very good analytical "closure approximations" to the exact KS exchange potential. The total CEDA and KLI energies nearly coincide with the EXX ones and the corresponding orbital energies epsilon(isigma) are rather close to each other for the light atoms and small molecules considered. The CEDA, KLI, EXX-epsilon(isigma) values provide the qualitatively correct order of ionizations and they give an estimate of VIPs comparable to that of the HF Koopmans' theorem. However, the additional off-diagonal orbital structure of v(xsigma)(CEDA) appears to be essential for the calculated response properties of molecular chains. KLI already considerably improves the calculated (hyper)polarizabilities of the prototype hydrogen chains H-n over local density approximation (LDA) and standard generalized gradient approximations (GGAs), while the CEDA results are definitely an improvement over the KLI ones. The reasons of this success are the specific orbital structures of the CEDA and KLI response potentials, which produce in an external field an ultranonlocal field-counteracting exchange potential. (C) 2002 American Institute of Physics.

Threshold Optimization for Energy Detection-Based Spectrum Sensing Over Hyper-Rayleigh Fading Channels

Spectrum sensing is a key function of cognitive radio systems. Sensing performance is determined by three main factors including the wireless channel between the primary system and the cognitive radio nodes, the detection threshold, and the sensing time. In this letter a closed-form expression for the average probability of detection for energy detection based spectrum sensing over two-wave with diffuse power fading channels is derived. This expression is then used to optimize the detection threshold for cognitive radio nodes, which operate in confined structures that exhibit worse than Rayleigh fading conditions. Such fading conditions can represent a behavioral model of cognitive machine-to-machine systems deployed in enclosed structures such as in-vehicular environments.

Broad balmer wings in BA Hyper/Supergiants distorted by diffuse interstellar bands: five examples in the 30 Doradus Region from the VLT-Flames Tarantula Survey

Extremely broad emission wings at Hβ and Hα have been found in VLT-FLAMES Tarantula Survey data for five very luminous BA supergiants in or near 30 Doradus in the Large Magellanic Cloud. The profiles of both lines are extremely asymmetrical, which we have found to be caused by very broad diffuse interstellar bands (DIBs) in the longward wing of Hβ and the shortward wing of Hα. These DIBs are well known to interstellar but not to many stellar specialists, so that the asymmetries may be mistaken for intrinsic features. The broad emission wings are generally ascribed to electron scattering, although we note difficulties for that interpretation in some objects. Such profiles are known in some Galactic hyper/supergiants and are also seen in both active and quiescent Luminous Blue Variables (LBVs). No prior or current LBV activity is known in these 30 Dor stars, although a generic relationship to LBVs is not excluded; subject to further observational and theoretical investigation, it is possible that these very luminous supergiants are approaching the LBV stage for the first time. Their locations in the HRD and presumed evolutionary tracks are consistent with that possibility. The available evidence for spectroscopic variations of these objects is reviewed, while recent photometric monitoring does not reveal variability. A search for circumstellar nebulae has been conducted, with an indeterminate result for one of them.

An 8000-year history of landscape, climate and copper exploitation in the Middle East: the Wadi Faynan and the Wadi Dana National Reserve in southern Jordan

Investigations of geomorphology, geoarchaeology, pollen, palynofacies, and charcoal indicate the comparative scales and significance of palaeoenvironmental changes throughout the Holocene at the junction between the hyper-arid hot Wadi â??Arabah desert and the front of the Mediterranean-belt Mountains of Edom in southern Jordan through a series of climatic changes and episodes of intense mining and smelting of copper ores. Early Holocene alluviation followed the impact of Neolithic grazers but climate drove fluvial geomorphic change in the Late Holocene, with a major arid episode corresponding chronologically with the â??Little Ice Ageâ?? causing widespread alluviation. The harvesting of wood for charcoal may have been sufficiently intense and widespread to affect the capacity of intensively harvested tree species to respond to a period of greater precipitation deduced for the Roman-Byzantine period - a property that affects both taphonomic and biogeographical bases for the interpretation of palynological evidence from arid-lands with substantial industrial histories. Studies of palynofacies have provided a record of human and climatic causes of soil erosion, and the changing intensity of the use of fire over time. The patterns of vegetational, climatic change and geomorphic changes are set out for this area for the last 8000 years.

Low-dose studies of bystander cell killing with targeted soft X rays

The Gray Cancer Institute ultrasoft X-ray microprobe was used to quantify the bystander response of individual V79 cells exposed to a focused carbon K-shell (278 eV) X-ray beam. The ultrasoft X-ray microprobe is designed to precisely assess the biological response of individual cells irradiated in vitro with a very fine beam of low-energy photons. Characteristic C-K X rays are generated by a focused beam of 10 keV electrons striking a graphite target. Circular diffraction gratings (i.e. zone plates) are then employed to focus the X-ray beam into a spot with a radius of 0.25 mum at the sample position. Using this microbeam technology, the correlation between the irradiated cells and their nonirradiated neighbors can be examined critically. The survival response of V79 cells irradiated with a C-K X-ray beam was measured in the 0-2-Gy dose range. The response when all cells were irradiated was compared to that obtained when only a single cell was exposed. The cell survival data exhibit a linear-quadratic response when all cells were targeted (with evidence for hyper-sensitivity at low doses). When only a single cell was targeted within the population, 10% cell killing was measured. In contrast to the binary bystander behavior reported by many other investigations, the effect detected was initially dependent on dose (200 mGy). In the low-dose region (