(Solid plus liquid) solubility of organic compounds in organic solvents - correlation and extrapolation

peer-reviewedA semi-empirical model is developed for the regression of (solid + liquid) solubility data with temperature. The model fulfils the required boundary conditions, allowing for robust extrapolation to higher and lower temperatures. The model combines a representation of the solid-state activity which accommodates a temperature-dependent heat capacity difference contribution with a scaled three-parameter Weibull function representing the temperature dependence of the solution activity coefficient at equilibrium. Evaluation of the model is based on previously published experimental calorimetric and solubility data of four organic compounds, fenoxycarb, fenofibrate, risperidone and butyl paraben, in five common organic solvents, methanol, ethyl acetate, acetone, acetonitrile, and toluene. The temperature dependence of the van't Hoff enthalpy of solution and its components is analysed and discussed. Among the four compounds the influence of temperature on the enthalpy of fusion varies from moderate to substantial. Based on the semi-empirical model, a new equation containing three adjustable parameters is proposed for regression and extrapolation of solubility data for cases when only melting data and solubility data is available. The equation is shown to provide good accuracy and robustness when evaluated against the full semi-empirical model as well as against commonly used, more simple empirical equations. It is shown how such a model can be used to obtain an estimate of the heat capacity difference for cases where accurate solubility data is available in multiple solvents. (C) 2014 Elsevier Ltd. All rights reserved.ACCEPTEDpeer-reviewe

Hydroxyl, water, ammonia, carbon monoxide and neutral carbon towards the Sgr A complex

We observed OH, H$_2$O, HN$_3$, C$^{18}$O, and C$_I$ towards the +50 km/s cloud (M-0.02-0.07), the CND and the +20 km/s (M-0.13-0.08) cloud in the Sgr A complex with the VLA, Odin and SEST. Strong OH absorption, H$_2$O emission and absorption lines were seen at all three positions. Strong C$^{18}$O emissions were seen towards the +50 and +20 km/s clouds. The CND is rich in H$_2$O and OH, and these abundances are considerably higher than in the surrounding clouds, indicating that shocks, star formation and clump collisions prevail in those objects. A comparison with the literature reveals that it is likely that PDR chemistry including grain surface reactions, and perhaps also the influences of shocks has led to the observed abundances of the observed molecular species studied here. In the redward high-velocity line wings of both the +50 and +20 km/s clouds and the CND, the very high H$_2$O abundances are suggested to be caused by the combined action of shock desorption from icy grain mantles and high-temperature, gas-phase shock chemistry. Only three of the molecules are briefly discussed here. For OH and H$_2$O three of the nine observed positions are shown, while a map of the C$^{18}$O emission is provided. An extensive paper was recently published with Open Access (Karlsson et al. 2013; http://www.aanda.org/articles/aa/pdf/2013/06/aa20471-12.pdf ).Comment: Proc. of a Conf. on IAU Symposium No.303: The Galactic Center: Feeding and Feedback in a Normal Galactic Nucleus 2013, Santa Fe, NM (USA

A Solution to the Protostellar Accretion Problem

Accretion rates of order 10^-8 M_\odot/yr are observed in young protostars of approximately a solar mass with evidence of circumstellar disks. The accretion rate is significantly lower for protostars of smaller mass, approximately proportional to the second power of the stellar mass, \dot{M}_accr\propto M^2. The traditional view is that the observed accretion is the consequence of the angular momentum transport in isolated protostellar disks, controlled by disk turbulence or self--gravity. However, these processes are not well understood and the observed protostellar accretion, a fundamental aspect of star formation, remains an unsolved problem. In this letter we propose the protostellar accretion rate is controlled by accretion from the large scale gas distribution in the parent cloud, not by the isolated disk evolution. Describing this process as Bondi--Hoyle accretion, we obtain accretion rates comparable to the observed ones. We also reproduce the observed dependence of the accretion rate on the protostellar mass. These results are based on realistic values of the ambient gas density and velocity, as inferred from numerical simulations of star formation in self--gravitating turbulent clouds.Comment: 4 pages, 2 figures, ApJ Letters, in pres

Insulin receptor-like ectodomain genes and splice variants are found in both arthropods and human brain cDNA

Truncated receptor ectodomains have been described for several classes of cell surface receptors, including those that bind to growth factors, cytokines, immunoglobulins, and adhesion molecules. Soluble receptor isoforms are typically generated by proteolytic cleavage of the cell surface receptor or by alternative splicing of RNA transcripts arising from the same gene encoding the full-length receptor. Both the epidermal growth factor receptor (EGFR) and the insulin receptor (INSR) families produce soluble receptor splice variants in vertebrates and truncated forms of insulin receptor-like sequences have previously been described in Drosophila. The EGFR and INSR ectodomains share significant sequence homology with each other suggestive of a common evolutionary origin. We discovered novel truncated insulin receptor-like variants in several arthropod species. We performed a phylogenetic analysis of the conserved extracellular receptor L1 and L2 subdomains in invertebrate species. While the segregation of insulin receptor-like L1 and L2 domains indicated that an internal domain duplication had occurred only once, the generation of truncated insulin receptor-like sequences has occurred multiple times. The significance of this work is the previously unknown and widespread occurrence of truncated isoforms in arthropods, signifying that these isoforms play an important functional role, potentially related to such isoforms in mammals

Critical role of astroglial apolipoprotein E and liver X receptor-α expression for microglial Aβ phagocytosis

Liver X receptors (LXRs) regulate immune cell function and cholesterol metabolism, both factors that are critically involved in Alzheimer's disease (AD). To investigate the therapeutic potential of long-term LXR activation in amyloid-β (Aβ) peptide deposition in an AD model, 13-month-old, amyloid plaque-bearing APP23 mice were treated with the LXR agonist TO901317. Postmortem analysis demonstrated that TO901317 efficiently crossed the blood–brain barrier. Insoluble and soluble Aβ levels in the treated APP23 mice were reduced by 80% and 40%, respectively, compared with untreated animals. Amyloid precursor protein (APP) processing, however, was hardly changed by the compound, suggesting that the observed effects were instead mediated by Aβ disposal. Despite the profound effect on Aβ levels, spatial learning in the Morris water maze was only slightly improved by the treatment. ABCA1 (ATP-binding cassette transporter 1) and apolipoprotein E (ApoE) protein levels were increased and found to be primarily localized in astrocytes. Experiments using primary microglia demonstrated that medium derived from primary astrocytes exposed to TO901317 stimulated phagocytosis of fibrillar Aβ. Conditioned medium from TO901317-treated ApoE−/−or LXRα−/−astrocytes did not increase phagocytosis of Aβ. In APP23 mice, long-term treatment with TO901317 strongly increased the association of microglia and Aβ plaques. Short-term treatment of APP/PS1 mice with TO901317 also increased this association, which was dependent on the presence of LXRα and was accompanied by increased ApoE lipidation. Together, these data suggest that astrocytic LXRα activation and subsequent release of ApoE by astrocytes is critical for the ability of microglia to remove fibrillar Aβ in response to treatment with TO901317.</jats:p

Geodetic constraints on cratonic microplates and broad strain during rifting of thick Southern African lithosphere

Southern Africa is typically considered to belong to a single tectonic plate, Nubia, despite active faulting along the southwestern branch of the East African Rift System. We analyze regional Global Navigation Satellite System (GNSS) measurements, and find that the “San” microplate, situated south of the southwestern branch of the East African Rift, is statistically distinct from Nubia, with 0.4–0.7 mm/yr of extension across the boundary. Adding nine new campaign GNSS sites, we show that the extension rate across the southern Malawi Rift is 2.2 ± 0.3 mm/yr, with 75% of the relative velocity occurring over 890 km, despite the surface expression of faulting being <150 km wide. Thus, for the first time, we use geodetic measurements to describe the accommodation of strain in broad zones between Archean cratons in southern Africa's thick continental lithosphere

A Model System for In Vitro Studies of Bank Vole Borne Viruses

The bank vole (Myodes glareolus) is a common small mammal in Europe and a natural host for several important emerging zoonotic viruses, e.g. Puumala hantavirus (PUUV) that causes hemorrhagic fever with renal syndrome (HFRS). Hantaviruses are known to interfere with several signaling pathways in infected human cells, and HFRS is considered an immune-mediated disease. There is no in vitro-model available for infectious experiments in bank vole cells, nor tools for analyses of bank vole immune activation and responses. Consequently, it is not known if there are any differences in the regulation of virus induced responses in humans compared to natural hosts during infection. We here present an in vitro-model for studies of bank vole borne viruses and their interactions with natural host cell innate immune responses. Bank vole embryonic fibroblasts (VEFs) were isolated and shown to be susceptible for PUUV-infection, including a wild-type PUUV strain (only passaged in bank voles). The significance of VEFs as a model system for bank vole associated viruses was further established by infection studies showing that these cells are also susceptible to tick borne encephalitis, cowpox and Ljungan virus. The genes encoding bank vole IFN-β and Mx2 were partially sequenced and protocols for semi-quantitative RT-PCR were developed. Interestingly, PUUV did not induce an increased IFN-β or Mx2 mRNA expression. Corresponding infections with CPXV and LV induced IFN-β but not Mx2, while TBEV induced both IFN-β and Mx2

Pancreatitis-diabetes-pancreatic cancer: summary of an NIDDK-NCI workshop

A workshop sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the National Cancer Institute (NCI) on "Pancreatitis-Diabetes-Pancreatic Cancer" focused on the risk factors of chronic pancreatitis (CP) and diabetes mellitus (DM) on the development of pancreatic ductal adenocarcinoma (PDAC). Sessions were held on (a) an overview of the problem of PDAC; (b) CP as a risk factor of PDAC; (c) DM as a risk factor of PDAC; (d) pancreatogenic, or type 3c, DM; (e) genomic associations of CP, DM, and PDAC; (f) surveillance of high-risk populations and early detection of PDAC; and (g) effects of DM treatment on PDAC. Recent data and current understandings of the mechanisms of CP- and DM-associated factors on PDAC development were discussed, and a detailed review of the possible risks of DM treatment on the development of PDAC was provided by representatives from academia, industry, and the Food and Drug Administration. The current status of possible biomarkers of PDAC and surveillance strategies for high-risk populations were discussed, and the gaps in knowledge and opportunities for further research were elucidated. A broad spectrum of expertise of the speakers and the discussants provided an unusually productive workshop, the highlights of which are summarized in the accompanying article

Comparison of Radioimmunoprecipitation With Luciferase Immunoprecipitation for Autoantibodies to GAD65 and IA-2β

OBJECTIVE - To compare the sensitivity and specificity of luciferase immunoprecipitation (LIPS) with radioimmunoprecipitation (RIP) for the measurement of autoantibodies to the type 1 diabetes autoantigens glutamic acid decarboxylase 65 (GAD65) and insulinoma-associated protein (IA)-2 beta. RESEARCH DESIGN AND METHODS - Sera from 49 type 1 diabetic patients and 100 nondiabetic control subjects from Diabetes Antibody Standardization Program 2007 were used to screen for autoantibodies to GAD65. An additional 200 type 1 diabetic patients and 200 nondiabetic control subjects were used to validate the GAD65 results and screen for autoantibodies to IA-2 beta. RESULTS - LIPS showed equal sensitivity and specificity to RIP for detecting autoantibodies to GAD65 and IA-2 beta. Receiver-operating characteristic analysis revealed that the detection of autoantibodies to GAD65 and IA-2 beta by LIPS and RIP were not statistically different. CONCLUSIONS - The LIPS assay does not require the use of radioisotopes or in vitro transcription/translation and is a practical alternative at the clinical level for the RIP assay

Thermodynamics of the enantiotropic pharmaceutical compound benzocaine and solubility in pure organic solvents

peer-reviewedThe thermodynamic relationship between FI and FII of ethyl 4-aminobenzoate (benzocaine) has been investigated. Slurry conversion experiments show that the transition temperature below which FI is stable is located between 302 K–303 K (29 °C–30 °C). The polymorphs FI and FII have been characterised by infrared spectroscopy (IR), Raman spectroscopy, transmission powder X-ray diffraction (XRPD) and differential scanning calorimetry (DSC). The isobaric solid state heat capacities have been measured by DSC. The quantitative thermodynamic stability relationship has been determined in a comprehensive thermodynamic analysis of the calorimetric data. The solubility of both polymorphs has been determined in eight pure organic solvents over the temperature range 278 K–323 K by a gravimetric method. The mole fraction solubility of benzocaine decreases in the order: 1,4-dioxane, acetone, ethyl acetate, chloroform, acetonitrile, methanol, n-butanol and toluene. Comparison with the determined activity of solid benzocaine forms shows that negative deviation from Raoult's law ideality is found in dioxane, acetone and ethyl acetate solutions, and positive deviation in solutions of the other investigated solvents