Simple calix[n]arenes and calix[4]resorcinarenes as drug solubilizing agents

Many drug molecules have low solubility in aqueous media and, hence, poor bioavailability. The formation of a host-guest complex with some other compound which has a good solubility profile can facilitate solubilization of hydrophobic drugs. Complex formation relies upon the formation of non-covalent interactions between the host molecule and the drug guest. The use of calix[n]arenes, a well-characterized class of cyclic oligomers, has been investigated for their ability to form complexes with a variety of ionic and molecular species. This review highlights those studies which have demonstrated the potential of calix[n]arenes as host molecules in novel drug delivery systems

The Effect of Temperature on the Absorption and Fluorescence Spectra of Impurity Crystals

A meta-analysis approach was used to assess the effect of dredging induced changes in sediment composition, under different conditions of natural physical disturbance, for the structure and function of marine benthic macrofaunal communities. Results showed the sensitivity of macrofaunal communities increased as both the proportion of gravel increased and the level of natural physical disturbance decreased. These findings may be explained by the close association of certain taxa with the gravel fraction, and the influence of natural physical disturbance which, as it increases, tends to restrict the colonisation by these species. We conclude that maintaining the gravel content of surface sediments after dredging and, where practicable, locating extraction sites in areas of higher natural disturbance will minimise the potential for long-term negative impacts on the macrofauna

Generalized Species Sampling Priors with Latent Beta reinforcements

Many popular Bayesian nonparametric priors can be characterized in terms of exchangeable species sampling sequences. However, in some applications, exchangeability may not be appropriate. We introduce a {novel and probabilistically coherent family of non-exchangeable species sampling sequences characterized by a tractable predictive probability function with weights driven by a sequence of independent Beta random variables. We compare their theoretical clustering properties with those of the Dirichlet Process and the two parameters Poisson-Dirichlet process. The proposed construction provides a complete characterization of the joint process, differently from existing work. We then propose the use of such process as prior distribution in a hierarchical Bayes modeling framework, and we describe a Markov Chain Monte Carlo sampler for posterior inference. We evaluate the performance of the prior and the robustness of the resulting inference in a simulation study, providing a comparison with popular Dirichlet Processes mixtures and Hidden Markov Models. Finally, we develop an application to the detection of chromosomal aberrations in breast cancer by leveraging array CGH data.Comment: For correspondence purposes, Edoardo M. Airoldi's email is [email protected]; Federico Bassetti's email is [email protected]; Michele Guindani's email is [email protected] ; Fabrizo Leisen's email is [email protected]. To appear in the Journal of the American Statistical Associatio

Constructing 3D crystal templates for photonic band gap materials using holographic optical tweezers

A simple and robust method is presented for the construction of 3-dimensional crystals from silica and polystyrene microspheres. The crystals are suitable for use as templates in the production of three-dimensional photonic band gap (PBG) materials. Manipulation of the microspheres was achieved using a dynamic holographic assembler (DHA) consisting of computer controlled holographic optical tweezers. Attachment of the microspheres was achieved by adjusting their colloidal interactions during assembly. The method is demonstrated by constructing a variety of 3-dimensional crystals using spheres ranging in size from 3 µm down to 800 nm. A major advantage of the technique is that it may be used to build structures that cannot be made using self-assembly. This is illustrated through the construction of crystals in which line defects have been deliberately included, and by building simple cubic structures

Palaeoproterozoic magnesite: lithological and isotopic evidence for playa/sabkha environments

Magnesite forms a series of 1- to 15-m-thick beds within the approximate to2.0 Ga (Palaeoproterozoic) Tulomozerskaya Formation, NW Fennoscandian Shield, Russia. Drillcore material together with natural exposures reveal that the 680-m-thick formation is composed of a stromatolite-dolomite-'red bed' sequence formed in a complex combination of shallow-marine and non-marine, evaporitic environments. Dolomite-collapse breccia, stromatolitic and micritic dolostones and sparry allochemical dolostones are the principal rocks hosting the magnesite beds. All dolomite lithologies are marked by delta C-13 values from +7.1 parts per thousand to +11.6 parts per thousand (V-PDB) and delta O-18 ranging from 17.4 parts per thousand to 26.3 parts per thousand (V-SMOW). Magnesite occurs in different forms: finely laminated micritic; stromatolitic magnesite; and structureless micritic, crystalline and coarsely crystalline magnesite. All varieties exhibit anomalously high delta C-13 values ranging from +9.0 parts per thousand to +11.6 parts per thousand and delta O-18 values of 20.0-25.7 parts per thousand. Laminated and structureless micritic magnesite forms as a secondary phase replacing dolomite during early diagenesis, and replaced dolomite before the major phase of burial. Crystalline and coarsely crystalline magnesite replacing micritic magnesite formed late in the diagenetic/metamorphic history. Magnesite apparently precipitated from sea water-derived brine, diluted by meteoric fluids. Magnesitization was accomplished under evaporitic conditions (sabkha to playa lake environment) proposed to be similar to the Coorong or Lake Walyungup coastal playa magnesite. Magnesite and host dolostones formed in evaporative and partly restricted environments; consequently, extremely high delta C-13 values reflect a combined contribution from both global and local carbon reservoirs. A C- 13-rich global carbon reservoir (delta C-13 at around +5 parts per thousand) is related to the perturbation of the carbon cycle at 2.0 Ga, whereas the local enhancement in C-13 (up to +12 parts per thousand) is associated with evaporative and restricted environments with high bioproductivity

Poly(allylamine) magnetomicelles for image guided drug delivery.

Polymeric micelles have received considerable interest for their use as drug delivery vehicles for hydrophobic drug solubilisation. Inorganic metallic nanoparticles have already been exploited clinically in diagnostics for their contrast ability, using magnetic resonance imaging. The combination of these two platforms results in a multifunctional drug carrier for image-guided drug delivery. Here we report the synthesis and evaluation of a new class of poly(allylamine) (PAA) polymer grafted with hydrophobic oxadiazole (Ox) pendant group in a 5% molar monomer: pendant ratio. Further, the thiol-containing pendant group facilitated the attachment of hybrid iron oxide-gold nanoparticles (HNPs) via dative covalent bonding. Physicochemical characterisation of both PAA-Ox5 and PAA-Ox5-HNP polymers was carried out using elemental analysis, nuclear magnetic resonance (NMR), fourier transform infrared spectroscopy (FTIR) and photon correlation spectroscopy (PCS). The drug loading potential of these novel aggregates was investigated, through direct conjugation of hydrophilic and encapsulation of hydrophobic drugs, respectively. The model hydrophobic drugs 2,6- diisopropylphenol (propofol) and (2S,6'R)-7-chloro-2',4,6-trimethoxy-6'-methyl-3H,4'H-spiro[1-benzofuran-2,1'- cyclohex[2]ene]-3,4'-dione (griseofulvin), and the chemotherapeutic agents bisnapthalamidopropyldiaminooctane (BNIPDaoct) and 6-Thioguanine (6-TG) were used. The data showed that the addition of HNPs onto the PAA-Ox5 structure resulted in aggregates of 175 nm in diameter. The PAA-Ox5-HNP nano-aggregates were capable of high drug solubilisation capacities (25.79 mgmL-1, 1.68 mgmL-1 and 0.92 mgmL-1) for propofol, griseofulvin and BNIPDaoct, respectively. 6-TG was also successfully conjugated into the polymer structure (2.8 mgmL-1). In vitro assays on human pancreatic adenocarcinoma cells (BxPC-3) showed increased drug uptake and decreased IC50 values using the novel formulations compared with free drug. This study highlights the potential of PAA-Ox5-HNP as a bi-functional imaging and drug delivery platform

Moduli and (un)attractor black hole thermodynamics

We investigate four-dimensional spherically symmetric black hole solutions in gravity theories with massless, neutral scalars non-minimally coupled to gauge fields. In the non-extremal case, we explicitly show that, under the variation of the moduli, the scalar charges appear in the first law of black hole thermodynamics. In the extremal limit, the near horizon geometry is $AdS_2\times S^2$ and the entropy does not depend on the values of moduli at infinity. We discuss the attractor behaviour by using Sen's entropy function formalism as well as the effective potential approach and their relation with the results previously obtained through special geometry method. We also argue that the attractor mechanism is at the basis of the matching between the microscopic and macroscopic entropies for the extremal non-BPS Kaluza-Klein black hole.Comment: 36 pages, no figures, V2: minor changes, misprints corrected, expanded references; V3: sections 4.3 and 4.5 added; V4: minor changes, matches the published versio

Processing of ultrafine-size particulate metal matrix composites by advanced shear technology

Copyright @ 2009 ASM International. This paper was published in Metallurgical & Materials Transactions A 40A(3) and is made available as an electronic reprint with the permission of ASM International. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplications of any material in this paper for a fee or for commercial purposes, or modification of the content of this paper are prohibited.Lack of efficient mixing technology to achieve a uniform distribution of fine-size reinforcement within the matrix and the high cost of producing components have hindered the widespread adaptation of particulate metal matrix composites (PMMCs) for engineering applications. A new rheo-processing method, the melt-conditioning high-pressure die-cast (MC-HPDC) process, has been developed for manufacturing near-net-shape components of high integrity. The MC-HPDC process adapts the well-established high shear dispersive mixing action of a twin-screw mechanism to the task of overcoming the cohesive force of the agglomerates under a high shear rate and high intensity of turbulence. This is followed by direct shaping of the slurry into near-net-shape components using an existing cold-chamber die-casting process. The results indicate that the MC-HPDC samples have a uniform distribution of ultrafine-sized SiC particles throughout the entire sample in the as-cast condition. Compared to those produced by conventional high-pressure die casting (HPDC), MC-HPDC samples have a much improved tensile strength and ductility.EP-SR

Telomere fusion threshold identifies a poor prognostic subset of breast cancer patients

Telomere dysfunction and fusion can drive genomic instability and clonal evolution in human tumours, including breast cancer. Telomere length is a critical determinant of telomere function and has been evaluated as a prognostic marker in several tumour types, but it has yet to be used in the clinical setting. Here we show that high-resolution telomere length analysis, together with a specific telomere fusion threshold, is highly prognostic for overall survival in a cohort of patients diagnosed with invasive ductal carcinoma of the breast (n = 120). The telomere fusion threshold defined a small subset of patients with an extremely poor clinical outcome, with a median survival of less than 12 months (HR = 21.4 (7.9-57.6), P < 0.0001). Furthermore, this telomere length threshold was independent of ER, PGR, HER2 status, NPI, or grade and was the dominant variable in multivariate analysis. We conclude that the fusogenic telomere length threshold provides a powerful, independent prognostic marker with clinical utility in breast cancer. Larger prospective studies are now required to determine the optimal way to incorporate high-resolution telomere length analysis into multivariate prognostic algorithms for patients diagnosed with breast cancer

Processing of aluminum-graphite particulate metal matrix composites by advanced shear technology

Copyright @ 2009 ASM International. This paper was published in Journal of Materials Engineering and Performance 18(9) and is made available as an electronic reprint with the permission of ASM International. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplications of any material in this paper for a fee or for commercial purposes, or modification of the content of this paper are prohibited.To extend the possibilities of using aluminum/graphite composites as structural materials, a novel process is developed. The conventional methods often produce agglomerated structures exhibiting lower strength and ductility. To overcome the cohesive force of the agglomerates, a melt conditioned high-pressure die casting (MC-HPDC) process innovatively adapts the well-established, high-shear dispersive mixing action of a twin screw mechanism. The distribution of particles and properties of composites are quantitatively evaluated. The adopted rheo process significantly improved the distribution of the reinforcement in the matrix with a strong interfacial bond between the two. A good combination of improved ultimate tensile strength (UTS) and tensile elongation (e) is obtained compared with composites produced by conventional processes.EPSR