The Role of α1-Adrenoceptor Antagonists in the Treatment of Prostate and Other Cancers

This review evaluates the role of α-adrenoceptor antagonists as a potential treatment of prostate cancer (PCa). Cochrane, Google Scholar and Pubmed were accessed to retrieve sixty-two articles for analysis. In vitro studies demonstrate that doxazosin, prazosin and terazosin (quinazoline α-antagonists) induce apoptosis, decrease cell growth, and proliferation in PC-3, LNCaP and DU-145 cell lines. Similarly, the piperazine based naftopidil induced cell cycle arrest and death in LNCaP-E9 cell lines. In contrast, sulphonamide based tamsulosin did not exhibit these effects. In vivo data was consistent with in vitro findings as the quinazoline based α-antagonists prevented angiogenesis and decreased tumour mass in mice models of PCa. Mechanistically the cytotoxic and antitumor effects of the α-antagonists appear largely independent of α 1-blockade. The proposed targets include: VEGF, EGFR, HER2/Neu, caspase 8/3, topoisomerase 1 and other mitochondrial apoptotic inducing factors. These cytotoxic effects could not be evaluated in human studies as prospective trial data is lacking. However, retrospective studies show a decreased incidence of PCa in males exposed to α-antagonists. As human data evaluating the use of α-antagonists as treatments are lacking; well designed, prospective clinical trials are needed to conclusively demonstrate the anticancer properties of quinazoline based α-antagonists in PCa and other cancers.     

Glass with hydration-induced compressive stress profiles

A novel potassium phospho-aluminosilicate composition is described that can be strengthened by water vapor to achieve deep compressive stress (CS) profiles. Water vapor treatment at (A) 85°C and 85% relative humidity for 40 days results in a CS of 389 ± 20 MPa and a compressive depth of layer (DOL) of 18 ± 2 μm. When treated at (B) 160°C and 0.1 MPa for 7 days, a CS of 245 ± 20 MPa and a DOL of 40 ± 2 μm is achieved. Glasses with hydration-induced stress profiles can provide high retained strength following flaw introduction compared with ion-exchanged soda-lime silicate glass. Sample treatment B also has an exemplary Vickers indentation cracking threshold value greater than 20 kgf. The hydration profile determined by secondary ion mass spectrometry (SIMS) is shown to closely match the stress profile for these samples. SIMS analysis also shows that the depth of water enrichment correlates well with the depletion depth of phosphorus. The high tendency towards water-induced strengthening for this new type of glass even enables self-strengthening by the generation of a near-surface CS profile following exposure to ambient conditions.     

Improved additive manufacturing of silicon carbide parts via pressureless electric field-assisted sintering

High solids loading silicon carbide (SiC)-based aqueous slurries containing only .5 wt. % organic additives were utilized to create specimens of various geometries via an extrusion-based additive manufacturing (AM) technique. Pressureless electric field-assisted sintering was performed to densify each specimen without deformation. The combination of these techniques produced parts with >98% relative density despite containing only 5 wt.% oxide sintering additives. After sintering, specimens contained only the α-SiC and yttrium aluminum perovskite phases. This suggests the evolution of a nonequilibrium yttrium aluminate phase, as well as transformation from β-SiC to α-SiC. The fabrication method presented in this work has advantages over other AM techniques commonly used with SiC, because it does not require significant organic additives nor additional postprocessing steps such as chemical vapor infiltration or polymer impregnation and pyrolysis.     

Storage stability of poultry fat and diesel fuel mixtures: Part II - Chemical properties

This publication continues previously published work from the authors which evaluates the storage potential of poultry fat for its use as an unmodified biofuel in heat and steam generating systems [1]. The previous work examined the physical properties of these fats while this study is concerned with chemical properties. In this study poultry fat (biofuel) and its 20%, 40%, 60% and 80% mixtures with #2 pump diesel fuel were stored for 1 year at bench scale (1L) under controlled laboratory conditions at 4, 38, 54.4 °C and at 22 °C. One hundred percent of poultry fat was studied under these same conditions with and without an antioxidant additive. Twenty and eighty percent of poultry fat mixtures were also stored at pilot scale (250 gallons) under outdoor, ambient conditions. Chemical properties relevant to the use of these mixtures as a biofuel for industrial boilers were studied and tracked. These properties include Energy Values (BTU), Ultimate Analysis (carbon, hydrogen, oxygen, ash, nitrogen, and sulfur), moisture, impurities, unsaponafiables (MIU), and Free Fatty Acid Content. Energy content of the biofuel samples dropped over the course of the study with untreated biofuel losing 18.9% of its BTU value over the course of a year. Ultimate analyses showed an overall increase in carbon composition and a decrease in oxygen content. Hydrogen levels increased in most treatments as did overall ash and sulfur percent composition. MIU values increased, this overall increase was attributable to variable increases in insolubles and unsaponifiables. Free fatty acid levels increased in all treatments. Most of the chemical changes observed in this study were reduced by the addition of antioxidant to 100% biofuel.     

Applications of the psychotherapy phase model to clinically significant deterioration.

While previous research on deterioration has focused on identifying individuals at risk for negative outcomes, little is known about the nature or pattern by which deterioration occurs. The problem of deterioration is especially salient in training clinics; a setting in which higher deterioration rates have been reported. Two studies were designed to test the applicability of the phase model to deterioration in a training clinic and to replicate the model with a training clinic referral-base sample. In Study 1, the course of therapy was monitored for 135 clients. For the 38 clients who deteriorated during therapy, a model where increased symptoms (demediation) reliably preceded both decreased functioning (dehabilitation) and decreased well-being (demoralization) was found. In Study 2, the same three phases were prospectively monitored for 914 undergraduate students on a weekly basis throughout a single semester. For the 158 individuals who deteriorated during this time, a model where demediation reliably preceded dehabilitation, which preceded demoralization was found. These results have clinical implications for the use of tailored intervention strategies focusing on the deterioration phases. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Analysis of a complete DNA–protein affinity landscape

Properties of biological fitness landscapes are of interest to a wide sector of the life sciences, from ecology to genetics to synthetic biology. For biomolecular fitness landscapes, the information we currently possess comes primarily from two sources: sparse samples obtained from directed evolution experiments; and more fine-grained but less authentic information from ‘in silico’ models (such as NK-landscapes). Here we present the entire protein-binding profile of all variants of a nucleic acid oligomer 10 bases in length, which we have obtained experimentally by a series of highly parallel on-chip assays. The resulting complete landscape of sequence-binding pairs, comprising more than one million binding measurements in duplicate, has been analysed statistically using a number of metrics commonly applied to synthetic landscapes. These metrics show that the landscape is rugged, with many local optima, and that this arises from a combination of experimental variation and the natural structural properties of the oligonucleotides.