bcl-2 and c-erbB-2 proteins are involved in the regulation of VEGF and of thymidine phosphorylase angiogenic activity in non-small-cell lung cancer

Tumour angiogenesis has been recently recognised as one of the most important prognostic factors in lung cancer. Although a variety of angiogenic factors have been identified, the angiogenesis process remains poorly understood. Bcl-2, c-erbB-2 and p53 are well-known oncogenes involved in non- small-cell lung cancer pathogenesis. A direct correlation of thymidine phosphorylase (TP) and of vascular endothelial growth factor (VEGF) with intratumoural angiogenesis has been reported. In the present study we investigated the possible regulatory role if bcl-2, c-erB-2 proteins in angiogenesis and in VEGF and TP expression in non-small-cell lung cancer. Two hundred sixteen specimens from T1,2-NO, 1 staged patients treated with surgery alone were immunohistochemically examined. Bcl-2 and c-erbB-2 were significantly inversely related to each other (P = 0.04) and both were inversely associated with microvessel density (P < 0.02). High TP and VEGF reactivity was statistically related to loss of bcl-2 expression (P < 0.01). A significant co-expression of c-erbB-2 with TP was noted (P = 0.01). However, TP expression was related to high angiogenesis only in cases with absence of c-erB-2 expression (P < 0.0001). c-erbB-2 expression in poorly vascularised tumours was linked with poor outcome (P = 0.03). The present study provides strong evidence that the bcl-2 gene has a suppressive function over genes involved in both angiogenesis (VEGF and TP) and cell migration (c- erbB-2) in NSCLC. TP and c-erbB-2 proteins are significantly, and often simultaneously, expressed in bcl-2 negative cases. However, expression of the c-erbB-2 abolishes the TP-related angiogenic activity. Whether this is a result of a direct activity of the c-erbB-2 protein or a consequence of a c- erbB-2-related immune response remains to be further investigated.

C. elegans RNA-dependent RNA polymerases rrf-1 and ego-1 silence Drosophila transgenes by differing mechanisms

Drosophila possesses the core gene silencing machinery but, like all insects, lacks the canonical RNA-dependent RNA polymerases (RdRps) that in C. elegans either trigger or enhance two major small RNA-dependent gene silencing pathways. Introduction of two different nematode RdRps into Drosophila showed them to be functional, resulting in differing silencing activities. While RRF-1 enhanced transitive dsRNA-dependent silencing, EGO-1 triggered dsRNA-independent silencing, specifically of transgenes. The strain w; da-Gal4; UAST-ego-1, constitutively expressing ego-1, is capable of silencing transgene including dsRNA hairpin upon a single cross, which created a powerful tool for research in Drosophila. In C. elegans, EGO-1 is involved in transcriptional gene silencing (TGS) of chromosome regions that are unpaired during meiosis. There was no opportunity for meiotic interactions involving EGO-1 in Drosophila that would explain the observed transgene silencing. Transgene DNA is, however, unpaired during the pairing of chromosomes in embryonic mitosis that is an unusual characteristic of Diptera, suggesting that in Drosophila, EGO-1 triggers transcriptional silencing of unpaired DNA during embryonic mitosis. © 2012 Springer Basel.

Intranasal immunization with C. muridarum major outer membrane protein (MOMP) and cholera toxin elicits local production of neutralising IgA in the prostate

Successful control of sexually transmitted diseases (STDs) through vaccination will require the development of vaccine strategies that target protective immunity to both the female and male reproductive tracts (MRT). In the male, the immune privileged nature of the male reproductive tract provides a barrier to entry of serum immunoglobulins into the male reproductive ducts, thereby preventing the induction of protective immunity using conventional injectable vaccination techniques. In this study we investigated the potential of intranasal (IN) immunization to elicit anti-chlamydial immunity in BALB/c male mice. Intranasal immunization with Chlamydia muridarum major outer membrane protein (MOMP) admixed with cholera toxin (CT) resulted in high levels of MOMP-specific IgA in prostatic fluids (PF) and MOMP-specific IgA-secreting cells in the prostate. Prostatic fluid IgA inhibited in vitro infection of McCoy cells with C. muridarum. Using RT-PCR we also show that mRNA for the polymeric immunoglobulin receptor (PIgR), which transports IgA across mucosal epithelia, is expressed only in the prostate but not in other regions of the male reproductive ducts upstream of the prostate. These data suggest that using intranasal immunization to target IgA to the prostate may protect males against STDs while at the same time maintaining the state of immune privilege within the MRT.

Book review: ‘Cornea. Color Atlas & Synopsis of Clinical Ophthalmology. Wills Eye Institute’, by C.J. Rapuano. Wolters Kluwer/Lippincott Williams & Wilkins, Philadelphia 2012

This book is one in a series of seven atlases covering the ophthalmic sub-specialties: cornea, retina, glaucoma, oculoplastics, neuro-ophthalmology, uveitis and paediatrics. The author of Cornea and editor of the series is Christopher Rapuano, Attending Surgeon and Director of the Cornea Service at Wills Eye Hospital in Philadelphia, Pennsylvania, USA. In the introduction to the book, Rapuano states ‘The goal of this series is to provide an up-to-date clinical overview of the major areas of ophthalmology for students, residents and practitioners in all the healthcare professions’...

The first x-ray diffraction peak of water as a function of temperature in the range 4 – 63 °C

X-ray diffraction structure functions for water flowing in a 1.5 mm diameter siphon in the temperature range 4 – 63 °C were obtained using a 20 keV beam at the Australian Synchrotron. These functions were compared with structure functions obtained at the Advanced Light Source for a 0.5 mm thick sample of water in the temperature range 1 – 77 °C irradiated with an 11 keV beam. The two sets of structure functions are similar, but there are subtle differences in the shape and relative position of the two functions suggesting a possible differences between the structure of bulk and siphon water. In addition, the first structural peak (Q0) for water in a siphon, showed evidence of a step-wise increase in Q0 with increasing temperature rather than a smoothly varying increase. More experiments are required to investigate this apparent difference.

Incorporating anchored learning in a C# Intelligent Tutoring System

Learning programming is known to be difficult. One possible reason why students fail programming is related to the fact that traditional learning in the classroom places more emphasis on lecturing the material instead of applying the material to a real application. For some students, this teaching model may not catch their interest. As a result they may not give their best effort to understand the material given. Seeing how the knowledge can be applied to real life problems can increase student interest in learning. As a consequence, this will increase their effort to learn. Anchored learning that applies knowledge to solve real life problems may be the key to improving student performance. In anchored learning, it is necessary to provide resources that can be accessed by the student as they learn. These resources can be provided by creating an Intelligent Tutoring System (ITS) that can support the student when they need help or experience a problem. Unfortunately, there is no ITS developed for the programming domain that has incorporated anchored learning in its teaching system. Having an ITS that supports anchored learning will not only be able to help the student learn programming effectively but will also make the learning process more enjoyable. This research tries to help students learn C# programming using an anchored learning ITS named CSTutor. Role playing is used in CSTutor to present a real world situation where they develop their skills. A knowledge base using First Order Logic is used to represent the student's code and to give feedback and assistance accordingly.

The politics of open-access publishing : M/C Journal, Public Intellectualism, and Academic Discourses of Legitimacy

This article investigates the discourses of academic legitimacy that surround the production, consumption, and accreditation of online scholarship. Using the web-based media and cultural studies journal (http://journal.media-culture.org.au) as a case study, it examines how online scholarly journals often position themselves as occupying a space between the academic and the popular and as having a functional advantage over print-based media in promoting a spirit of public intellectualism. The current research agenda of both government and academe prioritises academic research that is efficient, self-promoting, and relevant to the public. Yet, although the cost-effectiveness and public-intellectual focus of online scholarship speak to these research priorities, online journals such as M/C Journal have occupied, and continue to occupy, an unstable position in relation to the perceived academic legitimacy of their content. Although some online scholarly journals have achieved a limited form of recognition within a system of accreditation that still privileges print-based scholarship, I argue that this, nevertheless, points to the fact that traditional textual notions of legitimate academic work continue to pervade the research agenda of an academe that increasingly promotes flexible delivery of teaching and online research initiatives.

Design of an integrated platform for V2X wireless communications and positioning supporting C-ITS safety applications

In this paper, an integrated inter-vehicles wireless communications and positioning system supporting alternate positioning techniques is proposed to meet the requirements of safety applications of Cooperative Intelligent Transportation Systems (C-ITS). Recent advances have repeatedly demonstrated that road safety problems can be to a large extent addressed via a range of technologies including wireless communications and positioning in vehicular environments. The novel communication stack utilizing a dedicated frequency spectrum (e.g. at 5.9 GHz band), known as Dedicated Short-Range Communications (DSRC), has been particularly designed for Wireless Access in Vehicular Environments (WAVE) to support safety applications in highly dynamic environments. Global Navigation Satellite Systems (GNSS) is another essential enabler to support safety on rail and roads. Although current vehicle navigation systems such as single frequency Global Positioning System (GPS) receivers can provide route guidance with 5-10 meters (road-level) position accuracy, positioning systems utilized in C-ITS must provide position solutions with lane-level and even in-lane-level accuracies based on the requirements of safety applications. This article reviews the issues and technical approaches that are involved in designing a vehicular safety communications and positioning architecture; it also provides technological solutions to further improve vehicular safety by integrating the DSRC and GNSS-based positioning technologies.

Organo-LDH synthesized via tricalcium aluminate hydration in the present of Na-dodecylbenzenesulfate aqueous solution and subsequent investigated by near-infrared and mid-infrared

Na-dodecylbenzenesulfate (SDBS), a natural anionic surfactant, has been successfully intercalated into a Ca based LDH host structure during tricalcium aluminate hydration in the presence of SDBS aqueous solution (CaAl-SDBS-LDH). The resulting product was characterized by powder X-ray diffraction (XRD), mid-infrared (MIR) spectroscopy combined with near-infrared (NIR) spectroscopy technique, thermal analysis (TG–DTA) and scan electron microscopy (SEM). The XRD results revealed that the interlayer distance of resultant product was expanded to 30.46 Å. MIR combined with NIR spectra offered an effective method to illustrate this intercalation. The NIR spectra (6000–5500 cm−1) displayed prominent bands to expound SDBS intercalated into hydration product of C3A. And the bands around 8300 cm−1 were assigned to the second overtone of the first fundamental of CH stretching vibrations of SDBS. In addition, thermal analysis showed that the dehydration and dehydroxylation took place at ca. 220 °C and 348 °C, respectively. The SEM results appeared approximately hexagonal platy crystallites morphology for CaAl-SDBS-LDH, with particle size smaller and thinner.

Does DE need a C? A proposal for a DE curriculum

The vision of a digital earth (DE) is continuously evolving, and the next-generation infrastructures, platforms and applications are being implemented. In this article, we attempt to initiate a debate within the DE and with affine communities about 'why' a digital earth curriculum (DEC) is needed, 'how' it should be developed, and 'what' it could look like. It is impossible to do justice to the Herculean effort of DEC development without extensive consultations with the broader community. We propose a frame for the debate (what, why, and how of a DEC) and a rationale for and elements of a curriculum for educating the coming generations of digital natives and indicate possible realizations. We particularly argue that a DEC is not a déjà vu of classical research and training agendas of geographic information science, remote sensing, and similar fields by emphasizing its unique characteristics.

On the importance of an acid additive in the synthesis of pyrido[1,2-a]benzimidazoles by direct copper-catalyzed amination

Pyrido[1,2-a]benzimidazoles1, 2a are interesting compounds both from the viewpoint of medicinal chemistry2–7 (solubility,7 DNA intercalation3) and materials chemistry8 (fluorescence). Of note among the former is the antibiotic drug Rifaximin,5 which contains this heteroaromatic core. The classical synthetic approach for the assembly of pyrido[1,2-a]benzimidazoles is by [3+3] cyclocondensation of benzimidazoles containing a methylene group at C2 with appropriate bielectrophiles.2a However, these procedures are often low-yielding, involve indirect/lengthy sequences, and/or provide access to a limited range of products, primarily providing derivatives with substituents located on the pyridine ring (A ring, Scheme 1).2–4 Theoretically, a good alternative synthetic method for the synthesis of pyrido[1,2-a]benzimidazoles with substituents in the benzene ring (C ring) should be accessible by intramolecular transition-metal-catalyzed CN bond formation in N-(2-chloroaryl)pyridin-2-amines, based on chemistry recently developed in our research group.9 These substrates themselves are easily available through SNAr or selective Pd-catalyzed amination10 of 2-chloropyridine with 2-chloroanilines.11 If a synthetic procedure that eliminated the need for preactivation of the 2-position of the 2-chloroarylamino entity could be developed, this would be even more powerful, as anilines are more readily commercially available than 2-chloroanilines. Therefore the synthesis of pyrido[1,2-a]benzimidazoles (4) by a transition-metal-catalyzed intramolecular CH amination approach from N-arylpyridin-2-amines (3) was explored (Scheme 1).

Reactions of simple and peptidic alpha-carboxylate radical anions with dioxygen in the gas phase

alpha-Carboxylate radical anions are potential reactive intermediates in the free radical oxidation of biological molecules (e. g., fatty acids, peptides and proteins). We have synthesised well-defined alpha-carboxylate radical anions in the gas phase by UV laser photolysis of halogenated precursors in an ion-trap mass spectrometer. Reactions of isolated acetate ((center dot)CH(2)CO(2)) and 1-carboxylatobutyl (CH(3)CH(2)CH(2)(center dot)CHCO(2)(-)) radical anions with dioxygen yield carbonate (CO(3)(center dot-)) radical anions and this chemistry is shown to be a hallmark of oxidation in simple and alkyl-substituted cross-conjugated species. Previous solution phase studies have shown that C(alpha)-radicals in peptides, formed from free radical damage, combine with dioxygen to form peroxyl radicals that subsequently decompose into imine and keto acid products. Here, we demonstrate that a novel alternative pathway exists for two alpha-carboxylate C(alpha)-radical anions: the acetylglycinate radical anion (CH(3)C(O)NH(center dot)CHCO(2)(-)) and the model peptide radical anion, YGGFG(center dot-). Reaction of these radical anions with dioxygen results in concerted loss of carbon dioxide and hydroxyl radical. The reaction of the acetylglycinate radical anion with dioxygen reveals a two-stage process involving a slow, followed by a fast kinetic regime. Computational modelling suggests the reversible formation of the C(alpha) peroxyl radical facilitates proton transfer from the amide to the carboxylate group, a process reminiscent of, but distinctive from, classical proton-transfer catalysis. Interestingly, inclusion of this isomerization step in the RRKM/ME modelling of a G3SX level potential energy surface enables recapitulation of the experimentally observed two-stage kinetics.

Electron capture of tetracyanoethylene oxide in the gas phase. Rearrangement of the parent radical anion to form [(NC)(3)C](-). A joint experimental and ab initio study

Capture of an electron by tetracyanoethylene oxide can initiate a number of decomposition pathways. One of these decompositions yields [(NC)3C]− as the ionic product. Ab initio calculations (at the B3LYP/6-31+G∗ level of theory) indicate that the formation of [(NC)3C]− is initiated by capture of an electron into the LUMO of tetracyanoethylene oxide to yield the anion radical [(NC)2C–O–C(CN)2]−· that undergoes internal nucleophilic substitution to form intermediate [(NC)3C–OCCN]−·. This intermediate dissociates to form [(NC)3C]− (m/z 90) as the ionic product. The radical (NC)3C· has an electron affinity of 4.0 eV (385 kJ mol−1). Ab initio calculations show that [(NC)3C]− is trigonal planar with the negative charge mainly on the nitrogens. A pictorial representation of this structure is the resonance structure formed from three degenerate contributing structures (NC)2–CCN−. The other product of the reaction is nominally (NCCO)·, but there is no definitive experimental evidence to indicate whether this radical survives intact, or decomposes to NC· and CO. The overall process [(NC)2C–O–C(CN)2]−· → [(NC)3C]− + (NCCO)· is calculated to be endothermic by 21 kJ mol−1 with an overall barrier of 268 kJ mol−1.

The Credit Act Advisory System (CAAS) : conversion from an expert system prototype to a C++ commercial system

CAAS is a rule-based expert system, which provides advice on the Victorial Credit Act 1984. It is currently in commercial use, and has been developed in conjunction with a law firm. It uses an object-oriented hybrid reasoning approach. The system was initially prototyped using the expert system shell NExpert Object, and was then converted into the C++ language. In this paper we describe the advantages that this methodology has, for both commercial and research development.