BRAF Gene and Melanoma: Back to the Future

As widely acknowledged, 40–50% of all melanoma patients harbour an activating BRAF mutation (mostly BRAF V600E). The identification of the RAS–RAF–MEK–ERK (MAP kinase) signalling pathway and its targeting has represented a valuable milestone for the advanced and, more recently, for the completely resected stage III and IV melanoma therapy management. However, despite progress in BRAF-mutant melanoma treatment, the two different approaches approved so far for metastatic disease, immunotherapy and BRAF+MEK inhibitors, allow a 5-year survival of no more than 60%, and most patients relapse during treatment due to acquired mechanisms of resistance. Deep insight into BRAF gene biology is fundamental to describe the acquired resistance mechanisms (primary and secondary) and to understand the molecular pathways that are now being investigated in preclinical and clinical studies with the aim of improving outcomes in BRAF-mutant patients.     

Effects of a single dose of N-Acetyl-5-methoxytryptamine (Melatonin) and resistance exercise on the growth hormone/IGF-1 axis in young males and females

Melatonin and resistance exercise alone have been shown to increase the levels of growth hormone (GH). The purpose of this study was to determine the effects of ingestion of a single dose of melatonin and heavy resistance exercise on serum GH, somatostatin (SST), and other hormones of the GH/insulin-like growth factor 1 (IGF-1) axis. Physically active males (n = 30) and females (n = 30) were randomly assigned to ingest either a melatonin supplement at 0.5 mg or 5.0 mg, or 1.0 mg of dextrose placebo. After a baseline blood sample, participants ingested the supplement and underwent blood sampling every 15 min for 60 min, at which point they underwent a single bout of resistance exercise with the leg press for 7 sets of 7 reps at 85% 1-RM. After exercise, participants provided additional blood samples every 15 min for a total of 120 min. Serum free GH, SST, IGF-1, IGFBP-1, and IGFBP-3 were determined with ELISA. Data were evaluated as the peak pre- and post-exercise values subtracted from baseline and the delta values analyzed with separate three-way ANOVA (p < 0.05). In males, when compared to placebo, 5.0 mg melatonin caused GH to increase (p = 0.017) and SST to decrease prior to exercise (p = 0.031), whereas both 0.5 and 5.0 mg melatonin were greater than placebo after exercise (p = 0.045) and less than placebo for SST. No significant differences occurred for IGF-1; however, males were shown to have higher levels of IGFBP-1 independent of supplementation (p = 0.004). The 5.0 mg melatonin dose resulted in higher IGFBP-3 in males (p = 0.017). In conclusion, for males 5.0 mg melatonin appears to increase serum GH while concomitantly lowering SST levels; however, when combined with resistance exercise both melatonin doses positively impacts GH levels in a manner not entirely dependent on SST.     

Effect of Visual Cues and a Mixture of Isothiocyanates on Trap Capture of Cabbage Seed Weevil, Ceutorhynchus assimilis

The effect of trap design, trap color, and a mixture of isothiocyanates on the capture of Ceutorhynchus assimilis (Paykull) was studied in a series of field experiments. Unbaited yellow water traps, a yellow sticky box trap, and a yellow sticky card trap, mounted vertically, or at 45° to the vertical with the yellow card facing upwards were effective for capturing seed weevils, but a horizontal yellow sticky card trap caught few. White, green, and black traps were unattractive. During migratory periods, trap catch could be enhanced two to four times with a lure consisting of a mixture of allyl, 3-butenyl, 4-pentenyl, and 2-phenylethyl isothiocyanates, but this bait did not attract in a trap with ineffective design. The sticky card trap, mounted at 45° to the vertical and baited with the isothiocyanate mixture, may be useful for monitoring movement of C. assimilis during migratory periods. However, during the colonization phase, lures of either a mixture of isothiocyanates or of allyl isothiocyanate alone were not attractive.     

Mobil Zeolite Catalysts for Monomers

It has been about 20 years since Plank, Rosinski, and Hawthorne reported their spectacular results with metal-modified zeolite cracking catalysts for more efficient production of gasoline [1]. This discovery has saved an estimated 200 million barrels of crude oil each year in the United States alone [2]. In 1972, a patent by Argauer and Landolt described the preparation of a member of a generation of new synthetic zeolites, called ZSM- 5. It was unique because of its high silica/alumina ratio and greatly reduced coking rates for reactions with hydrocarbons by comparison with known low silica zeolites [3]. This material was an early member of a series of over 50 synthetic zeolitic substances prepared in Mobil laboratories.     

Delayed conversion of squalene to sterols during development ofPinus pinea seeds

During germination of seeds of the gymnosperm,Pinus pinea, radioactivity from [2-¹⁴C]-mevalonate proceeded principally through the anaerobic reactions leading to squalene in the first 24 hr in both the haploid endosperm and the diploid embryo, and only with succeeding time (3–9 days) in both cases was label transferred to sterols in oxygen-requiring steps. The rates of turnover must be real and independent in the two tissues, since no consequential interchange of labelled lipids occurred between the endosperm and the embryo. Similar delayed conversion of squalene to sterols has been observed previously during germination of seeds of the angiosperm,Pisum sativum.     

Cellulose-binding domains: potential for purification of complex proteins

The endoglucanase CenA and the exoglucanase Cex from Cellulomonasfimi each contain a discrete cellulose-binding domain (CBD),at the amino-terminus or carboxyl-terminus respectively. Thegene fragment encoding the CBD can be fused to the gene of aprotein of interest. Using this approach hybrid proteins canbe engineered which bind reversibly to cellulose and exhibitthe biological activity of the protein partner. Alkaline phosphatase(PhoA) from Escherichia coli, and a ß-glucosidase(Abg) from an Agrobacterium sp. are dimeric proteins. The fusionpolypeptides CenA-PhoA and Abg-CBC_cex are sensitive to proteolysisat the junctions between the fusion partners. Proteolysis resultsin a mixture of homo- and heterodimers; these bind to celluloseif one or both of the monomers carry a CBD, e.g. CenA-PhoA/CenA-PhoAand CenA-PhoA/PhoA. CBD fusion polypeptides could be used inthis way to purify polypeptides which associate with the fusionpartner.     

Development of a virtual reality laboratory stressor

Virtual Reality - This research report describes the development of a virtual reality (VR) laboratory stressor to study the effects of exposure to stressful events. The aim of the research was to...     

Privacy Preserving Geo-Linkage in the Big Urban Data Era

Big data technologies and a range of Government open data initiatives provide the basis for discovering new insights into cities; how they are planned, how they managed and the day-to-day challenges they face in health, transport and changing population profiles. The Australian Urban Research Infrastructure Network (AURIN – www.aurin.org.au) project is one example of such a big data initiative that is currently running across Australia. AURIN provides a single gateway providing online (live) programmatic access to over 2000 data sets from over 70 major and typically definitive data-driven organizations across federal and State government, across industry and across academia. However whilst open (public) data is useful to bring data-driven intelligence to cities, more often than not, it is the data that is not-publicly accessible that is essential to understand city challenges and needs. Such sensitive (unit-level) data has unique requirements on access and usage to meet the privacy and confidentiality demands of the associated organizations. In this paper we highlight a novel geo-privacy supporting solution implemented as part of the AURIN project that provides seamless and secure access to individual (unit-level) data from the Department of Health in Victoria. We illustrate this solution across a range of typical city challenges in localized contexts around Melbourne. We show how unit level data can be combined with other data in a privacy-protecting manner. Unlike other secure data access and usage solutions that have been developed/deployed, the AURIN solution allows any researcher to access and use the data in a manner that meets all of the associated privacy and confidentiality concerns, without obliging them to obtain ethical approval or any other hurdles that are normally put in place on access to and use of sensitive data. This provides a paradigm shift in secure access to sensitive data with geospatial content.     

Pareto-based negotiation in distributed multidisciplinary design

The process of distributed engineering design calls for a methodology making use of the most recent advances in optimization-based design including multidisciplinary and multiobjective optimization. In distributed design, the participating teams do not have access to the design problems of other teams but may exchange limited information about their own current designs, making negotiation among themselves a key mechanism to reach a desired compromise which, nevertheless, is also a Pareto design to the original problem. A mathematical model of this distributed but decomposable design process is posed and solved using Lagrangian relaxation, while Pareto optimality is equivalently converted to single-objective optimality by means of multicriteria decision making strategies. The proposed coordination algorithm allows negotiation among the teams (subproblems) by sharing only limited information that is restricted to values of optimization quantities. The proposed modeling and solution scheme is applied to a numerical example representing the design of vehicle subsystems and components.