Genetic variants of angiotensin converting enzyme and methylenetetrahydrofolate reductase may act in combination to increase migraine susceptibility

Migraine, with and without aura (MA and MO), is a prevalent and complex neurovascular disorder that is likely to be influenced by multiple genes some of which may be capable of causing vascular changes leading to disease onset. This study was conducted to determine whether the ACE I/D gene variant is involved in migraine risk and whether this variant might act in combination with the previously implicated MTHFR C677T genetic variant in 270 migraine cases and 270 matched controls. Statistical analysis of the ACE I/D variant indicated no significant difference in allele or genotype frequencies (P > 0.05). However, grouping of genotypes showed a modest, yet significant, over-representation of the DD/ID genotype in the migraine group (88%) compared to controls (81%) (OR of 1.64, 95% CI: 1.00–2.69, P = 0.048). Multivariate analysis, including genotype data for the MTHFR C677T, provided evidence that the MTHFR (TT) and ACE (ID/DD) genotypes act in combination to increase migraine susceptibility (OR = 2.18, 95% CI: 1.15–4.16, P = 0.018). This effect was greatest for the MA subtype where the genotype combination corresponded to an OR of 2.89 (95% CI:1.47–5.72, P = 0.002). In Caucasians, the ACE D allele confers a weak independent risk to migraine susceptibility and also appears to act in combination with the C677T variant in the MTHFR gene to confer a stronger influence on the disease.

Vibrational spectroscopic characterization of the phosphate mineral barbosalite Fe2+Fe3+2(PO4)2(OH)2 : implications for the molecular structure

Natural single-crystal specimens of barbosalite from Brazil, with general formula Fe2+Fe3+ 2 (PO4)2(OH)2 were investigated by Raman and infrared spectroscopy. The mineral occurs as secondary products in granitic pegmatites. The Raman spectrum of barbosalite is characterized by bands at 1020, 1033 and 1044 cm−1 cm−1, assigned to ν1 symmetric stretching mode of the HOPO3- 3 and PO3- 4 units. Raman bands at around 1067, 1083 and 1138 cm−1 are attributed to both the HOP and PO antisymmetric stretching vibrations. The set of Raman bands observed at 575, 589 and 606 cm−1 are assigned to the ν4 out of plane bending modes of the PO4 and H2PO4 units. Raman bands at 439, 461, 475 and 503 cm−1 are attributed to the ν2 PO4 and H2PO4 bending modes. Strong Raman bands observed at 312, 346 cm−1 with shoulder bands at 361, 381 and 398 cm−1 are assigned to FeO stretching vibrations. No bands which are attributable to water vibrations were found. Vibrational spectroscopy enables aspects of the molecular structure of barbosalite to be assessed.

Vibrational spectroscopic characterization of the phosphate mineral althausite Mg2(PO4)(OH,F,O) – implications for the molecular structure

Natural single-crystal specimens of althausite from Brazil, with general formula Mg2(PO4)(OH,F,O) were investigated by Raman and infrared spectroscopy. The mineral occurs as a secondary product in granitic pegmatites. The Raman spectrum of althausite is characterized by bands at 1020, 1033 and 1044 cm-1, assigned to ν1 symmetric stretching modes of the HOPO33- and PO43- units. Raman bands at around 1067, 1083 and 1138 cm-1 are attributed to both the HOP and PO antisymmetric stretching vibrations. The set of Raman bands observed at 575, 589 and 606 cm-1 are assigned to the ν4 out of plane bending modes of the PO4 and H2PO4 units. Raman bands at 439, 461, 475 and 503 cm-1 are attributed to the ν2 PO4 and H2PO4 bending modes. Strong Raman bands observed at 312, 346 cm-1 with shoulder bands at 361, 381 and 398 cm-1 are assigned to MgO stretching vibrations. No bands which are attributable to water were found. Vibrational spectroscopy enables aspects of the molecular structure of althausite to be assessed.

Pro-osteogenic topographical cues promote early activation of osteoprogenitor differentiation via enhanced TGFβ, Wnt, and Notch signaling

Objectives Titanium implant surfaces with modified topographies have improved osteogenic properties in vivo. However, the molecular mechanisms remain obscure. This study explored the signaling pathways responsible for the pro-osteogenic properties of micro-roughened (SLA) and chemically/nanostructurally (modSLA) modified titanium surfaces on human alveolar bone-derived osteoprogenitor cells (BCs) in vitro. Materials and methods The activation of stem cell signaling pathways (TGFβ/BMP, Wnt, FGF, Hedgehog, Notch) was investigated following early exposure (24 and 72 h) of BCs to SLA and modSLA surfaces in the absence of osteogenic cell culture supplements. Results Key regulatory genes from the TGFβ/BMP (TGFBR2, BMPR2, BMPR1B, ACVR1B, SMAD1, SMAD5), Wnt (Wnt/β-catenin and Wnt/Ca2+) (FZD1, FZD3, FZD5, LRP5, NFATC1, NFATC2, NFATC4, PYGO2, LEF1) and Notch (NOTCH1, NOTCH2, NOTCH4, PSEN1, PSEN2, PSENEN) pathways were upregulated on the modified surfaces. These findings correlated with a higher expression of osteogenic markers bone sialoprotein (IBSP) and osteocalcin (BGLAP), and bone differentiation factors BMP2, BMP6, and GDF15, as observed on the modified surfaces. Conclusions These findings demonstrate that the activation of the pro-osteogenic cell signaling pathways by modSLA and SLA surfaces leads to enhanced osteogenic differentiation as evidenced after 7 and 14 days culture in osteogenic media and provides a mechanistic insight into the superior osseointegration on the modified surfaces observed in vivo.

RanGTPase : a candidate for myc-mediated cancer progression

Background Ras-related nuclear protein (Ran) is required for cancer cell survival in vitro and human cancer progression, but the molecular mechanisms are largely unknown. Methods We investigated the effect of the v-myc myelocytomatosis viral oncogene homolog (Myc) on Ran expression by Western blot, chromatin immunoprecipitation, and luciferase reporter assays and the effects of Myc and Ran expression in cancer cells by soft-agar, cell adhesion, and invasion assays. The correlation between Myc and Ran and the association with patient survival were investigated in 14 independent patient cohorts (n = 2430) and analyzed with Spearman's rank correlation and Kaplan-Meier plots coupled with Wilcoxon-Gehan tests, respectively. All statistical tests were two-sided. Results Myc binds to the upstream sequence of Ran and transactivates Ran promoter activity. Overexpression of Myc upregulates Ran expression, whereas knockdown of Myc downregulates Ran expression. Myc or Ran overexpression in breast cancer cells is associated with cancer progression and metastasis. Knockdown of Ran reverses the effect induced by Myc overexpression in breast cancer cells. In clinical data, a positive association between Myc and Ran expression was revealed in 288 breast cancer and 102 lung cancer specimens. Moreover, Ran expression levels differentiate better or poorer survival in Myc overexpressing breast (χ2 = 24.1; relative risk [RR] = 9.1, 95% confidence interval [CI] = 3.3 to 24.7, P <. 001) and lung (χ2 = 6.04; RR = 2.8, 95% CI = 1.2 to 6.3; P =. 01) cancer cohorts. Conclusions Our results suggest that Ran is required for and is a potential therapeutic target of Myc-driven cancer progression in both breast and lung cancers. © 2013 The Author.

Modeling the effectiveness of counterterrorism interventions

After the terrorist attacks in the United States on 11 September 2001, terrorism and counter-terrorism efforts moved to the front of popular consciousness and became the focus of national security for governments worldwide. With this increased attention came an urgent interest in understanding and identifying what works in fighting terrorism (Belasco 2010). For Australia, understanding the relative effectiveness of counter-terrorism efforts in nearby neighbours of Indonesia, Thailand and the Philippines is highly relevant for our country's national security. Indonesia, Thailand and the Philippines are all countries that are important to Australia not just because of geographic proximity, but also because of a history of economic ties and the role these countries play as Australia’s regional partners...

"Improper" caveats and compensation - section 130 of the Land Title Act 1994

This article examines some questions of statutory interpretation as they apply to section 130 of the Land Title Act 1994 (Qld)

Treatment plan complexity metrics for predicting IMRT pre-treatment quality assurance results

The planning of IMRT treatments requires a compromise between dose conformity (complexity) and deliverability. This study investigates established and novel treatment complexity metrics for 122 IMRT beams from prostate treatment plans. The Treatment and Dose Assessor software was used to extract the necessary data from exported treatment plan files and calculate the metrics. For most of the metrics, there was strong overlap between the calculated values for plans that passed and failed their quality assurance (QA) tests. However, statistically significant variation between plans that passed and failed QA measurements was found for the established modulation index and for a novel metric describing the proportion of small apertures in each beam. The ‘small aperture score’ provided threshold values which successfully distinguished deliverable treatment plans from plans that did not pass QA, with a low false negative rate.

Time pressure and coworker support mediate the curvilinear relationship between age and occupational well-being

As the proportion of older employees in the workforce is growing, researchers have become increasingly interested in the association between age and occupational well-being. The curvilinear nature of relationships between age and job satisfaction and between age and emotional exhaustion is well-established in the literature, with employees in their late 20s to early 40s generally reporting lower levels of occupational well-being than younger and older employees. However, the mechanisms underlying these curvilinear relationships are so far not well understood due to a lack of studies testing mediation effects. Based on an integration of role theory and research from the adult development and career literatures, this study examined time pressure, work–home conflict, and coworker support as mediators of the relationships between age and job satisfaction and between age and emotional exhaustion. Data came from 771 employees between 17 and 74 years of age in the construction industry. Results showed that employees in their late 20s to early 40s had lower job satisfaction and higher emotional exhaustion than younger and older employees. Time pressure and coworker support fully mediated both the U-shaped relationship between age and job satisfaction and the inversely U-shaped relationship between age and emotional exhaustion. These findings suggest that organizational interventions may help increase the relatively low levels of occupational well-being in certain age groups.

SiC-like phase and room-temperature photoluminescence of low-k SiOCH films

Carbon-doped hydrogenated silicon oxide (SiOCH) low-k films have been prepared using 13.56 MHz discharge in trimethylsilane (3MS) - oxygen gas mixtures at 3, 4, and 5 Torr sustained with RF power densities 1.3 - 2.6 W/cm2. The atomic structure of the SiOCH films appears to be a mixture the amorphous SiO2-like and the partially polycrystalline SiC-like phases. Results of the infra-red spectroscopy reflect the increment in the volume fraction of the SiC-like phase from 0.22 - 0.28 to 0.36 - 0.39 as the RF power increment. Steady-state near-UV laser-excited (364 nm wavelength, 40±2 mW) photoluminescence (PL) has been studied at room temperatures in the visible (1.8 eV - 3.1 eV) subrange of photon spectrum. Two main bands of the PL signal (at the photon energies of 2.5 - 2.6 eV and 2.8 - 2.9 eV) are observed. Intensities of the both bands are changed monotonically with RF power, whereas the bandwidth of ∼0.1 eV remains almost invariable. It is likely that the above lines are dumped by the non-radiative recombination involving E1-like centres in the amorphous-nanocrystalline SiC-like phases. Such explanation of the PL intensity dependences on the RF power density is supported by results of experimental studies of defect states spectrum in bandgap of the SiOCH films.

A non-malleable group key exchange protocol robust against active insiders

In this paper we make progress towards solving an open problem posed by Katz and Yung at CRYPTO 2003. We propose the first protocol for key exchange among n ≥2k+1 parties which simultaneously achieves all of the following properties: 1. Key Privacy (including forward security) against active attacks by group outsiders, 2. Non-malleability — meaning in particular that no subset of up to k corrupted group insiders can ‘fix’ the agreed key to a desired value, and 3. Robustness against denial of service attacks by up to k corrupted group insiders. Our insider security properties above are achieved assuming the availability of a reliable broadcast channel.

Altered JS-2 expression in colorectal cancers and its clinical pathological relevance

JS-2 is a novel gene located at 5p15.2 and originally detected in primary oesophageal cancer. There is no study on the role of JS-2 in colorectal cancer. The aim of this study is to determine the gene copy number and expression of JS-2 in a large cohort of patients with colorectal tumours and correlate these to the clinicopathological features of the cancer patients. We evaluated the DNA copy number and mRNA expression of JS-2 in 176 colorectal tissues (116 adenocarcinomas, 30 adenomas and 30 non-neoplastic tissues) using real-time polymerase chain reaction. JS-2 expression was also evaluated in two colorectal cancer cell lines and a benign colorectal cell line. JS-2 amplification was noted in 35% of the colorectal adenocarcinomas. Significant differences in relative expression levels for JS-2 mRNA between different colorectal tissues were noted (p = 0.05). Distal colorectal adenocarcinoma had significantly higher copy number than proximal adenocarcinoma (p = 0.005). The relative expression level of JS-2 was different between colonic and rectal adenocarcinoma (p = 0.007). Mucinous adenocarcinoma showed higher JS-2 expression than non-mucinous adenocarcinoma (p = 0.02). Early T-stage cancers appear to have higher JS-2 copy number and lower expression of JS-2 mRNA than later stage cancers (p = 0.001 and 0.03 respectively). Colorectal cancer cell lines showed lower expression of JS-2 than the benign colorectal cell line. JS-2 copy number change and expression were shown for the first time to be altered in the carcinogenesis of colorectal cancer. In addition, genetic alteration of JS-2 was found to be related to location, pathological subtypes and staging of colorectal cancer.

Improving boiler performance with modified boiler control systems

For timely processing of the crop, sugar factories need boiler stations that can reliably produce steam when fired with fuel of variable quality. The control systems installed on most sugar factory boilers have changed little in the last thirty years and in some cases the default control system response to changes in fuel and/or fuel quality is not correct and operator intervention is required to prevent factory stoppages or reductions in crushing rate caused by poor combustion. Some factories have recently modified their boiler control systems for improved combustion performance and reduced maintenance costs. This paper describes testing carried out to evaluate some of these control system modifications and identifies boiler control system changes that can be applied more widely in the sugar industry.