Polyalanine repeat polymorphism in RUNX2 is associated with site-specific fracture in post-menopausal females

Runt related transcription factor 2 (RUNX2) is a key regulator of osteoblast differentiation. Several variations within RUNX2 have been found to be associated with significant changes in BMD, which is a major risk factor for fracture. In this study we report that an 18bp deletion within the polyalanine tract (17A>11A) of RUNX2 is significantly associated with fracture. Carriers of the 11A allele were found to be nearly twice as likely to have sustained fracture. Within the fracture category, there was a significant tendency of 11A carriers to present with fractures of bones of intramembranous origin compared to bones of endochondral origin (p=0.005). In a population of random subjects, the 11A allele was associated with decreased levels of serum collagen cross links (CTx, p=0.01), suggesting decreased bone turnover. The transactivation function of the 11A allele was quantitatively decreased. Interestingly, we found no effect of the 11A allele on BMD at multiple skeletal sites, although these were not the sites where a relationship with fracture was most evident. These findings suggest that the 11A allele is a biologically relevant polymorphism that influences serum CTx and confers enhanced fracture risk in a site-selective manner related to intramembranous bone ossification.

Assessing the short-term effects of heatwaves on mortality and morbidity in Brisbane, Australia : comparison of case-crossover and time series analyses

Background Heat-related impacts may have greater public health implications as climate change continues. It is important to appropriately characterize the relationship between heatwave and health outcomes. However, it is unclear whether a case-crossover design can be effectively used to assess the event- or episode-related health effects. This study examined the association between exposure to heatwaves and mortality and emergency hospital admissions (EHAs) from non-external causes in Brisbane, Australia, using both case-crossover and time series analyses approaches. Methods Poisson generalised additive model (GAM) and time-stratified case-crossover analyses were used to assess the short-term impact of heatwaves on mortality and EHAs. Heatwaves exhibited a significant impact on mortality and EHAs after adjusting for air pollution, day of the week, and season. Results For time-stratified case-crossover analysis, odds ratios of mortality and EHAs during heatwaves were 1.62 (95% confidence interval (CI): 1.36–1.94) and 1.22 (95% CI: 1.14–1.30) at lag 1, respectively. Time series GAM models gave similar results. Relative risks of mortality and EHAs ranged from 1.72 (95% CI: 1.40–2.11) to 1.81 (95% CI: 1.56–2.10) and from 1.14 (95% CI: 1.06–1.23) to 1.28 (95% CI: 1.21–1.36) at lag 1, respectively. The risk estimates gradually attenuated after the lag of one day for both case-crossover and time series analyses. Conclusions The risk estimates from both case-crossover and time series models were consistent and comparable. This finding may have implications for future research on the assessment of event- or episode-related (e.g., heatwave) health effects.

Inpatients had mostly negative experiences of seclusion during short term treatment in a mental health facility

Design Semi-structured interviews. Setting 2 open, acute care units of a large tertiary mental health facility in Queensland, Australia. Patients 12 patients (58% men) who were 18–52 years of age and were secluded in the previous 7 days (mean duration 3.4 h). Methods Semi-structured, thematically organised interviews were audiotaped and transcribed. Transcripts were checked for errors against the audiotaped versions and were analysed using the process of meaning categorisation. Themes were identified and coded to produce categories. All members of the research team agreed on the final categorisations. These broad categories were further analysed, and themes were used to reflect patients' experiences of seclusion. Main findings 5 recurrent themes emerged. (1) Patients described the use of seclusion. Some patients thought that seclusion was used inappropriately and that the seclusion period was of more benefit to …

A cohort study of Chlamydia trachomatis treatment failure in women : a study protocol

Background Chlamydia trachomatis is the most commonly diagnosed bacterial sexually transmitted infection in the developed world and diagnosis rates have increased dramatically over the last decade. Repeat infections of chlamydia are very common and may represent re-infection from an untreated partner or treatment failure. The aim of this cohort study is to estimate the proportion of women infected with chlamydia who experience treatment failure after treatment with 1 gram azithromycin. Methods/design This cohort study will follow women diagnosed with chlamydia for up to 56 days post treatment. Women will provide weekly genital specimens for further assay. The primary outcome is the proportion of women who are classified as having treatment failure 28, 42 or 56 days after recruitment. Comprehensive sexual behavior data collection and the detection of Y chromosome DNA and high discriminatory chlamydial genotyping will be used to differentiate between chlamydia re-infection and treatment failure. Azithromycin levels in high-vaginal specimens will be measured using a validated liquid chromatography – tandem mass spectrometry method to assess whether poor azithromycin absorption could be a cause of treatment failure. Chlamydia culture and minimal inhibitory concentrations will be performed to further characterize the chlamydia infections. Discussion Distinguishing between treatment failure and re-infection is important in order to refine treatment recommendations and focus infection control mechanisms. If a large proportion of repeat chlamydia infections are due to antibiotic treatment failure, then international recommendations on chlamydia treatment may need to be re-evaluated. If most are re-infections, then strategies to expedite partner treatment are necessary.

Reduced biceps femoris myoelectrical activity influences eccentric knee flexor weakness after repeat sprint running

The aim of this study was to determine whether declines in knee flexor strength following overground repeat sprints were related to changes in hamstrings myoelectrical activity. Seventeen recreationally active males completed maximal isokinetic concentric and eccentric knee flexor strength assessments at 1800.s-1 before and after repeat sprint running. Myoelectrical activity of the biceps femoris (BF) and medial hamstrings (MH) was measured during all isokinetic contractions. Repeated measures mixed model (Fixed factors = time [pre- and post- repeat sprint] and leg [dominant and non-dominant], random factor = participants) design was fitted with the restricted maximal likelihood method. Repeat sprint running resulted in significant declines in eccentric, and concentric, knee flexor strength (eccentric = 25 ± 34 Nm, 15% p<0.001; concentric 11 Nm± 22 Nm, 10% p = 0.001). Eccentric BF myoelectrical activity was significantly reduced (10%; p= 0.033). Concentric BF and all MH myoelectrical activity were not altered. The declines in maximal eccentric torque were associated with the change in eccentric biceps femoris myoelectrical activity (p = 0.013). Following repeat sprint running there were preferential declines in the myoelectrical activity of the BF, which explained declines in eccentric knee flexor strength.

Differentiation of isomeric N-glycan structures by normal-phase liquid chromatography-MALDI-TOF/TOF tandem mass spectrometry

The detailed characterization of protein N-glycosylation is very demanding given the many different glycoforms and structural isomers that can exist on glycoproteins. Here we report a fast and sensitive method for the extensive structure elucidation of reducing-end labeled N-glycan mixtures using a combination of capillary normal-phase HPLC coupled off-line to matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and TOF/TOF-MS/MS. Using this method, isobaric N-glycans released from honey bee phospholipase A2 and Arabidopsis thaliana glycoproteins were separated by normal-phase chromatography and subsequently identified by key fragment ions in the MALDI-TOF/TOF tandem mass spectra. In addition, linkage and branching information were provided by abundant cross-ring and "elimination" fragment ions in the MALDI-CID spectra that gave extensive structural information. Furthermore, the fragmentation characteristics of N-glycans reductively aminated with 2-aminobenzoic acid and 2-aminobenzamide were compared. The identification of N-glycans containing 3-linked core fucose was facilitated by distinctive ions present only in the MALDI-CID spectra of 2-aminobenzoic acid-labeled oligosaccharides. To our knowledge, this is the first MS/MS-based technique that allows confident identification of N-glycans containing 3-linked core fucose, which is a major allergenic determinant on insect and plant glycoproteins.

Exploring influencing factors of short-lived buildings in China's urban renewal : evidence from Chongqing

With the fast development of urban sprawl and renewal in China, many buildings are “non-nature” short-lived, i.e. demolished after only a few years. For this concern, this research explores the influencing factors of short-lived buildings and provides the scientific foundation for sustainable urban management and planning. Cases for this research are 1734 buildings demolished in Jiangbei district, the middle region of Chongqing City. Internal and external factors for the short-lived buildings are identified by applying logistic analysis. The results indicate that nine factors have significant influence on short-lived buildings. This research also find that buildings with low density, utilization and compensation while high land development potential are more likely to become short-lived buildings.

Advanced Engineering of Lipid Metabolism in Nicotiana benthamiana Using a Draft Genome and the V2 Viral Silencing-Suppressor Protein

The transient leaf assay in Nicotiana benthamiana is widely used in plant sciences, with one application being the rapid assembly of complex multigene pathways that produce new fatty acid profiles. This rapid and facile assay would be further improved if it were possible to simultaneously overexpress transgenes while accurately silencing endogenes. Here, we report a draft genome resource for N. benthamiana spanning over 75% of the 3.1 Gb haploid genome. This resource revealed a two-member NbFAD2 family, NbFAD2.1 and NbFAD2.2, and quantitative RT-PCR (qRT-PCR) confirmed their expression in leaves. FAD2 activities were silenced using hairpin RNAi as monitored by qRT-PCR and biochemical assays. Silencing of endogenous FAD2 activities was combined with overexpression of transgenes via the use of the alternative viral silencing-suppressor protein, V2, from Tomato yellow leaf curl virus. We show that V2 permits maximal overexpression of transgenes but, crucially, also allows hairpin RNAi to operate unimpeded. To illustrate the efficacy of the V2-based leaf assay system, endogenous lipids were shunted from the desaturation of 18:1 to elongation reactions beginning with 18:1 as substrate. These V2-based leaf assays produced ~50% more elongated fatty acid products than p19-based assays. Analyses of small RNA populations generated from hairpin RNAi against NbFAD2 confirm that the siRNA population is dominated by 21 and 22 nt species derived from the hairpin. Collectively, these new tools expand the range of uses and possibilities for metabolic engineering in transient leaf assays. © 2012 Naim et al.

Role of short RNAs in gene silencing

Recent research has revealed the existence of an elegant defence mechanism in plants and lower eukaryotes. The mechanism, known in plants as post-transcriptional gene silencing, works through sequence-specific degradation of RNA. It appears to be directed by double-stranded RNA, associated with the production of short 21-25 nt RNAs, and spread through the plant by a diffusible signal. The short RNAs are implicated as the guides for both a nuclease complex that degrades the mRNA and a methyltransferase complex that methylates the DNA of silenced genes. It has also been suggested that these short RNAs might be the mobile silencing signal, a suggestion that has been challenged recently.

Improving short utterance i-vector speaker verification using utterance variance modelling and compensation techniques

This paper proposes techniques to improve the performance of i-vector based speaker verification systems when only short utterances are available. Short-length utterance i-vectors vary with speaker, session variations, and the phonetic content of the utterance. Well established methods such as linear discriminant analysis (LDA), source-normalized LDA (SN-LDA) and within-class covariance normalisation (WCCN) exist for compensating the session variation but we have identified the variability introduced by phonetic content due to utterance variation as an additional source of degradation when short-duration utterances are used. To compensate for utterance variations in short i-vector speaker verification systems using cosine similarity scoring (CSS), we have introduced a short utterance variance normalization (SUVN) technique and a short utterance variance (SUV) modelling approach at the i-vector feature level. A combination of SUVN with LDA and SN-LDA is proposed to compensate the session and utterance variations and is shown to provide improvement in performance over the traditional approach of using LDA and/or SN-LDA followed by WCCN. An alternative approach is also introduced using probabilistic linear discriminant analysis (PLDA) approach to directly model the SUV. The combination of SUVN, LDA and SN-LDA followed by SUV PLDA modelling provides an improvement over the baseline PLDA approach. We also show that for this combination of techniques, the utterance variation information needs to be artificially added to full-length i-vectors for PLDA modelling.

A short-term production scheduling methodology for open-pit mines

A multi-resource multi-stage scheduling methodology is developed to solve short-term open-pit mine production scheduling problems as a generic multi-resource multi-stage scheduling problem. It is modelled using essential characteristics of short-term mining production operations such as drilling, sampling, blasting and excavating under the capacity constraints of mining equipment at each processing stage. Based on an extended disjunctive graph model, a shifting-bottleneck-procedure algorithm is enhanced and applied to obtain feasible short-term open-pit mine production schedules and near-optimal solutions. The proposed methodology and its solution quality are verified and validated using a real mining case study.

Short-term traffic volume forecasting : a k-nearest neighbor approach enhanced by constrained linearly sewing principle component algorithm

To enhance the performance of the k-nearest neighbors approach in forecasting short-term traffic volume, this paper proposed and tested a two-step approach with the ability of forecasting multiple steps. In selecting k-nearest neighbors, a time constraint window is introduced, and then local minima of the distances between the state vectors are ranked to avoid overlappings among candidates. Moreover, to control extreme values’ undesirable impact, a novel algorithm with attractive analytical features is developed based on the principle component. The enhanced KNN method has been evaluated using the field data, and our comparison analysis shows that it outperformed the competing algorithms in most cases.

Automated surface sampling of lipids from worn contact lenses coupled with tandem mass spectrometry

The deposition of biological material (biofouling) onto polymeric contact lenses is thought to be a major contributor to lens discomfort and hence discontinuation of wear. We describe a method to characterize lipid deposits directly from worn contact lenses utilizing liquid extraction surface analysis coupled to tandem mass spectrometry (LESA-MS/MS). This technique effected facile and reproducible extraction of lipids from the contact lens surfaces and identified lipid molecular species representing all major classes present in human tear film. Our data show that LESA-MS/MS is a rapid and comprehensive technique for the characterization of lipid-related biofouling on polymer surfaces.

An improved chemically inducible gene switch that functions in the monocotyledonous plant sugar cane

Chemically inducible gene switches can provide precise control over gene expression, enabling more specific analyses of gene function and expanding the plant biotechnology toolkit beyond traditional constitutive expression systems. The alc gene expression system is one of the most promising chemically inducible gene switches in plants because of its potential in both fundamental research and commercial biotechnology applications. However, there are no published reports demonstrating that this versatile gene switch is functional in transgenic monocotyledonous plants, which include some of the most important agricultural crops. We found that the original alc gene switch was ineffective in the monocotyledonous plant sugar cane, and describe a modified alc system that is functional in this globally significant crop. A promoter consisting of tandem copies of the ethanol receptor inverted repeat binding site, in combination with a minimal promoter sequence, was sufficient to give enhanced sensitivity and significantly higher levels of ethanol inducible gene expression. A longer CaMV 35S minimal promoter than was used in the original alc gene switch also substantially improved ethanol inducibility. Treating the roots with ethanol effectively induced the modified alc system in sugar cane leaves and stem, while an aerial spray was relatively ineffective. The extension of this chemically inducible gene expression system to sugar cane opens the door to new opportunities for basic research and crop biotechnology.

Lattice mixing and vanishing trapdoors : a framework for fully secure short signatures and more

We propose a framework for adaptive security from hard random lattices in the standard model. Our approach borrows from the recent Agrawal-Boneh-Boyen families of lattices, which can admit reliable and punctured trapdoors, respectively used in reality and in simulation. We extend this idea to make the simulation trapdoors cancel not for a specific forgery but on a non-negligible subset of the possible challenges. Conceptually, we build a compactly representable, large family of input-dependent “mixture” lattices, set up with trapdoors that “vanish” for a secret subset which we hope the forger will target. Technically, we tweak the lattice structure to achieve “naturally nice” distributions for arbitrary choices of subset size. The framework is very general. Here we obtain fully secure signatures, and also IBE, that are compact, simple, and elegant.