Long non coding RNAs (lncRNAs) are dysregulated in Malignant Pleural Mesothelioma (MPM)

Malignant Pleural Mesothelioma (MPM) is an aggressive cancer that is often diagnosed at an advanced stage and is characterized by a long latency period (20-40 years between initial exposure and diagnosis) and prior exposure to asbestos. Currently accurate diagnosis of MPM is difficult due to the lack of sensitive biomarkers and despite minor improvements in treatment, median survival rates do not exceed 12 months. Accumulating evidence suggests that aberrant expression of long non-coding RNAs (lncRNAs) play an important functional role in cancer biology. LncRNAs are a class of recently discovered non-protein coding RNAs >200 nucleotides in length with a role in regulating transcription. Here we used NCode long noncoding microarrays to identify differentially expressed lncRNAs potentially involved in MPM pathogenesis. High priority candidate lncRNAs were selected on the basis of statistical (P<0.05) and biological significance (>3-fold difference). Expression levels of 9 candidate lncRNAs were technically validated using RT-qPCR, and biologically validated in three independent test sets: (1) 57 archived MPM tissues obtained from extrapleural pneumonectomy patients, (2) 15 cryopreserved MPM and 3 benign pleura, and (3) an extended panel of 10 MPM cell lines. RT-qPCR analysis demonstrated consistent up-regulation of these lncRNAs in independent datasets. ROC curve analysis showed that two candidates were able to separate benign pleura and MPM with high sensitivity and specificity, and were associated with nodal metastases and survival following induction chemotherapy. These results suggest that lncRNAs have potential to serve as biomarkers in MPM.

Long-term azithromycin for Indigenous children with non-cystic-fibrosis bronchiectasis or chronic suppurative lung disease (Bronchiectasis Intervention Study) : a multicentre, double-blind, randomised controlled trial

Background Indigenous children in high-income countries have a heavy burden of bronchiectasis unrelated to cystic fibrosis. We aimed to establish whether long-term azithromycin reduced pulmonary exacerbations in Indigenous children with non-cystic-fibrosis bronchiectasis or chronic suppurative lung disease. Methods Between Nov 12, 2008, and Dec 23, 2010, we enrolled Indigenous Australian, Maori, and Pacific Island children aged 1—8 years with either bronchiectasis or chronic suppurative lung disease into a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial. Eligible children had had at least one pulmonary exacerbation in the previous 12 months. Children were randomised (1:1 ratio, by computer-generated sequence with permuted block design, stratified by study site and exacerbation frequency [1—2 vs ≥3 episodes in the preceding 12 months]) to receive either azithromycin (30 mg/kg) or placebo once a week for up to 24 months. Allocation concealment was achieved by double-sealed, opaque envelopes; participants, caregivers, and study personnel were masked to assignment until after data analysis. The primary outcome was exacerbation (respiratory episodes treated with antibiotics) rate. Analysis of the primary endpoint was by intention to treat. At enrolment and at their final clinic visits, children had deep nasal swabs collected, which we analysed for antibiotic-resistant bacteria. This study is registered with the Australian New Zealand Clinical Trials Registry; ACTRN12610000383066. Findings 45 children were assigned to azithromycin and 44 to placebo. The study was stopped early for feasibility reasons on Dec 31, 2011, thus children received the intervention for 12—24 months. The mean treatment duration was 20·7 months (SD 5·7), with a total of 902 child-months in the azithromycin group and 875 child-months in the placebo group. Compared with the placebo group, children receiving azithromycin had significantly lower exacerbation rates (incidence rate ratio 0·50; 95% CI 0·35—0·71; p<0·0001). However, children in the azithromycin group developed significantly higher carriage of azithromycin-resistant bacteria (19 of 41, 46%) than those receiving placebo (four of 37, 11%; p=0·002). The most common adverse events were non-pulmonary infections (71 of 112 events in the azithromycin group vs 132 of 209 events in the placebo group) and bronchiectasis-related events (episodes or investigations; 22 of 112 events in the azithromycin group vs 48 of 209 events in the placebo group); however, study drugs were well tolerated with no serious adverse events being attributed to the intervention. Interpretation Once-weekly azithromycin for up to 24 months decreased pulmonary exacerbations in Indigenous children with non-cystic-fibrosis bronchiectasis or chronic suppurative lung disease. However, this strategy was also accompanied by increased carriage of azithromycin-resistant bacteria, the clinical consequences of which are uncertain, and will need careful monitoring and further study.

The “virtual” producer in the recording studio : media networks in long distance peripheral performances

The producer has for many years been a central agent in recording studio sessions; the validation of this role was, in many ways, related to the producer’s physical presence in the studio, to a greater or lesser extent. However, improvements in the speed of digital networks have allowed studio sessions to be produced long-distance, in real-time, through communication programs such as Skype or REDIS. How does this impact on the role of the producer, a “nexus between the creative inspiration of the artist, the technology of the recording studio, and the commercial aspirations of the record company” (Howlett 2012)? From observations of a studio recording session in Lisbon produced through Skype from New York, this article focuses on the role of the producer in these relatively new recording contexts involving long distance media networks. Methodology involved participant observation carried out in Estúdios Namouche in Lisbon (where the session took place), as part of doctoral research. This ethnographic approach also included a number of semi-directed ethnographic interviews of the different actors in this scenario—musicians, recording engineers, composers and producers. As a theoretical framework, the research of De Zutter and Sawyer on Distributed Creativity is used, as the recording studio sets an example of “a cognitive system where […] tasks are not accomplished by separate individuals, but rather through the interactions of those individuals” (DeZutter 2009:4). Therefore, creativity often emerges as a result of this interaction.

Optimization of an integrated model for automatic reduction and expansion of long queries

A long query provides more useful hints for searching relevant documents, but it is likely to introduce noise which affects retrieval performance. In order to smooth such adverse effect, it is important to reduce noisy terms, introduce and boost additional relevant terms. This paper presents a comprehensive framework, called Aspect Hidden Markov Model (AHMM), which integrates query reduction and expansion, for retrieval with long queries. It optimizes the probability distribution of query terms by utilizing intra-query term dependencies as well as the relationships between query terms and words observed in relevance feedback documents. Empirical evaluation on three large-scale TREC collections demonstrates that our approach, which is automatic, achieves salient improvements over various strong baselines, and also reaches a comparable performance to a state of the art method based on user’s interactive query term reduction and expansion.

GNSS ambiguity resolution with controllable failure rate for long baseline network RTK

Many large-scale GNSS CORS networks have been deployed around the world to support various commercial and scientific applications. To make use of these networks for real-time kinematic positioning services, one of the major challenges is the ambiguity resolution (AR) over long inter-station baselines in the presence of considerable atmosphere biases. Usually, the widelane ambiguities are fixed first, followed by the procedure of determination of the narrowlane ambiguity integers based on the ionosphere-free model in which the widelane integers are introduced as known quantities. This paper seeks to improve the AR performance over long baseline through efficient procedures for improved float solutions and ambiguity fixing. The contribution is threefold: (1) instead of using the ionosphere-free measurements, the absolute and/or relative ionospheric constraints are introduced in the ionosphere-constrained model to enhance the model strength, thus resulting in the better float solutions; (2) the realistic widelane ambiguity precision is estimated by capturing the multipath effects due to the observation complexity, leading to improvement of reliability of widelane AR; (3) for the narrowlane AR, the partial AR for a subset of ambiguities selected according to the successively increased elevation is applied. For fixing the scalar ambiguity, an error probability controllable rounding method is proposed. The established ionosphere-constrained model can be efficiently solved based on the sequential Kalman filter. It can be either reduced to some special models simply by adjusting the variances of ionospheric constraints, or extended with more parameters and constraints. The presented methodology is tested over seven baselines of around 100 km from USA CORS network. The results show that the new widelane AR scheme can obtain the 99.4 % successful fixing rate with 0.6 % failure rate; while the new rounding method of narrowlane AR can obtain the fix rate of 89 % with failure rate of 0.8 %. In summary, the AR reliability can be efficiently improved with rigorous controllable probability of incorrectly fixed ambiguities.

Higher uptake of long-acting reversible and permanent methods of contraception by Australian women living in rural and remote areas

Objectives: To examine factors associated with the uptake of i) long-acting reversible, ii) permanent and iii) traditional contraceptive methods among Australian women. Methods: Participants in the Australian Longitudinal Study on Women's Health born in 1973–78 reported on their contraceptive use at three surveys: 2003, 2006 and 2009. The participants were 5,849 women aged 25–30 in 2003 randomly sampled from Medicare. The main outcome measure was current contraceptive method at age 28–33 years categorised as long-acting reversible methods (implant, IUD, injection), permanent (tubal ligation, vasectomy), and traditional methods (oral contraceptive pills, condoms, withdrawal, safe period). Results: Compared to women living in major cities, women in inner regional areas were more likely to use long-acting (OR=1.26, 95%CI 1.03–1.55) or permanent methods (OR=1.43, 95%CI 1.17–1.76). Women living in outer regional/remote areas were more likely than women living in cities to use long-acting (OR=1.65, 95%CI 1.31–2.08) or permanent methods (OR=1.69, 95%CI 1.43–2.14). Conclusions: Location of residence is an important factor in women's choices about long-acting and permanent contraception in addition to the number and age of their children. Implications: Further research is needed to understand the role of geographical location in women's access to contraceptive options in Australia.

Venous leg ulcer recurrence : deciphering long term patient adherence to preventive treatments and activities

To better understand long term adherence to self-care activities to prevent the recurrence of venous leg ulcers, participants (n=80) were recruited to a prospective longitudinal study after experiencing healing of a venous leg ulcer. Data on demographics, health, psychosocial measures and adherence to prevention strategies (compression therapy, leg elevation and lower leg exercise) were collected every three months for one year after healing. Multivariable regression modelling was used to identify the factors that were independently associated with adherence. Over the year, a significant decline in adherence to all three strategies was observed, predominantly between 6–12 months after healing (p<0.01). Several factors were associated with adherence to more than one preventive activity. Regular follow-up care and a history of multiple previous ulcers were related to improved adherence (p<0.05), while scoring at higher risk for depression and restricted mobility were related to decreasing adherence over time (p<0.05). Patients with osteoarthritis had significantly reduced adherence to compression hosiery (p=0.026). These results provide information to assist care providers plan strategies for prevention of recurrent venous leg ulcers; and suggest a need for regular follow-up care which addresses both the physical and mental health of this population.

Painting anatase (TiO2) nanocrystals on long nanofibers to prepare photocatalysts with large active surface for dye degradation and organic synthesis

Anatase TiO2 nanocrystals were painted on H-titanate nanofibers by using an aqueous solution of titanyl sulfate. The anatase nanocrystals were bonded solidly onto the titanate fibers through formation of coherent interfaces at which the oxygen atoms were shared by the nanocrystals and the fiber. This approach allowed us to create large anatase surfaces on the nanofibers, which are active in photocatalytic reactions. This method was also applied successfully to coat anatase nanocrystals on surfaces of fly ash and layered clay. The painted nanofibers exhibited a much higher catalytic activity for the photocatalytic degradation of sulforhodamine B and the selective oxidation of benzylamine to the corresponding imine (with a product selectivity >99%) under UV irradiation than both the parent H-titanate nanofibers and a commercial TiO2 powder, P25. We found that gold nanoparticles supported on H-titanate nanofibers showed no catalytic activity for the reduction of nitrobenzene to azoxybenzene, whereas the gold nanoparticles supported on the painted nanofibers and P25 could efficiently reduce nitrobenzene to azoxybenzene as the sole product under visible light irradiation. These results were different from those from the reduction on the gold nanoparticles photocatalyst on ZrO2, in which the azoxybenzene was the intermediate and converted to azobenzene quickly. Evidently, the support materials significantly affect the product selectivity of the nitrobenzene reduction. Finally, the new photocatalysts could be easily dispersed into and separated from a liquid because of their fibril morphology, which is an important advantage for practical applications.

Long time, no see?

Long Time, No See? is a crowd-sourced project that asks people to reflect upon what kind of long term future they would each like to promote. It is an evolving experiment in the social practice of ‘everyday futuring’. To participate download the Long Time, No See? IPhone APP that gently guides you during a short walk, encouraging you to experience new places, sensations and thoughts in your locality. At nine stages along that journey you donate ‘field notes’ as images, texts, sounds and ‘themes’, offering a unique opportunity to reveal possible pathways towards more sustaining futures. The APP records the shape of your walk on the ground and draws an island on the ‘map’ shown here, populated by your nine sets of responses. The themes you have chosen then connect your island into an evolving ‘world’ map of connections and possibilities, which you can then explore at your leisure. In these ways, Long Time, No See? doesn’t ask you for lofty visions or ask you to lay out a program of action, but instead asks you to consider what is around you today, steering your eyes, ears and embodied experiences towards new futures that demonstrate your ‘care’ for what comes after you. Please use the contribute tab below to learn how to add your voice! PARTICIPATE To contribute 1: Download the APP {bit.do/ltns}, iPhone/iPad is supported right now. 2: Register a ‘walker name’. 3: Take a leisurely walk (30 -60mins) and contribute image, text, sound and themes when asked. 4: Wait while we verify and upload your walk (allow about 24 hours) 5: View your contributions via your ‘walker name’ and discover how it relates to others, here at the Cube and at www.long-time-no-see.org. NB You can undertake each walk over more than one day if that suits. You may even drive, cycle or move by other modes. DOWNLOAD THE APP: bit.do/ltns (insert QI Code) FIND OUT MORE www.long-time-no-see.org

Phenotypic changes associated with RNA interference silencing of chalcone synthase in apple (Malus × domestica)

We have identified in apple (Malus × domestica) three chalcone synthase (CHS) genes. In order to understand the functional redundancy of this gene family RNA interference knockout lines were generated where all three of these genes were down-regulated. These lines had no detectable anthocyanins and radically reduced concentrations of dihydrochalcones and flavonoids. Surprisingly, down-regulation of CHS also led to major changes in plant development, resulting in plants with shortened internode lengths, smaller leaves and a greatly reduced growth rate. Microscopic analysis revealed that these phenotypic changes extended down to the cellular level, with CHS-silenced lines showing aberrant cellular organisation in the leaves. Fruit collected from one CHS-silenced line was smaller than the 'Royal Gala' controls, lacked flavonoids in the skin and flesh and also had changes in cell morphology. Auxin transport experiments showed increased rates of auxin transport in a CHS-silenced line compared with the 'Royal Gala' control. As flavonoids are well known to be key modulators of auxin transport, we hypothesise that the removal of almost all flavonoids from the plant by CHS silencing creates a vastly altered environment for auxin transport to occur and results in the observed changes in growth and development.

RNA interference silencing of CHS greatly alters the growth pattern of apple (Malus x domestica)

Plants produce a vast array of phenolic compounds which are essential for their survival on land. One major class of polyphenols are the flavonoids and their formation is dependent on the enzyme chalcone synthase (CHS). In a recent study we silenced the CHS genes of apple (Malus × domestica Borkh.) and observed a loss of pigmentation in the fruit skin, flowers and stems. More surprisingly, highly silenced lines were significantly reduced in size, with small leaves and shortened internode lengths. Chemical analysis also revealed that the transgenic shoots contained greatly reduced concentrations of flavonoids which are known to modulate auxin flow. An auxin transport study verified this, with an increased auxin transport in the CHS-silenced lines. Overall, these findings suggest that auxin transport in apple has adapted to take place in the presence of high endogenous concentrations of flavonoids. Removal of these compounds therefore results in abnormal auxin movement and a highly disrupted growth pattern. © 2013 Landes Bioscience.

Effect of 5′UTR introns on gene expression in Arabidopsis thaliana

Background The majority of introns in gene transcripts are found within the coding sequences (CDSs). A small but significant fraction of introns are also found to reside within the untranslated regions (5′UTRs and 3′UTRs) of expressed sequences. Alignment of the whole genome and expressed sequence tags (ESTs) of the model plant Arabidopsis thaliana has identified introns residing in both coding and non-coding regions of the genome. Results A bioinformatic analysis revealed some interesting observations: (1) the density of introns in 5′UTRs is similar to that in CDSs but much higher than that in 3′UTRs; (2) the 5′UTR introns are preferentially located close to the initiating ATG codon; (3) introns in the 5′UTRs are, on average, longer than introns in the CDSs and 3′UTRs; and (4) 5′UTR introns have a different nucleotide composition to that of CDs and 3′UTR introns. Furthermore, we show that the 5′UTR intron of the A. thaliana EFIα-A3 gene affects the gene expression and the size of the 5′UTR intron influences the level of gene expression. Conclusion Introns within the 5′UTR show specific features that distinguish them from introns that reside within the coding sequence and the 3′UTR. In the EFIα-A3 gene, the presence of a long intron in the 5′UTR is sufficient to enhance gene expression in plants in a size dependent manner.

Coincident sequence-specific RNA degradation of linked transgenes in the plant genome

The expression of transgenes in plant genomes can be inhibited by either transcriptional gene silencing or posttranscriptional gene silencing (PTGS). Overexpression of the chalcone synthase-A (CHS-A) transgene triggers PTGS of CHS-A and thus results in loss of flower pigmentation in petunia. We previously demonstrated that epigenetic inactivation of CHS-A transgene transcription leads to a reversion of the PTGS phenotype. Although neomycin phosphotransferase II (nptII), a marker gene co-introduced into the genome with the CHS-A transgene, is not normally silenced in petunia, even when CHS-A is silenced, here we found that nptII was silenced in a petunia line in which CHS-A PTGS was induced, but not in the revertant plants that had no PTGS of CHS-A. Transcriptional activity, accumulation of short interfering RNAs, and restoration of mRNA level after infection with viruses that had suppressor proteins of gene silencing indicated that the mechanism for nptII silencing was posttranscriptional. Read-through transcripts of the CHS-A gene toward the nptII gene were detected. Deep-sequencing analysis revealed a striking difference between the predominant size class of small RNAs produced from the read-through transcripts (22 nt) and that from the CHS-A RNAs (21 nt). These results implicate the involvement of read-through transcription and distinct phases of RNA degradation in the coincident PTGS of linked transgenes and provide new insights into the destabilization of transgene expression.

Transient expression vectors for functional genomics, quantification of promoter activity and RNA silencing in plants

Background We describe novel plasmid vectors for transient gene expression using Agrobacterium, infiltrated into Nicotiana benthamiana leaves. We have generated a series of pGreenII cloning vectors that are ideally suited to transient gene expression, by removing elements of conventional binary vectors necessary for stable transformation such as transformation selection genes. Results We give an example of expression of heme-thiolate P450 to demonstrate effectiveness of this system. We have also designed vectors that take advantage of a dual luciferase assay system to analyse promoter sequences or post-transcriptional regulation of gene expression. We have demonstrated their utility by co-expression of putative transcription factors and the promoter sequence of potential target genes and show how orthologous promoter sequences respond to these genes. Finally, we have constructed a vector that has allowed us to investigate design features of hairpin constructs related to their ability to initiate RNA silencing, and have used these tools to study cis-regulatory effect of intron-containing gene constructs. Conclusion In developing a series of vectors ideally suited to transient expression analysis we have provided a resource that further advances the application of this technology. These minimal vectors are ideally suited to conventional cloning methods and we have used them to demonstrate their flexibility to investigate enzyme activity, transcription regulation and post-transcriptional regulatory processes in transient assays.

Summarisation of short-term and long-term videos using texture and colour

We present a novel approach to video summarisation that makes use of a Bag-of-visual-Textures (BoT) approach. Two systems are proposed, one based solely on the BoT approach and another which exploits both colour information and BoT features. On 50 short-term videos from the Open Video Project we show that our BoT and fusion systems both achieve state-of-the-art performance, obtaining an average F-measure of 0.83 and 0.86 respectively, a relative improvement of 9% and 13% when compared to the previous state-of-the-art. When applied to a new underwater surveillance dataset containing 33 long-term videos, the proposed system reduces the amount of footage by a factor of 27, with only minor degradation in the information content. This order of magnitude reduction in video data represents significant savings in terms of time and potential labour cost when manually reviewing such footage.