Integrated microfluidic tmRNA purification and real-time NASBA device for molecular diagnostics.

We demonstrate the first integrated microfluidic tmRNA purification and nucleic acid sequence-based amplification (NASBA) device incorporating real-time detection. The real-time amplification and detection step produces pathogen-specific response in < 3 min from the chip-purified RNA from 100 lysed bacteria. On-chip RNA purification uses a new silica bead immobilization method. On-chip amplification uses custom-designed high-selectivity primers and real-time detection uses molecular beacon fluorescent probe technology; both are integrated on-chip with NASBA. Present in all bacteria, tmRNA (10Sa RNA) includes organism-specific identification sequences, exhibits unusually high stability relative to mRNA, and has high copy number per organism; the latter two factors improve the limit of detection, accelerate time-to-positive response, and suit this approach ideally to the detection of small numbers of bacteria. Device efficacy was demonstrated by integrated on-chip purification, amplification, and real-time detection of 100 E. coli bacteria in 100 microL of crude lysate in under 30 min for the entire process

Size and shape constancy in consumer virtual reality

With the increase in popularity of consumer virtual reality headsets, for research and other applications, it is important to understand the accuracy of 3D perception in VR. We investigated the perceptual accuracy of near-field virtual distances using a size and shape constancy task, in two commercially available devices. Participants wore either the HTC Vive or the Oculus Rift and adjusted the size of a virtual stimulus to match the geometric qualities (size and depth) of a physical stimulus they were able to refer to haptically. The judgments participants made allowed for an indirect measure of their perception of the egocentric, virtual distance to the stimuli. The data show under-constancy and are consistent with research from carefully calibrated psychophysical techniques. There was no difference in the degree of constancy found in the two headsets. We conclude that consumer virtual reality headsets provide a sufficiently high degree of accuracy in distance perception, to allow them to be used confidently in future experimental vision science, and other research applications in psychology

Characterization of hunter-gatherer networks and implications for cumulative culture

Social networks in modern societies are highly structured, usually involving frequent contact with a small number of unrelated friends' 1. However, contact network structures in traditional small-scale societies, especially hunter-gatherers, are poorly characterized. We developed a portable wireless sensing technology (motes) to study within-camp proximity networks among Agta and BaYaka hunter-gatherers in fine detail. We show that hunter-gatherer social networks exhibit signs of increased efficiency 2 for potential information exchange. Increased network efficiency is achieved through investment in a few strong links among non-kin friends' connecting unrelated families. We show that interactions with non-kin appear in childhood, creating opportunities for collaboration and cultural exchange beyond family at early ages. We also show that strong friendships are more important than family ties in predicting levels of shared knowledge among individuals. We hypothesize that efficient transmission of cumulative culture 3-6 may have shaped human social networks and contributed to our tendency to extend networks beyond kin and form strong non-kin ties

Achieving a low-carbon society: CCS expertise and opportunity in the UK

The outcome of the Paris climate talks in late 2015 was hailed as a “turning point” for international action on climate change, with 195 countries agreeing to limit the increase in average global temperatures to 1.5oC by the end of this century. It is an ambitious and necessary goal, but is it achievable? An increasing emphasis on clean, renewable energy is essential, as are more efficient ways of using energy. However, the best of intentions will hit an insurmountable roadblock if we continue to burn fossil fuels without deploying Carbon Capture and Storage (CCS). CCS is a chain of proven technologies that can take us all the way to a zero-carbon future. For many economies that will be reliant on fossil fuels for several decades, CCS can support a gradual phasing in of renewable energy. CCS remains the only path to deep cuts in carbon emissions from products such as cement, steel and fertiliser - even whisky - and will effectively decarbonise power and heat generation. Deployed on gas or sustainable biomass power, it can plug the gaps in the intermittency of power supply from renewables. And there are many studies that show that the UK and its assets are best placed to deliver CCS for the whole of Europe. Although CCS is already operating in other parts of the world, this climate change technology has had a tough time making progress in the UK. The latest blow came in the last quarter of 2015, within days of the Paris talks. Two major UK CCS projects were poised to begin construction after completing front-end engineering and design (FEED) studies. Without warning, anticipated funding from the UK Government's £1 billion CCS Commercialisation Competition was withdrawn before these studies had been submitted. The Peterhead CCS Project, set to become the world's first CCS project on gas power, and White Rose, which would demonstrate oxyfuel with CCS technology on coal power, have had little choice but to consider closure. In the aftermath of the COP21 climate deal, and with the UK's own climate change advisers restating the importance of the technology in meeting the UK's Fifth Carbon Budget, the case for CCS remains as cogent as ever. In the UK, we have access to an immense CO2 storage asset beneath the North Sea, which could contain a century of Europe's carbon emissions. Added to that is an impressive track record of world-leading research and development (R&D), decades of oil and gas industry knowledge and skills and an infrastructure facing decommissioning that can be repurposed to put carbon back below ground. The progress and potential of CCS in the UK is much more than a government competition. This report describes why we need to get one of the most obvious and effective climate change tools back on track and highlights the strengths of and opportunities for the UK - and Scotland, in particular.The outcome of the Paris climate talks in late 2015 was hailed as a “turning point” for international action on climate change, with 195 countries agreeing to limit the increase in average global temperatures to 1.5oC by the end of this century. It is an ambitious and necessary goal, but is it achievable? An increasing emphasis on clean, renewable energy is essential, as are more efficient ways of using energy. However, the best of intentions will hit an insurmountable roadblock if we continue to burn fossil fuels without deploying Carbon Capture and Storage (CCS). CCS is a chain of proven technologies that can take us all the way to a zero-carbon future. For many economies that will be reliant on fossil fuels for several decades, CCS can support a gradual phasing in of renewable energy. CCS remains the only path to deep cuts in carbon emissions from products such as cement, steel and fertiliser - even whisky - and will effectively decarbonise power and heat generation. Deployed on gas or sustainable biomass power, it can plug the gaps in the intermittency of power supply from renewables. And there are many studies that show that the UK and its assets are best placed to deliver CCS for the whole of Europe. Although CCS is already operating in other parts of the world, this climate change technology has had a tough time making progress in the UK. The latest blow came in the last quarter of 2015, within days of the Paris talks. Two major UK CCS projects were poised to begin construction after completing front-end engineering and design (FEED) studies. Without warning, anticipated funding from the UK Government's £1 billion CCS Commercialisation Competition was withdrawn before these studies had been submitted. The Peterhead CCS Project, set to become the world's first CCS project on gas power, and White Rose, which would demonstrate oxyfuel with CCS technology on coal power, have had little choice but to consider closure. In the aftermath of the COP21 climate deal, and with the UK's own climate change advisers restating the importance of the technology in meeting the UK's Fifth Carbon Budget, the case for CCS remains as cogent as ever. In the UK, we have access to an immense CO2 storage asset beneath the North Sea, which could contain a century of Europe's carbon emissions. Added to that is an impressive track record of world-leading research and development (R&D), decades of oil and gas industry knowledge and skills and an infrastructure facing decommissioning that can be repurposed to put carbon back below ground. The progress and potential of CCS in the UK is much more than a government competition. This report describes why we need to get one of the most obvious and effective climate change tools back on track and highlights the strengths of and opportunities for the UK - and Scotland, in particular

ERCC1 expression as a predictive marker of squamous cell carcinoma of the head and neck treated with cisplatin-based concurrent chemoradiation

The excision repair cross-complementation group 1 (ERCC1) enzyme plays a rate-limiting role in the nucleotide excision repair pathway and is associated with resistance to platinum-based chemotherapy. The purpose of this study was to evaluate the role of ERCC1 expression as a predictive marker of survival in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) treated with cisplatin-based concurrent chemoradiotherapy (CCRT). ERCC1 expression was assessed by immunohistochemical staining. The median age of the 45 patients analysed was 56 years (range 27–75 years), and 82% were men; 73% of all specimens showed high expression of ERCC1. The overall tumour response rate after CCRT was 89%. The median follow-up was 53.6 months (95% CI, 34.5–72.7 months). The 3-year progression-free survival (PFS) and overall survival (OS) rates were 58.7 and 61.3%, respectively. Univariate analyses showed that patients with low expression of ERCC1 had a significantly higher 3-year PFS (83.3 vs 49.4%, P=0.036) and OS (91.7 vs 45.5%, P=0.013) rates. Multivariate analysis showed that low expression of ERCC1 was an independent predictor for prolonged survival (HR, 0.120; 95% CI, 0.016–0.934, P=0.043). These results suggest that ERCC1 expression might be a useful predictive marker of locally advanced SCCHN in patients treated with cisplatin-based CCRT

A Re-examination of the Portevin-Le Chatelier Effect in Alloy 718 in Connection with Oxidation-Assisted Intergranular Cracking

In Alloy 718, a sharp transition exists in the fracture path changing from an intergranular brittle mode to a transgranular ductile mode which is associated with a transition of flow behavior from smooth in the dynamic strain aging regime to a serrated one in the Portevin-Le Chatelier (PLC) regime. In order to better understand both deformation and rupture behavior, PLC phenomenon in a precipitation-hardened nickel-base superalloy was carefully investigated in a wide range of temperatures [573 K to 973 K (300°C to 700°C)] and strain rates (109^-5 to 3.2910^-2 s^-1 ). Distinction was made between two PLC domains characterized by different evolutions of the critical strain to the onset of the first serration namely normal and inverse behavior. The apparent activation energies associated with both domains were determined using different methods. Results showed that normal and inverse behavior domains are related to dynamic interaction of dislocations with, respectively, interstitial and substitutional solutes atoms. This analysis confirms that normal PLC regime may be associated to the diffusion of carbon atoms, whereas the substitutional species involves in the inverse regime is discussed with an emphasis on the role of Nb and Mo

A new small regulatory protein, HmuP, modulates haemin acquisition in Sinorhizobium meliloti

Sinorhizobium meliloti has multiple systems for iron acquisition, including the use of haem as an iron source. Haem internalization involves the ShmR haem outer membrane receptor and the hmuTUV locus, which participates in haem transport across the cytoplasmic membrane. Previous studies have demonstrated that expression of the shmR gene is negatively regulated by iron through RirA. Here, we identify hmuP in a genetic screen for mutants that displayed aberrant control of shmR. The normal induction of shmR in response to iron limitation was lost in the hmuP mutant, showing that this gene positively affects shmR expression. Moreover, the HmuP protein is not part of the haemin transporter system. Analysis of gene expression and siderophore production indicates that disruption of hmuP does not affect other genes related to the iron-restriction response. Our results strongly indicate that the main function of HmuP is the transcriptional regulation of shmR. Sequence alignment of HmuP homologues and comparison with the NMR structure of Rhodopseudomonas palustris CGA009 HmuP protein revealed that certain amino acids localized within predicted β-sheets are well conserved. Our data indicate that at least one of the β-sheets is important for HmuP activity

Phase II trial of the regulatory T cell-depleting agent, denileukin diftitox, in patients with unresectable stage IV melanoma

<p>Abstract</p> <p>Background</p> <p>We previously found that administration of an interleukin 2/diphtheria toxin conjugate (DAB/IL2; Denileukin Diftitox; ONTAK) to stage IV melanoma patients depleted CD4⁺CD25^HIFoxp3⁺regulatory T cells and expanded melanoma-specific CD8⁺T cells. The goal of this study was to assess the clinical efficacy of DAB/IL2 in an expanded cohort of stage IV melanoma patients.</p> <p>Methods</p> <p>In a single-center, phase II trial, DAB/IL2 (12 μg/kg; 4 daily doses; 21 day cycles) was administered to 60 unresectable stage IV melanoma patients and response rates were assessed using a combination of 2-[¹⁸F]-fluoro-2-deoxy-glucose (FDG)-positron emission tomography (PET) and computed tomography (CT) imaging.</p> <p>Results</p> <p>After DAB/IL2 administration, 16.7% of the 60 patients had partial responses, 5% stable disease and 15% mixed responses. Importantly, 45.5% of the chemo/immuno-naïve sub-population (11/60 patients) experienced partial responses. One year survival was markedly higher in partial responders (80 ± 11.9%) relative to patients with progressive disease (23.7 ± 6.5%; <it>p </it>value < 0.001) and 40 ± 6.2% of the total DAB/IL2-treated population were alive at 1 year.</p> <p>Conclusions</p> <p>These data support the development of multi-center, randomized trials of DAB/IL2 as a monotherapy and in combination with other immunotherapeutic agents for the treatment of stage IV melanoma.</p> <p>Trial registration</p> <p><a href="http://www.clinicaltrials.gov/ct2/show/NCT00299689">NCT00299689</a></p

Paleogenomic Analysis of the Short Arm of Chromosome 3 Reveals the History of the African and Asian Progenitors of Cultivated Rices

Rice is one of the most important crops, feeding more than half of the world population. There are two cultivated species, the African rice Oryza glaberrima and the Asian rice O. sativa. Although the African species is gradually replaced by O. sativa in most of African rice agrosystems, this species represents an important reservoir of genes of agronomical interest. Their exploitation for the development of modern African rice varieties requires a good understanding of the genetic relationships between the two cultivated species. We took advantage of the recent availability of the sequence of the chromosome 3 short arm of O. glaberrima to estimate the date of radiation between O. glaberrima and O. sativa lineages, using all the long terminal repeat (LTR)-retrotransposons as paleogenomic markers. We first demonstrated that in two distinct lineages, LTR-retrotransposons mutate at the same rate. Based on LTR-retrotransposons shared by both species in orthologous position, we then estimated that O. glaberrima and O. sativa progenitors diverged 1.2 Ma. This constitutes one of the first studies using such a large sample of transposable elements to reconstruct the phylogeny of species. Given the number of genome sequencing projects, there is no doubt that such approach will allow to resolve phylogenetic incongruities. The application of this method to other plant genomes will also facilitate further understanding of evolution of LTR-retrotransposons and eventually of the whole genome in divergent plant lineages

Knowledge and attitudes of primary health care physicians and nurses with regard to population screening for colorectal cancer in Balearic Islands and Barcelona

<p>Abstract</p> <p>Background</p> <p>Primary health care (PHC) professionals play a key role in population screening of colorectal cancer. The purposes of the study are: to assess knowledge and attitudes among PHC professionals with regard to colorectal cancer screening, as well as the factors that determine their support for such screening.</p> <p>Methods</p> <p>Questionnaire-based survey of PHC physicians and nurses in the Balearic Islands and in a part of the metropolitan area of Barcelona.</p> <p>Results</p> <p>We collected 1,219 questionnaires. About 84% of all professionals believe that screening for colorectal cancer by fecal occult blood test (FOBT) is effective. Around 68% would recommend to their clients a colorectal cancer screening program based on FOBT and colonoscopy. About 31% are reluctant or do not know. Professionals perceive the fear of undergoing a colonoscopy as the main obstacle in getting patients to participate, and the invasive nature of this test is the main reason behind their resistance to this program. The main barriers to support the screening program among PHC professionals are lack of knowledge (nurses) and lack of time (physicians). On multivariate analysis, the factors associated with reluctance to recommend colorectal cancer screening were: believing that FOBT has poor sensitivity and is complicated; that colonoscopy is an invasive procedure; that a lack of perceived benefit could discourage client participation; that only a minority of clients would participate; thinking that clients are fed up with screening tests and being unaware if they should be offered something to ensure their participation in the programme.</p> <p>Conclusions</p> <p>Two in every three PHC professionals would support a population screening program for colorectal cancer screening. Factors associated with reluctance to recommend it were related with screening tests characteristics as sensitivity and complexity of FOBT, and also invasive feature of colonoscopy. Other factors were related with patients' believes.</p