In situ loading and delivery of short single- And double-stranded dna by supramolecular organic frameworks

Short DNA represents an important class of biomacromolecules that are widely applied in gene therapy, editing, and modulation. However, the development of simple and reliable methods for their intracellular delivery remains a challenge. Herein, we describe that seven water-soluble, homogeneous supramolecular organic frameworks (SOFs) with a well-defined pore size and high stability in water that can accomplish in situ inclusion of single-stranded (ss) and double-stranded (ds) DNA (21, 23, and 58 nt) and effective intracellular delivery (including two noncancerous and six cancerous cell lines). Fluorescence quenching experiments for single and double endlabeled ss- and ds-DNA support that the DNA sequences can be completely enveloped by the SOFs. Confocal laser scanning microscopy and flow cytometry reveal that five of the SOFs exhibit excellent delivery efficiencies that, in most of the studied cases, outperform the commercial standard Lipo2000, even at low SOF-nucleic acid ratios. In addition to high delivery efficiencies, the watersoluble, self-assembled SOF carriers have a variety of advantages, including convenient preparation, high stability, and in situ DNA inclusion, which are all critical for practical applications in nucleic acid delivery

Selective-logging and oil palm: Multitaxon impacts, biodiversity indicators, and trade-offs for conservation planning

Strong global demand for tropical timber and agricultural products has driven large-scale logging and subsequent conversion of tropical forests. Given that the majority of tropical landscapes have been or will likely be logged, the protection of biodiversity within tropical forests thus depends on whether species can persist in these economically exploited lands, and if species cannot persist, whether we can protect enough primary forest from logging and conversion. However, our knowledge of the impact of logging and conversion on biodiversity is limited to a few taxa, often sampled in different locations with complex land-use histories, hampering attempts to plan cost-effective conservation strategies and to draw conclusions across taxa. Spanning a land-use gradient of primary forest, once- and twice-logged forests, and oil palm plantations, we used traditional sampling and DNA metabarcoding to compile an extensive data set in Sabah, Malaysian Borneo for nine vertebrate and invertebrate taxa to quantify the biological impacts of logging and oil palm, develop cost-effective methods of protecting biodiversity, and examine whether there is congruence in response among taxa. Logged forests retained high species richness, including, on average, 70% of species found in primary forest. In contrast, conversion to oil palm dramatically reduces species richness, with significantly fewer primary-forest species than found on logged forest transects for seven taxa.Using a systematic conservation planning analysis, we show that efficient protection of primary-forest species is achieved with land portfolios that include a large proportion of logged-forest plots. Protecting logged forests is thus a cost-effective method of protecting an ecologically and taxonomically diverse range of species, particularly when conservation budgets are limited. Six indicator groups (birds, leaf-litter ants, beetles, aerial hymenopterans, flies, and true bugs) proved to be consistently good predictors of the response of the other taxa to logging and oil palm. Our results confidently establish the high conservation value of logged forests and the low value of oil palm. Cross-taxon congruence in responses to disturbance also suggests that the practice of focusing on key indicator taxa yields important information of general biodiversity in studies of logging and oil palm

Npas4 is activated by melatonin, and drives the clock gene Cry1 in the ovine pars tuberalis

Seasonal mammalsintegrate changes in the duration of nocturnal melatonin secretion to drive annual physiologic cycles. Melatonin receptors within the proximal pituitary region, the pars tuberalis (PT), are essential in regulating seasonal neuroendocrine responses. In the ovine PT, melatonin is known to influence acute changes in transcriptional dynamics coupled to the onset (dusk) and offset (dawn) of melatonin secretion, leading to a potential interval-timing mechanism capable of decoding changes in day length (photoperiod). Melatonin offset at dawn is linked to cAMP accumulation, which directly induces transcription of the clock gene Per1. The rise of melatonin at dusk induces a separate and distinct cohort, including the clock-regulated genes Cry1 and Nampt, but little is known of the upstream mechanisms involved. Here, we used next-generation sequencing of the ovine PT transcriptome at melatonin onset and identified Npas4 as a rapidly induced basic helix-loop-helix Per-Arnt-Sim domain transcription factor. In vivo we show nuclear localization of NPAS4 protein in presumptive melatonin target cells of the PT (α-glycoprotein hormone-expressing cells), whereas in situ hybridization studies identified acute and transient expression in the PT of Npas4 in response to melatonin. In vitro, NPAS4 forms functional dimers with basic helix loop helix-PAS domain cofactors aryl hydrocarbon receptor nuclear translocator (ARNT), ARNT2, and ARNTL, transactivating both Cry1 and Nampt ovine promoter reporters. Using a combination of 5'-deletions and site-directed mutagenesis, we show NPAS4-ARNT transactivation to be codependent upon two conserved central midline elements within the Cry1 promoter. Our data thus reveal NPAS4 as a candidate immediate early-response gene in the ovine PT, driving molecular responses to melatonin

Determining appropriate approaches for using data in feature selection

Feature selection is increasingly important in data analysis and machine learning in big data era. However, how to use the data in feature selection, i.e. using either ALL or PART of a dataset, has become a serious and tricky issue. Whilst the conventional practice of using all the data in feature selection may lead to selection bias, using part of the data may, on the other hand, lead to underestimating the relevant features under some conditions. This paper investigates these two strategies systematically in terms of reliability and effectiveness, and then determines their suitability for datasets with different characteristics. The reliability is measured by the Average Tanimoto Index and the Inter-method Average Tanimoto Index, and the effectiveness is measured by the mean generalisation accuracy of classification. The computational experiments are carried out on ten real-world benchmark datasets and fourteen synthetic datasets. The synthetic datasets are generated with a pre-set number of relevant features and varied numbers of irrelevant features and instances, and added with different levels of noise. The results indicate that the PART approach is more effective in reducing the bias when the size of a dataset is small but starts to lose its advantage as the dataset size increases

Draft genome sequence of Pseudomonas syringae pathovar syringae strain FF5, causal agent of stem tip dieback disease on ornamental pear.

addresses: The Sainsbury Laboratory, John Innes Centre, Norwich, United Kingdom.notes: PMCID: PMC3393499types: Journal Article; Research Support, Non-U.S. Gov'tFree on Open AccessPseudomonas syringae FF5 causes stem tip dieback disease on ornamental pear (Pyrus calleryana). Its genome encodes a complete type III secretion system (T3SS) and HopAC1, HopM1, AvrE1, HopI1, HopAA1, HopJ1, HopAH2, HopAH1, HopAG1, and HopAZ1. Lacking detectable homologues of other T3SS effectors, it may encode novel, undiscovered effectors

Anion and Cation-yield Spectroscopy of Core-excited SF6

We report an extensive study on total and partial-ion-yield spectroscopy around both the S 2p and F 1s thresholds in SF6. All positive and negative single-ion channels have been measured. Below the F 1s threshold we detect a large variation in relative intensity of the resonant structures according to the specific channel monitored, indicating selective fragmentation. Above threshold, at variance with previous cases described by us, we detect high-intensity structures related to shape resonances not only in the cation channels but also for the anions. We discuss the applicability and limits of a model we have developed for the analysis of shape resonances in anion yields as a function of molecular size

Elliptic logarithms, diophantine approximation and the Birch and Swinnerton-Dyer conjecture

Most, if not all, unconditional results towards the abc-conjecture rely ultimately on classical Baker's method. In this article, we turn our attention to its elliptic analogue. Using the elliptic Baker's method, we have recently obtained a new upper bound for the height of the S-integral points on an elliptic curve. This bound depends on some parameters related to the Mordell-Weil group of the curve. We deduce here a bound relying on the conjecture of Birch and Swinnerton-Dyer, involving classical, more manageable quantities. We then study which abc-type inequality over number fields could be derived from this elliptic approach.Comment: 20 pages. Some changes, the most important being on Conjecture 3.2, three references added ([Mas75], [MB90] and [Yu94]) and one reference updated [BS12]. Accepted in Bull. Brazil. Mat. So

Research on edge-control methods in CNC polishing

Background: We have developed edge-control for the Precessions TM process suitable for fast fabrication of large mirror segments, and other applications sensitive to edge mis-figure. This has been applied to processing of European extremely large telescope (E-ELT) prototype mirror-segments, meeting the specification on maximum edge mis-figure. However we have observed residuals that have proved impossible to correct with this approach, being in part the legacy of asymmetries in the input edge-profiles. Methods: We have therefore compared different proposed methods experimentally and theoretically and report here on a new edge-rectification step, which operates locally on edges, does not disturb the completed bulk area. Results: A new toolpath has been developed and experiments have been carried out to demonstrate that local edge rectification can be carried out. Conclusions: With this method, the residue error on edges can be removed separately and has potential to reduce total process time