809 research outputs found

    siRNAdb: a database of siRNA sequences

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    Short interfering RNAs (siRNAs) are a popular method for gene-knockdown, acting by degrading the target mRNA. Before performing experiments it is invaluable to locate and evaluate previous knockdown experiments for the gene of interest. The siRNA database provides a gene-centric view of siRNA experimental data, including siRNAs of known efficacy and siRNAs predicted to be of high efficacy by a combination of methods. Linked to these sequences is information such as siRNA thermodynamic properties and the potential for sequence-specific off-target effects. The database enables the user to evaluate an siRNA's potential for inhibition and non-specific effects. The database is available at http://siRNA.cgb.ki.se

    Insensitivity of alkenone carbon isotopes to atmospheric CO<sub>2</sub> at low to moderate CO<sub>2</sub> levels

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    Atmospheric pCO2 is a critical component of the global carbon system and is considered to be the major control of Earth’s past, present and future climate. Accurate and precise reconstructions of its concentration through geological time are, therefore, crucial to our understanding of the Earth system. Ice core records document pCO2 for the past 800 kyrs, but at no point during this interval were CO2 levels higher than today. Interpretation of older pCO2 has been hampered by discrepancies during some time intervals between two of the main ocean-based proxy methods used to reconstruct pCO2: the carbon isotope fractionation that occurs during photosynthesis as recorded by haptophyte biomarkers (alkenones) and the boron isotope composition (δ11B) of foraminifer shells. Here we present alkenone and δ11B-based pCO2 reconstructions generated from the same samples from the Plio-Pleistocene at ODP Site 999 across a glacial-interglacial cycle. We find a muted response to pCO2 in the alkenone record compared to contemporaneous ice core and δ11B records, suggesting caution in the interpretation of alkenone-based records at low pCO2 levels. This is possibly caused by the physiology of CO2 uptake in the haptophytes. Our new understanding resolves some of the inconsistencies between the proxies and highlights that caution may be required when interpreting alkenone-based reconstructions of pCO2

    Review of Mipomersen Sodium (Kynamro®) for Familial Hypercholesterolemia

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    Objective: To review the pharmacology and pharmacokinetics, and to evaluate the clinical efficacy, safety, and place in therapy of mipomersen sodium (Kynamro®) for the treatment of familial hypercholesterolemia (FH).Data Sources: A literature search through Pub Med and clinicaltrials.gov (1984–May 2014; English language) was performed using the key words: homozygous familial hypercholesterolemia (HoFH), heterozygous familial hypercholesterolemia (HeFH), FH, dyslipidemia, apolipoprotein B-100 (apoB-100), low density lipoprotein cholesterol (LDL-C), antisense oligonucleotides (ASOs), and ISIS 301012. Searches were limited to published studies in humans.Study Selection and Data Extraction: All articles in English identified from reviews, abstracts, presentations, and clinical trials of mipomersen in humans were selected and included.Data Synthesis: Mipomersen sodium (Kynamro®), an oligonucleotide inhibitor of apoB-100 synthesis, is approved for reducing apoB-100, LDL-C, total cholesterol (TC), and non-high density lipoprotein cholesterol (non-HDL-C) in HoFH patients as an adjunctive treatment with other lipid lowering drugs and low fat diet.Conclusion: Mipomersen is effective in decreasing LDL-C, apoB-100, TC, and non-HDL-C in patients that are refractory to other lipid lowering drugs. Mipomersen is administered as 200 mg subcutaneous (s.c.) once weekly injection. The drug is contraindicated in patients with moderate to severe hepatic impairment. The most common adverse reactions include injection site reaction (ISRs), influenza-like symptoms and increases in serum hepatic transaminase. Kynamro® is only available through restricted program under Risk Evaluation and Mitigation Strategy (REMS) called Kynamro® REM

    Universal Shape Replicators via Self-Assembly with Attractive and Repulsive Forces

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    We show how to design a universal shape replicator in a self- assembly system with both attractive and repulsive forces. More precisely, we show that there is a universal set of constant-size objects that, when added to any unknown holefree polyomino shape, produces an unbounded number of copies of that shape (plus constant-size garbage objects). The constant-size objects can be easily constructed from a constant number of individual tile types using a constant number of preprocessing self-assembly steps. Our construction uses the well-studied 2-Handed Assembly Model (2HAM) of tile self-assembly, in the simple model where glues interact only with identical glues, allowing glue strengths that are either positive (attractive) or negative (repulsive), and constant temperature (required glue strength for parts to hold together). We also require that the given shape has specified glue types on its surface, and that the feature size (smallest distance between nonincident edges) is bounded below by a constant. Shape replication necessarily requires a self-assembly model where parts can both attach and detach, and this construction is the first to do so using the natural model of negative/repulsive glues (also studied before for other problems such as fuel-efficient computation); previous replication constructions require more powerful global operations such as an “enzyme” that destroys a subset of the tile types.National Science Foundation (U.S.) (Grant EFRI1240383)National Science Foundation (U.S.) (Grant CCF-1138967

    Universal Shape Replicators via Self-Assembly with Attractive and Repulsive Forces

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    We show how to design a universal shape replicator in a self- assembly system with both attractive and repulsive forces. More precisely, we show that there is a universal set of constant-size objects that, when added to any unknown holefree polyomino shape, produces an unbounded number of copies of that shape (plus constant-size garbage objects). The constant-size objects can be easily constructed from a constant number of individual tile types using a constant number of preprocessing self-assembly steps. Our construction uses the well-studied 2-Handed Assembly Model (2HAM) of tile self-assembly, in the simple model where glues interact only with identical glues, allowing glue strengths that are either positive (attractive) or negative (repulsive), and constant temperature (required glue strength for parts to hold together). We also require that the given shape has specified glue types on its surface, and that the feature size (smallest distance between nonincident edges) is bounded below by a constant. Shape replication necessarily requires a self-assembly model where parts can both attach and detach, and this construction is the first to do so using the natural model of negative/repulsive glues (also studied before for other problems such as fuel-efficient computation); previous replication constructions require more powerful global operations such as an “enzyme” that destroys a subset of the tile types.National Science Foundation (U.S.) (Grant EFRI1240383)National Science Foundation (U.S.) (Grant CCF-1138967

    Universal Shape Replicators via Self-Assembly with Attractive and Repulsive Forces

    Get PDF
    We show how to design a universal shape replicator in a self- assembly system with both attractive and repulsive forces. More precisely, we show that there is a universal set of constant-size objects that, when added to any unknown holefree polyomino shape, produces an unbounded number of copies of that shape (plus constant-size garbage objects). The constant-size objects can be easily constructed from a constant number of individual tile types using a constant number of preprocessing self-assembly steps. Our construction uses the well-studied 2-Handed Assembly Model (2HAM) of tile self-assembly, in the simple model where glues interact only with identical glues, allowing glue strengths that are either positive (attractive) or negative (repulsive), and constant temperature (required glue strength for parts to hold together). We also require that the given shape has specified glue types on its surface, and that the feature size (smallest distance between nonincident edges) is bounded below by a constant. Shape replication necessarily requires a self-assembly model where parts can both attach and detach, and this construction is the first to do so using the natural model of negative/repulsive glues (also studied before for other problems such as fuel-efficient computation); previous replication constructions require more powerful global operations such as an “enzyme” that destroys a subset of the tile types

    Large-scale culturing of Neogloboquadrina pachyderma, its growth in, and tolerance of, variable environmental conditions

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    The planktic foraminifera Neogloboquadrina pachyderma is a calcifying marine protist and the dominant planktic foraminifera species in the polar oceans, making it a key species in marine polar ecosystems. The calcium carbonate shells of foraminifera are widely used in palaeoclimate studies because their chemical composition reflects the seawater conditions in which they grow. This species provides unique proxy data for past surface ocean hydrography, which can provide valuable insight to future climate scenarios. However, little is known about the response of N. pachyderma to variable and changing environmental conditions. Here, we present observations from large-scale culturing experiments where temperature, salinity and carbonate chemistry were altered independently. We observed overall low mortality, calcification of new chambers and addition of secondary calcite crust in all our treatments. In-culture asexual reproduction events also allowed us to monitor the variable growth of N. pachyderma’s offspring. Several specimens had extended periods of dormancy or inactivity after which they recovered. These observations suggest that N. pachyderma can tolerate, adapt to and calcify within a wide range of environmental conditions. This has implications for the species-level response to ocean warming and acidification, for future studies aiming to culture N. pachyderma and use in palaeoenvironmental reconstruction

    Historical trends in pH and carbonate biogeochemistry on the Belize Mesoamerican barrier reef system

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    Coral reefs are important ecosystems that are increasingly negatively impacted by human activities. Understanding which anthropogenic stressors play the most significant role in their decline is vital for the accurate prediction of future trends in coral reef health and for effective mitigation of these threats. Here we present annually resolved boron and carbon isotope measurements of two cores capturing the past 90 years of growth of the tropical reef‐building coral Siderastrea siderea from the Belize Mesoamerican Barrier Reef System. The pairing of these two isotope systems allows us to parse the reconstructed pH change into relative changes in net ecosystem productivity and net ecosystem calcification between the two locations. This approach reveals that the relationship between seawater pH and coral calcification, at both a colony and ecosystem level, is complex and cannot simply be modeled as linear or even positive. This study also underscores both the utility of coupled δ11B‐δ13C measurements in tracing past biogeochemical cycling in coral reefs and the complexity of this cycling relative to the open ocean

    Development of the Continuously Variable Volume Reactor for Flow Injection AnalysisDesign, Capabilities and Testing

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    A new apparatus for mixing sample and reagent in flow injection analysis is described. The continuously variable volume reactor (CVVR) replaces the conventional mixing coil in a flow injection manifold to provide mixing and dilution. A linear actuator motor allows control of the chamber volume via Lab VIEW software. The chamber volume can be incremented in steps of 1 uL over the range 68-1704 uL. In addition, the chamber has an integral variable-speed stirring unit that is also under computer control. Experiments were performed to evaluate the dispersion characteristics of this new device, evaluate the volume reproducibility, and understand the mixing characteristics. Use of the chamber is shown in the determination of iron (II) in pond water, and in NIST SRM 1643d with excellent results and a detection limit of 3.7 ug/L iron(II). Advantages of the CVVR and future research activities using the device are discussed
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