Highly Productive Continuous Flow Synthesis of Di- and Tripeptides in Water

The reaction of amino acid derived N-carboxyanhydrides (NCAs) with unprotected amino acids under carefully controlled aqueous continuous flow conditions realized the formation of range of di- and tripeptide products in 60-85% conversion at productivities of up to 535 g.L-1h-1. This required a fundamental understanding of the physicochemical aspects of the reaction resulting in the design of a bespoke continuous stirred tank reactor (CSTR) with continuous solids addition, high shear mixing, automated pH control to avoid the use of buffer, and efficient heat removal to control the reaction at 1±1 °C

New Symmetries in Crystals and Handed Structures

For over a century, the structure of materials has been described by a combination of rotations, rotation-inversions and translational symmetries. By recognizing the reversal of static structural rotations between clockwise and counterclockwise directions as a distinct symmetry operation, here we show that there are many more structural symmetries than are currently recognized in right- or left-handed handed helices, spirals, and in antidistorted structures composed equally of rotations of both handedness. For example, though a helix or spiral cannot possess conventional mirror or inversion symmetries, they can possess them in combination with the rotation reversal symmetry. Similarly, we show that many antidistorted perovskites possess twice the number of symmetry elements as conventionally identified. These new symmetries predict new forms for "roto" properties that relate to static rotations, such as rotoelectricity, piezorotation, and rotomagnetism. They also enable symmetry-based search for new phenomena, such as multiferroicity involving a coupling of spins, electric polarization and static rotations. This work is relevant to structure-property relationships in all material structures with static rotations such as minerals, polymers, proteins, and engineered structures.Comment: 15 Pages, 4 figures, 3 Tables; Fig. 2b has error

After the sunset: the residual effect of temporary legislation

The difference between permanent legislation and temporary legislation is the default rule of termination: permanent legislation governs perpetually, while temporary legislation governs for a limited time. Recent literature on legislative timing rules considers the effect of temporary legislation to stop at the moment of expiration. When the law expires, so does its regulatory effect. This article extends that literature by examining the effect of temporary legislation beyond its expiration. We show that in addition to affecting compliance behavior which depends on statutory enforcement, temporary legislation also affects compliance behavior which does not depend on statutory enforcement, and more generally, organizational behavior after a sunset. When temporary legislation expires therefore, it can continue to administer regulatory and other effects. We specify the conditions for this process and give the optimal legislative response

Phenoloxidase activity acts as a mosquito innate immune response against infection with semliki forest virus

Several components of the mosquito immune system including the RNA interference (RNAi), JAK/STAT, Toll and IMD pathways have previously been implicated in controlling arbovirus infections. In contrast, the role of the phenoloxidase (PO) cascade in mosquito antiviral immunity is unknown. Here we show that conditioned medium from the Aedes albopictus-derived U4.4 cell line contains a functional PO cascade, which is activated by the bacterium Escherichia coli and the arbovirus Semliki Forest virus (SFV) (Togaviridae; Alphavirus). Production of recombinant SFV expressing the PO cascade inhibitor Egf1.0 blocked PO activity in U4.4 cell- conditioned medium, which resulted in enhanced spread of SFV. Infection of adult female Aedes aegypti by feeding mosquitoes a bloodmeal containing Egf1.0-expressing SFV increased virus replication and mosquito mortality. Collectively, these results suggest the PO cascade of mosquitoes plays an important role in immune defence against arboviruses

Subglacial lake drainage detected beneath the Greenland ice sheet

The contribution of the Greenland ice sheet to sea-level rise has accelerated in recent decades. Subglacial lake drainage events can induce an ice sheet dynamic response—a process that has been observed in Antarctica, but not yet in Greenland, where the presence of subglacial lakes has only recently been discovered. Here we investigate the water flow paths from a subglacial lake, which drained beneath the Greenland ice sheet in 2011. Our observations suggest that the lake was fed by surface meltwater flowing down a nearby moulin, and that the draining water reached the ice margin via a subglacial tunnel. Interferometric synthetic aperture radar-derived measurements of ice surface motion acquired in 1995 suggest that a similar event may have occurred 16 years earlier, and we propose that, as the climate warms, increasing volumes of surface meltwater routed to the bed will cause such events to become more common in the future

The perceived impact of location privacy: A web-based survey of public health perspectives and requirements in the UK and Canada

<p>Abstract</p> <p>Background</p> <p>The "place-consciousness" of public health professionals is on the rise as spatial analyses and Geographic Information Systems (GIS) are rapidly becoming key components of their toolbox. However, "place" is most useful at its most precise, granular scale – which increases identification risks, thereby clashing with privacy issues. This paper describes the views and requirements of public health professionals in Canada and the UK on privacy issues and spatial data, as collected through a web-based survey.</p> <p>Methods</p> <p>Perceptions on the impact of privacy were collected through a web-based survey administered between November 2006 and January 2007. The survey targeted government, non-government and academic GIS labs and research groups involved in public health, as well as public health units (Canada), ministries, and observatories (UK). Potential participants were invited to participate through personally addressed, standardised emails.</p> <p>Results</p> <p>Of 112 invitees in Canada and 75 in the UK, 66 and 28 participated in the survey, respectively. The completion proportion for Canada was 91%, and 86% for the UK. No response differences were observed between the two countries. Ninety three percent of participants indicated a requirement for personally identifiable data (PID) in their public health activities, including geographic information. Privacy was identified as an obstacle to public health practice by 71% of respondents. The overall self-rated median score for knowledge of privacy legislation and policies was 7 out of 10. Those who rated their knowledge of privacy as high (at the median or above) also rated it significantly more severe as an obstacle to research (<it>P </it>< 0.001). The most critical cause cited by participants in both countries was bureaucracy.</p> <p>Conclusion</p> <p>The clash between PID requirements – including granular geography – and limitations imposed by privacy and its associated bureaucracy require immediate attention and solutions, particularly given the increasing utilisation of GIS in public health. Solutions include harmonization of privacy legislation with public health requirements, bureaucratic simplification, increased multidisciplinary discourse, education, and development of toolsets, algorithms and guidelines for using and reporting on disaggregate data.</p

Interrogating domain-domain interactions with parsimony based approaches

<p>Abstract</p> <p>Background</p> <p>The identification and characterization of interacting domain pairs is an important step towards understanding protein interactions. In the last few years, several methods to predict domain interactions have been proposed. Understanding the power and the limitations of these methods is key to the development of improved approaches and better understanding of the nature of these interactions.</p> <p>Results</p> <p>Building on the previously published Parsimonious Explanation method (PE) to predict domain-domain interactions, we introduced a new Generalized Parsimonious Explanation (GPE) method, which (i) adjusts the granularity of the domain definition to the granularity of the input data set and (ii) permits domain interactions to have different costs. This allowed for preferential selection of the so-called "co-occurring domains" as possible mediators of interactions between proteins. The performance of both variants of the parsimony method are competitive to the performance of the top algorithms for this problem even though parsimony methods use less information than some of the other methods. We also examined possible enrichment of co-occurring domains and homo-domains among domain interactions mediating the interaction of proteins in the network. The corresponding study was performed by surveying domain interactions predicted by the GPE method as well as by using a combinatorial counting approach independent of any prediction method. Our findings indicate that, while there is a considerable propensity towards these special domain pairs among predicted domain interactions, this overrepresentation is significantly lower than in the iPfam dataset.</p> <p>Conclusion</p> <p>The Generalized Parsimonious Explanation approach provides a new means to predict and study domain-domain interactions. We showed that, under the assumption that all protein interactions in the network are mediated by domain interactions, there exists a significant deviation of the properties of domain interactions mediating interactions in the network from that of iPfam data.</p

Engineering supported membranes for cell biology

Cell membranes exhibit multiple layers of complexity, ranging from their specific molecular content to their emergent mechanical properties and dynamic spatial organization. Both compositional and geometrical organizations of membrane components are known to play important roles in life processes, including signal transduction. Supported membranes, comprised of a bilayer assembly of phospholipids on the solid substrate, have been productively served as model systems to study wide range problems in cell biology. Because lateral mobility of membrane components is readily preserved, supported lipid membranes with signaling molecules can be utilized to effectively trigger various intercellular reactions. The spatial organization and mechanical deformation of supported membranes can also be manipulated by patterning underlying substrates with modern micro- and nano-fabrication techniques. This article focuses on various applications and methods to spatially patterned biomembranes by means of curvature modulations and spatial reorganizations, and utilizing them to interface with live cells. The integration of biological components into synthetic devices provides a unique approach to investigate molecular mechanisms in cell biology