Distributed utterances

I propose an apparatus for handling intrasentential change in context. The standard approach has problems with sentences with multiple occurrences of the same demonstrative or indexical. My proposal involves the idea that contexts can be complex. Complex contexts are built out of (“simple”) Kaplanian contexts by ordered n-tupling. With these we can revise the clauses of Kaplan’s Logic of Demonstratives so that each part of a sentence is taken in a different component of a complex context. I consider other applications of the framework: to agentially distributed utterances (ones made partly by one speaker and partly by another); to an account of scare-quoting; and to an account of a binding-like phenomenon that avoids what Kit Fine calls “the antinomy of the variable.

N‐Substituted Nipecotic Acids as (S )‐SNAP‐5114 Analogues with Modified Lipophilic Domains

Potential mGAT4 inhibitors derived from the lead substance (S )‐SNAP‐5114 have been synthesized and characterized for their inhibitory potency. Variations from the parent compound included the substitution of one of its aromatic 4‐methoxy and 4‐methoxyphenyl groups, respectively, with a more polar moiety, including a carboxylic acid, alcohol, nitrile, carboxamide, sulfonamide, aldehyde or ketone function, or amino acid partial structures. Furthermore, it was investigated how the substitution of more than one of the aromatic 4‐methoxy groups affects the potency and selectivity of the resulting compounds. Among the synthesized test substances (S )‐1‐{2‐[(4‐formylphenyl)bis(4‐methoxyphenyl)‐methoxy]ethyl}piperidine‐3‐carboxylic acid, that features a carbaldehyde function in place of one of the aromatic 4‐methoxy moieties of (S )‐SNAP‐5114, was found to have a pIC50 value of 5.89±0.07, hence constituting a slightly more potent mGAT4 inhibitor than the parent substance while showing comparable subtype selectivity

Completability vs (In)completeness

In everyday conversation, no notion of “complete sentence” is required for syntactic licensing. However, so-called “fragmentary”, “incomplete”, and abandoned utterances are problematic for standard formalisms. When contextualised, such data show that (a) non-sentential utterances are adequate to underpin agent coordination, while (b) all linguistic dependencies can be systematically distributed across participants and turns. Standard models have problems accounting for such data because their notions of ‘constituency’ and ‘syntactic domain’ are independent of performance considerations. Concomitantly, we argue that no notion of “full proposition” or encoded speech act is necessary for successful interaction: strings, contents, and joint actions emerge in conversation without any single participant having envisaged in advance the outcome of their own or their interlocutors’ actions. Nonetheless, morphosyntactic and semantic licensing mechanisms need to apply incrementally and subsententially. We argue that, while a representational level of abstract syntax, divorced from conceptual structure and physical action, impedes natural accounts of subsentential coordination phenomena, a view of grammar as a “skill” employing domain-general mechanisms, rather than fixed form-meaning mappings, is needed instead. We provide a sketch of a predictive and incremental architecture (Dynamic Syntax) within which underspecification and time-relative update of meanings and utterances constitute the sole concept of “syntax”

Role of N-glycosylation in renal betaine transport

The osmolyte and folding chaperone betaine is transported by the renal Na+-coupled GABA (γ-aminobutyric acid) symporter BGT-1 (betaine/GABA transporter 1), a member of the SLC6 (solute carrier 6) family. Under hypertonic conditions, the transcription, translation and plasma membrane (PM) insertion of BGT-1 in kidney cells are significantly increased, resulting in elevated betaine and GABA transport. Re-establishing isotonicity involves PM depletion of BGT-1. The molecular mechanism of the regulated PM insertion of BGT-1 during changes in osmotic stress is unknown. In the present study, we reveal a link between regulated PM insertion and N-glycosylation. Based on homology modelling, we identified two sites (Asn171 and Asn183) in the extracellular loop 2 (EL2) of BGT-1, which were investigated with respect to trafficking, insertion and transport by immunogold-labelling, electron microscopy (EM), mutagenesis and two-electrode voltage clamp measurements in Xenopus laevis oocytes and uptake of radiolabelled substrate into MDCK (Madin–Darby canine kidney) and HEK293 (human embryonic kidney) cells. Trafficking and PM insertion of BGT-1 was clearly promoted by N-glycosylation in both oocytes and MDCK cells. Moreover, association with N-glycans at Asn171 and Asn183 contributed equally to protein activity and substrate affinity. Substitution of Asn171 and Asn183 by aspartate individually caused no loss of BGT-1 activity, whereas the double mutant was inactive, suggesting that N-glycosylation of at least one of the sites is required for function. Substitution by alanine or valine at either site caused a dramatic loss in transport activity. Furthermore, in MDCK cells PM insertion of N183D was no longer regulated by osmotic stress, highlighting the impact of N-glycosylation in regulation of this SLC6 transporter

Unhindered copper uptake by glutaraldehyde-polyethyleneimine coatings in an artificial seawater model system with adsorbed swollen polysaccharides and competing ligand EDTA

Shortly after a surface is submerged in the sea, a conditioning film is generally formed by adsorption of organic molecules, such as polysaccharides. This could affect transport of molecules and ions between the seawater and the surface. An artificial seawater model system was developed to understand how adsorbed polysaccharides impact copper binding by glutaraldehyde-crosslinked polyethyleneimine coatings. Coating performance was also determined when competed against copper-chelating EDTA. Polysaccharide adsorption and copper binding and distribution were investigated using advanced analytical techniques, including depth-resolved time-of-flight secondary ion mass spectroscopy, grazing incidence X-ray absorption near-edge spectroscopy, quartz crystal microbalance with dissipation monitoring and X-ray photoelectron spectroscopy. In artificial seawater, the polysaccharides adsorbed in a swollen state that copper readily penetrated and the glutaraldehyde-polyethyleneimine coatings outcompeted EDTA for copper binding. Furthermore, the depth distribution of copper species was determined with nanometre precision. The results are highly relevant for copper-binding and copper-releasing materials in seawater

Cu K-edge XANES: polymer, organic, inorganic spectra, and experimental considerations

In pursuit of design and characterisation of Cu adsorbing in thin films, we present data from a large variety of Cu-K edge X-ray Absorption Near Edge Spectroscopy (XANES) spectra obtained from organic and inorganic standards. Additionally, we have explored the impact of beam damage inducing redox alterations. Polymer nanoparticles were tested against films to produce higher concentration samples while maintaining high surface area to bulk effects. Spectra from nanoparticles were highly comparable to thin films of ~8 nm thickness, implying comparable contributions by surface effects on copper association. Finally, we observed no impact on Cu XANES spectra from vitrification with dimethyl sulfoxide to produce amorphous frozen, hydrated samples. The spectra should act as a valuable resource in assisting the design of experiments and identification of copper associations

Impact testing to determine the mechanical properties of articular cartilage in isolation and on bone

The original publication is available at www.springerlink.comNon peer reviewedPostprin

Immunospecific targeting of CD45 expressing lymphoid cells: Towards improved detection agents of the sentinel lymph node

This study was designed to demonstrate the potential of small nanoparticulate lymphotropic contrast agents designed to bind with high affinity to lymphoid cells overexpressing the CD45 antigen. To this end, small gold nanoparticles used as model were conjugated to anti-CD45 antibodies and injected in mice in the dorsal toe of the fore/hind paw. Chemical analysis demonstrated rapid uptake and transport of the nanoparticles in the lymphatic as well as significant retention of the nanoparticles with high binding affinity to lymphoid cells in the popliteal and axillary lymph nodes in comparison to non-targeted nanoparticles.Tianqing Liu, Aidan Cousins, Chia-Chi Chien, Ivan Kempson, Sarah Thompson, Yeukuang Hwu, Benjamin Thierr

Environmental copper sensor based on polyethylenimine-functionalized nanoporous anodic alumina interferometers

Anthropogenic copper pollution of environmental waters from sources such as acid mine drainage, antifouling paints, and industrial waste discharge is a major threat to our environment and human health. This study presents an optical sensing system that combines self-assembled glutaraldehyde-cross-linked double-layered polyethylenimine (PEI-GA-PEI)-modified nanoporous anodic alumina (NAA) interferometers with reflectometric interference spectroscopy (RIfS) for label-free, selective monitoring of ionic copper in environmental waters. Calibration of the sensing system with analytical solutions of copper shows a linear working range between 1 and 100 mg L-1, and a low limit of detection of 0.007 ± 0.001 mg L-1 (i.e., ∼0.007 ppm). Changes in the effective optical thickness (ΔOTeff) of PEI-GA-PEI-functionalized NAA interferometers are monitored in real-time by RIfS, and correlated with the amount of ionic copper present in aqueous solutions. The system performance is validated through X-ray photoelectron spectroscopy (XPS) and the spatial distribution of copper within the nanoporous films is characterized by time-of-flight-secondary ion mass spectroscopy (TOF-SIMS). The specificity and chemical selectivity of the PEI-GA-PEI-NAA sensor to Cu2+ ions is verified by screening six different metal ion solutions containing potentially interfering ions such as Al3+, Cd2+, Fe3+, Pb2+, Ni2+, and Zn2+. Finally, the performance of the PEI-GA-PEI-NAA sensor for real-life applications is demonstrated using legacy acid mine drainage liquid and tap water for qualitative and quantitative detection of copper ions. This study provides new opportunities to develop portable, cost-competitive, and ultrasensitive sensing systems for real-life environmental applications.Simarpreet Kaur, Cheryl Suwen Law, Nathan Hu Williamson, Ivan Kempson, Amirali Popat, Tushar Kumeria and Abel Santo