The impact of sodium contamination in tin sulfide thin-film solar cells

Through empirical observations, sodium (Na) has been identified as a benign contaminant in some thin-film solar cells. Here, we intentionally contaminate thermally evaporated tin sulfide (SnS) thin-films with sodium and measure the SnS absorber properties and solar cell characteristics. The carrier concentration increases from 2 × 10[superscript 16] cm[superscript −3] to 4.3 × 10[superscript17] cm[superscript−3] in Na-doped SnS thin-films, when using a 13 nm NaCl seed layer, which is detrimental for SnS photovoltaic applications but could make Na-doped SnS an attractive candidate in thermoelectrics. The observed trend in carrier concentration is in good agreement with density functional theory calculations, which predict an acceptor-type Na[subscriptSn] defect with low formation energy.United States. Department of Energy (SunShot Initiative, Contract No. DE-EE0005329)National Science Foundation (U.S.) (Grant No. CHE-11115577)Alexander von Humboldt FoundationNational Science Foundation (U.S.). Graduate Research Fellowship ProgramMIT Energy Initiative (Fellowship)United States. Department of Energy. Office of Energy Efficiency and Renewable Energy (Postdoctoral Research Award)National Science Foundation (U.S.) (Award No. DMR-08-19762)National Science Foundation (U.S.). Center for Nanoscale Systems (Award No. ECS-0335765

A Novel Strategy for Development of Recombinant Antitoxin Therapeutics Tested in a Mouse Botulism Model

Antitoxins are needed that can be produced economically with improved safety and shelf life compared to conventional antisera-based therapeutics. Here we report a practical strategy for development of simple antitoxin therapeutics with substantial advantages over currently available treatments. The therapeutic strategy employs a single recombinant ‘targeting agent’ that binds a toxin at two unique sites and a ‘clearing Ab’ that binds two epitopes present on each targeting agent. Co-administration of the targeting agent and the clearing Ab results in decoration of the toxin with up to four Abs to promote accelerated clearance. The therapeutic strategy was applied to two Botulinum neurotoxin (BoNT) serotypes and protected mice from lethality in two different intoxication models with an efficacy equivalent to conventional antitoxin serum. Targeting agents were a single recombinant protein consisting of a heterodimer of two camelid anti-BoNT heavy-chain-only Ab VH (VHH) binding domains and two E-tag epitopes. The clearing mAb was an anti-E-tag mAb. By comparing the in vivo efficacy of treatments that employed neutralizing vs. non-neutralizing agents or the presence vs. absence of clearing Ab permitted unprecedented insight into the roles of toxin neutralization and clearance in antitoxin efficacy. Surprisingly, when a post-intoxication treatment model was used, a toxin-neutralizing heterodimer agent fully protected mice from intoxication even in the absence of clearing Ab. Thus a single, easy-to-produce recombinant protein was as efficacious as polyclonal antiserum in a clinically-relevant mouse model of botulism. This strategy should have widespread application in antitoxin development and other therapies in which neutralization and/or accelerated clearance of a serum biomolecule can offer therapeutic benefit

A narrative review on pressure ulcer (PU) studies relevant to medical imaging

Pressure ulcers (PUs) are defined as localised injuries to the skin and/or underlying tissue as a result of pressure or pressure together with shear. PUs present significant health implications to patients; costing billions to manage and/or treat. The burden of PU prevention in hospitals must be the concern of all healthcare professionals, including radiographers. The purpose of this narrative review article is to identify and critically evaluate relevant literature and research conducted into pressure ulcers (PUs) relevant to medical imaging. It is expected that this review article will increase the level of awareness about PUs amongst radiographers and help to develop appropriate interventions to minimise the risk of PUs. A literature search was conducted in PubMed/Medline, Scopus, CINAHL, and Google Scholar to retrieve relevant articles. Also, books, professional body guidelines, magazines, grey and unpublished literatures were also searched. The search was limited to English Language articles. Only five articles were retrieved and reviewed. There are limited studies on PUs relevant to medical imaging. Available studies provide some evidence that radiographic procedures and settings subject patients attending for radiographic procedures to the risk of PUs. Further studies are needed into PU risk assessment, minimisation and management in medical imaging to help raise awareness and address the problem of the potential for PU development

BoNT/A intoxication is prevented in mice by co-administration of a single anti-BoNT/A VHH heterodimer and a clearing Ab.

<p>Symptoms of BoNT/A intoxication and lethality were monitored following administration of single- or double-tagged heterodimers of neutralizing or non-neutralizing anti-BoNT/A VHHs+/−clearing Ab, or no agents. Time to death is plotted as % survival as a function of time. (<b>A</b>) Heterodimers with a single E-tag consisting of two non-neutralizing VHHs (F12/D12(1E)) or two neutralizing VHHs (H7/B5(1E)) were co-administered to groups of five mice with or without anti-E-tag clearing Ab (αE) and the indicated dose of BoNT/A. (<b>B</b>) Heterodimers with two copies of the E-tag and consisting of two non-neutralizing VHHs (F12/D12(1E)) or two neutralizing VHHs (H7/B5(1E)) were co-administered to groups of five mice with or without anti-E-tag clearing Ab (αE) and the indicated dose of BoNT/A. An asterisk indicates that mice did not display any symptoms of intoxication.</p

Anti-BoNT/A VHH protection from lethality improves with higher affinity VHHs.

<p>(<b>A</b>) The K_Ds for four anti-BoNT/A VHHs that each recognize the same epitope (epitope A1; <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0029941#pone-0029941-t001" target="_blank">Table 1</a>) based on competition analysis. (<b>B</b>) Time to death is plotted as % survival following injection of the indicated dose of BoNT/A in groups of five mice co-administered with pools of different anti-BoNT/A VHHs and clearing Ab. Each VHH pool contained VHHs ciA-B5 and ciA-C2 and one of the four different VHHs recognizing BoNT/A epitope A1. The pool of ciA-VHHs or control (no agents) that were administered to the mice is indicated by arrows.</p

Summary of VHH characterization data.

A<p>VHH epitopes are named arbitrarily based on their inability to compete with the binding of VHHs recognizing other epitopes.</p>B<p>Subunit recognition was assessed by ELISA with purified BoNT light chain (Lc) or heavy chain (Hc). VHHs recognizing BoNT holotoxin without recognition of purified Lc or Hc are indicated as none. RBD indicates recognition of the 50 kDa carboxyl end receptor binding domain of Hc.</p>C<p>VHH neutralization was determined by the ability of the VHH to prevent intoxication of primary neurons by 10 pM BoNT/A (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0029941#pone-0029941-g001" target="_blank">Figure 1</a>). ‘Strong’ indicates that the presence of ≤0.1 nM VHH led to obvious toxin neutralization in primary neuron assays (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0029941#pone-0029941-g001" target="_blank">Figure 1</a>). ‘Weak’ indicates detectable toxin neutralization when the medium contained ≤1 nM VHH. None indicates no toxin neutralization was detected when the medium contained ≤10 nM VHH.</p>D<p>Surface plasmon resonance (SPR) studies were performed using chips coated with ciBoNTA for BoNT/A VHHs and ciBoNTB for BoNT/B VHHs as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0029941#s4" target="_blank">Methods and Materials</a>.</p

BoNT/A intoxication is prevented in mice by co-administration of a pool of epitopically tagged VHHs and an anti-tag mAb.

<p>Symptoms of intoxication and time to death were monitored following administration of the indicated dose of BoNT/A in groups of five mice co-administered with pools of anti-BoNT/A VHHs+/−clearing Ab. The time to death is plotted as % survival as a function of time following administration of the indicated dose of toxin (LD₅₀). The pool of ciA-VHHs or control (no agents) that was administered to the mice is indicated by arrows. The presence or absence (dashed lines) of the anti-E-tag clearing Ab (αE) is also indicated. (<b>A</b>) Protection from BoNT/A lethality by co-administration of pools containing two different anti-BoNT/A VHH monomers. (<b>B</b>) Protection from BoNT/A lethality by co-administration of pools containing three different anti-BoNT/A VHH monomers. (<b>C</b>) Protection from BoNT/A lethality by co-administration of pools containing four different anti-BoNT/A VHH monomers. An asterisk indicates that mice did not display any symptoms of intoxication.</p

BoNT/A intoxication is prevented by administering a single anti-BoNT/A VHH heterodimer in a clinically-relevant post-intoxication mouse model.

<p>A 10 LD₅₀ dose of toxin was administered by intraperitoneal injection either 1.5 or 3 hours prior to intravenous administration of antitoxin agents as indicated. Symptoms of BoNT/A intoxication and lethality were monitored following post-intoxication administration of double-tagged heterodimers of neutralizing or non-neutralizing anti-BoNT/A VHHs+/−clearing Ab. The time to death is plotted as % survival as a function of time following administration of toxin. Time to death for mice given no agents or the positive control sheep antitoxin are also shown. (<b>A</b>) The double-tagged heterodimer consisted of two non-neutralizing VHHs, ciA-F12 and ciA-D12 (F12/D12(2E)) and was administered with or without anti-E-tag clearing mAb (αE) as indicated. (<b>B</b>) The double-tagged heterodimer consisted of two BoNT/A neutralizing VHHs, ciA-H7 and ciA-B5 (H7/B5(2E)) and was administered with or without anti-E-tag clearing mAb (αE) as indicated.</p

VHH neutralization of BoNT/A in rat primary cerebellar neuron cultures.

<p>Purified anti-BoNT/A VHHs (ciA-) were added to the medium for cultured primary cerebellar neurons at the indicated concentrations and then BoNT/A (∼10 pM) or medium (Ctrl) was added. After overnight culture, the cells were harvested and the extent of SNAP25 cleavage was assessed by Western blot. The upper band represents uncleaved SNAP25 while the lower band is BoNT/A cleaved SNAP25. VHHs that clearly inhibited BoNT/A cleavage of SNAP25 at concentrations of 0.1 nM were considered to be strong neutralizing agents (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0029941#pone-0029941-t001" target="_blank">Table 1</a>). Data shown for each VHH were obtained within the same experiment and are representative of at least two independent experiments.</p

BoNT/B intoxication is prevented by heterodimer antitoxin agents in two models of BoNT/B intoxication in mice.

<p>Protection of mice from BoNT/B lethality by administration of a double-tagged heterodimer of anti-BoNT/B VHHs ciB-A11 and ciB-B5 (A11/B5(2E))+/−clearing Ab. Time to death is plotted as % survival as a function of time. An asterisk indicates that mice did not display any symptoms of intoxication. The results shown are combined from two replicate studies. (<b>A</b>) Groups of mice were co-administered the indicated LD₅₀ dose of BoNT/B together with no agents or the A11/B5(2E) heterodimer VHH with or without anti-E-tag clearing Ab (αE). (<b>B</b>) Groups of mice were administered a 10 LD₅₀ dose of BoNT/B and three hours later administered no agents, sheep anti-BoNT/B antiserum or the A11/B5(2E) heterodimer VHH with or without anti-E-tag clearing Ab (αE).</p