Adsorption of Phosphonate Antiscalant from Reverse Osmosis Membrane Concentrate onto Granular Ferric Hydroxide

Adsorptive removal of antiscalants offers a promising way to improve current reverse osmosis (RO) concentrate treatment processes and enables the reuse of the antiscalant in the RO desalination process. This work investigates the adsorption and desorption of the phosphonate antiscalant nitrilotris(methylenephosphonic acid) (NTMP) from RO membrane concentrate onto granular ferric hydroxide (GFH), a material that consists predominantly of akaganéite. The kinetics of the adsorption of NTMP onto GFH was predicted fairly well with two models that consider either combined film-pore or combined film-surface diffusion as the main mechanism for mass transport. It is also demonstrated that NTMP is preferentially adsorbed over sulfate by GFH at pH 7.85. The presence of calcium causes a transformation in the equilibrium adsorption isotherm from a Langmuir type to a Freundlich type with much higher adsorption capacities. Furthermore, calcium also increases the rate of adsorption substantially. GFH is reusable after regeneration with sodium hydroxide solution, indicating that NTMP can be potentially recovered from the RO concentrate. This work shows that GFH is a promising adsorbent for the removal and recovery of NTMP antiscalant from RO membrane concentrates.     

Rapid Combinatorial Synthesis and Chromatography Based Screening of Phosphorescent Iridium Complexes for Solution Processing

This work reports the combinatorial synthesis and screening of phosphorescent iridium complexes as solution processable emitters for OLEDs. The approach taken here allows for the rapid synthesis, isolation, spectroscopic characterization and identification of the libraries based on chromatographic methods. Subsequent analysis of the irradiation induced degradation provides insight on the stability of the complexes under continuous excitation. The method is versatile and can easily be applied to other metal complexes or organic dyes for various applications, e.g., in electroluminescence, photovoltaics and sensing.     

Spacer effects on in vivo properties of DOTA-conjugated dimeric [Tyr3]octreotate peptides synthesized by a "Cu(I)-click" and "sulfo-click" ligation method

We report on the SSTR2-binding properties of a series of four dimeric [Tyr3]octreotate analogues with different spacer lengths (nine, 19, 41, and 57 atoms) between the peptides. Two analogues (9 and 57 atoms) were selected as precursors for the design, synthesis, and biological evaluation of DOTA-conjugated dimeric [Tyr3]octreotate analogues for tumor targeting. These compounds were synthesized by using a two-stage click ligation procedure: a Cu(I) -catalyzed 1,3-dipolar cycloaddition ("copper-click" reaction) and a thio acid/sulfonyl azide amidation ("sulfo-click" reaction). The IC(50) values of these DOTA-conjugated [Tyr3]octreotate analogues were comparable, and internalization studies showed that the nine-atom (111) In-DOTA-labeled [Tyr3]octreotate dimer had rapid and high receptor binding. Biodistribution studies with BALB/c nude mice bearing subcutaneous AR42J tumors showed that the (111) In-labeled [Tyr3]octreotate dimer (nine atoms) had a high tumor uptake at 1 h p.i. (38.8 ± 8.3 % ID g(-1) ), and excellent tumor retention at 4 h p.i. (40.9 ± 2.5 % ID g(-1) ). However, the introduction of the extended hydrophilic 57 atoms spacer led to rapid clearance from the circulation; this limited tumor accumulation of the radiotracer (21.4 ± 4.9 % ID g(-1) at 1 h p.i.). These findings provide important insight on dimerization and spacer effects on the in vivo properties of DOTA-conjugated [Tyr3]octreotate dimers.     

Increasing the thermostability of sucrose phosphorylase by a combination of sequence- and structure-based mutagenesis

Sucrose phosphorylase is a promising biocatalyst for the glycosylation of a wide variety of acceptor molecules, but its low thermostability is a serious drawback for industrial applications. In this work, the stability of the enzyme from Bifidobacterium adolescentis has been significantly improved by a combination of smart and rational mutagenesis. The former consists of substituting the most flexible residues with amino acids that occur more frequently at the corresponding positions in related sequences, while the latter is based on a careful inspection of the enzyme's crystal structure to promote electrostatic interactions. In this way, a variant enzyme could be created that contains six mutations and whose half-life at the industrially relevant temperature of 60 °C has more than doubled compared with the wild-type enzyme. An increased stability in the presence of organic co-solvents could also be observed, although these effects were most noticeable at low temperatures.     

Risk factors and follow-up of recurrent laryngeal nerve paralysis after first surgeries of benign thyroid diseases. Results of a retrospective analysis of 1,556 patients

PATIENTS AND METHODS: risk factors of recurrent laryngeal nerve (RLN) palsy after thyroid gland surgery were evaluated retrospectively in 1556 patients who were submitted to an operation because of a benign thyroid disease. Recurrences were also excluded. RESULTS: RLN palsy occurred in 6.6%. In relation to the nerves at risk the incidence of primary postoperative nerve damages was 4.3%. After a long-term follow-up of in total 18 months the incidence of permanent nerve palsy was 1.6% (related to the nerves at risk: 1.1%) as 75.5% of the paralyses were transient in an average of 6.2 months. Substernal goitres especially when sternotomy became necessary, the ligature of the inferior laryngeal artery, serious perioperative complications and total lobectomy in comparison to subtotal resection were important risk factors for primary postoperative RLN palsy (p < 0.05 resp. p < 0.01). The ligature of the inferior laryngeal artery and the extension of resection were indeed significant risk factors also for permanent nerve damages, but the other factors had no influence on the risk of permanent RLN palsy. However, the non-exposure of RLN in subtotal lobectomy was significantly associated (p < 0.01) with permanent, but not with transient nerve palsy. CONCLUSION: The exposure of the RLN is one of the most important procedures during thyroid surgery and particular also during subtotal lobectomy to reduce the rate of permanent RLN damages.     

Mobile technology dominates school children’s IT use in an advantaged school community and is associated with musculoskeletal and visual symptoms

This paper describes the contemporary use of information technology devices by children in a socio-educationally advantaged school. A sample of 924 children (50% girls) from grades 5 to 12 (ages 10–19 years) completed an online survey in class. Total daily technology use was high and similar for girls (mean 219 (SD 148) mins/day) and boys (207 (142), p=.186). Tablet computer was the dominant device used in grades 5–9, with laptop computer the dominant device in grades 10–12. Patterns of exposure were influenced by gender, device, grade and purpose of use interactions. For example, girls used mobile phones more than boys for social purposes for grades 10 and 11, but not grade 12. Whilst children’s attitudes to technology use were positive, musculoskeletal and visual symptoms were commonly reported. Hours/day tablet and phone use was related to neck/shoulder discomfort (OR = 1.07; 1.13) and visual symptoms (OR = 1.10; 1.07).

Practitioner Summary: Technology use by children appears to be quite different now to a decade ago. This paper describes contemporary school children’s use of various devices for various purposes. The survey of >900 children found high technology use, dominated by new mobile technologies, and associations with musculoskeletal and visual symptoms.     

Identification of Phenylphthalazinones as a New Class of Leishmania infantum Inhibitors

Leishmaniasis is a neglected parasitic disease caused by over 20 different Leishmania species. Current treatments often rely on harsh regimes of pentavalent antimonials such as sodium stibogluconate, while more recent drugs suffer other shortcomings such as low stability and rapid emergence of treatment failure, amongst others. Furthermore, the effectiveness of drugs varies depending on the infecting Leishmania species, thus there is an urgent need for new and effective anti-leishmanial drugs. Screening of an in-house compound library identified the hexahydrophthalazinone NPD-2942 as a low micromolar hit with a pIC₅₀ of 5.8 against L. infantum and a pIC₅₀ of 4.6 for cytotoxicity against human MRC-5 fibroblasts. To derive structure–activity relationships, we modified the cyclohexyl ring of the hexahydrophthalazinone scaffold and 1,2,3-triazoles were attempted as replacement for the pyrazole ring, amongst others. Ultimately, the 2,3-pyrazole-substituted hexahydrophthalazinone NPD-1289 was identified as the most potent analogue in this series with a pIC₅₀ of 6.3, although some cytotoxicity toward MRC-5 cells (pIC₅₀=5.1) was recorded as well. Replacement of the unsubstituted 2,3-pyrazole with 1,2,3-triazoles led to compounds with lower anti-leishmanial activity. The current scaffold is a valuable new starting point for optimization toward novel anti-leishmanial drugs.     

A deeper understanding of the spontaneous derepression of the URA3 gene in MaV203 Saccharomyces cerevisiae and its implications for protein engineering and the reverse two-hybrid system

Within the field of protein-based biomaterials, the need exists for both covalent and oriented bioconjugation strategies for improved performance. Such bioconjugation reactions can be facilitated by engineering proteins with chemically activated amino acids at strategically chosen sites. The incorporation of these unnatural amino acids (uAAs) can be achieved by using the nonsense suppression technique. This requires an aminoacyl-tRNA-synthetase (aaRS) that exclusively recognizes the uAA and loads it to the corresponding tRNA. Appropriate (aaRS) mutants can be found through reverse engineering using the Saccharomyces cerevisiae strain MaV203. This strain contains a counterselectable, Gal4p-inducible SPAL10::URA3 fusion and deletions in the endogenous GAL80 and GAL4 genes. Therefore, it has been used extensively for the screening of aaRS mutant libraries. It is generally assumed that the SPAL10 promoter actively represses the URA3 gene in the absence of Gal4p, resulting in MaV203 cells with a Ura ⁻ phenotype. The current contribution reveals that in a small fraction of MaV203 cells, a basal expression of the URA3 gene occurs. The unexpected URA3 expression is reported for the first time, and the nature of the mutation causing this expression was identified as a spontaneous recessive mutation in a single gene of a protein involved in the repression of the SPAL10 promoter. The basal URA3 expression causes aaRS mutants to be missed, which affects the outcome of the library screening. It is demonstrated that the use of diploid cells can circumvent the MaV203 Ura⁺ phenotype, allowing for an optimization of S. cerevisiae library screening.