Synthesis of highly elastic biocompatible polyurethanes based on bio-based isosorbide and poly(tetramethylene glycol) and their properties.

Bio-based high elastic polyurethanes were prepared from hexamethylene diisocyanate and various ratios of isosorbide to poly(tetramethylene glycol) as a diol by a simple one-shot bulk polymerization without a catalyst. Successful synthesis of the polyurethanes was confirmed by Fourier transform-infrared spectroscopy and (1)H nuclear magnetic resonance. Thermal properties were determined by differential scanning calorimetry and thermogravimetric analysis. The glass transition temperature was -47.8℃. The test results showed that the poly(tetramethylene glycol)/isosorbide-based elastomer exhibited not only excellent stress-strain properties but also superior resilience to the existing polyether-based polyurethane elastomers. The static and dynamic properties of the polyether/isosorbide-based thermoplastic elastomer were more suitable for dynamic applications. Moreover, such rigid diols impart biocompatible and bioactive properties to thermoplastic polyurethane elastomers. Degradation tests performed at 37℃ in phosphate buffer solution showed a mass loss of 4-9% after 8 weeks, except for the polyurethane with the lowest isosorbide content, which showed an initial rapid weight loss. These polyurethanes offer significant promise due to soft, flexible and biocompatible properties for soft tissue augmentation and regeneration

Phase equilibria in the Fe-Mo-Ti ternary system at 1000 °C

An isothermal section of the Fe-Mo-Ti ternary system at 1000 °C has been constructed using data acquired from a series of seven alloys. The limit of solubility of Fe in the continuous A2 phase field between Ti and Mo has been determined, as have the extents to which Mo may be accommodated in the B2 TiFe phase, and Ti in the D8$_5$ Fe$_7$Mo$_6$ phase. The B2, D8$_5$ and C14 Fe$_2$ (Ti, Mo) intermetallics were found to have limited tolerance for non-stoichiometric compositions. The positions of the A2 + B2 + C14 and A2 + C14 + D8$_5$ three-phase fields were determined, along with the extents of the A2 + B2, A2 + D8$_5$, A2 + C14, C14 + B2 and C14 + D8$_5$ two-phase fields. No ternary phases were observed in any of the alloys studied.This work was support by the Rolls-Royce/EPSRC Strategic Partnership under EP/H022309/1, EP/H500375/1 and EP/M005607/1.This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.ijrmhm.2016.07.00

Data on a Laves phase intermetallic matrix composite in situ toughened by ductile precipitates

The data presented in this article are related to the research article entitled “Laves phase intermetallic matrix composite in situ toughened by ductile precipitates” (Knowles et al.) [1]. The composite comprised a Fe2(Mo, Ti) matrix with bcc (Mo, Ti) precipitated laths produced in situ by an aging heat treatment, which was shown to confer a toughening effect (Knowles et al.) [1]. Here, details are given on a focused ion beam (FIB) slice and view experiment performed on the composite so as to determine that the 3D morphology of the bcc (Mo, Ti) precipitates were laths rather than needles. Scanning transmission electron microscopy (S(TEM)) micrographs of the microstructure as well as energy dispersive X-ray spectroscopy (EDX) maps are presented that identify the elemental partitioning between the C14 Laves matrix and the bcc laths, with Mo rejected from the matrix into laths. A TEM selected area diffraction pattern (SADP) and key is provided that was used to validate the orientation relation between the matrix and laths identified in (Knowles et al.) [1] along with details of the transformation matrix determined

Bayesian optimization for materials design

We introduce Bayesian optimization, a technique developed for optimizing time-consuming engineering simulations and for fitting machine learning models on large datasets. Bayesian optimization guides the choice of experiments during materials design and discovery to find good material designs in as few experiments as possible. We focus on the case when materials designs are parameterized by a low-dimensional vector. Bayesian optimization is built on a statistical technique called Gaussian process regression, which allows predicting the performance of a new design based on previously tested designs. After providing a detailed introduction to Gaussian process regression, we introduce two Bayesian optimization methods: expected improvement, for design problems with noise-free evaluations; and the knowledge-gradient method, which generalizes expected improvement and may be used in design problems with noisy evaluations. Both methods are derived using a value-of-information analysis, and enjoy one-step Bayes-optimality

The impact of albendazole treatment on the incidence of viral- and bacterial-induced diarrhea in school children in southern Vietnam: study protocol for a randomized controlled trial

Anthelmintics are one of the more commonly available classes of drugs to treat infections by parasitic helminths (especially nematodes) in the human intestinal tract. As a result of their cost-effectiveness, mass school-based deworming programs are becoming routine practice in developing countries. However, experimental and clinical evidence suggests that anthelmintic treatments may increase susceptibility to other gastrointestinal infections caused by bacteria, viruses, or protozoa. Hypothesizing that anthelmintics may increase diarrheal infections in treated children, we aim to evaluate the impact of anthelmintics on the incidence of diarrheal disease caused by viral and bacterial pathogens in school children in southern Vietnam.This is a randomized, double-blinded, placebo-controlled trial to investigate the effects of albendazole treatment versus placebo on the incidence of viral- and bacterial-induced diarrhea in 350 helminth-infected and 350 helminth-uninfected Vietnamese school children aged 6-15 years. Four hundred milligrams of albendazole, or placebo treatment will be administered once every 3 months for 12 months. At the end of 12 months, all participants will receive albendazole treatment. The primary endpoint of this study is the incidence of diarrheal disease assessed by 12 months of weekly active and passive case surveillance. Secondary endpoints include the prevalence and intensities of helminth, viral, and bacterial infections, alterations in host immunity and the gut microbiota with helminth and pathogen clearance, changes in mean z scores of body weight indices over time, and the number and severity of adverse events.In order to reduce helminth burdens, anthelmintics are being routinely administered to children in developing countries. However, the effects of anthelmintic treatment on susceptibility to other diseases, including diarrheal pathogens, remain unknown. It is important to monitor for unintended consequences of drug treatments in co-infected populations. In this trial, we will examine how anthelmintic treatment impacts host susceptibility to diarrheal infections, with the aim of informing deworming programs of any indirect effects of mass anthelmintic administrations on co-infecting enteric pathogens.ClinicalTrials.gov: NCT02597556 . Registered on 3 November 2015

The secreted triose phosphate isomerase of Brugia malayi is required to sustain microfilaria production in vivo

Human lymphatic filariasis is a major tropical disease transmitted through mosquito vectors which take up microfilarial larvae from the blood of infected subjects. Microfilariae are produced by long-lived adult parasites, which also release a suite of excretory-secretory products that have recently been subject to in-depth proteomic analysis. Surprisingly, the most abundant secreted protein of adult Brugia malayi is triose phosphate isomerase (TPI), a glycolytic enzyme usually associated with the cytosol. We now show that while TPI is a prominent target of the antibody response to infection, there is little antibody-mediated inhibition of catalytic activity by polyclonal sera. We generated a panel of twenty-three anti-TPI monoclonal antibodies and found only two were able to block TPI enzymatic activity. Immunisation of jirds with B. malayi TPI, or mice with the homologous protein from the rodent filaria Litomosoides sigmodontis, failed to induce neutralising antibodies or protective immunity. In contrast, passive transfer of neutralising monoclonal antibody to mice prior to implantation with adult B. malayi resulted in 60–70% reductions in microfilarial levels in vivo and both oocyte and microfilarial production by individual adult females. The loss of fecundity was accompanied by reduced IFNγ expression by CD4+ T cells and a higher proportion of macrophages at the site of infection. Thus, enzymatically active TPI plays an important role in the transmission cycle of B. malayi filarial parasites and is identified as a potential target for immunological and pharmacological intervention against filarial infections

Atomic structures of TDP-43 LCD segments and insights into reversible or pathogenic aggregation.

The normally soluble TAR DNA-binding protein 43 (TDP-43) is found aggregated both in reversible stress granules and in irreversible pathogenic amyloid. In TDP-43, the low-complexity domain (LCD) is believed to be involved in both types of aggregation. To uncover the structural origins of these two modes of β-sheet-rich aggregation, we have determined ten structures of segments of the LCD of human TDP-43. Six of these segments form steric zippers characteristic of the spines of pathogenic amyloid fibrils; four others form LARKS, the labile amyloid-like interactions characteristic of protein hydrogels and proteins found in membraneless organelles, including stress granules. Supporting a hypothetical pathway from reversible to irreversible amyloid aggregation, we found that familial ALS variants of TDP-43 convert LARKS to irreversible aggregates. Our structures suggest how TDP-43 adopts both reversible and irreversible β-sheet aggregates and the role of mutation in the possible transition of reversible to irreversible pathogenic aggregation