Toward Hybrid Materials: Group Transfer Polymerization of 3-(Trimethoxysilyl)propyl Methacrylate

Front Cover: Group transfer polymerisation (GTP), a living polymerization technique that is easy to scale up, enables the one-pot fabrication of class-II hybrid materials. Specifically a star polymer is synthesized with a 3-(trimethoxy-silyl)propyl methacrylate, alkoxysilane group containing functional monomer. The polymer is then cross-linked to produce an organic-inorganic class-II hybrid material, which can be used in various applications such as thin films and biomaterials. Further details can be found in the article by J. J. Chung, J. R. Jones, and T. K. Georgiou* on page 1806

Anaerobic digestion in a multi-stage plug flow bioreactor: Revisiting an age-old process with modern molecular tools

To address knowledge gaps in the complex interacting microbial associations that underpin anaerobic digestion, a mesophilic (25°C) continuous-flow four-stage reactor was constructed to separate both spatially and temporally the component microbial groups. The reactor influent consisted of primary settled sewage sludge (PSSS) and the organic fraction of municipal solid waste (OFMSW). Chemical (volatile fatty acids, sulphate, sulphide, chemical oxygen demand, gas) and molecular analyses were made during an operation period of 15 months. Spatial separation of the microbial groups resulted in process instability where acidogenesis/acetogenesis produced an effluent with a pH between 2 and 4 that inhibited the subsequent catabolic steps. An organic loading rate of 6.5 g COD d-1 prevented reactor acidification but resulted in low biogas production (0.04-0.12 l biogas l-1 hydraulic load d-1). Fluctuations in chemical and molecular profiles/characteristics, which may have been due to the inherently heterogeneous PSSS and OFMSW, were recorded and these were countered by the development of a model medium. The medium was then used to: explore reactor efficacy; and study pertinent microbial diversity and functional interactions

Randomised, double-blind, placebo controlled study of fluticasone propionate in patients with moderate to severe chronic obstructive pulmonary disease: the ISOLDE trial study

Objectives To determine the effect of long term inhaled corticosteroids on lung function, exacerbations, and health status in patients with moderate to severe chronic obstructive pulmonary disease. Design Double blind, placebo controlled study. Setting Eighteen UK hospitals. Participants 751 men and women aged between 40 and 75 years with mean forced expiratory volume in one second (FEV1) 50% of predicted normal. Interventions Inhaled fluticasone propionate 500 ìg twice daily from a metered dose inhaler or identical placebo. Main outcome measures Efficacy measures: rate of decline in FEV1 after the bronchodilator and in health status, frequency of exacerbations, respiratory withdrawals. Safety measures: morning serum cortisol concentration, incidence of adverse events. Results There was no significant difference in the annual rate of decline in FEV1 (P = 0.16). Mean FEV1 after bronchodilator remained significantly higher throughout the study with fluticasone propionate compared with placebo (P < 0.001). Median exacerbation rate was reduced by 25% from 1.32 a year on placebo to 0.99 a year on with fluticasone propionate (P = 0.026). Health status deteriorated by 3.2 units a year on placebo and 2.0 units a year on fluticasone propionate (P = 0.0043). Withdrawals because of respiratory disease not related to malignancy were higher in the placebo group (25% v19%, P = 0.034). Conclusions Fluticasone propionate 500 ìg twice daily did not affect the rate of decline in FEV1 but did produce a small increase in FEV1. Patients on fluticasone propionate had fewer exacerbations and a slower decline in health status. These improvements in clinical outcomes support the use of this treatment in patients with moderate to severe chronic obstructive pulmonary disease

Efficacy of temsirolimus in metastatic chromophobe renal cell carcinoma

<p>Background: Renal cell carcinoma (RCC) is a histopathologically and molecularly heterogeneous disease with the chromophobe subtype (chRCC) accounting for approximately 5% of all cases. The median overall survival of advanced RCC has improved significantly since the advent of tyrosine kinase inhibitors and mammalian target of rapamycin (mTOR) inhibitors. However, high-quality evidence for the use of new generation tyrosine kinase inhibitors in patients with advanced chRCC is lacking. Few published case reports have highlighted the use of temsirolimus in chRCC.</p> <p>Case presentation: Here, we report the case of a 36-year-old Caucasian woman with metastatic chRCC with predominantly skeletal metastases who was refractory to sunitinib who demonstrated a durable clinical response to temsirolimus lasting 20 months. We review the available evidence pertaining to the use of new generation molecularly targeted agents, in particular mTOR inhibitors in chRCC and discuss their emerging role in the management of this disease which would aid the oncologists faced with the challenge of treating this rare type of RCC.</p> <p>Conclusion: Conducting randomised clinical trials in this rarer sub-group of patients would be challenging and our case report and the evidence reviewed would guide the physicians to make informed decision regarding the management of these patients.</p&gt

Selective Constraints on Amino Acids Estimated by a Mechanistic Codon Substitution Model with Multiple Nucleotide Changes

Empirical substitution matrices represent the average tendencies of substitutions over various protein families by sacrificing gene-level resolution. We develop a codon-based model, in which mutational tendencies of codon, a genetic code, and the strength of selective constraints against amino acid replacements can be tailored to a given gene. First, selective constraints averaged over proteins are estimated by maximizing the likelihood of each 1-PAM matrix of empirical amino acid (JTT, WAG, and LG) and codon (KHG) substitution matrices. Then, selective constraints specific to given proteins are approximated as a linear function of those estimated from the empirical substitution matrices. Akaike information criterion (AIC) values indicate that a model allowing multiple nucleotide changes fits the empirical substitution matrices significantly better. Also, the ML estimates of transition-transversion bias obtained from these empirical matrices are not so large as previously estimated. The selective constraints are characteristic of proteins rather than species. However, their relative strengths among amino acid pairs can be approximated not to depend very much on protein families but amino acid pairs, because the present model, in which selective constraints are approximated to be a linear function of those estimated from the JTT/WAG/LG/KHG matrices, can provide a good fit to other empirical substitution matrices including cpREV for chloroplast proteins and mtREV for vertebrate mitochondrial proteins. The present codon-based model with the ML estimates of selective constraints and with adjustable mutation rates of nucleotide would be useful as a simple substitution model in ML and Bayesian inferences of molecular phylogenetic trees, and enables us to obtain biologically meaningful information at both nucleotide and amino acid levels from codon and protein sequences.Comment: Table 9 in this article includes corrections for errata in the Table 9 published in 10.1371/journal.pone.0017244. Supporting information is attached at the end of the article, and a computer-readable dataset of the ML estimates of selective constraints is available from 10.1371/journal.pone.001724

Body odor quality predicts behavioral attractiveness in humans

Growing effort is being made to understand how different attractive physical traits co-vary within individuals, partly because this might indicate an underlying index of genetic quality. In humans, attention has focused on potential markers of quality such as facial attractiveness, axillary odor quality, the second-to-fourth digit (2D:4D) ratio and body mass index (BMI). Here we extend this approach to include visually-assessed kinesic cues (nonverbal behavior linked to movement) which are statistically independent of structural physical traits. The utility of such kinesic cues in mate assessment is controversial, particularly during everyday conversational contexts, as they could be unreliable and susceptible to deception. However, we show here that the attractiveness of nonverbal behavior, in 20 male participants, is predicted by perceived quality of their axillary body odor. This finding indicates covariation between two desirable traits in different sensory modalities. Depending on two different rating contexts (either a simple attractiveness rating or a rating for long-term partners by 10 female raters not using hormonal contraception), we also found significant relationships between perceived attractiveness of nonverbal behavior and BMI, and between axillary odor ratings and 2D:4D ratio. Axillary odor pleasantness was the single attribute that consistently predicted attractiveness of nonverbal behavior. Our results demonstrate that nonverbal kinesic cues could reliably reveal mate quality, at least in males, and could corroborate and contribute to mate assessment based on other physical traits

Inspiratory muscle warm-up does not improve cycling time-trial performance

Purpose: This study examined the effects of an active cycling warm-up, with and without the addition of an inspiratory muscle warm-up (IMW), on 10-km cycling time-trial performance

Enzyme degradable star polymethacrylate/silica hybrid inks for 3D printing of tissue scaffolds

There is unmet clinical need for scaffolds that can share load with the host tissue while biodegrading under the action of enzymes present at the site of implantation. The aim here was to create the first enzyme cleavable inorganic–organic hybrid “inks” that can be 3D printed as scaffolds for bone regeneration. Inorganic–organic hybrids are co-networks of inorganic and organic components. Although previous hybrids performed well under cyclic loads, there was little control over their degradation. Here we synthesised new hybrids able to degrade in response to endogenous tissue specific metallo proteinases (collagenases) that are involved in natural remodeling of bone. Three well-defined star polymers, of the monomer 3-(trimethoxysilyl)propyl methacrylate (TMSPMA) and of methyl methacrylate (MMA), of different architectures were prepared by RAFT polymerisation. The linear arms were connected together at an enzyme degradable core using a collagenase cleavable peptide sequence (GLY-PRO-LEU-GLY-PRO-LYS) modified with dimethacryloyl groups as a crosslinker for RAFT polymerisation. The effect of polymer architecture, i.e. the position of the TMSPMA groups on the polymers, on bonding between networks, mechanical properties, biodegradation rate and 3D printability, via direct ink writing, was investigated for the first time and was proven to be critical for all three properties. Specifically, hybrids made with star polymers with the TMSPMA close to the core exhibited the best mechanical properties, improved printability and a higher degradation rate