Ribe na početku života

This work was supported by EPSRC (grants EP/J018139/1, EP/K00445X/1 (NJW), the EPSRC funded CRITICAT Centre for Doctoral Training (Ph.D. studentship to IP; EP/L016419/1) and EPSRC Doctoral Prize Fellowship (CSL)A new method has been developed to enable the modification of the organosolv technical lignin. Using a walnut shell butanol alkoxasolv lignin as a source of high β-O-4 content material, the β-O-4 γ-position has been selectively modified via tosylation, azidation and copper-catalyzed azide-alkyne triazole formation . In addition, extensive model studies were used to aid the detailed characterization of the modified lignin structure. The copper catalyzed click reaction was used to attach modified PEG chains and the resulting lignin-based co-polymer displayed improved thermal stability. This protocol was also used to incorporate a novel BODIPY-type fluorophore, generating a fluorescent lignin. Copper catalytic loadings were effective as low as 0.3 weight% and were found to catalyze the cycloaddition efficiently. This efficient and generic approach to preparing lignin-derived polymers is relevant to the core societal challenge of improving biorefinery efficiency.PostprintPeer reviewe

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care

Process improvement for the production of fermentable sugars using paper pulp derived from municipal solid waste

Sugar-lignin bio-refineries using renewable lignocellulosic carbon as an input material could be used in the future to produce a variety of value added products including fuels and specialty chemicals. The bio-refinery aims to replace a proportion of goods currently produced using fossil fuels. Lignocellulosic material has a significant sugar potential in the form of cellulose and hemicellulose and this can be accessed using enzymatic hydrolysis. The lignocellulosic feedstock used in this research was paper pulp derived from municipal solid waste (MSW) and the aim of the work was to maximise the efficiency of producing a concentrated sugar solution from the cellulose (or glucan) component of MSW using commercial enzyme preparations.Analysis of the pulp by acid hydrolysis showed a ratio of 56: 12: 27: 5 of Glucan: Hemicellulosic sugar chains other than glucan: Lignin & pseudo lignin: Ash on total solids (TS). The hydrolysis behaviour of this pulp was similar to that of other lignocellulosic substrates even though the matrix of this material is perhaps more complex. Glucan conversion could be increased by 6% if the pulp was extracted with acetone to remove solvent soluble compounds. Using the additive PEG 6000 increased conversion by 15 % over 48 hours, and allowed a 40 % reduction in the enzyme requirement. PEG also increased the centrifugal dewaterability of the substrate by up to 13%.These results were obtained in single stage batch experiments. It was found, however, that both the glucose concentration in solution and the overall glucan conversion in the substrate could be improved by using a two-stage hydrolysis strategy. Using 50 mg enzyme g-1 pulp at high total solids content >18.5% TS single-stage enzyme hydrolysis gave a maximum glucan conversion of 68%. It was found that two-stage hydrolysis could give higher conversion if sugar inhibition was removed by an intermediate fermentation step between hydrolysis stages. This, however, was not as effective as direct removal of the sugar products, including xylose, by washing of the residual pulp at pH 5. This improved the water availability and allowed reactivation of the pulp-bound enzymes. Inhibition of enzyme activity could further be alleviated by replenishment of β-glucosidase which was shown to be removed during the wash step. The two-stage hydrolysis process developed could give an overall glucan conversion of 88%, with an average glucose concentration of 7.5 wt% in 4 days after combining the hydrolysates of the first and second stage of hydrolysis.The residual washwater from the two-stage hydrolysis with intermediate wash step process contained a dilute amount of sugar. It was found that this washwater could be used as dilution water for a new batch of hydrolysis without any detriment to conversion efficiency. Thus, to further the work above a washwater recycle strategy was applied to the two-stage hydrolysis process. Washwater at various pHs and with or without the addition of PEG 6000 was used as dilution water for a subsequent round of hydrolysis, where up to 6 rounds of 48-hour hydrolysis were completed to reach a steady stage configuration. In these strategies the enzyme dose was reduced to 30 mg C-Tec3 g-1 pulp. Use of a pH 5 or pH 9 wash resulted in an increase in conversion of up to 5% in the first-stage hydrolysis rounds, indicating that enzyme carryover was occurring. The sugar augmentation and enzyme carryover consistently resulted in glucose yields above 7.0 wt% in the first stage hydrolysate when using this lower enzyme dose.The best result achieved in this strategy was obtained when using 0.25 wt% PEG 6000 in the reaction medium and washwater. By reducing the amount of liquid in the second-stage of hydrolysis, it was found that an overall average glucan conversion of 81% could be achieved over the two hydrolysis stages with an average glucose concentration of over 8 wt% in a 4 or 5 day reaction period. This result is significant, as it meets the downstream processing requirements for bioethanol, a major bio-refinery product, and does this with a low enzyme loading. Furthermore, the waste discharge is minimised due to the high glucan conversion

Improving the performance of enzymes in hydrolysis of high solids paper pulp derived from MSW

BackgroundThe research aimed to improve the overall conversion efficiency of the CTec® family of enzymes by identifying factors that lead to inhibition and seeking methods to overcome these through process modification and manipulation. The starting material was pulp derived from municipal solid waste and processed in an industrial-scale washing plant.ResultsAnalysis of the pulp by acid hydrolysis showed a ratio of 55 : 12 : 6 : 24 : 3 of glucan : xylan : araban/galactan/mannan : lignin : ash. At high total solids content (>18.5% TS) single-stage enzyme hydrolysis gave a maximum glucan conversion of 68%. It was found that two-stage hydrolysis could give higher conversion if sugar inhibition was removed by an intermediate fermentation step between hydrolysis stages. This, however, was not as effective as direct removal of the sugar products, including xylose, by washing of the residual pulp at pH 5. This improved the water availability and allowed reactivation of the pulp-bound enzymes. Inhibition of enzyme activity could further be alleviated by replenishment of ?-glucosidase which was shown to be removed during the wash step.ConclusionsThe two-stage hydrolysis process developed could give an overall glucan conversion of 88%, with an average glucose concentration close to 8% in 4 days, thus providing an ideal starting point for ethanol fermentation with a likely yield of 4 wt%. This is a significant improvement over a single-step process. This hydrolysis configuration also provides the potential to recover the sugars associated with residual solids which are diluted when washing hydrolysed pulp

The MicroArray Quality Control (MAQC)-II study of common practices for the development and validation of microarray-based predictive models

Gene expression data from microarrays are being applied to predict preclinical and clinical endpoints, but the reliability of these predictions has not been established. In the MAQC-II project, 36 independent teams analyzed six microarray data sets to generate predictive models for classifying a sample with respect to one of 13 endpoints indicative of lung or liver toxicity in rodents, or of breast cancer, multiple myeloma or neuroblastoma in humans. In total, >30,000 models were built using many combinations of analytical methods. The teams generated predictive models without knowing the biological meaning of some of the endpoints and, to mimic clinical reality, tested the models on data that had not been used for training. We found that model performance depended largely on the endpoint and team proficiency and that different approaches generated models of similar performance. The conclusions and recommendations from MAQC-II should be useful for regulatory agencies, study committees and independent investigators that evaluate methods for global gene expression analysis. © 2010 Nature America, Inc. All rights reserved.0SCOPUS: ar.jinfo:eu-repo/semantics/publishe