Dynamic modelling of aqueous two-phase systems to quantify the impact of bioprocess design, operation and variability

Aqueous two-phase extraction (ATPE) is a promising downstream separation technology as an alternative, or addition, to chromatography in the production of biological products. Increasing demand for therapeutic proteins have triggered manufacturers to consider continuous upstream technologies to achieve greater process efficiencies; however, such technologies have an inherent variability, resulting in output streams of varying compositions and properties. It is therefore important to understand how this variability impacts on the downstream separation processes. Exploring all potential sources of variability is challenging due to resource and time constraints, however, the use of targeted mathematical modelling can significantly reduce the need for expensive and time consuming experimentation. In this work, we present a dynamic equilibrium stage process model, and a methodology for prediction of key process parameters from limited experiments, capable of describing ATPE separations under both multi-cycle batch and continuous counter-current modes of operation. The capabilities of the proposed methodology are demonstrated using a case study separation of the enzyme α-amylase from impurities in a PEG 4000–phosphate aqueous two phase system (ATPS) containing NaCl. The model can be used to predict the separation performance of the process, as well as for the investigation of suitable design and operating conditions

Comparison of Two Tricalcium Phosphate Varnishes and a Comparator Fluoride Varnish on Tubular Occlusion

Objectives The aim of the present study involved comparing the tubular occluding properties of three varnishes, two Clinpro™ varnishes and a Colgate® Duraphat® Varnish. Method Nine caries-free premolar dentine discs were prepared and treated with the three varnishes and subsequently observed under SEM at 0o and 90o angle to assess their ability to cover the dentine surface. The tubule occluding properties were measured using a modified Pashley cell hydraulic conductance model. A further 9 caries-free extracted molars were sectioned into 500μ thick dentine discs. The fluid flow rate was assessed after a) immersing the discs in 6% citric acid for 2 minutes, b) treating the dentine disc with the experimental varnishes and c) subjecting the treated discs to an acid challenge (6% citric acid for 2 minutes). Results SEM investigation showed uniform occlusion of the dentinal tubules, with varying depths of penetration. Hydraulic conductance tests showed no statistically significant differences in the fluid flow rate (expressed as percentages) when all the three varnishes were compared at different stages of treatment (p = 0.33). However, after subjecting the discs to an acid challenge, there was a statistically significant increase in the fluid flow rate with the Colgate® Duraphat® Varnish treated discs, whereas the ClinproTM White Varnish and Clinpro™ XT Varnish discs showed no statistically significant differences (p = 0.99 and p= 0.83 respectively). Conclusions All the tested varnishes (Colgate® Duraphat® Varnish, ClinproTM White Varnish and ClinproTM XT varnish) were effective in blocking the dentinal tubules as demonstrated in this in vitro study. However, the tricalcium phosphate varnishes (ClinproTM) were more resistant to an in vitro acid challenge compared to the sodium fluoride varnish (Colgate® Duraphat®)

Validation of the Physical Simulations of a Stirred Molten Metal Using Particle Image Velocimetry Data

© 2018 The Author(s) Melt shearing refines the as-cast structure and the mechanism suggested beforehand is that of enhanced nucleation through oxide dispersion and fragmentation. The efficiency of processing by a rotor–stator mixer depends strongly on the treated volume of liquid metal. In this article the analytical modeling is validated by particle image velocimetry (PIV). The radius of the mixed region (a) has been described as a linear function of rotational speed (N) and the scale-up rules are given. Water model predictions have been confirmed experimentally by liquid metal shearing

Exploring the roles of urinary HAI-1, EpCAM and EGFR in bladder cancer prognosis and risk stratification

Objectives: To investigate whether elevated urinary HAI-1, EpCAM and EGFR are independent prognostic biomarkers within non-muscle-invasive bladder cancer (NMIBC) patients, and have utility for risk stratification to facilitate treatment decisions. Results: After accounting for EAU risk group in NMIBC patients, the risk of BC-specific death was 2.14 times higher (95% CI: 1.08 to 4.24) if HAI-1 was elevated and 2.04 times higher (95% CI: 1.02 to 4.07) if EpCAM was elevated. The majority of events occurred in the high-risk NMIBC group and this is where the biggest difference is seen in the survival curves when plotted for EAU risk groups separately. In MIBC patients, being elevated for any of the three biomarkers was significantly associated with BC-specific mortality after accounting for other risk factors, HR = 4.30 (95% CI: 1.85 to 10.03). Patients and Methods: Urinary levels of HAI-1, EpCAM and EGFR were measured by ELISA in 683 and 175 patients with newly-diagnosed NMIBC and MIBC, respectively, recruited to the Bladder Cancer Prognosis Programme. Associations between biomarkers and progression, BC-specific mortality and all-cause mortality were evaluated using univariable and multivariable Cox regression models, adjusted for European Association of Urology (EAU) NMIBC risk groups. The upper 25% of values for each biomarker within NMIBC patients were considered as elevated. Exploratory analyses in urine from MIBC patients were also undertaken. Conclusion: Urinary HAI-1 and EpCAM are prognostic biomarkers for NMIBC patients. These biomarkers have potential to guide treatment decisions for high-risk NMIBC patients. Further analyses are required to define the roles of HAI-1, EpCAM and EGFR in MIBC patients

Doubly Encapsulated Perylene Diimides: Effect of Molecular Encapsulation on Photophysical Properties

Intermolecular interactions play a fundamental role on the performance of conjugated materials in organic electronic devices, as they heavily influence their optoelectronic properties. Synthetic control over the solid state properties of organic optoelectronic materials is crucial to access real life applications. Perylene diimides (PDIs) are one of the most highly studied classes of organic fluorescent dyes. In the solid state, π–π stacking suppresses their emission, limiting their use in a variety of applications. Here, we report the synthesis of a novel PDI dye that is encapsulated by four alkylene straps. X-ray crystallography indicates that intermolecular π–π stacking is completely suppressed in the crystalline state. This is further validated by the photophysical properties of the dye in both solution and solid state and supported by theoretical calculations. However, we find that the introduction of the encapsulating “arms” results in the creation of charge-transfer states which modify the excited state properties. This article demonstrates that molecular encapsulation can be used as a powerful tool to tune intermolecular interactions and thereby gain an extra level of control over the solid state properties of organic optoelectronic materials

Layered Double Hydroxide Fluoride Release in Dental Applications: A Systematic Review.

This systematic review appraises studies conducted with layered double hydroxides (LDHs) for fluoride release in dentistry. LDH has been used as antacids, water purification in removing excess fluoride in drinking water and drug delivery. It has great potential for controlled fluoride release in dentistry, e.g., varnishes, fissure sealants and muco-adhesive strips, etc. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement was followed with two reviewers performing a literature search using four databases: PubMed, Web of Science, Science Direct and Ovid Medline with no date restrictions. Studies including any LDH for ion/drug release in dentistry were included, while assessing the application of LDH and the value of the methodology, e.g., ion release protocol and the LDH production process. Results: A total of 258 articles were identified and four met the inclusion criteria. Based on two in vitro studies and one clinical study, LDH was previously studied in dental materials, such as dental composites and buccal muco-adhesive strips for fluoride release, with the latter studied in a clinical environment. The fourth study analysed LDH powder alone (without being incorporated into dental materials). It demonstrated fluoride release and the uptake of volatile sulphur compounds (VSC), which may reduce halitosis (malodour). Conclusion: LDHs incorporated in dental materials have been previously evaluated for fluoride release and proven to be clinically safe. LDHs have the potential to sustain a controlled release of fluoride (or other cariostatic ions) in the oral environment to prevent caries. However, further analyses of LDH compositions, and clinical research investigating any other cariostatic effects, are required

Surgical margins and survival after head and neck cancer surgery

BACKGROUND: Mixed results exist as to whether positive surgical margins impact survival. The aim of this study was to determine whether positive surgical margins are indeed associated with decreased survival in patients with primary head and neck cancer. METHODS: We conducted a retrospective cohort study of 261 cases diagnosed with cancer of the larynx or tongue between 1995 and 1999. Cases were followed through December 31, 2002. Survival curves by margin status were generated by Kaplan-Meier methods. Categorical data were evaluated with odds ratios (OR). RESULTS: All-cause mortality was markedly higher in cases with positive margins as compared with those with negative margins (54% versus 29%, P = 0.005). This pattern also appeared after adjusting for age and sex (OR = 2.97, 95% CI: 1.29 – 6.84). CONCLUSION: Our findings suggest that positive surgical margin status is associated with increased mortality. This association also generally persists after adjustment for tumor size, stage, and adjuvant therapy

Sub-picomolar relaxin signalling by a pre-assembled RXFP1, AKAP79, AC2, β-arrestin 2, PDE4D3 complex

This study defines a new paradigm for cAMP signalling, namely sub-picomolar response to relaxin through a pre-assembled signalling complex. It therefore extends the complexity of GPCR-signalling, despite the fact that future work will have to proof whether pre-assembled complexes represent a widespread phenomenon

A patient on RIPE therapy presenting with recurrent isoniazid-associated pleural effusions: a case report

<p>Abstract</p> <p>Introduction</p> <p>The clinical scenario of a new or worsening pleural effusion following the initiation of antituberculous therapy has been classically referred to as a 'paradoxical' pleural response, presumably explained by an immunological rebound phenomenon. Emerging evidence suggests that there also may be a role for a lupus-related reaction in the pathophysiology of this disorder.</p> <p>Case presentation</p> <p>An 84-year-old Asian man treated with isoniazid, along with rifampin, pyrazinamide and ethambutol for suspected extrapulmonary tuberculosis, presented with a recurrent pleural effusion, his third episode since the initiation of this therapy. The first effusion occurred one month after the start of treatment, without any prior evidence of pulmonary tuberculosis involvement. Follow-up testing, including thoracoscopic pleural biopsies, never confirmed tuberculosis infection. Further evaluation yielded serological evidence suggesting drug-induced lupus. No effusions recurred following the discontinuation of isoniazid, although other antituberculosis medications were continued.</p> <p>Conclusion</p> <p>The immunological rebound construct is inconsistent with the evolution of this case, which indicates rather that drug-induced lupus may explain at least some cases of new pleural effusions following the initiation of isoniazid.</p