Optimisation and Landscape Analysis of Computational Biology Models: A Case Study

This is the author accepted manuscript. The final version is available from ACM via the DOI in this record.The parameter explosion problem is a crucial bottleneck in modelling gene regulatory networks (GRNs), limiting the size of models that can be optimised to experimental data. By discretising state, but not time, Boolean delay equations (BDEs) provide a signi ficant reduction in parameter numbers, whilst still providing dynamical complexity comparable to more biochemically detailed models, such as those based on differential equations. Here, we explore several approaches to optimising BDEs to timeseries data, using a simple circadian clock model as a case study. We compare the ffectiveness of two optimisers on our problem: a genetic algorithmf(GA) and an elite accumulative sampling (EAS) algorithm that provides robustness to data discretisation. Our results show that both methods are able to distinguish effectively between alternative architectures, yielding excellent ts to data. We also perform a landscape analysis, providing insights into the properties that determine optimiser performance (e.g. number of local optima and basin sizes). Our results provide a promising platform for the analysis of more complex GRNs, and suggest the possibility of leveraging cost landscapes to devise more effi cient optimisation schemes.This work was financially supported by the Engineering and Physical Sciences Research Council [grant numbers EP/N017846/1, EP/N014391/1], and made use of the Zeus and Isca supercomputing facilities provided by the University of Exeter HPC Strategy

On the Exploitation of Search History and Accumulative Sampling in Robust Optimisation

This is the author accepted manuscript. The final version is available from ACM via the DOI in this record.Efficient robust optimisation methods exploit the search history when evaluating a new solution by using information from previously visited solutions that fall in the new solution’s uncertainty neighbourhood. We propose a full exploitation of the search history by updating the robust fitness approximations across the entire search history rather than a fixed population. Our proposed method shows promising results on a range of test problems compared with other approaches from the literature.This work was supported by the Engineering and Physical Sciences Research Council [grant number EP/N017846/1]

Development of self-repair nano-rod scaffold materials for implantation of osteosarcoma affected bone tissue

Osteosarcoma is the most widely recognized fatal bone disease in children and young adults. The osteosarcoma affected places of bone implant materials lose their activity after a period of time due to the possibility of regenerating sarcoma cells. Hence, the complete recovery of this disease is very challenging. Subsequently, new helpful methodologies, including natural antioxidant loaded bone implant materials, are effectively used to treat osteosarcoma cells. In this regard, nano-hydroxyapatite reinforced with a xylitol based poly(xylitol sebacate) PXS co-polymer together with a capsaicin loaded scaffold was investigated on osteosarcoma cells. The physicochemical properties of the scaffold were evaluated by FT-IR (Fourier transform infrared spectroscopy), SEM (scanning electron microscopy), TEM (transmission electron microscopy), and XRD (X-ray diffraction). The in vitro release and antioxidant activity of the capsaicin loaded nHAP/PXS/CAP scaffold were evaluated by UV-Visible spectroscopy. Cytotoxicity against the Saos-2 cancer line and cell viability in the osteoblast cell MG63 are reported. Eventually, the composite enlarges the creation of reactive oxygen species (ROS) in Saos-2 cells

Clinical investigation of the novel iron-chelating agent, CP94, to enhance topical photodynamic therapy of nodular basal cell carcinoma.

Clinical TrialMulticenter StudyThis is the peer reviewed version of the article which has been published in final form at DOI: 10.1111/j.1365-2133.2008.08668.x This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.© 2008 The AuthorsJournal Compilation © 2008 British Association of DermatologistsBACKGROUND: Photodynamic therapy (PDT) involves the activation of a photosensitizer by visible light to produce activated oxygen species within target cells, resulting in their destruction. Evidence-based guidelines support the efficacy of PDT using topical 5-aminolaevulinic acid (ALA-PDT) in actinic keratoses, Bowen disease and basal cell carcinoma (BCC). Efficacy for nodular BCC appears inferior to that for superficial BCC unless prior debulking or repeat treatments are performed. Objectives The aim of this study was to assess the safety and efficacy of adding a novel iron-chelating agent, CP94 (1,2-diethyl-3-hydroxypyridin-4-one hydrochloride), to topical ALA, to temporarily increase the accumulation of the photosensitizer in the tumour. METHODS: A mixed topical formulation of ALA + increasing concentrations of CP94 was used to carry out PDT on previously biopsied nodular BCC with no prior lesion preparation using standard light delivery. The area was assessed clinically and surgically excised 6 weeks later for histological examination. RESULTS: Enhanced PDT using 40% CP94 resulted in significantly greater clearance rates in nodular BCC than with ALA-PDT alone, in our protocol of single-treatment PDT with no lesion preparation. CONCLUSIONS: The results of this study demonstrate the safe and effective use of an enhanced ALA-PDT protocol for nodular BCC using CP94, with no adverse reactions to this modification. This is the first time this formulation has been used in patients. This formulation is now the focus of further study

An examination of the impact of foreign and local managers on firm resources: A case of micro and small serviced apartments in Riyadh - Saudi Arabia

Saudi Arabia (the largest oil exporting country in the world) is making an effort to diversify its economy, to decrease their dependence on the oil sector. The tourism market in Saudi Arabia is one of the biggest in the region and one of the most profitable sectors in the Middle East. The government has made a strong effort to improve and expand the tourism sector (e.g. introducing electronic visas). Accommodation is a vital element in the tourism sector, and it is very important to a destination’s image and competitiveness. As a part of the Saudisation policy, the Government has decided to localise the managers of hotels and serviced apartments by the end of 2020. This means hotels are more likely to be managed by local managers rather than foreign managers which has been the norm in Saudi Arabia. The Saudisation policy could have either a negative or a positive impact on firms’ performance. Riyadh is one of main cities to attract tourists and is dominated by micro and small serviced apartment enterprises. This decision might affect these enterprises since they depend on managers’ actions which, in turn, will affect the tourism industry. Therefore, it is important to investigate how local and foreign managers manage firm resources so that appropriate business support policy can be developed. The Resource-Based View has been the dominant theory for studying the relationship between firm resources and business performance. Existing studies have investigated the impact of different entrepreneurial characteristics of managers, and general traits such as age, gender and level of education on firm resources. However, no previous study examines the impact that managers’ background (local vs foreign) has on the development of firm resources. This research will be applying the concepts of Resource-Based Theory to examine the role played by local and foreign managers on firm resources. In doing so, this study will extend the boundary of Resource-Based View framework. To understand the different roles of local and foreign managers, it is also necessary to identify the key resources of micro and small serviced apartments. In order to accomplish this objective, existing studies related to local/foreign managers, micro and small enterprises, serviced apartments and four of the firms’ resources were critically analysed. I found that finance, human resources, technology and collaboration are critical for self-catering apartments and have a strong propensity to influence business performance. Following that, seven in-depth interviews were conducted at public institutions and nineteen interviews were conducted with local/foreign managers of micro and small serviced apartments. This study found that local and foreign managers take different approaches in developing firm resources and also face different sets of challenges while consuming them. The findings of this study provide useful recommendations to owners and managers of micro and small serviced apartments and to policy makers

Perception Among Dental Health Care Workers on Use of Biomimetic Materials in Conservative Dentistry and Endodontics.

Introduction: Dentistry was one of the fields where biomimetic methods were thoroughly investigated. Our goal was to assess the amount of knowledge and willingness to use these materials among general practitioners, endodontists, and postgraduate students of endodontics and dental interns in the Qassim region. Methodology: The cross-sectional study was carried out among two dental clusters, of Qassim region among the four groups of postgraduate students, Operative dentist, General practitioners & Interns. To measure the awareness and attitude, a study-specific questionnaire of 10 questions was used. Data was analysed using IBM SPSS statistic version 25, chi square test and Fisher\u27s exact test have been utilized. Results: The majority of dental health care workers 92 (92.0) were aware about the use of biomimetic material in dentistry.  The knowledge about biomimetic material was found to significantly high among Operative Dentist/ Endodontist 20 (90.0), followed by dental intern 28 (70.0) and general dentist 19 (63.3). Conclusion: Based on the opinions of the majority of dental healthcare professionals, the current study supports the use of biomimetics and applications in the field of restorative dentistry

Treatment outcome of perforation repair with bio-ceramic based materials: A retrospective study

INTRODUCTION: The aim of this retrospective cohort study was to assess the treatment outcome of orthograde perforation repair using bio-ceramic based materials. METHODs: Data from the VCU graduate endodontic practice were analyzed retrospectively. Treatment had been conducted by VCU endodontic residents under the supervision of qualified endodontists during the period from August 2014-December 2020. All cases in which a bio-ceramic based material had been used as a perforation repair material were included. Bio-ceramic based materials included MTA, EndoSequence Root Repair Material Putty and Paste (ERRM), and iRoot BP Plus Root Repair Material (BP-RRM). Perforation repair was performed using a dental operating microscope. Two calibrated examiners assessed the radiographic outcome 6 to 24 months after treatment. The relationship between the pre-operative factors and treatment outcome was analyzed using binary logistic regression analysis. RESULTS: Forty-seven cases were initially identified from August 2014 to December 2020. Of these, 24 cases were examined at follow-up (51% recall rate). Overall, 16 of the included teeth (66%) were classified as healed/healing, and 8 teeth (33%) were classified as non-healing. The results of the binary logistic regression analysis showed that none of the 7-pre-operative variables included in the model were significantly associated with the outcome (p \u3e 0.05). CONCLUSION: Based on the binary logistic regression model, newer calcium silicate-based materials, ERRM and BP-RRM, are comparable to the clinical performance of MTA in perforation repair procedures