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Engineering Nannochloropsis oceanica for the production of diterpenoid compounds

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mLife 2023年第4期2卷 428-437页

作者： Zhi-Yan Du Wajid W.Bhat Eric Poliner Sean Johnson conor Bertucci Eva Farre Bjoern Hamberger Department of Molecular Biosciences and Bioengineering University of Hawaii at ManoaHonoluluHawaiiUSA Department of Biochemistry and Molecular Biology Michigan State UniversityEast LansingMichiganUSA Department of Plant Biology Michigan State UniversityEast LansingMichiganUSA New England Biolabs Inc. 240 County Roadlpswich01938 MAUSA

Photosynthetic microalgae like Nannochloropsis hold enormous potential as sustainable,light-driven biofactories for the production of high-value natural products such as *** oceanica is distinguished as a particularly robust host with extensive genomic and transgenic resources *** capacity to grow in wastewater,brackish,and sea waters,coupled with advances in microalgal metabolic engineering,genome editing,and synthetic biology,provides an excellent *** the present work,we demonstrate how *** can be engineered to produce the diterpene casbene—an important intermediate in the biosynthesis of pharmacologically relevant macrocyclic *** accumulated after stably expressing and targeting the casbene synthase from Daphne genkwa(DgTPS1)to the algal *** engineered strains yielded production titers of up to 0.12 mg g^(−1) total dry cell weight(DcW)*** overexpression and chloroplast targeting of two upstream rate-limiting enzymes in the 2-c-methyl-d-erythritol 4-phosphate pathway,coleus forskohlii 1-deoxy-d-xylulose-5-phosphate synthase and geranylgeranyl diphosphate synthase genes,further enhanced the yield of casbene to a titer up to 1.80 mg g^(−1) *** results presented here form a basis for further development and production of complex plant diterpenoids in microalgae.

关键词： casbene microalgae plastid targeting synthetic biology terpene synthase

combined Median Score Increasing Sensitivity of carpal Tunnel Syndrome Diagnosis

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World Journal of Neuroscience 2022年第3期12卷 125-135页

作者： conor P. O’Brien Sports Surgery clinic Dublin Ireland

carpal tunnel syndrome (cTS) is the most common of all focal neuropathies. Electrodiagnostic (EXD) of cTS has advanced to include combined Sensory Indexes (cSI) improving the specificity and sensitivity of EXD by employing intra-hand comparative data. Ultrasound (US) is a popular tool for the assessment of cTS. cross Sectional Area (cSA) is the most consistent US parameter, but as a single test, it has a similar false negative profile to EXD. This study describes a dual method of cTS interrogation by EXD and US with the results applied to a single numerical score;the combined Median Score (cMS). This is the product of cSA of median nerve at carpal Tunnel inlet and cSI. In a series of 100 suspected cases, standard EDX identified 89 positive cases, cSI identified 92 positives, cMS identified 95 positives. This new method further reduced the false negative rate in cTS.

关键词： carpal Tunnel Syndrome Ultrasound Median Nerve combined Sensory In-dex combined Median Score

Tarsal Tunnel Syndrome—A New Way to Diagnose an Old Problem

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World Journal of Neuroscience 2017年第1期7卷 172-180页

作者： conor O’Brien Rob Byrden Neurophysiology Department Sports Surgery Clinic Santry Dublin Ireland Department of Engineering University College Dublin Ireland

Tarsal Tunnel Syndrome [TTS] is the most common lower limb focal neuropathy but it has a poor pick up rate in most Electrodiagnostic (EXD) Laboratories. There is no gold standard for assessing TTS. The tibial nerve has a complex branching system with 4 main branches and 9 different patterns of division. This study evaluated potential TTS with a similar and extensive assessment of the tibial nerve. The protocol involved 2 tibial motor studies to the Adductor Hallucis Longus (AH) and Adductor Digiti Quinti (ADQ) muscles, assessing amplitudes and distal latencies;medial plantar, lateral plantar and calcaneal sensory studies assessing amplitudes and distal latencies. A needle EMG to the tibial innervated AH and ADQ muscles was also performed. This protocol evaluated 12 different parameters which significantly increased the diagnostic yield. TTS has a low pick up rate using current standard assessment methods accounting for between 0.5% and 0.6% of positive cases referred to electrodiagnostic laboratories. This study had a pick up rate of 3.3% with 40 positive cases identified out of a population of 1210 patients referred to an electrodiagnostic laboratory in a calendar year. A combination of positive findings was observed. There were on average 4.3 positive parameters. The calcaneal sensory study and the needle EMG to the distal AH and ADQ muscles were the most sensitive tests. These 3 tests are not routinely performed in most labs. Of the 40 cases of TTS over 80% had a history of either prior injury or surgery to affected lower limb. This study suggests that this 12 parameter assessment will increase diagnostic sensitivity.

关键词： Tarsal Tunnel Syndrome Electrodiagnostic Tibial Nerve Focal Neuropathy Adductor Hallucis Longus Adductor Digiti Quinti

A Multi-Objective Optimal Experimental Design Framework for Enhancing the Efficiency of Online Model Identification Platforms

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Engineering 2019年第6期5卷 1049-1059页

作者： Arun Pankajakshan conor Waldron Marco Quaglio Asterios Gavriilidis Federico Galvanin Department of chemical Engineering University College LondonLondon WC1E 7JEUK

Recent advances in automation and digitization enable the close integration of physical devices with their virtual counterparts, facilitating the real-time modeling and optimization of a multitude of processes in an automatic way. The rich and continuously updated data environment provided by such systems makes it possible for decisions to be made over time to drive the process toward optimal targets. In many man- ufacturing processes, in order to achieve an overall optimal process, the simultaneous assessment of mul- tiple objective functions related to process performance and cost is necessary. In this work, a multi- objective optimal experimental design framework is proposed to enhance the ef ciency of online model-identi cation platforms. The proposed framework permits exibility in the choice of trade-off experimental design solutions, which are calculated online that is, during the execution of experiments. The application of this framework to improve the online identi cation of kinetic models in ow reactors is illustrated using a case study in which a kinetic model is identi ed for the esteri cation of benzoic acid and ethanol in a microreactor.

关键词： Multi-objective optimization Optimal design of experiments Online

Outcome following incomplete surgical cytoreduction combined with intraperitoneal chemotherapy for colorectal peritoneal metastases

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World Journal of Gastrointestinal Oncology 2015年第12期7卷 445-454页

作者： Roisin Mary Heaney conor Shields Jurgen Mulsow Peritoneal Malignancy Institute Mater Misericordiae University Hospital

cytoreductive surgery combined with intraperitoneal chemotherapy can improve survival in appropriately selected patients with colorectal peritoneal metastases. Outcomes are best in those patients in whom a complete cytoreduction can be achieved. Unresectabledisease is however encountered in approximately one-quarter of patients at laparotomy. The merits, or otherwise, of proceeding with an incomplete cytoreduction in this setting are unclear. We performed a review of published outcomes following incomplete cytoreduction for colorectal peritoneal metastases. Using the electronic databases, Pub Med and MEDLINE, a systematic search of available literature published during the period January 1997 to September 2014 was conducted. Following application of exclusion criteria, 19 papers were identified and included in this review. These comprised fifteen case series, 3 case control studies and one randomised control trial. In the nineteen studies included in this review, 2790 patients underwent cytoreductive surgery with or without intraperitoneal chemotherapy for peritoneal metastases of colorectal origin. Of these, 1732(62%) underwent a complete cytoreduction while 986(35%) patients underwent an incomplete cytoreduction. Median survival in the complete cytoreduction group ranged from 11 to 62 mo while survival in the latter group ranged from 2.4 to 32 mo. Of the 986 patients with an incomplete cytoreduction, 331 patients received intraperitoneal chemotherapy and survival in this cohort ranged from 4.5 to 32 mo. An incomplete cytoreduction, with or without intraperitoneal chemotherapy, does not appear to confer a survival benefit. The limited available data points to a palliative benefit in a subset of patients. In the absence of high quality data, the decision as to whether or not to proceed with surgery should be made on an individual patient basis.

关键词： colorectal carcinoma Peritoneal metastases carcino

Identification and preliminary characterization of novel B3-type metallo-β-lactamases

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American Journal of Molecular Biology 2013年第4期3卷 198-203页

作者： Manfredi Miraula conor SBrunton Gerhard Schenk Natasa Mitić Department of chemistry National University of Ireland—MaynoothMaynoothCo.KildareIreland School of chemistry and Molecular Biosciences The University of QueenslandBrisbaneAustralia

Antibiotic resistance has emerged as a major global threat to human health. Among the strategies employed by pathogens to acquire resistance the use of metallo-β-lactamases (MBLs), a family of dinuclear metalloenzymes, is among the most potent. MBLs are subdivided into three groups (i.e. B1, B2 and B3) with most of the virulence factors belonging to the B1 group. The recent discovery of AIM-1, a B3-type MBL, however, has illustrated the potential health threat of this group of MBLs. Here, we employed a bioinformatics approach to identify and characterize novel B3-type MBLs from Novosphingobium pentaromativorans and Simiduia agarivorans. These enzymes may not yet pose a direct risk to human health, but their structures and function may provide important insight into the design and synthesis of a still elusive universal MBL inhibitor.

关键词： Antibiotic Resistance β-Lactam Antibiotics Metallo-β-Lactamases Sequence Homology Novosphingobium Pentaromativorans Simiduia Agarivorans

Patterning Functionalized Surfaces of 2D Materials by Nanoshaving

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Nanomanufacturing and Metrology 2022年第1期5卷 23-31页

作者： Katie O'Neill Rob Greig Rita Tilmann Lisanne Peters conor P.cullen Graeme cunningham cian Bartlam cormac O coileain Niall McEvoy Georg S.Duesberg School of Physics Trinity College DublinDublin 2 D02 PN40Ireland AMBER centre CRANN InstituteTrinity College DublinDublin 2Ireland Institute of Physics EIT 2Faculty of Electrical Engineering and Information TechnologyUniversitat der Bundeswehr Miinchen85579 NeubibergGermany School of chemistry Trinity College DublinDublin 2Ireland

Atomic force microscopy(AFM)and scanning probe lithography can be used for the mechanical treatment of various surfaces,including polymers,metals,and *** technique of nanoshaving,in which materials are removed using the AFM tip,is employed in this work to produce nanopatterns of self-assembled monolayers(SAMs)on two-dimensional(2D)*** materials used are monolayers of transition metal dichalcogenides(TMDs),namely,MoS_(2)and WS_(2),which are noncovalently functionalized with perylene diimide(PDI),a perylene *** approach involves rastering an AFM probe across the surface at a controlled increased load in ambient *** a result of the strong bond between PDI SAM and TMD,loads in excess of 1|1N are required to pattern the *** predefined patterns,including a grating pattern with feature sizes below 250 nm,are *** indicate the high precision of nanoshaving as an accurate and nondestructive lithographic technique for 2D *** work functions of shaved heterostructures are also examined using Kelvin probe force microscopy.

关键词： Nanoshaving AFM KPFM Perylene diimide 2D materials MoS_(2) WS_(2) Noncovalent functionalization

Unlocking quality in endoscopic mucosal resection

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World Journal of Gastrointestinal Endoscopy 2023年第5期15卷 338-353页

作者： Eoin Keating Jan Leyden Donal B O'connor conor Lahiff Department of Gastroenterology Mater Misericordiae University HospitalDublin 7Ireland School of Medicine University College DublinDublin 4Ireland Department of Surgery Tallaght University HospitalDublin 24Ireland School of Medicine Trinity College DublinDublin 2Ireland

A review of the development of the key performance metrics of endoscopic mucosal resection(EMR),learning from the experience of the establishment of widespread colonoscopy quality *** future performance markers for both colonoscopy and EMR are also evaluated to ensure continued high quality performance is maintained with a focus service framework and predictors of patient outcome.

关键词： Endoscopic mucosal resection colonoscopy Quality in endoscopy Advanced therapeutic endoscopy Large non pedunculated colorectal polyps Key performance indicators

cYSTIc FIBROSIS TRANSDUcTANcE REGULATOR IS INVOLVED IN MOUSE HEART IScHEMIc PREcONDITIONING

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CYSTIC FIBROSIS TRANSDUCTANCE REGULATOR IS INVOLVED IN MOUSE...