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https://www.readbyqxmd.com/read/28637248/expression-and-comparison-of-codon-optimised-aspergillus-tubingensis-amylase-variants-in-saccharomyces-cerevisiae
#1
Rosemary A Cripwell, Shaunita H Rose, Willem H van Zyl
The expression of codon optimised genes is a popular genetic engineering approach for the production of industrially relevant proteins. This study investigates and compares the expression of codon optimised and codon adapted amylase variants. The Aspergillus tubingensis raw starch hydrolysing α-amylase (amyA) and glucoamylase (glaA) encoding genes were redesigned using synonymous codons and expressed in S. cerevisiae Y294. Codon optimisation to favour S. cerevisiae codon bias resulted in a decrease in extracellular enzyme activity of 72% (30...
June 15, 2017: FEMS Yeast Research
https://www.readbyqxmd.com/read/28637173/crystallographic-analyses-illustrate-significant-plasticity-and-efficient-recoding-of-meganuclease-target-specificity
#2
Rachel Werther, Jazmine P Hallinan, Abigail R Lambert, Kyle Havens, Mark Pogson, Jordan Jarjour, Roberto Galizi, Nikolai Windbichler, Andrea Crisanti, Tony Nolan, Barry L Stoddard
The retargeting of protein-DNA specificity, outside of extremely modular DNA binding proteins such as TAL effectors, has generally proved to be quite challenging. Here, we describe structural analyses of five different extensively retargeted variants of a single homing endonuclease, that have been shown to function efficiently in ex vivo and in vivo applications. The redesigned proteins harbor mutations at up to 53 residues (18%) of their amino acid sequence, primarily distributed across the DNA binding surface, making them among the most significantly reengineered ligand-binding proteins to date...
June 20, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28634692/crispr-cas-orthologues-and-variants-optimizing-the-repertoire-specificity-and-delivery-of-genome-engineering-tools
#3
Alberto Cebrian-Serrano, Benjamin Davies
Robust and cost-effective genome editing in a diverse array of cells and model organisms is now possible thanks to the discovery of the RNA-guided endonucleases of the CRISPR-Cas system. The commonly used Cas9 of Streptococcus pyogenes shows high levels of activity but, depending on the application, has been associated with some shortcomings. Firstly, the enzyme has been shown to cause mutagenesis at genomic sequences resembling the target sequence. Secondly, the stringent requirement for a specific motif adjacent to the selected target site can limit the target range of this enzyme...
June 20, 2017: Mammalian Genome: Official Journal of the International Mammalian Genome Society
https://www.readbyqxmd.com/read/28632013/task-demands-in-osces-influence-learning-strategies
#4
Alexandre Lafleur, Jonathan Laflamme, Jimmie Leppink, Luc Côté
THEORY: Models on pre-assessment learning effects confirmed that task demands stand out among the factors assessors can modify in an assessment to influence learning. However, little is known about which tasks in objective structured clinical examinations (OSCEs) improve students' cognitive and metacognitive processes. Research is needed to support OSCE designs that benefit students' metacognitive strategies when they are studying, reinforcing a hypothesis-driven approach. With that intent, hypothesis-driven physical examination (HDPE) assessments ask students to elicit and interpret findings of the physical exam to reach a diagnosis ("Examine this patient with a painful shoulder to reach a diagnosis")...
March 2, 2017: Teaching and Learning in Medicine
https://www.readbyqxmd.com/read/28631029/syngas-biorefinery-and-syngas-utilization
#5
Sashini De Tissera, Michael Köpke, Sean D Simpson, Christopher Humphreys, Nigel P Minton, Peter Dürre
Autotrophic acetogenic bacteria are able to capture carbon (CO or CO2) through gas fermentation, allowing them to grow on a spectrum of waste gases from industry (e.g., steel manufacture and oil refining, coal, and natural gas) and to produce ethanol. They can also consume syn(thesis) gas (CO and H2) made from the gasification of renewable/sustainable resources, such as biomass and domestic/agricultural waste. Acetogenic gas fermentation can, therefore, produce ethanol in any geographic region without competing for food or land...
June 20, 2017: Advances in Biochemical Engineering/biotechnology
https://www.readbyqxmd.com/read/28630620/cloud-model-based-artificial-immune-network-for-complex-optimization-problem
#6
Mingan Wang, Shuo Feng, Jianming Li, Zhonghua Li, Yu Xue, Dongliang Guo
This paper proposes an artificial immune network based on cloud model (AINet-CM) for complex function optimization problems. Three key immune operators-cloning, mutation, and suppression-are redesigned with the help of the cloud model. To be specific, an increasing half cloud-based cloning operator is used to adjust the dynamic clone multipliers of antibodies, an asymmetrical cloud-based mutation operator is used to control the adaptive evolution of antibodies, and a normal similarity cloud-based suppressor is used to keep the diversity of the antibody population...
2017: Computational Intelligence and Neuroscience
https://www.readbyqxmd.com/read/28630449/effect-of-dna-sequence-of-fab-fragment-on-yield-characteristics-and-cell-growth-of-e-coli
#7
Antti Kulmala, Tuomas Huovinen, Urpo Lamminmäki
Codon usage is one of the factors influencing recombinant protein expression. We were interested in the codon usage of an antibody Fab fragment gene exhibiting extreme toxicity in the E. coli host. The toxic synthetic human Fab gene contained domains optimized by the "one amino acid-one codon" method. We redesigned five segments of the Fab gene with a "codon harmonization" method described by Angov et al. and studied the effects of these changes on cell viability, Fab yield and display on filamentous phage using different vectors and bacterial strains...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28622347/rna-guided-transcriptional-activation-via-crispr-dcas9-mimics-overexpression-phenotypes-in-arabidopsis
#8
Jong-Jin Park, Emma Dempewolf, Wenzheng Zhang, Zeng-Yu Wang
Clustered regularly interspaced short palindromic repeats (CRISPR) and the CRISPR associated protein 9 (Cas9) system allows effective gene modification through RNA-guided DNA targeting. The Cas9 has undergone a series of functional alterations from the original active endonuclease to partially or completely deactivated Cas9. The catalytically deactivated Cas9 (dCas9) offers a platform to regulate transcriptional expression with the addition of activator or repressor domains. We redesigned a CRISPR/Cas9 activation system by adding the p65 transactivating subunit of NF-kappa B and a heat-shock factor 1 (HSF) activation domain to dCas9 bound with the VP64 (tetramer of VP16) activation domain for application in plants...
2017: PloS One
https://www.readbyqxmd.com/read/28619478/constrained-tracking-control-for-nonlinear-systems
#9
Fatemeh Khani, Mohammad Haeri
This paper proposes a tracking control strategy for nonlinear systems without needing a prior knowledge of the reference trajectory. The proposed method consists of a set of local controllers with appropriate overlaps in their stability regions and an on-line switching strategy which implements these controllers and uses some augmented intermediate controllers to ensure steering the system states to the desired set points without needing to redesign the controller for each value of set point changes. The proposed approach provides smooth transient responses despite switching among the local controllers...
June 12, 2017: ISA Transactions
https://www.readbyqxmd.com/read/28616394/new-method-of-sudomotor-function-measurement-to-detect-microvascular-disease-and-sweat-gland-nerve-or-unmyelinated-c-fiber-dysfunction-in-adults-with-retinopathy
#10
John E Lewis, Steven E Atlas, Ammar Rasul, Ashar Farooqi, Laura Lantigua, Oscar L Higuera, Andrea Fiallo, Lianette Laria, Renata Picciani, Ken Wals, Zohar Yehoshua, Armando Mendez, Janet Konefal, Sharon Goldberg, Judi Woolger
BACKGROUND: Diabetes-associated microvascular complications such as retinopathy and neuropathy often lead to end-organ and tissue damage. Impaired skin microcirculation often precedes the detection of other advanced diabetic complications. The ANS-1 system contains a redesigned sympathetic skin response (ANS-1 SSR) device that measures sudomotor function, a photoplethysmography sensor, and a blood pressure device to comprehensively assess cardiac autonomic neuropathy and endothelial dysfunction...
2017: Journal of Diabetes and Metabolic Disorders
https://www.readbyqxmd.com/read/28614127/a-hospital-is-not-just-a-factory-but-a-complex-adaptive-system-implications-for-perioperative-care
#11
Aman Mahajan, Salim D Islam, Michael J Schwartz, Maxime Cannesson
Many methods used to improve hospital and perioperative services productivity and quality of care have assumed that the hospital is essentially a factory, and therefore, that industrial engineering and manufacturing-derived redesign approaches such as Six Sigma and Lean can be applied to hospitals and perioperative services just as they have been applied in factories. However, a hospital is not merely a factory but also a complex adaptive system (CAS). The hospital CAS has many subsystems, with perioperative care being an important one for which concepts of factory redesign are frequently advocated...
July 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28609248/using-statewide-data-on-health-care-quality-to-assess-the-effect-of-a-patient-centered-medical-home-initiative-on-quality-of-care
#12
Nathan D Shippee, Michael Finch, Douglas Wholey
Patient-centered medical homes comprise a large portion of modern health care redesign. However, most efforts have reflected rigid, limited models of transformation. In addition, evaluations of their impact on quality of care have relied on data designed for other purposes. Minnesota's Health Care Home (HCH) initiative is a statewide medical home model relying on state-run, adaptive certification and supportive data infrastructure. This longitudinal study leverages a unique statewide system of clinic-reported, patient-level quality data (2010-2013) to assess the effect of being in a HCH clinic on health care quality...
June 13, 2017: Population Health Management
https://www.readbyqxmd.com/read/28609089/light-triggered-ternary-device-and-inverter-based-on-heterojunction-of-van-der-waals-materials
#13
Jaewoo Shim, Seo-Hyeon Jo, Minwoo Kim, Young Jae Song, Jeehwan Kim, Jin-Hong Park
Multivalued logic (MVL) devices/circuits have received considerable attention because the binary logic used in current Si complementary metal-oxide-semiconductor (CMOS) technology cannot handle the predicted information throughputs and energy demands of the future. To realize MVL, the conventional transistor platform needs to be redesigned to have two or more distinctive threshold voltages (VTHs). Here, we report a finding: the photoinduced drain current in graphene/WSe2 heterojunction transistors unusually decreases with increasing gate voltage under illumination, which we refer to as the light-induced negative differential transconductance (L-NDT) phenomenon...
June 13, 2017: ACS Nano
https://www.readbyqxmd.com/read/28605651/fast-str-allele-identification-with-strait-razor-3-0
#14
August E Woerner, Jonathan L King, Bruce Budowle
The short tandem repeat allele identification tool (STRait Razor), a program used to characterize the haplotypes of short tandem repeats (STRs) in massively parallel sequencing (MPS) data, was redesigned. STRait Razor v3.0 performs ∼660× faster allele identification than its previous version (v2s), a speedup that is largely due to a novel indexing strategy used to perform "fuzzy" (approximate) string matching of anchor sequences. Written in a portable compiled language, C++, STRait Razor v3.0 functions on all major operating systems including Microsoft Windows, and it has cross-platform multithreading support...
June 1, 2017: Forensic Science International. Genetics
https://www.readbyqxmd.com/read/28604260/developing-high-functioning-teams-factors-associated-with-operating-as-a-real-team-and-implications-for-patient-centered-medical-home-development
#15
Somava Stout, Leah Zallman, Lisa Arsenault, Assaad Sayah, Karen Hacker
Team-based care is a foundation of health care redesign models like the patient-centered medical home (PCMH). Yet few practices rigorously examine how the implementation of PCMH relates to teamwork. We identified factors associated with the perception of a practice operating as a real team. An online workforce survey was conducted with all staff of 12 primary care sites of Cambridge Health Alliance at different stages of PCMH transformation. Bivariate and multivariate analyses of factors associated with teamwork perceptions were conducted...
January 1, 2017: Inquiry: a Journal of Medical Care Organization, Provision and Financing
https://www.readbyqxmd.com/read/28603989/%C3%AE-conotoxin-s9a-txid-potently-discriminates-between-%C3%AE-3%C3%AE-4-and-%C3%AE-6-%C3%AE-3%C3%AE-4-nicotinic-acetylcholine-receptors
#16
Yong Wu, Dongting Zhangsun, Xiaopeng Zhu, Quentin Kaas, Manqi Zhangsun, Peta J Harvey, David J Craik, J Michael McIntosh, Sulan Luo
α3β4 nAChRs have been implicated in various pathophysiological conditions. However, the expression profile of α3β4 nAChRs and α6/α3β4 nAChRs overlap in a variety of tissues. To distinguish between these two subtypes, we redesigned peptide 1 (α-conotoxin TxID), which inhibits α3β4 and α6/α3β4 nAChR subtypes. We systematically mutated 1 to evaluate analogue selectivity for α3β4 vs α6/α3β4 nAChRs expressed in Xenopus laevis oocytes. One analogue, peptide 7 ([S9A]TxID), had 46-fold greater potency for α3β4 versus α6/α3β4 nAChRs...
June 21, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28602172/robustness-testing-of-an-in-situ-caesium-extraction-unit
#17
Ilonka Bokor, Sandra Sdraulig, Masoumeh Sanagou
Following on from the successful development and validation of a prototype automated unit for the extraction of radiocaesium from seawater, the unit was redesigned to be smaller, easier to transport and better suited for field work. An extension of the validation process was undertaken to include robustness testing. Robustness testing evaluates the behaviour of a procedure when deliberate small changes are made. This requires the identification and testing of experimental factors which could have an impact on the results...
June 8, 2017: Journal of Environmental Radioactivity
https://www.readbyqxmd.com/read/28601794/obstacles-opportunities-and-priorities-for-advancing-metastatic-breast-cancer-research
#18
Margaret Flowers, Stephanie Birkey Reffey, Shirley A Mertz, Marc Hurlbert
In January 2016, the Metastatic Breast Cancer Alliance (the Alliance) convened a think tank of stakeholders from academia, government, industry, and patient advocacy to discuss gaps and opportunities in clinical and translational research in metastatic breast cancer. Priorities that emerged from the meeting included the following: the need for innovative preclinical model systems to study metastatic disease; increased sharing of resources and data; collaboration across cancer care teams and scientists; biorepositories for studies to identify biomarkers for treatment response; creation of patient registries to increase access to clinical trials and tissue procurement; and redesign of clinical trials in metastatic breast cancer...
June 10, 2017: Cancer Research
https://www.readbyqxmd.com/read/28599658/-holding-the-line-a-qualitative-study-of-the-role-of-evidence-in-early-phase-decision-making-in-the-reconfiguration-of-stroke-services-in-london
#19
Alec Fraser, Juan I Baeza, Annette Boaz
BACKGROUND: Health service reconfigurations are of international interest but remain poorly understood. This article focuses on the use of evidence by senior managerial decision-makers involved in the reconfiguration of stroke services in London 2008-2012. Recent work comparing stroke service reconfiguration in London and Manchester emphasises the ability of senior managerial decision-makers in London to 'hold the line' in the crucial early phases of the stroke reconfiguration programme...
June 9, 2017: Health Research Policy and Systems
https://www.readbyqxmd.com/read/28598747/overarching-challenges-to-the-implementation-of-competency-based-medical-education
#20
Kelly J Caverzagie, Markku T Nousiainen, Peter C Ferguson, Olle Ten Cate, Shelley Ross, Kenneth A Harris, Jamiu Busari, M Dylan Bould, Jacques Bouchard, William F Iobst, Carol Carraccio, Jason R Frank
Medical education is under increasing pressure to more effectively prepare physicians to meet the needs of patients and populations. With its emphasis on individual, programmatic, and institutional outcomes, competency-based medical education (CBME) has the potential to realign medical education with this societal expectation. Implementing CBME, however, comes with significant challenges. This manuscript describes four overarching challenges that must be confronted by medical educators worldwide in the implementation of CBME: (1) the need to align all regulatory stakeholders in order to facilitate the optimization of training programs and learning environments so that they support competency-based progression; (2) the purposeful integration of efforts to redesign both medical education and the delivery of clinical care; (3) the need to establish expected outcomes for individuals, programs, training institutions, and health care systems so that performance can be measured; and (4) the need to establish a culture of mutual accountability for the achievement of these defined outcomes...
June 2017: Medical Teacher
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