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William Henry Bothfeld, Grace Kapov, Keith Tyo
Many biosynthetic strategies are coupled to growth, which is inherently limited, as (1) excess feedstock (e.g., sugar) may be converted to biomass, not product, (2) essential genes must be maintained and (3) growth toxicity must be managed. A decoupled growth and production phase strategy could avoid these issues. We have developed a toggle switch that uses glucose sensing to enable this two-phase strategy. Temporary glucose starvation precisely and autonomously activates product expression in rich or minimal media, obviating the requirement for expensive inducers...
March 8, 2017: ACS Synthetic Biology
Mariana L Stevens, Praneet Chaturvedi, Scott A Rankin, Melissa Macdonald, Sajjeev Jagannathan, Masashi Yukawa, Artem Barski, Aaron M Zorn
Digestive system development is orchestrated by combinatorial signaling interactions between endoderm and mesoderm, but how these signals are integrated in the genome is poorly understood. Here we identified the transcriptomes of Xenopus foregut and hindgut progenitors, which are conserved with mammals. Using RNA-seq and ChIP-seq we show that BMP/Smad1 regulates dorsal-ventral gene expression in both the endoderm and mesoderm, whereas Wnt/β-catenin acts as a genome-wide toggle between foregut and hindgut programs...
February 20, 2017: Development
D Bailey, J Spaans, L Kumaraswamy, M Podgorsak
PURPOSE: To quantify the effect of the Measurement Uncertainty function on planar dosimetry pass rates, as analyzed with Sun Nuclear Corporation analytic software ("MapCHECK" or "SNC Patient"). This optional function is toggled on by default upon software installation, and automatically increases the user-defined dose percent difference (%Diff) tolerance for each planar dose comparison. METHODS: Dose planes from 109 IMRT fields and 40 VMAT arcs were measured with the MapCHECK 2 diode array, and compared to calculated planes from a commercial treatment planning system...
June 2016: Medical Physics
M Yewondwossen, J Robar, D Parsons
PURPOSE: During radiotherapy treatment, lung tumors can display substantial respiratory motion. This motion usually necessitates enlarged treatment margins to provide full tumour coverage. Unfortunately, these margins limit the dose that can be prescribed for tumour control and cause complications to normal tissue. Options for real-time methods of direct detection of tumour position, and particularly those that obviate the need for inserted fiducial markers, are limited. We propose a method of tumor tracking without implanted fiducial markers using a novel fast switching-target that toggles between a FFF copper/tungsten therapy mode and a FFF low-Z target mode for imaging...
June 2016: Medical Physics
Hongwei Wu, Yunyun Zhou, Liyuan Yin, Cheng Hang, Xin Li, Hans Ågren, Tao Yi, Qing Zhang, Liangliang Zhu
In nanoscience, chirality has shown a significant ability to tune materials' electronic properties, whereas imposing macrochirality into the regulation of singlet-triplet features of organic optoelectronics remains a challenging research topic. Since the tuning for singlet and triplet excited-state properties in a single π-functional molecule connects to its multicolor luminescent application and potential improvement of internal quantum efficiency, we here report that supramolecular chirality can be employed to toggle the singlet and triplet emissions in a well-designed asterisk-shaped molecule...
January 18, 2017: Journal of the American Chemical Society
Oleksandr Buchnev, Nina Podoliak, Thomas Frank, Malgosia Kaczmarek, Liudi Jiang, Vassili A Fedotov
Stiction is one of the major reliability issues limiting practical application of nano-electro-mechanical systems (NEMS), an emerging device technology that exploits mechanical movements on the scale of an integrated electronic circuit. We report on a discovery that stiction can be eliminated by infiltrating NEMS with nematic liquid crystals. We demonstrate this experimentally using a NEMS-based tunable photonic metamaterial, where reliable switching of optical response was achieved for the entire range of nanoscopic structural displacements admitted by the metamaterial design...
December 27, 2016: ACS Nano
Yue Shao, Kenichiro Taniguchi, Katherine Gurdziel, Ryan F Townshend, Xufeng Xue, Koh Meng Aw Yong, Jianming Sang, Jason R Spence, Deborah L Gumucio, Jianping Fu
Amniogenesis-the development of amnion-is a critical developmental milestone for early human embryogenesis and successful pregnancy. However, human amniogenesis is poorly understood due to limited accessibility to peri-implantation embryos and a lack of in vitro models. Here we report an efficient biomaterial system to generate human amnion-like tissue in vitro through self-organized development of human pluripotent stem cells (hPSCs) in a bioengineered niche mimicking the in vivo implantation environment...
December 12, 2016: Nature Materials
Miriam Leon, Mae L Woods, Alex J H Fedorec, Chris P Barnes
BACKGROUND: Genetic switches exhibit multistability, form the basis of epigenetic memory, and are found in natural decision making systems, such as cell fate determination in developmental pathways. Synthetic genetic switches can be used for recording the presence of different environmental signals, for changing phenotype using synthetic inputs and as building blocks for higher-level sequential logic circuits. Understanding how multistable switches can be constructed and how they function within larger biological systems is therefore key to synthetic biology...
December 7, 2016: BMC Systems Biology
Janica C Wong, Katherine C Krueger, Maria José Costa, Abhishek Aggarwal, Hongqing Du, Tracey L McLaughlin, Brian J Feldman
Obesity is driven by excess caloric intake, which leads to the expansion of adipose tissue by hypertrophy and hyperplasia. Adipose tissue hyperplasia results from the differentiation of adipocyte precursor cells (APCs) that reside in adipose depots. Investigation into this process has elucidated a network of mostly transcription factors that drive APCs through the differentiation process. Using in vitro and in vivo approaches, our study revealed a signaling pathway that inhibited the initiation of the adipocyte differentiation program...
October 25, 2016: Science Signaling
Otti D'Huys, Johannes Lohmann, Nicholas D Haynes, Daniel J Gauthier
Autonomous Boolean networks are commonly used to model the dynamics of gene regulatory networks and allow for the prediction of stable dynamical attractors. However, most models do not account for time delays along the network links and noise, which are crucial features of real biological systems. Concentrating on two paradigmatic motifs, the toggle switch and the repressilator, we develop an experimental testbed that explicitly includes both inter-node time delays and noise using digital logic elements on field-programmable gate arrays...
September 2016: Chaos
Ruben Perez-Carrasco, Pilar Guerrero, James Briscoe, Karen M Page
During tissue development, patterns of gene expression determine the spatial arrangement of cell types. In many cases, gradients of secreted signalling molecules-morphogens-guide this process by controlling downstream transcriptional networks. A mechanism commonly used in these networks to convert the continuous information provided by the gradient into discrete transitions between adjacent cell types is the genetic toggle switch, composed of cross-repressing transcriptional determinants. Previous analyses have emphasised the steady state output of these mechanisms...
October 2016: PLoS Computational Biology
Kaiwen Ivy Liu, Muhammad Nadzim Bin Ramli, Cheok Wei Ariel Woo, Yuanming Wang, Tianyun Zhao, Xiujun Zhang, Guo Rong Daniel Yim, Bao Yi Chong, Ali Gowher, Mervyn Zi Hao Chua, Jonathan Jung, Jia Hui Jane Lee, Meng How Tan
CRISPR-Cas9 has emerged as a powerful technology that enables ready modification of the mammalian genome. The ability to modulate Cas9 activity can reduce off-target cleavage and facilitate precise genome engineering. Here we report the development of a Cas9 variant whose activity can be switched on and off in human cells with 4-hydroxytamoxifen (4-HT) by fusing the Cas9 enzyme with the hormone-binding domain of the estrogen receptor (ERT2). The final optimized variant, termed iCas, showed low endonuclease activity without 4-HT but high editing efficiency at multiple loci with the chemical...
November 2016: Nature Chemical Biology
Yong Xu, Yongge Li, Hao Zhang, Xiaofan Li, Jürgen Kurths
A bistable toggle switch is a paradigmatic model in the field of biology. The dynamics of the system induced by Gaussian noise has been intensively investigated, but Gaussian noise cannot incorporate large bursts typically occurring in real experiments. This paper aims to examine effects of variations from one protein imposed by a non-Gaussian Lévy noise, which is able to describe even large jumps, on the coherent switch and the on/off switch via the steady-state probability density, the joint steady-state probability density, and the mean first passage time...
2016: Scientific Reports
Ashkan Pourkand, Christina Salas, Jasmin Regalado, Krishan Bhakta, Rachel Tufaro, Deana Mercer, David Grow
BACKGROUND: Orthopedics is a motor skills-demanding surgical specialty requiring surgical skills training outside of the operating room. Unfortunately, limited quantitative techniques exist to determine the effectiveness of these surgical skills training programs. Using a variety of drill, surgeon, and specimen mounted sensors, we evaluated orthopedic surgery residents during a surgical skills training course approved by the American Board of Orthopaedic Surgeons (ABOS). This evaluation consisted of quantitative measures of various kinematic and kinetic parameters with the goal of relating these to clinically-significant outcomes...
2016: Iowa Orthopaedic Journal
Harry S Hothi, Andreas C Panagiotopoulos, Robert K Whittaker, Paul J Bills, Rebecca A McMillan, John A Skinner, Alister J Hart
BACKGROUND: Material loss at the taper junction of metal-on-metal total hip arthroplasties has been implicated in their early failure. The mechanisms of material loss are not fully understood; analysis of the patterns of damage at the taper can help us better understand why material loss occurs at this junction. METHODS: We mapped the patterns of material loss in a series of 155 metal-on-metal total hip arthroplasties received at our center by scanning the taper surface using a roundness-measuring machine...
January 2017: Journal of Arthroplasty
Sudhakar Gaikwad, Abir Goswami, Soumen De, Michael Schmittel
The nanomechanical switch 1 with its three orthogonal binding motifs-the zinc(II) porphyrin, azaterpyridine, and shielded phenanthroline binding station-is quantitatively and reversibly toggled back and forth between four different switching states by means of addition and removal of appropriate metal-ion inputs. Two of the four switching stages are able to initiate catalytic transformations (ON1, ON2), while the two others shut down any reaction (OFF1, OFF2). Thus, in a cyclic four-state switching process the sequential transformation A+B+C→AB+C→ABC can be controlled, which proceeds stepwise along the switching states OFF1→ON1 (click reaction: A+B→AB)→OFF2→ON2 (Michael addition: AB+C→ABC)→OFF1...
August 22, 2016: Angewandte Chemie
Marina Frank, Mark D Johnstone, Guido H Clever
This Review covers design strategies, synthetic challenges, host-guest chemistry, and functional properties of interlocked supramolecular cages. Some dynamic covalent organic structures are discussed, as are selected examples of interpenetration in metal-organic frameworks, but the main focus is on discrete coordination architectures, that is, metal-mediated dimers. Factors leading to interpenetration, such as geometry, flexibility and chemical makeup of the ligands, coordination environment, solvent effects, and selection of suitable counter anions and guest molecules, are discussed...
September 26, 2016: Chemistry: a European Journal
Marc Weber, Javier Buceta
Inspired by the Ising model, we introduce a gene regulatory network that induces a phase transition that coordinates robustly the behaviour of cell ensembles. The building blocks of the design are the so-called toggle switch interfaced with two quorum sensing modules, Las and Lux. We show that as a function of the transport rate of signalling molecules across the cell membrane the population undergoes a spontaneous symmetry breaking from cells individually switching their phenotypes to a global collective phenotypic organization...
June 2016: Journal of the Royal Society, Interface
Nikolay Martyushenko, Sigurd Hagen Johansen, Cheol-Min Ghim, Eivind Almaas
BACKGROUND: Genetic switches are ubiquitous in nature, frequently associated with the control of cellular functions and developmental programs. In the realm of synthetic biology, it is of great interest to engineer genetic circuits that can change their mode of operation from monostable to bistable, or even to multistable, based on the experimental fine-tuning of readily accessible parameters. In order to successfully design robust, bistable synthetic circuits to be used as biomolecular probes, or understand modes of operation of such naturally occurring circuits, we must identify parameters that are key in determining their characteristics...
2016: BMC Systems Biology
C E Cameron, I M Moustafa, J J Arnold
Using poliovirus (PV) and its RNA-dependent RNA polymerase (RdRp) as our primary model system, we have advanced knowledge fundamental to the chemistry and fidelity of nucleotide addition by nucleic acid polymerase. Two fidelity checkpoints exist prior to nucleotide addition. The first toggles the enzyme between a nucleotide binding-occluded state and a nucleotide binding-competent state. The second represents an ensemble of conformational states of conserved structural motifs that permits retention of the incoming nucleotide in a state competent for phosphoryl transfer long enough for chemistry to occur...
2016: Enzymes
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