Contribution of a DNA Nick to DNA Bendability Depending on the Bending Force

2021 ◽  
Author(s):  
Sanghun Yeou ◽  
Nam Ki Lee
Keyword(s):  
Bending Force ◽  
Dna Bendability

scholarly journals Inhibition of CRISPR-Cas12a DNA targeting by nucleosomes and chromatin

2021 ◽  
Vol 7 (11) ◽  
pp. eabd6030
Author(s):  
Isabel Strohkendl ◽  
Fatema A. Saifuddin ◽  
Bryan A. Gibson ◽  
Michael K. Rosen ◽  
Rick Russell ◽  
...  
Keyword(s):  
Histone Modifications ◽  
Dna Cleavage ◽  
Genome Engineering ◽  
Eukaryotic Cells ◽  
Loop Formation ◽  
Chromatin Compaction ◽  
Dna Targeting ◽  
Genomic Regions ◽  
Dna Bendability ◽  
Nucleosome Arrays

Genome engineering nucleases must access chromatinized DNA. Here, we investigate how AsCas12a cleaves DNA within human nucleosomes and phase-condensed nucleosome arrays. Using quantitative kinetics approaches, we show that dynamic nucleosome unwrapping regulates target accessibility to Cas12a and determines the extent to which both steps of binding—PAM recognition and R-loop formation—are inhibited by the nucleosome. Relaxing DNA wrapping within the nucleosome by reducing DNA bendability, adding histone modifications, or introducing target-proximal dCas9 enhances DNA cleavage rates over 10-fold. Unexpectedly, Cas12a readily cleaves internucleosomal linker DNA within chromatin-like, phase-separated nucleosome arrays. DNA targeting is reduced only ~5-fold due to neighboring nucleosomes and chromatin compaction. This work explains the observation that on-target cleavage within nucleosomes occurs less often than off-target cleavage within nucleosome-depleted genomic regions in cells. We conclude that nucleosome unwrapping regulates accessibility to CRISPR-Cas nucleases and propose that increasing nucleosome breathing dynamics will improve DNA targeting in eukaryotic cells.

Berechnung kinetischer Isotopeneffekte für die Reaktion von Methyljodid mit Cyanid-Ion

1966 ◽  
Vol 21 (9) ◽  
pp. 1377-1384
Author(s):  
A. V. Willi
Keyword(s):  
Transition State ◽  
Secular Equation ◽  
Isotope Effects ◽  
Force Constants ◽  
Bond Breaking ◽  
Bending Force ◽  
A Value ◽  
Order Of Magnitude ◽  
Deuterium Isotope Effects ◽  
The Difference

Kinetic carbon-13 and deuterium isotope effects are calculated for the SN2 reaction of CH3I with CN-. The normal vibrational frequencies of CH3I, the transition state I · · · CH3 · · · CN, and the corresponding isotope substituted reactants and transition states are evaluated from the force constants by solving the secular equation on an IBM 7094 computer.Values for 7 force constants of the planar CH3 moiety in the transition state (with an sp2 C atom) are obtained by comparison with suitable stable molecules. The stretching force constants related to the bonds being broken or newly formed (fCC, fCC and the interaction between these two stretches, /12) are chosen in such a way that either a zero or imaginary value for νʟ≠ will result. Agreement between calculated and experimental methyl-C13 isotope effects (k12/ k13) can be obtained only in sample calculations with sufficiently large values of f12 which lead to imaginary νʟ≠ values. Furthermore, the difference between fCI and fCC must be small (in the order of 1 mdyn/Å). The bending force constants, fHCI and fHCC, exert relatively little influence on k12/k13. They are important for the D isotope effect, however. As soon as experimental data on kH/kD are available it will be possible to derive a value for fHCC in the transition state if fHCI is kept constant at 0.205 mdynA, and if fCI, fCC and f12 are held in a reasonable order of magnitude. There is no agreement between experimental and calculated cyanide-C13 isotope effects. Possible explanations are discussed. — Since fCI and fCC cannot differ much it must be concluded that the transition state is relatively “symmetric”, with approximately equal amounts of bond making and bond breaking.

Force Exerted by a Single Cilium of Mytilus Edulis. I

1960 ◽  
Vol 37 (3) ◽  
pp. 461-468 ◽  
Author(s):  
MITSUKI YONEDA
Keyword(s):  
Mytilus Edulis ◽  
Bending Force

1. A bending balance made of a flexible glass micro-needle was prepared, and its bending characteristic was determined by direct matching with calibrated needles. 2. The force produced by a large abfrontal cilium of Mytilus was measured by allowing the bending balance to arrest the effective stroke of the cilium. 3. The bending force generated by the cilium is described in terms of a torque, referred to the base of the cilium, amounting to 2-8 x 10-7dyne.cm. (mean, 4 x 10-7 dyne.cm.).

Rotating Loosening Mechanism of a Nut Connecting a Rotary Disk Under Rotating-Bending Force

2005 ◽  
Vol 127 (6) ◽  
pp. 1191-1197 ◽  
Author(s):  
Yasuo Fujioka ◽  
Tomotsugu Sakai
Keyword(s):  
High Pressure ◽  
Contact Area ◽  
The Other ◽  
Bearing Surface ◽  
Bending Force ◽  
Rotary Disk ◽  
Rotating Bending ◽  
Dimensional Errors ◽  
The Revolution

Structures composed of a rotary disk and a shaft, which are fastened with bolts and nuts having tapered bearing surfaces, are loaded with a rotating-bending force. Upon investigation, two rotating mechanisms of the nut were derived. In one mechanism a high-pressure contact area is formed at the nearest loading point on threads and bearing surfaces. This leads to a difference in the curvature radii between the bearing surface of the disk and that of the nut. During the revolution of the disk, two friction torques occur in opposite directions on the bearing surface and the threads, respectively. The relative rotating direction of the nut is dominated by the greater torque. The other mechanism is due to the eccentricities caused by dimensional errors of the bolt, nut, and disk. By combining the two mechanisms, the rotations of the nuts either cause a loosening or tightening after many revolutions of the disk.

A novel testing system for biomechanical evaluation of the bone or bone fixator

Sensor Review ◽  
2018 ◽  
Vol 38 (4) ◽  
pp. 405-411
Author(s):  
Zhanshe Guo ◽  
Zhaojun Guo ◽  
Xiangdang Liang ◽  
Shen Liu
Keyword(s):  
Good Condition ◽  
Force Sensor ◽  
Biomechanical Properties ◽  
Biomechanical Study ◽  
Sensor Calibration ◽  
Testing System ◽  
Static Force ◽  
Content Type ◽  
New Device ◽  
Bending Force

Purpose Biomechanical properties of bones and fixators are important. The aim of this study was to develop a new device to simulate the real mechanical environment and to evaluate biomechanical properties of the bone with a fixation device, including the static force and the fatigue characters. Design/methodology/approach In this paper, the device is mainly composed of three parts: pull-pressure transmission system, bending force applying system and torsion applying system, which can successfully simulate the pre-introduced pull-pressure force, bending force and torsion force, respectively. To prove the feasibility of the design, theoretical analysis is used. It is concluded from the simulated result that this scheme of design can successfully satisfy the request of the evaluation. Findings Finally, on the basis of the force sensor calibration, the static force experiment and fatigue experiment are carried out using the tibia of the sheep as the specimen. It is concluded from the result that the relationship between the micro displacement and the applied axial force is nearly linear. Under the condition of 1 Hz in frequency, 500 N in loading force and 18,000 reciprocating cycles, the bone fixator can still be in good condition, which proves the feasibility of the design. Originality/value Biomechanical properties of bones and fixators are studied by researchers. However, few simulate a real force environment and combine forces in different directions. So a novel system is designed and fabricated to evaluate the biomechanical properties of the bones and fixators. Results of the experiments show that this new system is reliable and stable, which can support the biomechanical study and clinical treatment.

Geometrical Arrangement in the Needle Loop of Multifilament Yarn using Genetic Algorithm

2014 ◽  
Vol 9 (4) ◽  
pp. 155892501400900
Author(s):  
Ramin Bakhshpour ◽  
Saeed Ajeli ◽  
Hossein Hasani ◽  
Ali Asghar Asgharyan Jeddi
Keyword(s):  
Genetic Algorithm ◽  
Method Comparison ◽  
Knitted Fabrics ◽  
Bending Force ◽  
Buckling Behavior ◽  
Classic Theory ◽  
Proposed Model ◽  
Genetic Algorithm Method ◽  
Post Buckling ◽  
Multifilament Yarns

In this paper, the loop structure of plain knitted fabrics, constructed from multifilament yarns is geometrically modeled. This model is based on post-buckling behavior of multifilament yarns composed of two, three or seven filaments by assuming that their cross-section is circular. In the first step of modeling, 2-D post buckled shape of each filament within the yarn structure was investigated regarding the classic theory of Elastica. In this step, volumetric intersections between the filaments occurred. In the second step, the arrangement of the filaments in 3-D space after applying an out-plane bending force, was predicted. Genetic Algorithm was used to find the minimum bending force and reduced the volumetric intersections between the yarn's constitutive filaments using the Genetic Algorithm method, constant forces between the filaments is replaced with a concentrated out-plane force which results in reducing the problems of complexity and optimization. The geometry position of yarn filaments is also modeled using finite element method. Comparison of results indicated a small difference between the two models and confirms that the analytical proposed model is acceptable.

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