Tether Length Research Articles

Usefulness of 3D echocardiographic parameters of tricuspid valve morphology to predict residual tricuspid regurgitation after tricuspid annuloplasty

Tricuspid valve (TV) annuloplasty is an effective treatment for tricuspid regurgitation (TR). However, the impact of TV morphology on outcome of TV annuloplasty remains unknown. We sought to investigate the relationship between preoperative TV morphology and residual TR after annuloplasty. Two-dimensional transthoracic and three-dimensional (3D) transesophageal echocardiography were performed in 97 patients with functional TR before and after surgery. 3D quantitative assessment including annular dimension, tenting height and volume, and lengths and tethering angles of the 3 leaflets was performed. The TV morphological score was derived from the preoperative 3D echocardiography to score a leaflet mobility, leaflet thickening, subvalvular thickening, and calcification. TR severity was determined by the averaged vena contracta measured from the apical and parasternal inflow views. Multivariable analysis revealed that a shorter total leaflet length (P = 0.007), larger tenting volume (P < 0.001), and higher TV morphological score (P < 0.001) were independently associated with residual TR. A TV-Echo score was determined as a sum of points based on receiver operator characteristics analysis: total leaflet length >61.0 mm, 61.0 to 53.5 mm, and <53.5 mm; tenting volume <2.3 mL, 2.3 to 3.5 mL, and >3.5 mL; and TV morphological score <7, 7 to 18, and >18; each variable was associated with 0 and 1 point and 2 points, respectively. The TV-Echo score ≥2 was associated with significant residual TR with a sensitivity of 85.7% and a specificity of 71.0%. In addition to tethering and short length of the leaflets, TV morphological abnormality predicted residual TR after TV annuloplasty.

Impact of Backbone Tether Length and Structure on the Electrochemical Performance of Viologen Redox Active Polymers

The design of chemically stable and electrochemically reversible redox active polymers (RAPs) is of great interest for energy storage technologies. Particularly, RAPs are new players for flow batteries relying on a size-exclusion based mechanism of electrolyte separation, but few studies have provided detailed molecular understanding of redox polymers in solution. Here, we use a systematic molecular design approach to investigate the impact of linker and redox-pendant electronic interactions on the performance of viologen RAPs. We used scanning electrochemical microscopy, cyclic voltammetry, bulk electrolysis, temperature-dependent absorbance, and spectroelectrochemistry to study the redox properties, charge transfer kinetics, and self-exchange of electrons through redox active dimers and their equivalent polymers. Stark contrast was observed between the electrochemical properties of viologen dimers and their corresponding polymers. Electron self-exchange kinetics in redox active dimers that only differ b...

Bis-Michael Acceptors as Novel Probes to Study the Keap1/Nrf2/ARE Pathway.

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a master regulator that promotes the transcription of cytoprotective genes in response to oxidative/electrophilic stress. Various Michael-type compounds were designed and synthesized, and their potency to activate the Keap1/Nrf2/ARE pathway was evaluated. Compounds bearing two Michael-type acceptors proved to be the most active. Tether length and rigidity between the acceptors was crucial. This study will help to understand how this feature disrupts the interaction between Keap1 and Nrf2.

Tuning the selectivity and sensitivity of an OmpG nanopore sensor by adjusting ligand tether length.

We have previously shown that a biotin ligand tethered to the rim of an OmpG nanopore can be used to detect biotin-binding proteins. Here, we investigate the effect of the length of the polyethylene glycol tether on the nanopore's sensitivity and selectivity. When the tether length was increased from 2 to 45 ethylene repeats, sensitivity decreased substantially for a neutral protein streptavidin and slightly for a positively charged protein (avidin). In addition, we found that two distinct avidin binding conformations were possible when using a long tether. These conformations were sensitive to the salt concentration and applied voltage. Finally, a longer tether resulted in reduced sensitivity due to slower association for a monoclonal anti-biotin antibody. Our results highlight the importance of electrostatic, electroosmotic and electrophoretic forces on nanopore binding kinetics and sensor readout.

A Series of Pyrene‐Substituted Silicon Phthalocyanines as Near‐IR Sensitizers in Organic Ternary Solar Cells

An attractive method to broaden the absorption bandwidth of polymer/fullerene‐based bulk heterojunction (BHJ) solar cells is to blend near infrared (near‐IR) sensitizers into the host system. Axial substitution of silicon phthalocyanines (Pcs) opens a possibility to modify the chemical, thermodynamic, electronic, and optical properties. Different axial substitutions are already designed to modify the thermodynamic properties of Pcs, but the impact of extending the π‐conjugation of the axial ligand on the opto‐electronic properties, as a function of the length of the alkyl spacer, has not been investigated yet. For this purpose, a novel series of pyrene‐substituted silicon phthalocyanines (SiPc‐Pys) with varying lengths of alkyl chain tethers are synthesized. The UV–vis and external quantum efficiency (EQE) results exhibit an efficient near IR sensitization up to 800 nm, clearly establishing the impact of the pyrene substitution. This yields an increase of over 20% in the short circuit current density (J SC) and over 50% in the power conversion efficiency (PCE) for the dye‐sensitized ternary device. Charge generation, transport properties, and microstructure are studied using different advanced technologies. Remarkably, these results provide guidance for the diverse and judicious selection of dye sensitizers to overcome the absorption limitation and achieve high efficiency ternary solar cells.

Nanomechanical properties of protein-DNA layers with different oligonucleotide tethers.

The multi-ligand binding flavoprotein dodecin is reconstituted on top of flavin-terminated oligonucleotide monolayers. A detailed quartz crystal microbalance with a dissipation monitoring (QCM-D) study showing how the length and flexibility of the oligonucleotide tethers influence the stability and the viscoelastic properties of the resulting DNA-protein layers is presented. Relatively dense protein layers can be obtained, if the length of the tethers is in the same range as the diameter of dodecin. When significantly longer tethers are used, less dense layers are formed. When rather short tethers are used, the reaching area of individual tethers is too low to capture single apododecin molecules cooperatively, and the formation of stable and dense protein layers is not possible. On top of the DNA-dodecin layers additional flavin-DNA ligands may be captured to form sandwich-type DNA-protein-DNA layers. Differences in the binding and unbinding behavior of flavin-dsDNA and flavin-ssDNA ligands are measured by QCM-D and surface plasmon fluorescence spectroscopy (SPFS). Both type of ligands show relatively low kon values, which might be explained by the structural rigidity of the binding pockets allowing a ligand to enter only when it approaches precisely in the right orientation. Apparently apododecin-flavin binding follows Fischer's classic lock-and-key binding model.

Proposed Mechanisms of Tethered Antimicrobial Peptide Chrysophsin-1 as a Function of Tether Length Using QCM-D.

Rising antibiotic resistance has led to a call for the development of alternative antibiotics. Antimicrobial peptides (AMPs) are promising, but their potential has not been fully explored because of toxicity and lack of stability in vivo. Multiple recent studies have focused on surface immobilization of AMPs to maximize antimicrobial activity and stability while mitigating toxicity. We covalently tethered cysteine-modified chrysophsin-1 (C-CHY1) via PEG of three molecular weights, 866, 2000, and 7500. Quartz crystal microbalance with dissipation (QCM-D) was used to characterize thickness and grafting density of tethered C-CHY1, which were related to its activity against Staphylococcus aureus and Escherichia coli and found to be important in determining mechanisms leading to activity. The PEG 866 tether promoted an antimicrobial mechanism that caused displacement of positive cations from bacterial membranes. The PEG 7500 tether maintained C-CHY1's ability to effectively form membrane pores, promoting the highest activity. When AMP was tethered with PEG 2000, antimicrobial activity was limited, apparently because neither mechanism of AMP activity was able to occur with this tether. Using QCM-D, we calculated thickness and density of PEG-tethered C-CHY1 and correlated it with antimicrobial effectiveness to determine the mechanisms by which tethered C-CHY1 acts against bacteria.

Study of the triple-mass Tethered Satellite System under aerodynamic drag and J2 perturbations

The dynamics of multi-tethered satellite formations consisting of three masses are studied in this paper. The triple-mass triple-tethered satellite system is modeled under the low Earth orbit perturbations of drag and Earth’s oblateness and its equilibrium conditions are derived. It is modeled as three equal end-masses connected by a uniform-mass straight tether. The lengths of tethers are supposed to be constant and in this manner the angles of the plane consisting the masses are taken as the state variables of the system. The governing equations of motion are derived using Lagrangian approach. The aerodynamic drag perturbation is expressed as an external non-conservative force and the Earth oblateness (J2 perturbation) is considered as a term of potential energy. The equilibrium conditions of this system are found and their stability is investigated through the linear stability theory. Then, the results are verified by using a nonlinear simulation for three types of equilibrium conditions.

ChemInform Abstract: Divergent Reactivity of Homologue ortho‐Allenylbenzaldehydes Controlled by the Tether Length: Chromone versus Chromene Formation.

AbstractMicrowave‐assisted hydroarylation reactions of substrates (I) provide chromene derivatives.

Patterned Grafted Lewis-Acid Sites on Surfaces: Olefin Epoxidation Catalysis Using Tetrameric Ti(IV)–Calix[4]arene Complexes

Tetrameric Ti(IV)–calix[4]arene complexes were synthesized and characterized as well as grafted on a hydroxylated SiO2 inorganic support as an example of patterned Lewis-acid sites on an inorganic oxide surface. These complexes consist of a novel calixarene organic ligand with varying lengths of tethers to a central aromatic core, and with the calixarene coordinating four titanium(IV)-cations via tetrahedral recognition on the lower rim. Catalysis of these materials was investigated with a probe reaction consisting of the epoxidation 1-octene with tert-butylhydroperoxide as the oxidant, and a comparison of their hydrolytic stability was performed. The oligomeric calix[4]arenes showed similar behavior in catalysis to the monomeric control, with the exception of the material with the shortest tether length, which shows a 1.3-fold higher activity that may be due to a modest cooperativity effect. In hydrolytic leaching tests, the oligomeric complexes showed higher stability compared to the monomeric complex, and this stability appeared to be more thermodynamic rather than kinetic in nature. We hypothesize that encapsulatation of the tetrameric active site within a silica mesopore of the support contributes to this stability.

Nonlinear dynamics of a rotating triangular tethered satellite formation near libration points

The nonlinear coupled dynamics of a rotating triangular tethered satellite formation near libration points is presented. Based on Hill's approximation, the dynamical formulation for a rotating triangular tethered system near libration points is developed. The formulation comprises a set of strong nonlinear coupled equations. Numerical simulations using the full nonlinear and time-varying motion equations are performed for the station-keeping stages. The dynamic characteristics of the triangular tethered formation are analyzed. The numerical results demonstrate that the rotation rate has a significant impact on the stability of the system, whereas the orbital amplitude has a moderate impact on the stability of the system. Tether length has little effect on the motion of the system's center of mass. It can be served as a basis to solve the problem of rotating triangular tethered systems in any arbitrary plane.

Influence of Tether Length in the Response Behavior of Square Tension Leg Platform in Regular Waves

The tension leg platform (TLP) is a vertically moored structure with excess buoyancy. The TLP is regarded as moored structure in horizontal plan, while inherit stiffness of fixed platform in vertical plane. In this paper, a numerical study using modified Morison equation was carried out in the time domain to investigate the influence of nonlinearities due to hydrodynamic forces and the coupling effect between surge, sway, heave, roll, pitch and yaw degrees of freedom on the dynamic behavior of TLP's. The stiffness of the TLP was derived from a combination of hydrostatic restoring forces and restoring forces due to cables and the nonlinear equations of motion were solved utilizing Newmark's beta integration scheme. The effect of tethers length and wave characteristics such as wave period and wave height on the response of TLP's was evaluated. Only uni-directional waves in the surge direction was considered in the analysis. It was found that for short wave periods (i.e. 10 sec.), the surge response consisted of small amplitude oscillations about a displaced position that is significantly dependent on tether length, wave height; whereas for longer wave periods, the surge response showed high amplitude oscillations about that is significantly dependent on tether length.

Probing tethered targets of a single biomolecular complex with atomic force microscopy

DNA origami shows tremendous promise as templates for the assembly of nano-components and detection of molecular recognition events. So far, the method of choice for evaluating these structures has been atomic force microscopy (AFM), a powerful tool for imaging nanoscale objects. In most cases, tethered targets on DNA origami have proven to be highly effective samples for investigation. Still, while maximal assembly of the nanostructures might benefit from the greatest flexibility in the tether, AFM imaging requires a sufficient stability of the adsorbed components. The balance between the tether flexibility and sample stability is a major, poorly understood, concern in such studies. Here, we investigated the dependence of the tethering length on molecular capture events monitored by AFM. In our experiments, single biotin molecules were attached to DNA origami templates with various linker lengths of thymidine nucleotides, and their interaction with streptavidin was observed with AFM. Our results show that the streptavidin-biotin complexes are easily detected with short tethered lengths, and that their morphological features clearly change with the tethering length. We identify the functionally useful tether lengths for these investigations, which are also expected to prove useful in the construction and further application of DNA origami in bio-nanotechnology studies.

Influence of Tether Length in the Response Behavior of Square Tension Leg Platform in Regular Waves

Influence of Tether Length in the Response Behavior of Square Tension Leg Platform in Regular Waves

Self-Assembly of Amphiphilic Plasmonic Micelle-Like Nanoparticles in Selective Solvents

Amphiphilic plasmonic micelle-like nanoparticles (APMNs) composed of gold nanoparticles (AuNPs) and amphiphilic block copolymers (BCPs) structurally resemble polymer micelles with well-defined architectures and chemistry. The APMNs can be potentially considered as a prototype for modeling a higher-level self-assembly of micelles. The understanding of such secondary self-assembly is of particular importance for the bottom-up design of new hierarchical nanostructures. This article describes the self-assembly, modeling, and applications of APMN assemblies in selective solvents. In a mixture of water/tetrahydrofuran, APMNs assembled into various superstructures, including unimolecular micelles, clusters with controlled number of APMNs, and vesicles, depending on the lengths of polymer tethers and the sizes of AuNP cores. The delicate interplay of entropy and enthalpy contributions to the overall free energy associated with the assembly process, which is strongly dependent on the spherical architecture of APMNs, yields an assembly diagram that is different from the assembly of linear BCPs. Our experimental and computational studies suggested that the morphologies of assemblies were largely determined by the deformability of the effective nanoparticles (that is, nanoparticles together with tethered chains as a whole). The assemblies of APMNs resulted in strong absorption in near-infrared range due to the remarkable plasmonic coupling of Au cores, thus facilitating their biomedical applications in bioimaging and photothermal therapy of cancer.

How reliable are pseudocontact shifts induced in proteins and ligands by mobile paramagnetic metal tags? A modelling study

The anisotropic component of the magnetic susceptibility tensor (Δχ tensor) associated with various paramagnetic metal ions can induce pseudocontact shifts (PCSs) and residual dipolar couplings (RDCs) in proteins, yielding valuable restraints in structural studies. In particular, PCSs have successfully been used to study ligands that bind to proteins tagged with a paramagnetic metal ion, which is of great interest in fragment-based drug design. To create easy-to-interpret PCSs, the metal ion must be attached to the protein in a rigid manner. Most of the existing methods for site-specific attachment of a metal tag, however, result in tethers with residual flexibility. Here we present model calculations to quantify the extent, to which mobility of the metal-binding tag can compromise the quality of the Δχ tensor that can be determined from the PCSs observed in the protein. Assuming that the protein can be approximated by a sphere and the tag is attached by a single tether, the results show that a single effective ∆χ tensor can describe the PCSs and RDCs of the protein spins very well even in the presence of substantial tag mobility, implying that PCSs of ligands in binding pockets of the protein can be predicted with similar accuracy. In contrast, the quality of the PCS prediction for nuclear spins positioned above the surface of the protein is significantly poorer, with implications for studies of protein-protein complexes. The simulations probed the sensitivity of the effective Δχ tensor to different parameters, including length of the tether between protein and metal ion, protein size, type and amplitude of tag motion, tensor orientation relative to the protein and direction of tag motion. Tether length and amplitude of motion were identified as two key parameters. It is shown that the amplitude of tag motions cannot be quantified by simple comparisons of the effective Δχ tensor with the alignment tensor determined from RDCs.

Force Spectroscopy with Dual-Trap Optical Tweezers: Molecular Stiffness Measurements and Coupled Fluctuations Analysis

Dual-trap optical tweezers are often used in high-resolution measurements in single-molecule biophysics. Such measurements can be hindered by the presence of extraneous noise sources, the most prominent of which is the coupling of fluctuations along different spatial directions, which may affect any optical tweezers setup. In this article, we analyze, both from the theoretical and the experimental points of view, the most common source for these couplings in dual-trap optical-tweezers setups: the misalignment of traps and tether. We give criteria to distinguish different kinds of misalignment, to estimate their quantitative relevance and to include them in the data analysis. The experimental data is obtained in a, to our knowledge, novel dual-trap optical-tweezers setup that directly measures forces. In the case in which misalignment is negligible, we provide a method to measure the stiffness of traps and tether based on variance analysis. This method can be seen as a calibration technique valid beyond the linear trap region. Our analysis is then employed to measure the persistence length of dsDNA tethers of three different lengths spanning two orders of magnitude. The effective persistence length of such tethers is shown to decrease with the contour length, in accordance with previous studies.

Influence of Chronic Tethering of the Mitral Valve on Mitral Leaflet Size and Coaptation in Functional Mitral Regurgitation

The purposes of this study were to examine whether tethering of the mitral leaflets affects coaptation in patients with functional mitral regurgitation (FMR) and to assess the interaction between the mitral coaptation and mitral regurgitation severity. Functional mitral regurgitation causes restriction of leaflet closure as a result of enhanced tethering of the mitral leaflets and papillary muscle (PM) displacement. Three-dimensional transesophageal echocardiography was performed in 44 patients with FMR related to the bilateral PM displacement and in 56 controls. The distance between the tip of the anterior or posterior PM and the intervalvular fibrosa were measured as the lateral or medial tethering length (TL) in midsystole. To evaluate the degree of coaptation, coaptation length (CL) at medial, middle, and lateral sites of mitral valve and an estimate of coaptation area (CA) were measured. The FMR group showed the significantly decreased CA (1.3 ± 0.4 cm(2) vs. 1.6 ± 0.4 cm(2), p = 0.005) and CL (medial 3.2 ± 0.9 mm vs. 4.8 ± 0.6 mm, middle 3.8 ± 1.3 mm vs. 5.8 ± 0.7 mm, lateral 3.3 ± 0.9 mm vs. 4.8 ± 0.6 mm; all p < 0.0001) compared with the controls. Each CL correlated negatively and significantly with both medial and lateral TL (all p < 0.0001). Annular area (p = 0.004) was significantly smaller and leaflet-to-annular area ratio (p < 0.0001) was significantly larger in patients with nonsignificant FMR than in the patients with significant (moderate to severe) FMR. Significant correlations were found between effective regurgitant orifice area and CA or each CL (all p < 0.0001). Coaptation decreased significantly in patients with FMR. The CL at each region was related to PM displacement and the indexes of coaptation were associated with mitral regurgitation severity.

Reverse Cope Elimination of Hydroxylamines and Alkenes or Alkynes: Theoretical Investigation of Tether Length and Substituent Effects

Quantum mechanical calculations have been used to study the intramolecular additions of hydroxylamines to alkenes and alkynes ("reverse Cope eliminations"). In intermolecular reverse Cope eliminations, alkynes are more reactive than alkenes. However, competition experiments have shown that tethering the hydroxylamine to the alkene or alkyne can reverse the reactivity order from that normally observed. The exact outcome depends on the length of the tether. In agreement with experiment, a range of density functional theory methods and CBS-QB3 calculations predict that the activation energies for intramolecular reverse Cope eliminations follow the order 6-exo-dig < 5-exo-trig < 5-exo-dig ≈ 7-exo-dig. The order of the barriers for the 5-, 6-, and 7-exo-dig reactions of alkynes arises mainly from differences in tether strain in the transition states (TSs), but is also influenced by the TS interaction between the hydroxylamine and alkyne. Cyclization onto an alkene in the 5-exo-trig fashion incurs slightly less tether strain than a 6-exo-dig alkyne cyclization, but its activation energy is higher because the hydroxylamine fragment must distort more before the TS is reached. If the alkene terminus is substituted with two methyl groups, the barrier becomes so much higher that it is also disfavored compared to the 5- and 7-exo-dig cyclizations.

Tricuspid Leaflet Augmentation to Eliminate Residual Regurgitation in Severe Functional Tricuspid Regurgitation

We describe a technique for treating severe functional tricuspid regurgitation (TR) when residual regurgitation cannot be eliminated with ring annuloplasty alone. The anterior leaflet and the anterior half of the posterior leaflet are augmented with an elliptic pericardial patch before implantation of a rigid annuloplasty ring. We successfully performed this procedure in 9 patients with severe TR due to severe leaflet tethering or short coaptation length and achieved complete elimination of TR with sufficient coaptation length in tricuspid valve leaflets for all patients.