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Hydrogen-bonding-induced planar, rigid, and zigzag oligoanthranilamides. Synthesis, characterization, and self-assembly of a metallocyclophane.

Four oligoanthranilamides 1-4, which are incorporated with three, five, seven, or nine benzene units, respectively, have been synthesized and characterized. X-ray analysis, 1D and 2D (1)H NMR, and IR experiments reveal that all the new oligoamides adopt rigid, planar and zigzagged conformations in both solution and solid state, which are stabilized by intramolecular three-center hydrogen bonding. A 5-mer oligomer 22, which is incorporated with two acetylene groups at the ends, has also been synthesized and utilized for the self-assembly of a rigid hydrogen-bonded metallocyclophane. The new rigid oligoanthranilamides represent useful building blocks for the construction of supramolecular architectures.

Journal Article↗

Shape of fluid vesicles anchored by rigid rod.

A method combined the self-consistent field theory (SCFT) for the rigid rod with the Helfrich curvature elasticity theory for the vesicle has been developed for studying the shape of vesicles anchored by rigid rod. Both the deformation of the vesicle and the density distribution of rod segments can be obtained. Because of the vesicle's impenetrability for the rod segments and the decrease of the available space for the rod orientational configurations, the anchored rod segments exert the inhomogeneous entropic pressure on the vesicle and induce the change of vesicle shape. The interaction between the rod segments and the vesicle membrane exerts an extra tension to the membrane. Thus the interaction between the vesicle membrane and the rod segments, the rod length, and the bending rigidity of vesicle are investigated as the important factors to the shape transformation of the vesicle and the density distribution of rod segments. This method can be extended to more complicated and real biological systems, such as polymers with different topological architectures/vesicle, multiple chains/vesicle, protein inclusions, etc.

Algorithms↗

Effect of bending rigidity and interfacial permeability on the dynamical behavior of water-in-water emulsions.

Phase separation in aqueous biopolymer mixtures results in the formation of an interface, separating two aqueous bulk phases. The properties of that interface are key parameters to understand and predict phenomena, such as the phase-separation process and deformation of droplets in a flow field. In these processes, the structures and sizes of the morphologies depend on the balance between viscous and interfacial forces. Normally, one assumes that the interfacial tension is the only important parameter regarding the interfacial forces. However, we will show that in these water-in-water emulsions, bending rigidity and interfacial permeability also play an important role. Spinning drop experiments show that at long time scales the interface is permeable to both dissolved biopolymers and water. From droplet relaxation experiments, we could conclude that, for shorter time scales, water is the only ingredient that can diffuse through the interface. Due to this permeability, these methods cannot be used to calculate the interfacial tension accurately, without taking into account the permeability of the interface. Including the permeability, we give a full description for the relaxation time of deformed droplets. From this description, the interfacial tension and the permeability of the interface can be deduced simultaneously. We also incorporate the permeability and the bending rigidity into the description of the kinetics of phase separation. From this theoretical description, we predict four different regimes to occur in the phase-separation process depending on the size of the domains. For the scaling of the domain size with time, we find an exponent of (1)/(4) for bending- and permeability-dominated coarsening, an exponent of (1)/(3) for bending-dominated coarsening, an exponent of (1)/(2) for interfacial tension- and permeability-dominated coarsening, and an exponent of 1 for interfacial tension-dominated coarsening. The crossover between the different regimes depends on two different critical radii, R(c), equal to (2k/gamma)(1/2) and R(lambda), equal to etalambda(eff). Taking values for the interfacial properties, we find these critical radii to be larger than a micrometer, indicating that both bending rigidity and permeability are of importance during phase separation.

Adsorption↗

A molecular-field-based similarity study of non-nucleoside HIV-1 reverse transcriptase inhibitors. 2. The relationship between alignment solutions obtained from conformationally rigid and flexible matching.

An analysis of the relationship among alignment solutions obtained from field-based matching of a representative set of rigid conformers of three non-nucleoside HIV-1 reverse transcriptase inhibitors and solutions obtained from flexible matching of the same conformers is presented. In some cases, different alignment solutions obtained from rigid matching converge to the same solution when conformational rigidity is relaxed, indicating that a reduced set of conformers per molecule may be sufficient in many field-based similarity studies. Furthermore, the results also indicate the importance of going beyond the pairwise similarity level to obtain consistent solutions in flexible-matching studies. In this respect, the best conformationally flexible multi-molecule alignment obtained is found to be in good agreement with the relative binding geometry and orientation found experimentally from protein-ligand crystal structures. The rms separation between corresponding atoms in computed and 'experimental' sets of three inhibitor structures is 0.94 A.

Acetamides↗

Intermittent capnography during high-frequency jet ventilation for prolonged rigid bronchoscopy.

BACKGROUND: Gas exchange during high-frequency jet ventilation (HFJV) for prolonged rigid bronchoscopy (RBS) is usually monitored by arterial blood gas analysis. Capnography of expired gases during brief HFJV discontinuation may be a reliable and noninvasive supplemental method. Capnography can be performed either for single breaths or with respiratory rate (RR) reduced to 10 x min(-1). The aim of this study was to demonstrate that capnography during short periods of HFJV discontinuation represents a reliable measure of PaCO2 during prolonged RBS. METHODS: We prospectively investigated 100 consecutive patients (75 male and 25 female) undergoing HFJV for RBS. HFJV was delivered through the rigid bronchoscope at the following settings: working pressure 1.2 bar, rate 100 x min(-1), FIO2 0.99, t(i)/t(tot)0.6. The light guiding channel ending at the distal tip of the rigid bronchoscope was used for gas sampling. Capnograms were assessed at 5 min intervals and compared to PaCO2 from arterial blood samples drawn simultaneously. The accuracy of single breath CO2 sampling was compared with sampling at RR=10 x min(-1). RESULTS: Mean duration of RBS was 30+/-21 min. A significant correlation between capnography (PetCO2) and arterial blood gas analysis (PaCO2) was observed, being r=0.90 for the RR= 10 x min(-1) method and r=0.91 for the single breath method. Mean difference between PaCO2 and PetCO2 was 0.37+/-0.2 kPa throughout the entire study period. No significant differences between single breath sampling or sampling at RR=10 x min(-1) were observed. CONCLUSION: Capnography performed during short periods of HFJV discontinuation reliably and noninvasively reflects PaCO2 during prolonged endoscopic procedures. Capnography during HFJV for RBS may reduce the frequency of arterial blood gas sampling, the duration of unmonitored intervals and costs.

Adult↗

Comparison of transcutaneous and endtidal CO2-monitoring for rigid bronchoscopy during high-frequency jet ventilation.

OBJECTIVE: To compare endtidal and transcutaneous respiratory monitoring of high-frequency jet ventilation (HFJV) in rigid bronchoscopy. Both techniques provide a noninvasive measurement of pCO2. METHODS: High-frequency jet ventilation was applied via a rigid bronchoscope. Driving pressure (DP) was initially adapted to ensure normal ventilation. It was then changed twice by +/- 30% from the initial value. Endtidal and transcutaneous data were compared with arterial blood gas monitoring (ABG). RESULTS: Results were analyzed separately for the time just after changing the driving pressure (10 min) and the remaining time until the next change of the driving pressure (4 min). The first part was called the dynamic phase, and the second part the steady-state phase. Correlation coefficient between endtidal capnography and ABG was 0.96 for the steady state and 0.94 for the dynamic phase, respectively. Bland-Altman analysis revealed a bias of -0.21 kPa with limits of agreement (LOA) 1.63 kPa for the steady state and -0.25 kPa, 2.08 kPa for the dynamic phase, respectively. Correlation coefficient between transcutaneous monitoring and ABG for the steady state phase was 0.83, and was 0.72 for the dynamic phase. Bland-Altman analysis resulted in a bias of -0.89 kPa with LOA - 3.84 kPa during steady state and 0.92 kPa, 4.06 kPa for the dynamic phase, respectively. CONCLUSION: Endtidal capnography offers accurate respiratory monitoring of HFJV. Transcutaneous monitoring showed a good correlation to ABG only during steady-state conditions. For the dynamic phase the accuracy was significantly lower. Thus, we cannot recommend transcutaneous respiratory monitoring for the specific indication of rigid bronchoscopy using HFJV.

Adult↗

Misperceptions of angular velocities influence the perception of rigidity in the kinetic depth effect.

Accuracy in discriminating rigid from nonrigid motion was investigated for orthographic projections of three-dimension rotating objects. In 3 experiments the hypothesis that magnitudes of angular velocity are misperceived in the kinetic depth effect was tested, and in 4 other experiments the hypothesis that misperceiving angular velocities leads to misperceiving rigidity was tested. The principal findings were (a) the magnitude of perceived angular velocity is derived heuristically as a function of a property of the first-order optic flow called deformation and (b) perceptual performance in discriminating rigid from nonrigid motion is accurate in cases when the variability of the deformations of the individual triplets of points of the stimulus displays favors this interpretation and not accurate in other cases.

Depth Perception↗

Visual information about rigid and nonrigid motion: a geometric analysis.

A mathematical analysis is presented that attempts to describe the available visual information about rigid and nonrigid motion and the three-dimensional structure of rigidly moving objects. Unlike other approaches, the analysis is based on the geometric relations among a set of trajectories defined over an extended region of space-time. Two experiments are reported in which observers viewed computer simulations of moving objects and were required to judge whether the observed motion appeared to be rigid or nonrigid. The results suggest that the mathematical limitations of a trajectory-based analysis of visual information are consistent with the perceptual limitations of actual human observers.

Discrimination Learning↗

Mutations in SEPN1 cause congenital muscular dystrophy with spinal rigidity and restrictive respiratory syndrome.

One form of congenital muscular dystrophy, rigid spine syndrome (MIM 602771), is a rare neuromuscular disorder characterized by early rigidity of the spine and respiratory insufficiency. A locus on 1p35-36 (RSMD1) was recently found to segregate with rigid spine muscular dystrophy 1 (ref. 1). Here we refine the locus and find evidence of linkage disequilibrium associated with SEPN1, which encodes the recently described selenoprotein N (ref. 2). Our identification and analysis of mutations in SEPN1 is the first description of a selenoprotein implicated in a human disease.

Amino Acid Sequence↗

Increased rigidity of the chiral centre of tocainide favours stereoselectivity and use-dependent block of skeletal muscle Na(+) channels enhancing the antimyotonic activity in vivo.

1. Searching for the structural requirements improving the potency and the stereoselectivity of Na(+) channel blockers as antimyotonic agents, new derivatives of tocainide, in which the chiral carbon atom is constrained in a rigid alpha-proline or pyrrolo-imidazolic cycle, were synthesized as pure enantiomers. 2. Their ability to block Na(+) currents, elicited from -100 to -20 mV at 0.3 Hz (tonic block) and 2-10 Hz (use-dependent block) frequencies, was investigated in vitro on single fibres of frog semitendinosus muscle using the vaseline-gap voltage-clamp method. 3. The alpha-proline derivative, To5, was 5 and 21 fold more potent than tocainide in producing tonic and 10 Hz-use-dependent block, respectively. Compared to To5, the presence of one methyl group on the aminic (To6) or amidic (To7) nitrogen atom decreased use-dependence by 2- and 6-times, respectively. When methylene moieties were present on both nitrogen atoms (To8), both tonic and use-dependent block were reduced. 4. Contrarily to tocainide, all proline derivatives were stereoselective in relation to an increased rigidity. A further increase in the molecular rigidity as in pyrrolo-imidazolic derivatives markedly decreased the drug potency with respect to tocainide. 5. Antimyotonic activity, evaluated as the shortening of the time of righting reflexes of myotonic adr/adr mice upon acute drug in vivo administration was 3 fold more effective for R-To5 than for R-Tocainide. 6. Thus, constraining the chiral centre of tocainide in alpha-proline cycle leads to more potent and stereoselective use-dependent Na(+) channel blockers with improved therapeutic potential.

Animals↗

Synthetic multifunctional pores: lessons from rigid-rod beta-barrels.

In this account, studies on synthetic multifunctional pores formed by rigid-rod beta-barrels are summarized comprehensively. The first section outlines the evolution of synthetic multifunctional pores from the introduction of rigid-rod molecules in bioorganic chemistry and the discovery of synthetic beta-barrels in comparison with pertinent developments in related areas of research. Design strategies to position active sites at the inner surface of rigid-rod beta-barrel pores are described in the second section. The third section focuses on the characteristics of transmembrane barrel-stave pores, emphasizing the dynamic nature of supramolecular oligomers with the aid of notional phase and energy diagrams. Section four introduces multifunctionality with the use of synthetic pores as hosts of a rich collection of guests, reaching from inorganic cations to organic macromolecules like peptides, oligonucleotides, polysaccharides and polyacetylenes. In section five, practical applicability of molecular recognition by synthetic multifunctional pores is documented with non-invasive fluorometric enzyme sensing. The application of host-guest chemistry within synthetic pores to couple molecular recognition and translocation with molecular transformation is the topic of section six. The last section mentions some perspectives and challenges with synthetic multifunctional pores.

Biosensing Techniques↗

Ab initio rigid water: effect on water structure, ion hydration, and thermodynamics.

We investigate the liquid structure, ion hydration, and some thermodynamic properties associated with the rigid geometry approximation to water by applying ab initio molecular dynamics simulations (AIMD) with the Perdew-Burke-Ernzerhof (PBE) exchange-correlation functional at T = 320 K. We vary the rigid water geometry in order to locate a class of practical water models that yield reasonable liquid structure and dynamics, and to examine the progression of AIMD-predicted water behavior as the OH bond length varies. Water constrained at the optimal PBE gas phase geometry yields reasonable pair correlation functions. The predicted liquid phase pressure, however, is large ( approximately 8.0 kbar). Although the O-H bond in water should elongate when transferred from gas to the condensed phase, when it is constrained to 0.02, or even just 0.01 A longer than the optimal gas phase value, liquid water is predicted to be substantially overstructured compared to experiments. Zero temperature calculations of the thermodynamic properties of cubic ice underscore the sensitivity toward small variations in the O-H bond length. We examine the hydration structures of potassium, chloride, and formate ions in one rigid PBE water model. The results are in reasonable agreement with unconstrained AIMD simulations.

Computer Simulation↗

Sutural expansion using rigidly integrated endosseous implants: an experimental study in rabbits.

Rigidly integrated implants offer great promise for orthodontic and orthopedic anchorage in the oral and midfacial regions. Rigid anchorage can be used to control unwanted tooth movement, provide abutments in edentulous arches, and open the vertical dimension of occlusion. To evaluate the use of endosseous implants in the midface region, two flanged titanium implants were placed on either side of the midnasal suture of 18 New Zealand White rabbits. The rabbits were divided into an unloaded control and two experimental groups. One experimental group was loaded at 1 Newton (N) and the other at 3 N. All rabbits were euthanized after 12 weeks of loading. Stereologic point-hit and line-intercept methods were used to analyze microradiographic and multiple fluorochrome histology of the suture. All implants remained stable during the loading period. The distance between the implants increased significantly in the loaded groups compared with the control, and was significantly higher in the 3 N group than in the 1 N group. Percent bone volume was significantly decreased, while the percent suture volume tended to be increased in the loaded groups. Mineral apposition and bone formation rates at the sutural surfaces were increased in the loaded groups (P < 0.05), but did not differ between loaded groups. These results indicate that relatively low loads (1 or 3 N) applied to rigidly integrated endosseous implants across an unfused suture are satisfactory for achieving expansion under the conditions of this study. The 3 N load resulted in slightly more expansion, but did not affect the rate of bone formation at the suture.

Animals↗

Remifentanil vs. fentanyl during interventional rigid bronchoscopy under general anaesthesia and spontaneous assisted ventilation.

The treatment of tracheo-bronchial diseases with rigid bronchoscopy requires general anaesthesia without tracheal intubation. Spontaneous assisted ventilation is a safe modality of ventilation. In this study the use of remifentanil and fentanyl is compared during rigid bronchoscopy with spontaneous assisted ventilation. Ninety high-risk patients received fentanyl or remifentanil with propofol for general anaesthesia. During the maintenance fentanyl was delivered at 6.1 +/- 4.6 micrograms kg-1 h-1 and remifentanil at 0.15 +/- 0.07 microgram kg-1 min-1. The same degree of intra-operative respiratory acidosis with similar good operating conditions resulted in both groups. Patients treated with remifentanil recovered more quickly compared with those in the fentanyl group (3.8 +/- 2 vs. 10.4 +/- 9.2 min, P < 0.001). In conclusion, the use of remifentanil during rigid bronchoscopy under general anaesthesia with spontaneous assisted ventilation is safe and assures good operating conditions. Moreover, remifentanil permits a more rapid recovery than fentanyl. The dose of remifentanil is higher than previously described for spontaneously breathing patients.

Anesthesia, General↗

A comparative study of flexible (Polyactive) versus rigid (hydroxylapatite) permucosal dental implants. II. Histological aspects.

Of the many materials that are applied in dental implantology, most have a high Young's modulus. In the concept of osseointegration, which is generally preferred, chewing forces are therefore directly transmitted from rigid implant materials to the relatively flexible surrounding bone. Polyactive is an elastomeric polyethylene-oxide polybutylene-terephthalate (PEO:PBT) copolymer, with a low modulus of elasticity, that exhibits bone-bonding characteristics. Previous finite-element analysis emphasized the benefit of the application of flexible implant materials. To assess the validity of this finite element model, one dense and two porous types of flexible Polyactive permucosal dental implants and one rigid hydroxylapatite (HA) implant were clinically tested in a beagle dog study and were compared during 30 weeks of loading. In an earlier report, it was concluded that dense Polyactive implants function clinically adequately and resemble the mobility of natural teeth. In the current study, the amount of bone contact was quantitatively assessed. Polyactive implants showed a statistically significantly higher bone contact, as compared to the HA implants, probably due to a significant water uptake and a subsequent increase in the volume of the denser Polyactive. Morphological analysis, based on back-scatter electron microscopy and light microscopy, revealed little remodelling activity of the bone surrounding the Polyactive implants. Few remodelling lacunae were seen and de novo bone formation was rarely observed. At some locations, a continuity between calcification zones with the polymer surface and the surrounding interfacial bone was observed, indicating the occurrence of bone-bonding. Also, the bone surrounding the HA implants showed little remodelling activity, although large resorption lacunae were observed, in which HA particles were present. Based on the observations of this study, flexible bone bonding implants might be more capable of transferring stresses to the surrounding bone and are therefore promising alternatives to "routine' rigid implants.

Alveolar Process↗

Rigid ureteroscopy in pregnant women.

OBJECTIVE: To report our experience with rigid ureteroscopy in pregnant women. PATIENTS AND METHODS: Ten pregnant women (mean age 25 years, SD 4.5, range 22-33) with ureteric stones were treated by ureteroscopy. The mean (SD, range) gestation time was 24 (6.5, 19-33) weeks. A standard rigid ureteroscope of 11.5 F was used in eight patients and 9.5 F in two. The procedure was carried out with no ureteric dilatation in three patients and with easy dilatation in seven. Fluoroscopy was not used before or during ureteroscopy in any case. Ultrasonography was available throughout the procedures for constant renal and obstetric monitoring. RESULTS: Mid and lower ureteric stones were extracted by basket or forceps in three patients and had to be disintegrated by ultrasound in two. Upper ureteric stones were displaced to the kidney, with placement of double-pigtail ureteric stents, in three patients who were subsequently treated after delivery. Ureteric oedema was seen in one patient and the endoscopic findings were normal in the remaining patient. There were no obstetric complications. Two patients had a urinary tract infection and one complained of stent-induced bladder irritation. CONCLUSIONS: Rigid ureteroscopy is a safe and reliable method in the diagnosis and treatment of ureteric calculi during pregnancy. The procedure can be performed with ultrasonographic monitoring and without using fluoroscopy.

Adult↗

Computerized analysis of resorbable polymer plates and screws for the rigid fixation of mandibular angle fractures.

PURPOSE: This computer-based study used finite element analysis (FEA) to assess whether rigid fixation by resorbable polymer plates and screws can provide the required stiffness and strength for a typical mandibular angle fracture. MATERIALS AND METHODS: Two separate 3-dimensional FEA models of the mandible were generated using 8-noded hexahedral elements. The jaw segments in 1 model were fixed with titanium plates and screws as those in common use today. The jaw segments in the other model were fixed with resorbable polymer plates and screws as used in a developmental product currently in trials. A commercial finite element solver was then applied to this mesh to compute stresses and bone interfragmentary displacements for both titanium fixation and resorbable fixation. Calculated displacements were compared with each other and to established norms for healthy bone regrowth. Calculated stresses were compared with the yield strength of each material. Finally, overall stress patterns in the fractured mandibles were compared with each other. RESULTS: The study results indicate that titanium fixation more rigidly fixes the 2 bone segments in relative position. However, they also show that resorbable polymers provide sufficient stiffness to meet currently established norms for fracture immobility. Furthermore, the analyses show that resorbable polymers are capable of withstanding the stresses generated by the bite loads of postsurgical patients. The results indicate that mandibles, fixed with either titanium or resorbable materials, show nearly identical stress patterns. CONCLUSIONS: The resorbable polymer-based plates and screws tested in this investigation are of adequate strength and stiffness for their successful application to the rigid fixation of mandibular angle fractures.

Absorbable Implants↗

Multidirectional projectional rigid neuro-endoscopy: prototype and initial experience.

INTRODUCTION: The role of neuro-endoscopy is emerging. Traditional endoscopy is complicated by limited 2D views that make surgical interventions difficult. We have developed a rigid endoscope with a variable direction view that provides 3D visualization. MATERIALS AND METHODS: A prototype of the EndActive endoscope was used to examine 2 brain/intraventricular models. A 360-degree view is controlled via integrated joystick. Alternatively, the computer can volumetrically capture the ventricular surface. The captured video image can be viewed later or processed to create a flat projection map. The performance of this endoscope was compared to standard endoscopy with fixed directions of view. To simulate endoscopy, the center of the first brain model had eight labeled projections. The model was inspected with the multidirectional endoscope, standard rigid endoscopes (0-, 30- and 70-degree), and via a projection map. Ten neurosurgeons proficient in neuro-endoscopy were recruited for the experiments. The second brain model was labeled with 32 intraventricular tumors. RESULTS: With a 0-degree endoscope, only the number directly opposite the site of entry was visualized. With increasing angles, additional numbers were visualized. The 70-degree endoscope allowed 4 of 8 numbers to be visualized. Using the multidirectional endoscope, all 8 numbers were visualized. The multidirectional endoscope was more accurate in identifying markers compared to standard endoscopy (p = 0.031). The mean endoscopy times using the multidirectional endoscope and standard endoscopy were 143 and 117 seconds, respectively (p = 0.243). The best performance was obtained when the flat projection map was read (p < 0.01). Using the endoscope prototype, an average of 30.8 (96%) tumors was identified on the brain model. CONCLUSION: The EndActive endoscope is a rigid endoscope that provides complete visualization of a 3D space by controlling an adjustable viewing direction. In our study, the multidirectional endoscope provided superior visualization compared to standard endoscopy.

Humans↗