scholarly journals Stability Enhancement of a Dimeric HER2-Specific Affibody Molecule through Sortase A-Catalyzed Head-to-Tail Cyclization

Molecules ◽  
2021 ◽  
Vol 26 (10) ◽  
pp. 2874
Author(s):  
Kristina Westerlund ◽  
Anders Myrhammar ◽  
Hanna Tano ◽  
Maxime Gestin ◽  
Amelie Eriksson Karlström
Keyword(s):  
Specific Binding ◽  
Cyclic Dimer ◽  
Sortase A ◽  
Apparent Difference ◽  
Her2 Receptor ◽  
Linear Dimer ◽  
Fold Reduction ◽  
Before And After ◽  
The Stability ◽  
Head To Tail Cyclization

Natural backbone-cyclized proteins have an increased thermostability and resistance towards proteases, characteristics that have sparked interest in head-to-tail cyclization as a method to stability-enhance proteins used in diagnostics and therapeutic applications, for example. In this proof-of principle study, we have produced and investigated a head-to-tail cyclized and HER2-specific ZHER2:342 Affibody dimer. The sortase A-mediated cyclization reaction is highly efficient (>95%) under optimized conditions, and renders a cyclic ZHER3:342-dimer with an apparent melting temperature, Tm, of 68 °C, which is 3 °C higher than that of its linear counterpart. Circular dichroism spectra of the linear and cyclic dimers looked very similar in the far-UV range, both before and after thermal unfolding to 90 °C, which suggests that cyclization does not negatively impact the helicity or folding of the cyclic protein. The cyclic dimer had an apparent sub-nanomolar affinity (Kd ~750 pM) to the HER2-receptor, which is a ~150-fold reduction in affinity relative to the linear dimer (Kd ~5 pM), but the anti-HER2 Affibody dimer remained a high-affinity binder even after cyclization. No apparent difference in proteolytic stability was detected in an endopeptidase degradation assay for the cyclic and linear dimers. In contrast, in an exopeptidase degradation assay, the linear dimer was shown to be completely degraded after 5 min, while the cyclic dimer showed no detectable degradation even after 60 min. We further demonstrate that a site-specifically DyLight 594-labeled cyclic dimer shows specific binding to HER2-overexpressing cells. Taken together, the results presented here demonstrate that head-to-tail cyclization can be an effective strategy to increase the stability of an Affibody dimer.

The stability of dislocation networks under various oxygen-doping conditions in superconducting Bi2Sr2CaCu2Oy single crystals and their influence on the flux pinning properties

1994 ◽  
Vol 52 ◽  
pp. 802-803
Author(s):  
Y. Feng ◽  
X. Y. Cai ◽  
R. J. Kelley ◽  
D. C. Larbalestier
Keyword(s):  
Single Crystals ◽  
Oxygen Content ◽  
Basal Plane ◽  
Flux Pinning ◽  
Pinning Centers ◽  
Before And After ◽  
Anomalous Peak ◽  
Basal Plane Dislocation ◽  
The Stability ◽  
Further Development

The issue of strong flux pinning is crucial to the further development of high critical current density Bi-Sr-Ca-Cu-O (BSCCO) superconductors in conductor-like applications, yet the pinning mechanisms are still much debated. Anomalous peaks in the M-H (magnetization vs. magnetic field) loops are commonly observed in Bi2Sr2CaCu2Oy (Bi-2212) single crystals. Oxygen vacancies may be effective flux pinning centers in BSCCO, as has been found in YBCO. However, it has also been proposed that basal-plane dislocation networks also act as effective pinning centers. Yang et al. proposed that the characteristic scale of the basal-plane dislocation networksmay strongly depend on oxygen content and the anomalous peak in the M-H loop at ˜20-30K may be due tothe flux pinning of decoupled two-dimensional pancake vortices by the dislocation networks. In light of this, we have performed an insitu observation on the dislocation networks precisely at the same region before and after annealing in air, vacuumand oxygen, in order to verify whether the dislocation networks change with varying oxygen content Inall cases, we have not found any noticeable changes in dislocation structure, regardless of the drastic changes in Tc and the anomalous magnetization. Therefore, it does not appear that the anomalous peak in the M-H loops is controlled by the basal-plane dislocation networks.

Sorbitol enhances the physicochemical stability of B12 vitamers

2020 ◽  
Vol 90 (5-6) ◽  
pp. 439-447 ◽  
Author(s):  
Andrew Hadinata Lie ◽  
Maria V Chandra-Hioe ◽  
Jayashree Arcot
Keyword(s):  
Ascorbic Acid ◽  
Uv Light ◽  
Heat Exposure ◽  
Water Soluble ◽  
Uv Exposure ◽  
Physicochemical Stability ◽  
Before And After ◽  
The Stability

Abstract. The stability of B12 vitamers is affected by interaction with other water-soluble vitamins, UV light, heat, and pH. This study compared the degradation losses in cyanocobalamin, hydroxocobalamin and methylcobalamin due to the physicochemical exposure before and after the addition of sorbitol. The degradation losses of cyanocobalamin in the presence of increasing concentrations of thiamin and niacin ranged between 6%-13% and added sorbitol significantly prevented the loss of cyanocobalamin (p<0.05). Hydroxocobalamin and methylcobalamin exhibited degradation losses ranging from 24%–26% and 48%–76%, respectively; added sorbitol significantly minimised the loss to 10% and 20%, respectively (p < 0.05). Methylcobalamin was the most susceptible to degradation when co-existing with ascorbic acid, followed by hydroxocobalamin and cyanocobalamin. The presence of ascorbic acid caused the greatest degradation loss in methylcobalamin (70%-76%), which was minimised to 16% with added sorbitol (p < 0.05). Heat exposure (100 °C, 60 minutes) caused a greater loss of cyanocobalamin (38%) than UV exposure (4%). However, degradation losses in hydroxocobalamin and methylcobalamin due to UV and heat exposures were comparable (>30%). At pH 3, methylcobalamin was the most unstable showing 79% degradation loss, which was down to 12% after sorbitol was added (p < 0.05). The losses of cyanocobalamin at pH 3 and pH 9 (~15%) were prevented by adding sorbitol. Addition of sorbitol to hydroxocobalamin at pH 3 and pH 9 reduced the loss by only 6%. The results showed that cyanocobalamin was the most stable, followed by hydroxocobalamin and methylcobalamin. Added sorbitol was sufficient to significantly enhance the stability of cobalamins against degradative agents and conditions.

Calcium and the Fc Receptor on Human Platelets

1987 ◽  
Vol 57 (03) ◽  
pp. 298-301
Author(s):  
William F Clark ◽  
Gerald J M Tevaarwerk ◽  
Bruce D Reid ◽  
Suzanne Hall ◽  
Anita Caveney ◽  
...  
Keyword(s):  
Specific Binding ◽  
Normal Subjects ◽  
Human Platelets ◽  
Fc Receptor ◽  
Normal Male ◽  
Scatchard Analysis ◽  
Normal Female ◽  
Apparent Difference ◽  
Binding Data ◽  
Direct Binding

SummaryWe have described the calcium dependence of the IgG Fc receptor (Fc-R) on human platelets by analyzing the direct binding of radiolabelled Fc fragments, monomers and dimers of IgG. Specific binding to platelets was undetectable at 37° C in a calcium-free preparation but readily detected when calcium was restored. Scatchard analysis of the binding data for the calcium-restored platelets permitted calculation of the available Fc-R and the Ka of binding for the different IgG ligands. The mean Ka of binding for 12 normal subjects varied from 107 to 108 L/M, with an equal receptor number measured by Fc fragments and dimers of IgG, but a lesser amount for monomeric IgG. There was no apparent difference in Fc-R number for platelets from 6 normal male versus 6 normal female subjects.At 4° C binding was detectable for dimers and polymers of IgG in a calcium-free preparation and this was markedly increased with recalcification. Thus, our data are consistent with an Fc receptor population on human platelets whose avidity for binding is significantly enhanced in a calcium-restored medium.

scholarly journals Investigation of Hydrothermally Stressed Silicone Rubber/Silica Micro and Nanocomposite for the Coating High Voltage Insulation Applications

Materials ◽  
2021 ◽  
Vol 14 (13) ◽  
pp. 3567
Author(s):  
Faiza Faiza ◽  
Abraiz Khattak ◽  
Safi Ullah Butt ◽  
Kashif Imran ◽  
Abasin Ulasyar ◽  
...  
Keyword(s):  
Silicone Rubber ◽  
Structural Changes ◽  
Polymer Chains ◽  
Hydrothermal Conditions ◽  
Silica Filler ◽  
Before And After ◽  
Aging Conditions ◽  
The Stability ◽  
Micro Silica ◽  
Applied Stresses

Silicone rubber is a promising insulating material that has been performing well for different insulating and dielectric applications. However, in outdoor applications, environmental stresses cause structural and surface degradations that diminish its insulating properties. This effect of degradation can be reduced with the addition of a suitable filler to the polymer chains. For the investigation of structural changes and hydrophobicity four different systems were fabricated, including neat silicone rubber, a micro composite (with 15% micro-silica filler), and nanocomposites (with 2.5% and 5% nanosilica filler) by subjecting them to various hydrothermal conditions. In general, remarkable results were obtained by the addition of fillers. However, nanocomposites showed the best resistance against the applied stresses. In comparison to neat silicone rubber, the stability of the structure and hydrophobic behavior was better for micro-silica, which was further enhanced in the case of nanocomposites. The inclusion of 5% nanosilica showed the best results before and after applying aging conditions.

Regulation of Laijiapu Waterway in Jingjiang Reach

2014 ◽  
Vol 501-504 ◽  
pp. 2001-2006
Author(s):  
Ya Liu ◽  
Li Zheng ◽  
Cheng Tao Huang ◽  
Zhao Biao Huang ◽  
Lin Liu
Keyword(s):  
Yangtze River ◽  
Three Gorges Reservoir ◽  
Three Gorges ◽  
The Yangtze River ◽  
Point Bar ◽  
The Three Gorges Reservoir ◽  
The Three Gorges ◽  
Before And After ◽  
The Stability ◽  
Channel Bar

After impoundment of the Three Gorges Reservoir, Jingjiang reach, in the middle of the Yangtze River, has gradually shown a series of atypical fluvial features, adversely affecting the maintenance of waterways. Citing the Laijiapu Waterway, a meandering segment in the lower Jingjiang for example, this paper compared the fluvial features of the channel before and after the impoundment, summed up its navigation-obstructing features, and proposed guarding the point bar on the convex bank and channel bar in the widening section as a key to maintaining the stability of the navigation channels.

scholarly journals Efficacy of Selective Grinding Guided by an Occlusal Splint in Management of Myofascial Pain: A Prospective Clinical Trial

2017 ◽  
Vol 11 (1) ◽  
pp. 301-311
Author(s):  
Felipe J. Fernández-González ◽  
Jorge Cabero-López ◽  
Aritza Brizuela ◽  
Ivan Suazo ◽  
Esteban Pérez-Pevida ◽  
...  
Keyword(s):  
Temporomandibular Joint ◽  
Myofascial Pain ◽  
Vertical Displacement ◽  
Occlusal Splint ◽  
Significant Difference ◽  
Before And After ◽  
Skeletal Pattern ◽  
Condylar Position ◽  
The Stability ◽  
Facial Types

Background:For patients whose centric relation (CR) has not been considered at the start and during treatment, the task of achieving an occlusal scheme that works together with the temporomandibular joint, the muscles, and the structures of the stomatognathic apparatus becomes a major concern.Objective:This study aims to describe a reproducible, predictable and to date unreported procedure of selective grinding guided by an occlusal splint and to analyze condylar position (CP) based on the skeletal pattern.Methods:A total of 72 symptomatic patients (38 females and 34 males) were classified into three groups: hyperdivergent, intermediate and hypodivergent. CP was quantified by mounted casts on a measures condyle displacement (MCD) device. Helkimo index was also performed in order to assess the severity of the temporomandibular joint (TMJ) disorders attending to clinical dysfunction, occlusal state and anamnestic dysfunction. Once the stability had been obtained, the splint was progressively reduced until the maximum intercuspation (MIC) was achieved.Results:The vertical displacement was found to be significantly different between the hyperdivergent and other two groups (p<0.01). Comparisons of MCD analysis before and after the selective grinding procedure identified a statistically significant difference in the horizontal and vertical CP (p<0.01) between the different groups whereas the Helkimo Index showed a clear improvement of TMJ disorders.Conclusion:All facial types, specially the hyperdivergent face type, showed a reduction in condylar displacement (CD) and less craniomandibular symptoms using this procedure, making it an excellent technique for clinicians.

scholarly journals Survival and echocardiographic evaluation of dogs with idiopathic dilated cardiomyopathy treated with carvedilol

2010 ◽  
Vol 62 (3) ◽  
pp. 555-563 ◽  
Author(s):  
E.C. Soares ◽  
G.G. Pereira ◽  
L.C. Petrus ◽  
M. Leomil Neto ◽  
F.L. Yamaki ◽  
...  
Keyword(s):  
Dilated Cardiomyopathy ◽  
Ventricular Remodeling ◽  
Left Ventricular ◽  
Idiopathic Dilated Cardiomyopathy ◽  
P Value ◽  
Echocardiographic Evaluation ◽  
Before And After ◽  
Group A ◽  
The Stability ◽  
Group B

Sixty dogs with idiopathic dilated cardiomyopathy were randomly treated with traditional therapy - digitalis, diuretics, angiotensin-converting inhibitors - (group A) or treated with these drugs plus carvedilol (group B). Echocardiographic variables were measured before and after 3, 13, 26, and 52 weeks of treatment or until death. Comparisons between groups and time were performed. No significant differences between groups were found in the most of the echocardiographic variables. The left ventricular end-systolic diameter indexed to body surface area (LVESDi) increased significantly in the group A dogs compared to the group B animals. The survival of groups A and B dogs were not different (P-value=0.1137). In conclusion, the stability of the LVESDi observed in the group treated with carvedilol may represent the beneficial effect over the ventricular remodeling.

scholarly journals The Efficiency of a Group Counseling Program Based on Psychodrama in Enhancing Self-awareness and Reducing Tension among tenth Grade Students In Qalqilia City

2019 ◽  
Vol 3 (18) ◽  
Author(s):  
Said Yousef Swilem
Keyword(s):  
Group Counseling ◽  
Control Group ◽  
Self Awareness ◽  
Counseling Program ◽  
Before And After ◽  
Tenth Grade ◽  
Post Test ◽  
Group Members ◽  
The Stability ◽  
And Control

The purpose of this study is to examine the efficiency of a group counseling program based on psychodrama in improving self-awareness and reducing tension among tenth grade students in Qalqilia City and examining the nature and the direction of the relationship between self-consciousness and tension, the sample of study consisted of (20) students whom were distributed randomly equally to two groups the first is an experimental contains (10) students and the second is a control group contains (10) students in light of a tension variable, they are drawn out from (152) students in governmental schools who obtained the highest stress scale for the current study, a counseling program has been built based on the principles and methodology methods of psychodrama which contained (13) sessions, the current study used a measure of self-awareness and tension before and after the program. The researcher used the semi-experimental design to verify the validity of the two instruments they were presented to a group of specialized consultants. The stability coefficient was then calculated using Cronbach Alpha, where the stability value of the self-awareness scale was 0.81 and tension scale was 0.90. The mean and standard deviations were calculated and the Shapiro-Wilk test was used to examine the normal distribution probability of the variables of self-awareness and tension. The results revealed in the non-moderate distribution of individual responses to the two variables. The Mann-Whitney test, the Wilcoxon Signed Ranks Test, and the Spearman Product-Moment Correlation Coefficient test were used. The results showed differences between the experimental and control groups in the post-test of self-awareness and stress measures and for group members this is an indication of the effectiveness of the psychodrama -based counseling program in improving self-awareness and reducing stress among tenth grade students in Qalqilia city and the absence of differences in experimental group members between the tribal and remote testing methods of self-awareness and differences in group members for testing between the two pre-test and post- test of stress. The researcher recommends that self-awareness and stress in the adolescent group should be addressed through the psychodrama -based counseling programs.    

scholarly journals Effect of Modified Kiln Dust and a Cationic Surfactant on the Removal of Aromatic and Heavy Metal Compounds from Fuels

2019 ◽  
Vol 35 (5) ◽  
pp. 1508-1513
Author(s):  
Noura Yahya El Mehbad
Keyword(s):  
Heavy Metals ◽  
Cationic Surfactant ◽  
Oil Quality ◽  
Cement Kiln ◽  
Polar Molecules ◽  
Optimum Conditions ◽  
Metal Compounds ◽  
Before And After ◽  
The Stability ◽  
Kiln Dust

This paper aims to investigate removal of aromatic and heavy metals compounds from fuels using cement kiln dust, and a cationic surfactant. The effect of a cationic surfactant and the composition of kiln dust on the stability of fuel was studied. The optimum conditions of adsorption were investigated. The stability of fuels was improved after adsorption because of the absorption of heavy metals, which act as catalysts. The concentrations of kiln dust and additives are effective for the absorption of heteroatoms of polar and nonpolar molecules. The addition of different concentrations of the cationic surfactant to kiln dust enhances the removal of polar molecules in fuel. The relation between the efficiency of the cationic surfactant and the enhanced removal of polar molecules was established. This study suggests a new mechanism to remove polar molecules according to the structure of the additive. Several parameters that affect the performance of the removal process were investigated under all optimum conditions. A complete chemical analysis of the fuels before and after treatment was performed, and the stability of the fuel was evaluated at different conditions. The prepared additive could enhance the oil quality and is environmentally safe. The adsorption behaviour of kiln dust was investigated to find a new mechanism of its efficiency. The results confirm the role of the cationic surfactant in the purification of fuels and the effectiveness of kiln dust in improving the stability of fuels, which depend on the concentration of the cationic surfactant and the nature of the kiln dust.

scholarly journals Flexible Tranmission Elements for Grid Optimization

2021 ◽  
Vol 21 (2) ◽  
pp. 53-61
Keyword(s):  
Power Systems ◽  
Electric Power ◽  
Emergency Operation ◽  
Power Losses ◽  
Current Transmission ◽  
Before And After ◽  
Grid Optimization ◽  
Flexible Alternating Current Transmission ◽  
Active Power Losses ◽  
The Stability

The article dwells upon optimizing, reduction of losses in, and improving the stability of grids by implementing devices that affect the parameters and power flows in a grid. State-of-the-art technology for better control is crucial for the development of electric power systems. FACTS technologies or flexible alternating current transmission systems, essentially transform the grid from a passive electricity transport into a device that actively controls the grid parameters. The article analyzes the development of a 500/220/110 kV grid that uses parameter-affective devices: SVC, BSK, LCD. Steady-state parameters, active power losses, and electric power losses were calculated for a year before and after the devices were deployed. Each device was therefore analyzed for effectiveness. The parameters of the SVC-equipped 500/220/110 kV grid were calculated for emergency operation with the 500 kV line being offline. Thus, the paper also analyzes the emergency performance of the SVC.

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