Conformational Integrity Research Articles

Drug Carriers

In recent years, there has been an exponential interest in the development of novel drug delivery systems using drug carriers. Drug carriers offer significant advantages over the conventional drug delivery systems in terms of high stability, high specificity, high drug loading capacity, controlled release of drug and ability to deliver both hydrophilic and hydrophobic drugs. As a result of their unique behaviors, drug carriers have a wide range of biomedical and industrial applications. Nanospheres are associated with a lot of benefits such as ease of administration to target sites, reduction in toxicity level and ease of passage via the capillary vessels. Hydrogel nanoparticles are useful in the treatment of inflammatory diseases, as bioresponsive hydrogels in drug delivery system and as a carrier in controlled drug delivery system. Carbon nanotubes have a large surface area which has the ability to adsorb or conjugate with a wide variety of therapeutic and diagnostic agents. They are useful in the areas of gene delivery, tissue regeneration and biosensor diagnosis. Liposomes are known to target a drug to a specific site. They entrap drugs which are released for subsequent absorption. They are used to achieve active targeting, increase efficacy and therapeutic index of drugs. Niosomes improve the solubility and oral bioavailability of poorly soluble drugs. They protect drugs from biological environment, increase the stability of entrapped drugs and they can easily reach the site of action. Aquasomes are nanoparticulate carriers that can be characterized for structural analysis. They preserve conformational integrity and biochemical stability of drugs. Ethosomes are noninvasive delivery carriers that enable drugs to reach the deep skin layers and the systemic circulation. They contain phospholipids which could be in form of phosphatidyl choline (PC), hydrogenated PC, phosphatidic acid (PA), Phosphatidyl serine (PS) and phosphatidyl inositol (PI). Ethosomes are known to increase skin permeation of drugs, improve biological activity and pharmacodynamics profile of drugs. This review aims to emphasize the importance of drug carriers in drug delivery system, and applications of drug carriers in various areas of research, technology and treatment.

Highly stretchable van der Waals thin films for adaptable and breathable electronic membranes.

The conformal integration of electronic systems with irregular, soft objects is essential for many emerging technologies. We report the design of van der Waals thin films consisting of staggered two-dimensional nanosheets with bond-free van der Waals interfaces. The films feature sliding and rotation degrees of freedom among the staggered nanosheets to ensure mechanical stretchability and malleability, as well as a percolating network of nanochannels to endow permeability and breathability. With an excellent mechanical match to soft biological tissues, the freestanding films can naturally adapt to local surface topographies and seamlessly merge with living organisms with highly conformal interfaces, rendering living organisms with electronic functions, including leaf-gate and skin-gate transistors. On-skin transistors allow high-fidelity monitoring and local amplification of skin potentials and electrophysiological signals.

Stress-responsive regulation of extracellular proteostasis

Genetic, environmental, and aging-related insults can promote the misfolding and subsequent aggregation of secreted proteins implicated in the pathogenesis of numerous diseases. This has led to considerable interest in understanding the molecular mechanisms responsible for regulating proteostasis in extracellular environments such as the blood and cerebrospinal fluid (CSF). Extracellular proteostasis is largely dictated by biological pathways comprising chaperones, folding enzymes, and degradation factors localized to the ER and extracellular space. These pathways limit the accumulation of nonnative, potentially aggregation-prone proteins in extracellular environments. Many reviews discuss the molecular mechanisms by which these pathways impact the conformational integrity of the secreted proteome. Here, we instead focus on describing the stress-responsive mechanisms responsible for adapting ER and extracellular proteostasis pathways to protect the secreted proteome from pathologic insults that challenge these environments. Further, we highlight new strategies to identify stress-responsive pathways involved in regulating extracellular proteostasis and describe the pathologic and therapeutic implications for these pathways in human disease.

Conformable fractional order controller design and optimization for sensorless control of induction motor

PurposeIn recent years, use of sensorless control methods for electrical motor-based variable speed drive systems has been increasing rapidly to compensate the increasing costs in industrial systems. Also, use of induction motors is popular for a long time to decrease the cost of these industrial systems. This study aims to design an effective controller to improve the sensorless speed control performance of induction motor. To achieve this, a conformable fractional order proportional integral (CFOPI) controller is designed.Design/methodology/approachThe system is modeled based on small signal analysis by using the input–output data, experimentally. To do this, system identification toolbox of Matlab is used. The proposed controller is established on conformable fractional integral approach proposed by Khalil et al. (2014). CFOPI controller coefficients are optimized using particle swarm optimization method on the created small signal-based simulation model of the system to minimize the integral time absolute error. To prove the success of the proposed method, a traditional fractional order proportional integral (TFOPI) controller is tested under the same experimental system with the CFOPI controller.FindingsTFOPI and CFOPI controllers are tested with the optimum parameters. Reference and actual speed trends are obtained for both methods. In induction motor start-up test, settling-times are measured as 8.73 and 8.44 s and steady-state oscillations are 2.66% and 0% (almost) for TFOPI and CFOPI controllers, respectively. In variable referenced speed tracking test, CFOPI performs well at all speed levels, while TFOPI fails to reach the reference speed at most speed levels.Practical implicationsProposed CFOPI control method can be easily implemented in industrial systems, thanks to its simple algorithm. digital signal peripheral interface controller (dsPIC) based driver circuit with designed CFOPI controller used in this study can be applied directly to industrial systems such as elevators, conveyors, cranes and drills. Moreover, it can improve the performance of induction motor-based variable speed drive systems.Originality/valueThe proposed method provides robust performance for induction motor used in control systems. Additionally, it does this by using less complex algorithm written on the processors according to the traditional fractional order controllers.

Hermite-Hadamard-Fejér Type Inequalities with Generalized K-Fractional Conformable Integrals and Their Applications

In this work, we introduce new definitions of left and right-sides generalized conformable K-fractional derivatives and integrals. We also prove new identities associated with the left and right-sides of the Hermite-Hadamard-Fejér type inequality for ϕ-preinvex functions. Moreover, we use these new identities to prove some bounds for the Hermite-Hadamard-Fejér type inequality for generalized conformable K-fractional integrals regarding ϕ-preinvex functions. Finally, we also present some applications of the generalized definitions for higher moments of continuous random variables, special means, and solutions of the homogeneous linear Cauchy-Euler and homogeneous linear K-fractional differential equations to show our new approach.

Immunochemical and biophysical characterization of inactivated Sabin poliovirus products: Insights into rapid quality assessment tools

The aim of this study was to demonstrate the strength of combining immunochemical and biophysical analysis tools for assessing the quality of Sabin inactivated poliovirus vaccine (Sabin-IPV) bulk products. We assessed Sabin-IPV serotypes 1, 2 and 3 from six different manufacturers and evaluated their comparability through biosensor analysis and biophysical characterization methods, including tryptophan fluorescence and asymmetrical flow field-flow fractionation – multi-angle light scattering analysis. These methods enabled us to assess antigenic as well as conformational and structural integrity profiles, respectively. Based on Sabin-IPV samples that were subjected to accelerated storage conditions, we revealed that existing immunochemical methods exhibit remarkably similar trends to the results obtained by the biophysical characterization methods. While the results underpin that the comparability of Sabin-IPV bulk products of different manufacturers is weak, information about their quality can rapidly be obtained by using both immunochemical and biophysical methods. Furthermore, the study highlights that quality assessment of Sabin-IPV can be obtained through biophysical techniques can complement the assessments performed with monoclonal antibodies and suggests that similar techniques could be employed to characterize other enteroviruses.

Some New Inequalities for p‐Convex Functions via a K‐Fractional Conformable Integral

The intention of this paper is to develop some new Hermite–Jensen–Mercer type inequalities for p−convex functions via k−fractional conformable integrals. Several existing results are also discussed which can be deduced from our results.

Expressão de tetraspanina co029 como biomarcador tumoral para preparação de anticorpos monoclonais: avaliação antigênica em células de câncer colorretal

INTRODUCTION: The identification of innovative cancer biomarkers is a very relevant ongoing quest. Moreover, their role in cancer diagnosis and clinical management has been radically changed in the last few years with the major emphasis on cancer molecular classification, therapeutic target identification, and therapeutic protocol responsivity. tetraspanins are a family of transmembrane proteins correlated with tumor stage, tumor type and patient outcome affecting cell growth, morphology, invasion, and metastasis. METHODS: We expressed the 31kDa transmembrane human tetraspanin co029 antigen in Escherichia coli expression host cells using Gateway® platform. Western blotting and ELISA techniques, together with gene sequencing, confirmed the identity of TSP co029 recombinant protein. Forty clones producing antibodies against TSP co029 were obtained. These antibodies were incubated with human colorectal cancer cells in different conditions. ELISA and immunohistochemistry were also performed. RESULTS: The expressed tetraspanin had an appropriate conformation and antigenic integrity to produce antibodies with affinity to the native TSP co029 biomarker. The affinity of the purified recombinant protein and antibodies were confirmed by western blotting, florescent staining of human colorectal cancer cells in fluorescence and confocal microscopies and by ELISA and immunohistochemistry. CONCLUSION: Our data showed that the recombinant protein and antibodies produced in this study allowed the confirmation of tetraspanin co029 protein presented on the surface of human colorectal cancer cells.

Soft Plasmonics: Design, Fabrication, Characterization, and Applications

AbstractPlasmonic nanostructures are important building blocks in modern nanoscience and nanotechnology. Significant research efforts have been directed toward developing solution‐based or rigid‐substrate‐supported metallic nanostructures for novel applications in biophotonics, sensing, energy, and medicine. In parallel, there has been an increasing interest in the fabrication of plasmonic nanostructures on elastomeric substrates and exploring the impact of mechanical deformation including bending, torsion, and stretching on the collective plasmonic resonance properties. This burgeoning field may be defined as soft plasmonics (or soft mechanoplasmonics), analogous to soft electronics. This review describes the recent progress in the design, fabrication, characterization, properties, and applications of soft plasmonics. Soft plasmonics are expected to afford complementary features and functions to the field of soft electronics, enabling applications that are difficult or impossible to achieve with traditional rigid plasmonic structures, such as conformal attachment or integration with soft biological systems for real‐time sensing, actuation, and close‐loop feedback.

Expression Patterns of the Heat Shock Protein 90 (Hsp90) Gene Suggest Its Possible Involvement in Maintaining the Dormancy of Dinoflagellate Resting Cysts.

Heat shock protein 90 (Hsp90) is a highly conserved molecular chaperone functioning in cellular structural folding and conformational integrity maintenance and thus plays vital roles in a variety of biological processes. However, many aspects of these functions and processes remain to be fully elucidated, particularly for non-model organisms. Dinoflagellates are a group of eukaryotes that are exceedingly important in primary production and are responsible for the most harmful algal blooms (HABs) in aquatic ecosystems. The success of dinoflagellates in dominating the plankton community is undoubtedly pertinent to their remarkable adaptive strategies, characteristic of resting cyst production and broad tolerance to stresses of temperature and others. Therefore, this study was conducted to examine the putative roles of Hsp90 in the acclimation to temperature stress and life stage alterations of dinoflagellates. Firstly, we isolated the full-length cDNA of an Hsp90 gene (StHsp90) via RACE from the cosmopolitan HAB species Scrippsiella trochoidea and tracked its transcriptions in response to varied scenarios via real-time qPCR. The results indicated that StHsp90 displayed significant mRNA augment patterns, escalating during 180-min treatments, when the cells were exposed to elevated and lowered temperatures. Secondly, we observed prominently elevated StHsp90 transcriptions in the cysts that were stored at the cold and dark conditions compared to those in newly formed resting cysts and vegetative cells. Finally, and perhaps most importantly, we identified 29 entries of Hsp90-encoding genes with complete coding regions from a dinoflagellate-specific environmental cDNA library generated from marine sediment assemblages. The observed active transcription of these genes in sediment-buried resting cysts was fully supported by the qPCR results for the cold-stored resting cysts of S. trochoidea. Hsp90s expressions in both laboratory-raised and field-collected cysts collectively highlighted the possible involvement and engagement of Hsp90 chaperones in the resting stage persistence of dinoflagellates.

New integral inequalities for geometrically convex functions via conformable fractional integral operators

We establish several basic inequalities versions of the Hermite-Hadamard type inequalities for GA− and GG−convexity for conformable fractional integrals. Several special cases are also discussed, which can be deduced from our main result.

A new type electromagnetic curves in optical fiber and rotation of the polarization plane using fractional calculus

In the present paper, the geometric properties of the linearly polarized light wave are researched along an optical fiber using the conformable fractional derivative and integral in 3D Riemannian manifold. Since the optical fiber is supposed to be a one-dimensional object imbedded in a 3D Riemannian manifold, the evolution of a linearly polarized light wave is associated with geometric phase. So, we generate a new type of geometric phase model with fractional derivative. Also, we introduce a magnetic curves which are generated by the electric field E. Finally, examples consistent with the theory are examined and visualized for different values of the conformable fractional derivative. The difference of this study from others is the use of conformal fractional derivatives and integrals in calculations. Fractional calculus has applications in many fields such as physics, engineering, mathematical biology, fluid mechanics, signal processing, etc. Fractional derivatives and integrals have become an extremely important and new mathematical method in solving various problems in many sciences.

Structural Dynamics of RNA in the Presence of Choline Amino Acid Based Ionic Liquid: A Spectroscopic and Computational Outlook.

Ribonucleic acid (RNA) is exceedingly sensitive to degradation compared to DNA. The current protocol for storage of purified RNA requires freezing conditions below −20 °C. Recent advancements in biological chemistry have identified amino acid-based ionic liquids as suitable preservation media for RNA, even in the presence of degrading enzymes. However, the mechanistic insight into the interaction between ILs and RNA is unclear. To the best of our knowledge, no attempts are made so far to provide a molecular view. This work aims to establish a detailed understanding of how ILs enable structural stability to RNA sourced from Torula yeast. Herein, we manifest the hypothesis of multimodal binding of IL and its minimal perturbation to the macromolecular structure, with several spectroscopic techniques such as time-resolved fluorescence and fluorescence correlation spectroscopy (FCS) aided with molecular dynamics at microsecond time scales. Relevant structural and thermodynamic details from biophysical experiments confirm that even long-term RNA preservation with ILs is a possible alternative devoid of any structural deformation. These results establish a unifying mechanism of how ILs are maintaining conformational integrity and thermal stability. The atomistic insights are transferable for their potential applications in drug delivery and biomaterials by considering the advantages of having maximum structural retention and minimum toxicity.

Ulam's type stabilities for conformable fractional differential equations with delay

In this paper, we investigate the existence and uniqueness of solutions and Ulam's type stabilities including the well‐known Ulam–Hyers stability and the newly extended Ulam–Hyers conformable exponential stability for two classes of fractional differential equations with the conformable fractional derivative and the time delay. The Banach contraction principle, the technique of Picard operator, the Grönwall integral inequalities, and generalized iterated integral inequality in the sense of conformable fractional integral are the main tools for deriving our main results. Finally, several illustrative examples will be presented to demonstrate our work.

Novel improved fractional operators and their scientific applications

The motivation of this research is to introduce some new fractional operators called “the improved fractional (IF) operators”. The originality of these fractional operators comes from the fact that they repeat the method on general forms of conformable integration and differentiation rather than on the traditional ones. Hence the convolution kernels correlating with the IF operators are served in conformable abstract forms. This extends the scientific application scope of their fractional calculus. Also, some results are acquired to guarantee that the IF operators have advantages analogous to the familiar fractional integral and differential operators. To unveil the inverse and composition properties of the IF operators, certain function spaces with their characterizations are presented and analyzed. Moreover, it is remarkable that the IF operators generalize some fractional and conformable operators proposed in abundant preceding works. As scientific applications, the resistor–capacitor electrical circuits are analyzed under some IF operators. In the case of constant and periodic sources, this results in novel voltage forms. In addition, the overall influence of the IF operators on voltage behavior is graphically simulated for certain selected fractional and conformable parameter values. From the standpoint of computation, the usage of new IF operators is not limited to electrical circuits; they could also be useful in solving scientific or engineering problems.

Stable, high yield expression of gp145 Env glycoprotein from HIV-1 in mammalian cells

The HIV-1 derived gp145 protein is being investigated by research groups as preclinical studies have shown high promise for this protein as a vaccine against HIV. However, one of the main challenges with manufacturing this promising protein has been ascribed to the low yield obtained in mammalian cell cultures. Significant improvements in gp145 production are needed to address this issue to test the gp145 protein as a potentially effective, safe, and affordable HIV vaccine. Here we describe the application of a novel expression technology to create GMP-grade CHO cell lines expressing approximately 50 μg/ml in non-optimized fed-batch culture, which is an order of magnitude higher than that obtained in existing processes. Top producing clones show a high degree of similarity in the glycosylation patterns of the purified protein to the reference standard. Conformational integrity and functionality was demonstrated via high-affinity binding to soluble CD4, using a panel of antibodies including VRC01, F105, Hk20, PG9 and 17b. In summary, we were able to generate CHO cell lines expressing HIV gp145 with significantly higher overall expression yields than currently accessible, and high product quality that could potentially be suitable for future studies assessing the efficacy and safety of gp145-based HIV vaccines.

Yangian bootstrap for massive Feynman integrals

We extend the study of the recently discovered Yangian symmetry of massive Feynman integrals and its relation to massive momentum space conformal symmetry. After proving the symmetry statements in detail at one and two loop orders, we employ the conformal and Yangian constraints to bootstrap various one-loop examples of massive Feynman integrals. In particular, we explore the interplay between Yangian symmetry and hypergeometric expressions of the considered integrals. Based on these examples we conjecture single series representations for all dual conformal one-loop integrals in D spacetime dimensions with generic massive propagators.

Ultra‐Flexible Visible‐Blind Optoelectronics for Wired and Wireless UV Sensing in Harsh Environments

AbstractExploring remote destinations on Earth and in space such as the Antarctic and Mars is of great significance to science and technology. Ultraviolet (UV) irradiation at those locations is usually strong due to the depletion or absence of ozone, which is often accompanied by strong visible light interference and harsh environments with extreme temperatures. Those exploration missions extensively utilize flexible and foldable membranes and shells to meet the extreme requirements on structural size and weight. Ultra‐flexible UV photodetectors (PDs) capable of surviving harsh environments with additional ability to integrate on flexible and foldable structures for in situ visible‐blind UV sensing are critical to the protection of human explorers and engineering materials. However, the development of such UV PDs remains challenging. Here, this work introduces wired and wireless optoelectronic devices based on visible‐blind, ultra‐flexible, sub‐micron nanocomposites of zinc oxide nanoparticles and single‐walled carbon nanotubes. In‐depth studies demonstrate their operation at cold and hot temperatures and low air pressure. Those PDs can employ flexible near‐field communication circuits for wireless, battery‐free data acquisition. Their ultra‐flexibility allows folding into a sharp crease and conformal integration to flexible and origami structures, bringing further opportunities for UV detection in demanding missions on Earth and in space.

Inequalities for $tgs$-convex functions via some conformable fractional integrals

In this research article, we establish several Hermite-Hadamard type inequalities for tgs-convex functions via conformable fractional integrals and new fractional conformable integral operators.

A novel strategy for site selective spin-labeling to investigate bioactive entities by DNP and EPR spectroscopy

A novel specific spin-labeling strategy for bioactive molecules is presented for eptifibatide (integrilin) an antiplatelet aggregation inhibitor, which derives from the venom of certain rattlesnakes. By specifically labeling the disulfide bridge this molecule becomes accessible for analytical techniques such as Electron Paramagnetic Resonance (EPR) and solid state Dynamic Nuclear Polarization (DNP). The necessary spin-label was synthesized and inserted into the disulfide bridge of eptifibatide via reductive followed by insertion by a double Michael addition under physiological conditions. This procedure is universally applicable for disulfide containing biomolecules and is expected to preserve their tertiary structure with minimal change due to the small size of the label and restoring of the previous disulfide connection. HPLC and MS analysis show the successful introduction of the spin label and EPR spectroscopy confirms its activity. DNP-enhanced solid state NMR experiments show signal enhancement factors of up to 19 in 13C CP MAS experiments which corresponds to time saving factors of up to 361. This clearly shows the high potential of our new spin labeling strategy for the introduction of site selective radical spin labels into biomolecules and biosolids without compromising its conformational integrity for structural investigations employing solid-state DNP or advanced EPR techniques.