Single Constituent Research Articles

A simple method for decellularizing a cell-derived matrix for bone cell cultivation and differentiation

The extracellular matrix regulates cell survival, proliferation, and differentiation. In vitro two-dimensional cell experiments are typically performed on a plastic plate or a substrate of a single extracellular matrix constituent such as collagen or calcium phosphate. As these approaches do not include extracellular matrix proteins or growth factors, they fail to mimic a complex cell microenvironment. The cell-derived matrix is an alternative platform for better representing the in vivo microenvironment in vitro. Standard decellularization of a cell-derived matrix is achieved by combining chemical and physical methods. In this study, we compared the decellularization efficacy of several methods: ammonium hydroxide, sodium dodecyl sulfate (SDS), or Triton X-100 with cold or heat treatment on a matrix of Saos-2 cells. We found that the protocols containing SDS were cytotoxic during recellularization. Heat treatment at 47 °C was not cytotoxic, removed cellular constituents, inactivated alkaline phosphatase activity, and maintained the levels of calcium deposition. Subsequently, we investigated the differentiation efficiency of a direct bone coculture system in the established decellularized Saos-2 matrix, an inorganic matrix of calcium phosphate, and a plastic plate as a control. We found that the decellularized Saos-2 cell matrix obtained by heat treatment at 47 °C enhanced osteoclast differentiation and matrix mineralization better than the inorganic matrix and the control. This simple and low-cost method allows us to create a Saos-2 decellularized matrix that can be used as an in vivo-like support for the growth and differentiation of bone cells.

Production of magnetite-polyvinyl butyral composites using a Nano Spray Dryer

Bio composites as nacre show outstanding mechanical properties which surpasses those of their single constituents. This is due to their complex structure, in which the small building blocks of the hard component are embedded in a softer matrix, thus combining strength and toughness. This combination makes such materials interesting for various applications, e.g. for tooth replacement materials but also for industrial structural materials. Therefore, the interest is to develop scalable processes for the production of artificial composites. In this work a Nano Spray Dryer is used to produce polymer-encapsulated magnetite particles from a magnetite-polymer-suspension. A Design of Experiment study is conducted which identified the suspension composition as the major influencing factor on the product properties. The particles are then warm-compacted and the composite pellets are examined for their mechanical properties and structure. With this method composites with bending strength of 91.2 MPa and Young's modulus of 9.2 GPa were produced.

A deep learning driven pseudospectral PCE based FFT homogenization algorithm for complex microstructures

This work is directed to uncertainty quantification of homogenized effective properties for composite materials with complex, three dimensional microstructure. The uncertainties arise in the material parameters of the single constituents as well as in the fiber volume fraction. They are taken into account by multivariate random variables. Uncertainty quantification is achieved by an efficient surrogate model based on pseudospectral polynomial chaos expansion and artificial neural networks. An artificial neural network is trained on synthetic binary voxelized unit cells of composite materials with uncertain three dimensional microstructures, uncertain linear elastic material parameters and different loading directions. The prediction goals of the artificial neural network are the corresponding effective components of the elasticity tensor, where the labels for training are generated via a fast Fourier transform based numerical homogenization method. The trained artificial neural network is then used as a deterministic solver for a pseudospectral polynomial chaos expansion based surrogate model to achieve the corresponding statistics of the effective properties. Three numerical examples deal with the comparison of the presented method to the literature as well as the application to different microstructures. It is shown, that the proposed method is able to predict central moments of interest while being magnitudes faster to evaluate than traditional approaches.

The solubility product extends the buffering concept to heterotypic biomolecular condensates.

Biomolecular condensates are formed by liquid-liquid phase separation (LLPS) of multivalent molecules. LLPS from a single ("homotypic") constituent is governed by buffering: above a threshold, free monomer concentration is clamped, with all added molecules entering the condensed phase. However, both experiment and theory demonstrate that buffering fails for the concentration dependence of multicomponent ("heterotypic") LLPS. Using network-free stochastic modeling, we demonstrate that LLPS can be described by the solubility product constant (Ksp): the product of free monomer concentrations, accounting for the ideal stoichiometries governed by the valencies, displays a threshold above which additional monomers are funneled into large clusters; this reduces to simple buffering for homotypic systems. The Ksp regulates the composition of the dilute phase for a wide range of valencies and stoichiometries. The role of Ksp is further supported by coarse-grained spatial particle simulations. Thus, the solubility product offers a general formulation for the concentration dependence of LLPS.

Signs of alkylcarbonate formation in water-lean solvents: VLE-based understanding of pKa and pKs effects

Water-lean solvents are solvents for CO2 capture which contain at least one amine and one organic diluent. Carbamate-forming amines in nonaqueous water-lean solvents typically absorb CO2 through the formation of carbamate species. Conversely, tertiary amines in nonaqueous amino-organic mixtures cannot form carbamate nor undergo bicarbonate formation. However, protic organic diluents might take part in an alkylcarbonate formation pathway: in this route, the diluent is deprotonated by the amine, and its conjugate base is then able to react directly with CO2 to form an alkylcarbonate. This is an interesting reaction mechanism, as it offers a possibility for formulating solvents that deviate from the two most common reaction pathways for CO2 absorption (i.e., carbamate and bicarbonate formation). The present study introduces a simple way for evaluating alkylcarbonate-forming water-lean solvents based on the properties of its single constituents, namely the basicity of the amine and the autoprotolysis constant of the organic diluent. Our theoretical framework shows that higher CO2 absorption capacities can be obtained for solvents containing amines with high pKa and diluents with low pKs. We assess both the challenges and possibilities for alkylcarbonate-forming solvents and propose a framework for their development and utilization in the industry.

Associations of fine particulate matter and constituents with pediatric emergency room visits for respiratory diseases in Shanghai, China.

Although ambient fine particulate matter (PM2.5) has been associated with adverse respiratory outcomes in children, few studies have examined PM2.5 constituents with respiratory diseases in children in China. To investigate the associations of short-term exposure to PM2.5 and its constituents with pediatric emergency room visits (ERVs) for respiratory diseases in Shanghai, China. We collected daily concentrations of PM2.5 and its constituents in urban Shanghai from January 1, 2016, to December 31, 2018. Daily pediatric ERVs for four major respiratory diseases, including upper respiratory tract infection, bronchitis, pneumonia, and asthma, were obtained from 66 hospitals in Shanghai during the same period. Associations of exposure to daily PM2.5 and constituents with respiratory ERVs were estimated using the over-dispersed generalized additive models. Short-term exposure to PM2.5 and its constituents were associated with increased pediatric ERVs for respiratory diseases. Specifically, an interquartile range increase in the 3-day average PM2.5 level (31μg/m3) was associated with 1.86% (95%CI: 0.52, 3.22), 1.53% (95%CI: 0.01, 3.08), 1.90% (95%CI: 0.30, 3.52), and 2.67% (95%CI: 0.70, 4.68) increase of upper respiratory tract infection, bronchitis, pneumonia, and asthma ERVs, respectively. As for PM2.5 constituents, we found organic carbon, ammonium, nitrate, selenium, and zinc were associated with higher risk of respiratory ERVs in the single constituent and the constituent-PM2.5 models. Short-term exposure to PM2.5 was associated with increased pediatric ERVs for respiratory diseases. Constituents related to anthropogenic combustion and traffic might be the dominant contributors of the observed associations.

A Mixed Numerical-Experimental Method to Characterize Metal-Polymer Interfaces for Crash Applications

Metallic (M) and polymer (P) materials as layered hybrid metal-polymer-metal (MPM) sandwiches offer a wide range of applications by combining the advantages of both material classes. The interfaces between the materials have a considerable impact on the resulting mechanical properties of the composite and its structural performance. Besides the fact that the experimental methods to determine the properties of the single constituents are well established, the characterization of interface failure behavior between dissimilar materials is very challenging. In this study, a mixed numerical–experimental approach for the determination of the mode I energy release rate is investigated. Using the example of an interface between a steel (St) and a thermoplastic polyolefin (PP/PE), the process of specimen development, experimental parameter determination, and numerical calibration is presented. A modified design of the Double Cantilever Beam (DCB) is utilized to characterize the interlaminar properties and a tailored experimental setup is presented. For this, an inverse calibration method is used by employing numerical studies using cohesive elements and the explicit solver of LS-DYNA based on the force-displacement and crack propagation results.

A Systematic Review of the Behavioral Responses by Stored-Product Arthropods to Individual or Blends of Microbially Produced Volatile Cues.

Microbes are ubiquitous and play important ecological roles in a variety of habitats. While research has been largely focused on arthropods and microbes separately in the post-harvest supply chain, less attention has been paid to their interactions with each other. Up to this point, there has been no attempt to systematically describe the patterns of behavioral responses by stored-product insects to microbially produced volatile organic compounds (MVOCs). Thus, our aims were to evaluate whether stored-product arthropods were primarily and significantly attracted, repelled, or had a net neutral effect (e.g., unaffected or mixed) by MVOCs presented as (1) complex headspace blends or (2) single constituents and known mixtures. In total, we found 43 articles that contained 384 sets of tests with different combinations of methodology and/or qualitative findings, describing the behavioral responses of 24 stored-product arthropod species from two classes, four orders, and 14 families to 58 individual microbial compounds and the complex headspace blends from at least 78 microbial taxa. A total of five and four stored-product arthropod species were significantly attracted and repelled by MVOCs across odor sources, respectively, while 13 were unaffected or exhibited mixed effects. We summarize the biases in the literature, including that the majority of tests have occurred in the laboratory with a limited subset of methodology and has largely only assessed the preference of adult arthropods. Finally, we identify foundational hypotheses for the roles that MVOCs play for stored-product arthropods as well as gaps in research and future directions, while highlighting that the behavioral responses to MVOCs are complex, context-, and taxon-dependent, which warrants further investigation.

Fiber-reinforced composites: nonlinear elasticity and beyond

A fiber-reinforced material comprised of a soft polymeric matrix reinforced with polymeric filaments is often modeled as an equivalent anisotropic nonlinearly elastic solid. Although the response of a single constituent polymeric material can be modeled by nonlinear thermo-elasticity over a large range of deformations and temperatures, there can be conditions requiring a theory that extends the range of application to account for other features, such as nonlinear viscoelasticity and an evolving microstructure due to a combination of mechanical and nonmechanical factors. In a multi-constituent fiber-reinforced material these effects can be expected to occur with different initial triggering and ongoing potency in the separate polymer matrix and fiber constituents. This paper summarizes a number of constitutive models for fiber-reinforced materials that include these features, discusses the connection of these models to a nonlinearly elastic scaffold, provides a framework for the incorporation of these features into the constitutive theory for an equivalent general simple solid, and shows how certain terms in the mathematical structure can be associated with the matrix constituent while other terms can associated with the fibrous constituent.

High Power Cathodes from Poly(2,2,6,6-Tetramethyl-1-Piperidinyloxy Methacrylate)/Li(NixMnyCoz)O2 Hybrid Composites

Lithium-ion batteries are today among the most efficient devices for electrochemical energy storage. However, an improvement of their performance is required to address the challenges of modern grid management, portable technology, and electric mobility. One of the most important limitations to solve is the slow kinetics of redox reactions associated to inorganic cathodic materials, directly impacting on the charging time and the power characteristics of the cells. In sharp contrast, redox polymers such as poly(2,2,6,6-tetramethyl-1-piperidinyloxy methacrylate) (PTMA) exhibit fast redox reaction kinetics and pseudocapacitors characteristics. In this contribution, we have hybridized high energy Li(NixMnyCoz)O2 mixed oxides (NMC) with PTMA. In this hybrid cathode configuration, the higher voltage NMC (ca. 3.7 V vs. Li/Li+) is able to transfer its energy to the lower voltage PTMA (3.6 V vs. Li/Li+) improving the discharge power performances and allowing high power cathodes to be obtained. However, the NMC-PTMA hybrid cathodes show an important capacity fading. Our investigations indicate the presence of an interface degradation reaction between NMC and PTMA transforming NMC into an electrochemically dead material. Moreover, the aqueous process used here to prepare the cathode is also shown to enable the degradation of NMC. Indeed, once NMC is immersed in water, alkaline surface species dissolve, increasing the pH of the slurry, and corroding the aluminum current collector. Additionally, the NMC surface is altered due to delithiation which enables the interface degradation reaction to take place. This reaction by surface passivation of NMC particles did not succeed in preventing the interfacial degradation. Degradation was, however, notably decreased when Li(Ni0.8Mn0.1Co0.1)O2 NMC was used and even further when alumina-coated Li(Ni0.8Mn0.1Co0.1)O2 NMC was considered. For the latter at a 20C discharge rate, the hybrids presented higher power performances compared to the single constituents, clearly emphasizing the benefits of the hybrid cathode concept.

Comparing the efficacy of γ- and electron-irradiation of PBMCs to promote secretion of paracrine, regenerative factors

Cell-free secretomes represent a promising new therapeutic avenue in regenerative medicine, and γ-irradiation of human peripheral blood mononuclear cells (PBMCs) has been shown to promote the release of paracrine factors with high regenerative potential. Recently, the use of alternative irradiation sources, such as artificially generated β- or electron-irradiation, is encouraged by authorities. Since the effect of the less hazardous electron-radiation on the production and functions of paracrine factors has not been tested so far, we compared the effects of γ- and electron-irradiation on PBMCs and determined the efficacy of both radiation sources for producing regenerative secretomes. Exposure to 60 Gy γ-rays from a radioactive nuclide and 60 Gy electron-irradiation provided by a linear accelerator comparably induced cell death and DNA damage. The transcriptional landscapes of PBMCs exposed to either radiation source shared a high degree of similarity. Secretion patterns of proteins, lipids, and extracellular vesicles displayed similar profiles after γ- and electron-irradiation. Lastly, we detected comparable biological activities in functional assays reflecting the regenerative potential of the secretomes. Taken together, we were able to demonstrate that electron-irradiation is an effective, alternative radiation source for producing therapeutic, cell-free secretomes. Our study paves the way for future clinical trials employing secretomes generated with electron-irradiation in tissue-regenerative medicine.

The influence of AA and AB stacking on the ground state magnetic properties of triangular bilayer graphene quantum dots

Using the tight-binding model, we have studied the impact of AA and AB (Bernal) stacking on eigenstates and eigenvalues of bilayer graphene nanoflakes with triangular geometry. The zero eigenvalues of any single layer nanoflake will be doubled through AB stacking. However, we have noticed that in AA stacking, the eigenvalues are simply achievable through merging two sets of single layer eigenvalues that once added to and once subtracted from inter-layer hopping. Besides, in a single layer within some strict zero energies, the AB stacking still maintains them sublattice-polarized. However, the AA-stacking neglects the sublattice-polarized character of zero states in single layers constituent. Next, we consider onsite electron–electron interaction utilizing single-orbital Hubbard model to show how the different stacking affects the onset of the ground state magnetization in bilayer quantum dots with different stackings. Especially, in AA stacking bilayer, the system always needs a nonzero onsite interaction strength (Uc) to be magnetized.

Comprehensive genetic analysis of adhesin proteins and their role in virulence of Candida albicans.

Candida albicans is a microbial fungus that exists as a commensal member of the human microbiome and an opportunistic pathogen. Cell surface-associated adhesin proteins play a crucial role in C. albicans' ability to undergo cellular morphogenesis, develop robust biofilms, colonize, and cause infection in a host. However, a comprehensive analysis of the role and relationships between these adhesins has not been explored. We previously established a CRISPR-based platform for efficient generation of single- and double-gene deletions in C. albicans, which was used to construct a library of 144 mutants, comprising 12 unique adhesin genes deleted singly, and every possible combination of double deletions. Here, we exploit this adhesin mutant library to explore the role of adhesin proteins in C. albicans virulence. We perform a comprehensive, high-throughput screen of this library, using Caenorhabditis elegans as a simplified model host system, which identified mutants critical for virulence and significant genetic interactions. We perform follow-up analysis to assess the ability of high- and low-virulence strains to undergo cellular morphogenesis and form biofilms in vitro, as well as to colonize the C. elegans host. We further perform genetic interaction analysis to identify novel significant negative genetic interactions between adhesin mutants, whereby combinatorial perturbation of these genes significantly impairs virulence, more than expected based on virulence of the single mutant constituent strains. Together, this study yields important new insight into the role of adhesins, singly and in combinations, in mediating diverse facets of virulence of this critical fungal pathogen.

Saraswati Panchak – A Novel Herbal Combination for Mental Health

Herbal medicines have a history of long therapeutic use and are still serving a lot of the health needs of a big population of the world. However, the quality control still remains a challenge because of the variation of chemical constituents involved. There are numerous compounds in herbal drugs that are in complex matrices in which no single active constituent is responsible for the overall efficacy. This creates a challenge in establishing quality control standards and standardization of finished herbal drugs. Saraswati Panchak is a novel combination given by Pandit Shri Ram Sharma Acharya for mental health. In this study, components of this novel herbal combination were explained for its potential utility in mental illness. In addition, the study also detailed how Saraswati Panchak Churna was converted into tablet form to increase the shelf life, make it easy to dispense, for dose fixation, etc. The tablet was subjected to organoleptic analysis and physico-chemical analysis to establish its efficacy. After performing complete analysis it was found that all the parameters are within the range. The coarse powder of these herbs may be used as havan samagri in brain related disorders because of the presence of nootropic herbs.

A deep learning driven uncertain full‐field homogenization method

AbstractThis work is directed to uncertainty quantification of homogenized effective properties of composite materials with a complex, three dimensional microstructure. The uncertainties arise in the material parameters of the single constituents as well as in the fiber volume fraction. They are taken into account by multivariate random variables. Uncertainty quantification is carried out by an efficient surrogate model based on pseudospectral polynomial chaos expansion and artificial neural networks, which is trained on a fast Fourier transformation based homogenization method. The numerical example deals with the comparison of the presented method to Monte Carlo‐type simulation for uncertain homogenization of spherical inclusions in a matrix material.

Biodegradable FeWOx nanoparticles for CT/MR imaging-guided synergistic photothermal, photodynamic, and chemodynamic therapy.

The development of a simple and effective single constituent multifunctional nanotheranostic platform producing a multimodality diagnostic signal and curing effect is still a challenge. Herein, we synthesized simple and biodegradable FeWOx ternary oxide nanoparticles and modified their surface with RGD-PEG-NH2 (FeWOx-PEG-RGD NPs), whereby resulting NPs possessed a (T2/T1) switchable MRI/CT dual-modal imaging ability and synergistic photothermal therapy (PTT)/photodynamic therapy (PDT)/chemodynamic therapy (CDT) capacity. We showed that FeWOx-PEG-RGD NPs enabled tumor accumulation under a magnetic field drive and RGD-mediated tumor penetration and implemented PTT/PDT treatment under 980 nm laser irradiation. In an acidic tumor microenvironment (TME) with a high hydrogen peroxide (H2O2) expression, NPs degraded to release Fe3+ and Fe2+, triggering a Fenton reaction to generate ˙OH for CDT. The released Fe2+ led to T2/T1 signal conversion for tracing cancer therapy, while the high X-ray attenuation coefficient of W also made it a good CT contrast agent for guided therapy. Thus, the structurally simple FeWOx-PEG-RGD was capable of mediating (T2/T1-weighted) MR/CT two modal imaging-guided PTT/PDT/CDT synergic therapy with a high accuracy and superb anticancer efficiency. The simple, degradable, rapid-clearance, and multifunctional FeWOx-PEG-RGD NPs provide a novel, promising, and versatile nanotheranostic platform.

Some notes on postverbal subjects in declarative (and other non-wh-) sentences

This paper discusses the syntactic and interpretative properties of sentences with immediately postverbal subjects (i.e. VSX constituent order) in European Portuguese. Two types of VSX word order are described and analyzed within the generative framework. One type in which, according to the proposed analysis, the verb and the postverbal subject stay inside the IP space and one type in which the verb or both the verb and the subject move to positions in the CP space, i.e. the sentential left periphery (Rizzi 1997, 2004, and subsequent cartographic approaches). The ‘IP type’ VSX sentences have a thetic, wide focus interpretation with no single constituent assigned any type of informational highlighting (Kuroda 1972, 2005). It is suggested that theticity is a kind of sensory (especially visual) evidentiality. This motivates the presence of an Evidential head in the functional structure of the IP, which is targeted by verb movement, deriving the postverbal position of the subject. Sentences with the ‘CP type’ VSX order do not constitute a homogeneous group, but share an evaluative import, generally conveying criticism. Under the proposed analysis, those bearing focus on the subject are derived by movement of the subject DP to Spec,FocusP (Rizzi 1997, 2004), which gives it the contrastive interpretation, and movement of the verb to a higher Evaluative head in the sentential left periphery (Ambar 1999, Corr 2016). Inverted conditionals (Iatridou and Embick 1994) and coordinate non-degree exclamatives (REFERENCE) share verb movement to Evaluative with subject-focus VSX sentences, but do not display contrastive or other highlighting of the subject, which signals that FocusP plays no role in their derivations.

Stratum corneum levels of inflammatory mediators and natural moisturizing factor in patch test reactions to thiurams and fragrances and their possible role in discrimination between irritant and allergic reactions to hapten mixtures.

Patch test (PT) reactions to thiuram mix (TM) and fragrance mix (FM) I or II without concomitant reactions to their single constituents are potentially caused by the irritant properties of the mixes. Comparing inflammatory profiles of PT reactions to TM, FM I, FM II, and their constituents and assessing their potential in discrimination of irritant and allergic reactions. Levels of 14 cytokines and natural moisturizing factor (NMF) were determined in stratum corneum samples collected from PT reactions to TM, FM I or II, their constituents, and petrolatum (pet.) control sites in 36 individuals. Levels of interleukin (IL)-16, chemokine (CXC motif) ligand (CXCL) 8, CXCL10, chemokine (CC motif) ligand (CCL) 17, and CCL22 were significantly increased in reactions (+, ++) to thiurams and fragrances compared to their petrolatum. controls, except for PT reactions to FM I/II with negative breakdown testing in which, however, decreased levels of NMF were observed. In doubtful reactions to FM I/II with negative breakdown testing, NMF was significantly lower than in petrolatum controls. PT reactions to thiurams and fragrances indicate a Th2-skewed inflammation. The inflammatory profiles suggest that weak or doubtful FM I/II reactions without accompanying reaction to a constituent were irritant. IL-16 might be suitable to distinguish irritant from allergic reaction.

STANDARDIZATION, QUALITY CONTROL AND ANTIMICROBIAL STUDY OF ARKA TAILA: AN AYURVEDA FORMULATION

Herbal medicines have a huge therapeutic history for a long period of time and still serving many more health requirements in the worldwide. Although there is a still very huge challenge in its quality control and quality assurance; because of the high variability of chemical compounds present in it. Herbal drugs, singularly and in combinations, contain numerous complex matrices in which not a single active constituent is responsible for the overall efficacy. This creates a challenge in establishing quality control standards and standardization of finished herbal drugs. Many drugs in Ayurveda describe regarding treatment of vicharchika (Atopic dermatitis). Arka taila is one of them. In this study Arka taila was subjected to study organoleptic analysis, phytochemical analysis, and qualitative analysis to detect the presence of various functional groups, and thin layer chromatography (TLC) examination by optimizing the solvent systems. The investigation revealed the density, Refractive index, Saponification value, Rancidity, Total fatty matter and Iodine value mainly and also subjected to in vitro antibacterial assay against human pathogens MTCC No.39-Klebsiella aerogenes, MTCC No.10239- Escherichia coli, MTCC No.1034- Pseudomonas aeruginosa, MTCC No.6908- Staphylococcus aureus by Mueller hinton agar well diffusion method. The results of this study suggest that Arka taila can be used as an antibacterial agent against infections caused by Klebsiella aerogenes, Escherichia coli, Staphylococcus aureus.

Book Parts. Ed. by Dennis Duncan and Adam Smyth

Book Parts is an attempt to think and write about the book through the mechanism of the blazon’, write editors Dennis Duncan and Adam Smyth in their introduction to this architectonic book. Duncan is a former Munby Fellow in Bibliography at Cambridge and is currently engaged in writing a history of the book index; Smyth’s interest in literary and material forms has most recently found expression in the new journal Inscription which experiments with design and typography (the first volume, published in Autumn 2020, is printed from both ends and has a hole drilled through the centre). Book Parts includes twenty-two chapters, each of which takes a single constituent part of the physical book as its subject, arranged in the order in which they are (theoretically) encountered. The chapters are short and sharp, and together cover European literature from antiquity to the digital age. It is undesirable to summarize twenty-two chapters in a book review, nor is it necessary when reviewing such a tightly edited volume. There are several threads of commonality—paratextual power struggles, historical emergence and decline—which mean that Book Parts retains a sense of cohesion even for the casual chapter hopper. This, then, is the book anatomized but not dissected.