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Ionic liquids have generated interest in applications as lubricants and as additives to conventional lubricants due to their unique physical properties. In these applications, the liquid thin film can be subjected simultaneously to extremely high shear and loads in addition to nanoconfinement effects. Here, we use molecular dynamics simulations with a coarse grained model to study a nanometric film of an ionic liquid confined between two planar solid surfaces both at equilibrium and at several shear rates. The strength of the interaction between the solid surface and the ions was changed by simulating three different surfaces with enhanced interactions with different ions. The increase of the interaction with either the cation or the anion leads to the formation of a solid-like layer that moves alongside the substrates, but this layer can exhibit different structures and stability. An increase in interaction with the high symmetry anion produces a more regular structure that is more resistant to the effects of shear and viscous heating. Two definitions were proposed and used for the calculation of the viscosity: a local definition based on microscopic characteristics of the liquid and an engineering definition based on the forces measured at the solid surfaces, with the former displaying a correlation with the layered structure induced by the surfaces. Because of the shear thinning behavior of the ionic liquids as well as the temperature rise brought on by viscous heating, both the engineering and the local viscosities decrease as the shear rate increases., 32 pages, 8 figures

Strong ionic interactions, as well as the consequent correlations between cation and anion dynamics, give ionic liquids various physical features that set them apart from ordinary organic solvents. In particular, they result in larger viscosities and larger densities than mixtures of neutral compounds with similar molecular structures. However, both the direct effect of electrostatic interactions and the increase of liquid density contribute to the high viscosity and so far no experimental or computational work enabled a clear quantification of those effects. Also, the effects over the shear thinning behavior, which may have important consequences for application as lubricants, were not considered yet. Here, these questions were tackled by performing non-equilibrium molecular dynamics (NEMD) simulations changing both the strength of ionic interactions and liquid density at several shear rates using a coarse grained model. The relative dielectric constant was adjusted to reproduce viscosity data from all-atoms simulations on both zero shear and high shear conditions. Elimination of ionic interactions results in a reduction of density and zero shear viscosity and also delays the beginning of shear thinning to higher shear rates. Restoring density to the ionic liquid's value only partially reverses the alterations. Correlations of the non-newtonian behavior and changes in the intermolecular structure and contact lifetimes were also explored.

Two polymerizable ionic liquids (or monomeric ionic liquids, mILs) namely 1-butyl-3-methylimidazolium and choline acrylates ([C4mim]A and ChA, respectively) were synthesized using the modified Fukumoto method from corresponding chlorides. The chemical structure of the prepared mILs was confirmed with FTIR and NMR study. Investigation of the thermal properties with DSC demonstrates that both mILs have a Tg temperature of about 180 K and a melting point around 310 K. It was shown that the temperature dependence of FTIR confirm the Tg to be below 200. Both mILs exhibited non-Newtonian shear thinning rheological behavior at shear rates >4 s−1. It was shown that [C4mim]A is able to dissolve bacterial cellulose (BC) leading to a decrease in its degree of polymerization and recrystallisation upon regeneration with water; although in the ChA, the crystalline structure and nanofibrous morphology of BC was preserved. It was demonstrated that the thixotropic and rheological properties of cellulose dispersion in ChA at room temperature makes this system a prospective ink for 3D printing with subsequent UV-curing. The 3D printed filaments based on ChA, containing 2 wt% of BC, and 1% of N,N′-methylenebisacrylamide after radical polymerization induced with 1% 2-hydroxy-2-methylpropiophenone, demonstrated Young’s modulus 7.1 ± 1.0 MPa with 1.2 ± 0.1 MPa and 40 ± 5% of strength and ultimate elongation, respectively.

Deep eutectic solvents (DESs) are similar to ionic liquids (IL) in terms of physicochemical properties and technical uses. In ILs, far-infrared (FIR) spectroscopy has been utilized to reveal ionic interactions and even to produce a signature of the strengthening of the cation-anion hydrogen bond. However, for the situation of the DES, where the mixing of a salt and a molecular species makes the interplay between multiple intermolecular interactions even more complex, a full investigation of FIR spectra is still absent. In this work, the FIR spectrum of the DES, often referred to as ethaline, which is a 1:2 mixture of choline chloride and ethylene glycol, is calculated using classical molecular dynamics (MD) simulations and compared to experimental data. To explore the induced dipole effect on the computed FIR spectrum, MD simulations were run with both nonpolarizable and polarizable models. The calculation satisfactorily reproduces the position of the peak at ∼110 cm

Objective: To investigate the association between insulin resistance markers and periodontitis in adolescents, analyzing confounder variables and the adiposity as a mediator. Methods: This is population-based study is representative of adolescents aged 17–18 years from public schools in São Luís, Brazil (n = 405). Insulin resistance was assessed using the Model of Assessment of the Homeostasis of the Insulin Resistance Index (HOMA-IR) and its percussor triglycerides/HDL-cholesterol ratio (TG/HDL-c). The outcome was Initial Periodontitis, a latent variable estimated by the common variance shared among bleeding on probing, probing depth ≥ 4 mm, and clinical attachment loss ≥ 4 mm. The association between insulin resistance and Initial Periodontitis was modeled via pathways triggered by socioeconomic status, smoking, alcohol, and Adiposity, using structural equation modeling. Results: Higher TG/HDL-c was directly associated with higher Initial Periodontitis (standardized coefficient [SC] = 0.130, p < 0.001). HOMA-IR was not associated with periodontal outcome (SC = 0.023, p = 0.075), but it was with Adiposity (SC = 0.495, p < 0.001). Higher TG/HDL-c was associated with Adiposity (SC = 0.202, p < 0.001). Conclusion: The insulin resistance markers were associated with early signs of periodontal breakdown among adolescents, suggesting a possible relationship between diabetes and periodontitis commences early in life.

Destaques: O trabalho em times distribuídos significa que ele não leva em consideração a localização e utiliza uma moderna comunicação e tecnologia computacional. Em termos de implicações gerenciais, o impacto da proximidade percebida pode agregar valor ao teletrabalho em times distribuídos. Os times distribuídos (ou times remotos) são aqueles nos quais os membros estão dispersos geograficamente. Alguns dos conflitos apresentados podem ser gerados pelo distanciamento da equipe do projeto em que estão trabalhando. Objetivo: Analisar o trabalho em times distribuídos via uso de tecnologias de informação e comunicação em empresas de diferentes setores. Desenho/Metodologia/Abordagem: No artigo, foram utilizadas pesquisas bibliográfica e de campo, com uma abordagem qualitativa. A pesquisa de campo foi baseada pelo método de estudos de casos múltiplos em setores como de educação, tecnologia, bebidas e gases industriais e medicinais, com entrevistados de formação superior. Além disso, foram utilizadas a observação não-participante e a entrevista semiestruturada auxiliada por roteiro de perguntas (abertas e fechadas), e as técnicas de amostragem não probabilística. Resultados: Os resultados indicam desafios, como o idioma, fuso horário, cultura, comprometimento, formação e confiança. Não houve concentração em um dos desafios, mas o idioma foi o único citado duas vezes pelos entrevistados. Limitações da investigação: O principal limite da pesquisa quanto ao método e aos resultados foi o número de empresas investigadas. Implicações práticas: Identificação de conflitos no trabalho em times distribuídos e dos benefícios das tecnologias de informação e comunicação (TICs) na sua redução. Originalidade/valor: Com a pandemia da COVID-19, os pesquisadores iniciam seus estudos em trabalhos com times distribuídos, mas o tema já é discutido há bastante tempo. A pesquisa foi feita em diferentes setores, com a análise de uma perspectiva brasileira dos problemas existentes entre os trabalhadores brasileiros e entre esses e outros colaboradores no exterior não foi identificado.

SummaryUnderstanding the underlying mechanisms of migration and metastasis is a key focus of cancer research. There is an urgent need to developin vitro3D tumor models that can mimic physiological cell-cell and cell-extracellular matrix interactions, with high reproducibility and that are suitable for high throughput (HTP) drug screening. Here, we developed a HTP 3D bioprinted migration model using a bespoke drop-on-demand bioprinting platform. This HTP platform coupled with tunable hydrogel systems enables (i) the rapid encapsulation of cancer cells withinin vivotumor mimicking matrices, (ii)in situand real-time measurement of cell movement, (iii) detailed molecular analysis for the study of mechanisms underlying cell migration and invasion, and (iv) the identification of novel therapeutic options. This work demonstrates that this HTP 3D bioprinted cell migration platform has broad applications across quantitative cell and cancer biology as well as drug screening.

O biotipo satisfatório para a produção de carne são animais com estrutura óssea, musculatura e comprimento corporal desenvolvidos, estas características auxiliam no potencial para deposição de músculos. A avaliação morfológica dos bovinos de corte contribui na seleção de animais mais produtivos ou na formação de lotes em função do sistema de produção. A seleção de animais para as características visuais de estrutura corporal, precocidade e musculosidade é uma importante estratégia na identificação dos bovinos com rendimento desejável para produção de carne, visto que essas características morfológicas estão relacionadas para a melhorias no desempenho. A estrutura corporal refere-se a forma física, permite o estimar a capacidade de desenvolvimento dos animais. A precocidade remete a habilidade do bovino em depositar gordura e aponta animais mais precoces para terminação. A musculosidade indica desenvolvimento da massa muscular e demonstra quais os indivíduos com maior potencial para ganho de peso. Objetiva-se construir um referencial teórico sobre avaliação visual de bovinos de corte. As avaliações morfológicas apresentam informações que promovem a seleção de bovinos com maior rendimento de ganho, visando incremento dos índices produtivos.

A bovinocultura de corte brasileira apresenta enorme potencial de produção de proteína animal, em função das características climáticas e extensão territorial. A maior parte dos bovinos são criados a pasto, sendo as forrageiras a principal fonte de alimentação para ruminantes. A época das águas proporciona condições para o desenvolvimento e boa composição bromatológica das forrageiras. No entanto, bovinos consumindo apenas forragem mesmo na época das águas podem não ter suas exigências nutricionais atendidas para elevado desempenho, e o uso de suplementos pode gerar incrementos de produtividade. Visando maximizar o desempenho animal a suplementação concentrada como estratégia alimentar é de suma relevância para que os bovinos possam expressar todo o seu potencial produtivo. O objetivo do trabalho é abordar os aspectos gerias da suplementação de bovinos de corte a pasto na época das águas. Dados da literatura apontam que a suplementação de bovinos a pasto no período das águas proporciona maior ganho de peso e produtividade. O ajuste da suplementação em função da composição química e oferta de forragem no período das águas pode resultar em maior eficiência de produção na pecuária de corte.

The low melting point of room temperature ionic liquids is usually explained in terms of the presence of bulky, low symmetry and flexible ions, with the first two factors related to the lattice energy while an entropic effect is attributed to the latter. By means of molecular dynamics simulations, the melting points of 1-ethyl-3-methylimidazolium hexafluorophosphate and 1-decyl-3-methyl-imidazolium hexafluorophosphate were determined and the effect of the molecular flexibility over the melting point was explicitly computed by restraining the rotation of dihedral angles in both the solid and the liquid phase. The rotational flexibility over the bond between the ring and the alkyl chain affects the relative ordering of the anions around the cations and results in substantial effects over both the enthalpy and the entropy of melting. For the other dihedral angles of the alkyl group, the contributions are predominantly entropic and an alternating behavior was found. The flexibility of some dihedral angles has negligible effects on the melting point, while others can lead to differences in the melting point as large as 20 K. This alternating behavior is rationalized by the different probabilities of conformation defects in the crystal., Article published in Journal of Chemical Physics in 2020. Contains 34 pages of the main article plus 23 pages of supporting information

Several calorimetric measurements have shown that 1-ethyl-3-methylimidazolium dicyanamide, [C2C1im][N(CN)2], is a glass-forming liquid, even though it is a low-viscous liquid at room temperature. Here we found slow crystallization during cooling of [C2C1im][N(CN)2] along Raman spectroscopy measurements. The low-frequency range of the Raman spectrum shows that the same crystalline phase is obtained at 210 K either by cooling or by reheating the glass (cold-crystallization). Another crystalline phase is formed at ca. 260 K just prior the melting at 270 K. X-ray diffraction and calorimetric measurements confirm that there are two crystalline phases of [C2C1im][N(CN)2]. The Raman spectra indicate that polymorphism is related to [C2C1im]+ with the ethyl chain on the plane of the imidazolium ring (the low-temperature crystal) or non-planar (the high-temperature crystal). The structural reason for the glass-forming ability of [C2C1im][N(CN)2], despite of the relatively simple molecular structures of the ions, was pursued by quantum chemistry calculations and molecular dynamics (MD) simulations. Density functional theory (DFT) calculations were performed for ionic pairs in order to draw free energy surfaces of the anion around the cation. The MD simulations using a polarizable model provided maps of occurrence of anions around cations. Both the quantum and classical calculations suggest that the delocalization of preferred positions of the anion around the cation, which adopts different conformations of the ethyl chain, is on the origin of the crystallization being hampered during cooling and the resulting glass-forming ability of [C2C1im][N(CN)2]., Author revised version of the paper published in J. Phys. Chem B in 2019. File contains 31 pages with 7 figures plus 8 pages of supporting information with 7 figures

Binary mixtures of the ionic liquids 1-ethyl-3-methylimidazolium dicyanamide and tributyl(methyl)ammonium dicyanamide, [C2C1im]x[N4441](1-x)[N(CN)2], are studied by means of their excess properties (enthalpy and volume), their viscosity, and their Raman spectra. The mixtures exhibit positive values of excess volume VE and excess enthalpy HE. The plot of the logarithm of viscosity as a function of composition is consistent with the finding HE > 0. The excess thermodynamic properties of the ionic liquid mixtures are compared with well-known results for binary mixtures of (high-temperature) molten salts. The asymmetry of the curve HE versus composition is reproduced by considering the volumetric fraction of the [C2C1im]x[N4441](1-x)[N(CN)2] mixtures according to basic results of the theory of regular solutions. The anion totally symmetric stretching mode νs(C≡N) was used to probe the local environment around the anion in a Raman spectroscopy investigation of the [C2C1im]x[N4441](1-x)[N(CN)2] mixtures as a function of the composition. The Raman band shape (peak frequency and bandwidth) of the νs(C≡N) mode changes as expected from the fluctuation of concentration around the probe oscillator according to models for vibrational spectroscopy of liquid mixtures. This thermodynamic and spectroscopic study leads to the classification of the [C2C1im]x[N4441](1-x)[N(CN)2] mixture as a regular solution. The application of the regular solution equation for HE to other ionic liquid binary mixtures is discussed.

The Raman band belonging to the totally symmetric stretching mode of the [BF4]− anion, νs(BF4), in 1-alkyl-3-methylimidazolium ionic liquids, [CnC1im][BF4], n = 4, 6, and 8, has been measured under high pressure using a diamond anvil cell. The pressure dependence of νs(BF4) frequency up to 2.0 GPa is converted to a function of density using high pressure extrapolations of equations of states as discussed in previous works. The density induced shift of the νs(BF4) frequency was calculated by a perturbed hard-sphere model by considering the probe oscillator as a pseudo-diatomic molecule. In contrast to previous findings for the stretching mode of [PF6]− in [CnC1im][PF6] ionic liquids, for which the calculation considered only the repulsive short-range forces, in the case of [CnC1im][BF4] the calculation indicates the role played by the attractive forces on the νs(BF4) frequency shift.

Poly(ionic liquid)s are an interesting class of compounds because of their unique chemical and physical properties gathering the characteristics of ionic liquids and polymers. Pressure and temperature have been demonstrated to be alternative parameters to obtain polymers from monomeric species using only physical tools. In this work, we investigate the reaction under high pressure and room temperature of the ionic liquid 1-allyl-3-methylimidazolium iodide by using the diamond anvil cell technique in combination with synchrotron X-ray diffraction and electronic and vibrational spectroscopies. The results indicate a chemical reaction happening through the terminal double bond of the allyl group both in crystalline and glassy phases with the onset of the reaction around ∼7 GPa. Vibrational spectra present evidence for an oligomerization reaction in both the phases. The reaction occurring both in glassy and crystal phases indicates a mechanism not driven by collective motions and likely related to local topological arrangements. The results presented herein extend our understanding of ionic liquid instability boundaries under high pressure and contribute to the development of alternative synthetic routes to achieve poly(ionic liquids).

To assess the prevalence of temporomandibular disorder (TMD) in adolescents and estimate possible associations with poverty.A cross-sectional study nested within a prospective birth cohort study conducted in São Luís, Maranhão, Brazil.2,412 adolescents aged 18-19 years.The presence of TMD, classified according to the Fonseca Anamnestic Index, was used as the outcome. The following explanatory variables were assessed: gender, household head, paved/asphalted street, piped water, and socioeconomic background, based on the Brazilian Association of Market Research criteria and the poverty income ratio (PIR). Logistic regression analysis was performed with the estimation of odds ratios (OR) and 95% confidence intervals.TMD was common (51.4%) and was associated with poverty, as it was more frequent among adolescents from social classes D-E (OR=2.60; 95% CI: 1.48-4.55) and C (OR=1.82; 95% CI: 1.12-2.99) compared to A/B, and among poor adolescents using the PIR (OR=1.50; 95% CI: 1.02-2.33).The prevalence of TMD in socioeconomically disadvantaged adolescents in São Luís is high, and these data allow the early identification of at-risk groups. We recommend carrying out other population-based studies, using diagnostic strategies with greater accuracy.

In vitro three-dimensional (3D) cell models have been accepted to better recapitulate aspects of in vivo organ environment than 2D cell culture. Currently, the production of these complex in vitro 3D cell models with multiple cell types and microenvironments remains challenging and prone to human error. Here we report a versatile bioink comprised of a 4-arm PEG based polymer with distal maleimide derivatives as the main ink component and a bis-thiol species as the activator that crosslinks the polymer to form the hydrogel in less than a second. The rapid gelation makes the polymer system compatible with 3D bioprinting. The ink is combined with a drop-on-demand 3D bioprinting platform consisting of eight independently addressable nozzles and high-throughput printing logic for creating complex 3D cell culture models. The combination of multiple nozzles and fast printing logic enables the rapid preparation of many complex 3D structures comprising multiple hydrogel environments in the one structure in a standard 96-well plate format. The platform compatibility for biological applications was validated using pancreatic ductal adenocarcinoma cancer (PDAC) cells with their phenotypic responses controlled by tuning the hydrogel microenvironment.

The effect of the shear rate on the viscosity and the structure of 1-ethyl-3-methylimidazolium based ionic liquids with three different anions (tetrafluoroborate, dicyanamide, and bis(trifluoromethylsulfonyl)imide) was studied by means of reverse non-equilibrium molecular dynamics (RNEMD) simulations using a polarizable force field. The three liquids display a Newtonian plateau followed by a shear thinning regime at shear rates of the order of GHz. Even though the main features of the liquid structure remains under shear, systematic changes were noticed at the GHz rates, with coordination shells becoming more diffuse as noticed by the reduction in the difference between consecutive maxima and minima in the radial distribution function. Interestingly, these structural changes with the shear rate can be precisely fitted using the Carreau equation, which is a well-known expression for the shear rate dependence of the viscosity. The fitting parameters for different distributions can be used to explain qualitatively the shear thinning behavior of these liquids. In the GHz range, the cations and, in a minor extension, some anions, tend to assume preferentially a parallel orientation with the flux, which contributes to the shear thinning behavior and may have consequences for adhesion in applications as lubricants.

The structure and dynamics of two ionic liquids based on imidazolium cations with the common anion dicyanamide, [N(CN)2]-, were studied and compared: one with an aromatic side chain, 1-benzyl-3-methylimidazolium dicyanamide [BzC1Im][N(CN)2], and another with a normal alkyl chain, 1-n-heptyl-3-methylimidazolium dicyanamide [C7C1Im][N(CN)2]. We use classical molecular dynamics (MD) simulations in order to unveil subtle structural differences between these two systems. The collective dynamics were analyzed by considering the spectra of the mass current correlation functions, which were analyzed within the framework of the Zwanzig-Mori formalism. This allowed to compare the effect of aromatic or non-aromatic substituents on the high-frequency collective dynamics and its relationship to a low-frequency transport property such as viscosity. It is found that even though the aromatic-substituted system is a denser and more viscous liquid, the high-frequency dynamics at finite momentum transfers and frequencies, i.e. within the length and timescales of the intermediate-range order (IRO), is only slightly altered. In the low-wavevector limit, however, there are significant differences in the vibrational density of states and viscosity. The scenario put forward by the MD simulations is that even though the role of ionic packing dominates over specific interactions, the different structural motifs within the IRO range imply signatures on the macroscopic dynamics of aromatic and aliphatic substituted imidazolium ionic liquids.

To analyze the association between systemic inflammatory burden of cardiovascular disease (CVD) risk and periodontitis in adolescents, including mediating pathways triggered by their common risk factors.Using a population-based sample study (n = 405) of Brazilian adolescents (17-18 years old), direct and mediation pathways triggered by "Socioeconomic Status," "Adiposity," Smoking, and "Blood Pressure" were modelled for the association between the "Systemic Circulating Inflammatory Burden of CVD Risk" (IL-1β, IL-6, IL-8, TNF-α) and the "Initial Periodontitis" (bleeding on probing (BoP), probing depth (PD) ≥ 4 mm, clinical attachment loss (CAL) ≥ 4 mm), both as continuous latent variables, using structural equation modeling. Sensitivity analysis was performed for the outcomes "Gingivitis" (visible plaque; BoP); "Moderate Periodontitis" (PD ≥ 5 mm and CAL ≥ 5 mm) and periodontitis (CDC-AAP case definition).Higher "Systemic Circulating Inflammatory Burden of CVD Risk" was directly associated with higher "Initial Periodontitis" (standardized coefficient [SC] = 0.178, P value0.001). Lower "Socioeconomic Status" (SC = - 0.022, P value = 0.015) and Smoking (SC = 0.030, P value = 0.021) triggered the "Initial Periodontitis", mediated by "Systemic Circulating Inflammatory Burden of CVD Risk". Sensitivity analysis showed a dose-response relationship between "Systemic Circulating Inflammatory Burden of CVD Risk" and "Moderate Periodontitis" (SC = 0.323, P value = 0.021)."Systemic Circulating Inflammatory Burden of CVD Risk" appeared as an underlying mechanism of early periodontal breakdown in adolescents, also triggered by social vulnerability and smoking.The association between periodontitis and CVD in adulthood seems to establish much earlier in life than had been previously studied, giving impetus to preventive approaches focused on their common risk factors.

Ionic liquids are called designer solvents because their physical properties can be tuned by the selection of different combinations cation and anion. Understanding the relation between the chemical structure and the viscosity and how the shear rate can affect the relative arrangements of the ions are important for practical applications specially as lubricants. Reverse non-equilibrium molecular dynamics (RNEMD) simulations were performed to study the effect of the shear rate over the viscosity and the structure at molecular level of four different imidazolium based ionic liquids. Since it is already well known that the absence of explicit electronic polarizability in usual classical force fields leads to artificially slow dynamics in ionic liquids, a Drude polarizable force field was employed in all simulations. Non-newtonian behavior is observed at shear rates at GHz scale, with a progressive reduction of the viscosity at the same time that the structure of second and further coordination shells are partially disrupted. The liquids that displayed the greater structural changes with increasing shear rate also displayed the strongest variation in the viscosities. At the highest shear rates studied, the imidazolium rings tends to align parallel to the induced flux, an effect similar to the well-known align of polymer chains under shear, despite becoming significant for ionic liquids only at extremely high rates.

Summary 3D in vitro cancer models are important therapeutic and biological discovery tools, yet formation of matrix-embedded multicellular spheroids prepared in high-throughput (HTP), and in a highly controlled manner, remains challenging. This is important to achieve robust and statistically relevant data. Here, we developed an enabling technology consisting of a bespoke drop-on-demand 3D bioprinter capable of HTP printing of 96-well plates of spheroids. 3D multicellular spheroids are embedded inside a hydrogel matrix with precise control over size and cell number, with the intra-experiment variability of embedded spheroid diameter coefficient of variation being between 4.2% and 8.7%. Application of 3D bioprinting HTP drug screening was demonstrated with doxorubicin. Measurements of IC50 values showed sensitivity to spheroid size, embedding, and how spheroids conform to the embedding, revealing parameters shaping biological responses in these models. Our study demonstrates the potential of 3D bioprinting as a robust HTP platform to screen biological and therapeutic parameters.

3D in vitro cancer models are important therapeutic and biological discovery tools, yet formation of multicellular spheroids in a throughput and highly controlled manner to achieve robust and statistically relevant data, remains challenging. Here, we developed an enabling technology consisting of a bespoke drop-on-demand 3D bioprinter capable of high-throughput printing of 96-well plates of spheroids. 3D-multicellular spheroids are embedded inside a tissue-like matrix with precise control over size and cell number. Application of 3D bioprinting for high-throughput drug screening was demonstrated with doxorubicin. Measurements showed that IC50 values were sensitive to spheroid size, embedding and how spheroids conform to the embedding, revealing parameters shaping biological responses in these models. Our study demonstrates the potential of 3D bioprinting as a robust high-throughput platform to screen biological and therapeutic parameters.Significance StatementIn vitro 3D cell cultures serve as more realistic models, compared to 2D cell culture, for understanding diverse biology and for drug discovery. Preparing 3D cell cultures with defined parameters is challenging, with significant failure rates when embedding 3D multicellular spheroids into extracellular mimics. Here, we report a new 3D bioprinter we developed in conjunction with bioinks to allow 3D-multicellular spheroids to be produced in a high-throughput manner. High-throughput production of embedded multicellular spheroids allowed entire drug-dose responses to be performed in 96-well plate format with statistically relevant numbers of data points. We have deconvoluted important parameters in drug responses including the impact of spheroid size and embedding in an extracellular matrix mimic on IC50 values.

The terahertz spectrum encodes information about dynamics, structure, and intermolecular interactions of liquids being probed both experimentally and computationally by techniques such as Raman and far-infrared spectroscopies and molecular dynamics (MD) simulation. In the case of room temperature ionic liquids (RTILs), there has been a debate whether a mode observed at about 1.5-2.7 THz (50-90 cm-1) is due to a quasi-lattice structure or the formation of complex ions. Here we show through the analysis of Raman and far-infrared spectra and MD simulation of a typical RTIL that this mode has a collective optic-like character. Then, employing a simple model based on the theory for optical phonons in crystals, we show that a correlation between the frequency of this mode and material parameters holds for different RTILs. These results, which encompass a wide range of samples, reinforce a quasi-lattice view of the liquid phase.

Analyze the association between higher added sugar exposure and periodontal disease in adolescents (18-19 years old).This was a cross-sectional study nested to RPS Cohorts Consortium, São Luís, Brazil (n = 2515). The exposure was percentage of daily calories from added sugar (≥ 10%), estimated from a quantitative food frequency. The outcome was periodontal disease estimated by the number of teeth affected by bleeding on probing, periodontal probing depth ≥ 4 mm, and clinical attachment level ≥ 4 mm at the same site. A theoretical model was depicted in a directed acyclic graph to identify the minimal sufficient adjustment set: household income, adolescent's educational level, sex, alcohol use, and smoking. Periodontal disease was categorized into2 teeth affected, 2 to 3 teeth affected, and ≥ 4 teeth affected to estimate prevalence ratios (PR) by multinomial logistic regression. To test for consistency, means ratio (MR) were estimated using zero-inflated Poisson.High sugar intake was associated with ≥ 4 teeth affected by periodontal disease (PR = 1.42; 95% confidence interval (CI) = 1.03-1.94; p = 0.030); consistency Poisson analysis reinforced these results (MR = 1.15; 95% CI = 1.03-1.29; p = 0.011).High level of added sugar intake was associated with greater extent of periodontal disease in adolescents.High sugar intake was associated with periodontal disease in adolescents, supporting the integrated hypothesis of dental caries and periodontal disease and giving impetus to future clinical investigation on the effect of restriction of added sugar consumption in periodontal parameters, which potentially may change traditional treatment protocols of periodontal disease.

This work discusses the remarkable differences in the mid- and far-infrared regions of the spectrum of the ionic liquid 1-ethyl-3-methylimidazolium hydrogen sulfate, [C2C1im][HSO4], in comparison to ionic liquids based on other anions. The infrared spectrum unveils the occurrence of anion–anion hydrogen bond in [C2C1im][HSO4]. The band related to the anion O H stretching mode, ν(OH), covers a large frequency range (2000–3400 cm−1) and exhibits the spectral pattern of strongly hydrogen bonded systems. The far-infrared (FIR) spectrum of [C2C1im][HSO4] also exhibits the signature of the anion–anion interaction, that is, the stretching mode of the hydrogen bond, ν(O…O), at ~170 cm−1. Hydrogen bond between [HSO4]− anions also occurs in ionic liquids containing imidazolium cation with longer alkyl chain ([C4C1im]+) or tetraalkylammonium cation. The vibrational frequencies of ν(OH) and ν(O…O) modes satisfy empirical correlations that characterize the anion–anion interaction in [C2C1Im][HSO4] as a strong hydrogen bond.

The intermolecular dynamics in the THz frequency range of the ionic liquids n-butyl-trimethylammonium bis(trifluoromethanesulfonyl)imide, [N1114][NTf2], and methyl-tributylammonium bis(trifluoromethanesulfonyl)imide, [N1444][NTf2], were investigated by a combined usage of inelastic neutron scattering (INS), Raman, and far-infrared (FIR) spectroscopies and the power spectrum calculated by molecular dynamics (MD) simulations. The collective dynamics of the simulated systems is also discussed by the calculation of time correlation functions of charge and mass currents that are projected onto acoustic- and optic-like motions. The INS and Raman measurements have been performed as a function of temperature in the glassy, crystalline, and liquid phases. The excess in the vibrational density of states over the expectation of the Debye theory, the so-called boson peak, is found in the INS and Raman spectra as a peak at ∼2 meV (∼16 cm-1) and also in the direct measurement of heat capacity at very low temperatures (4-20 K). This low-frequency vibration is incorporated into the curve fits of Raman, FIR, and MD data at room temperature. Fits of spectra from these different sources in the range below 100 cm-1 are consistently achieved with three components at ca. 25, 50, and 80 cm-1, but with distinct relative intensities among the different techniques. It is proposed as the collective nature of the lowest-frequency component and the anion-cation intermolecular vibration nature of the highest-frequency component. The MD results indicate that there is no clear distinction between acoustic and optic vibrations in the spectral range investigated in this work for the ionic liquids [N1114][NTf2] and [N1444][NTf2]. The analysis carried out here agrees in part, but not entirely, with other propositions in the literature, mainly from optical Kerr effect (OKE) and FIR spectroscopies, concerning the intermolecular dynamics of ionic liquids.

A Raman spectroscopy study of 1-ethyl-3-methylimidazolium hydrogen sulfate, [C2C1im][HSO4], as a function of temperature, has been performed to reveal the role played by anion–anion hydrogen bond on the phase transitions of this ionic liquid. Anion–anion hydrogen bonding implies high viscosity, good glass-forming ability, and also moderate fragility of [C2C1im][HSO4] in comparison with other ionic liquids. Heating [C2C1im][HSO4] from the glassy phase results in cold crystallization at ∼245 K. A solid–solid transition (crystal I → crystal II) is barely discernible in calorimetric measurements at typical heating rates, but it is clearly revealed by Raman spectroscopy and X-ray diffraction. Raman spectroscopy indicates that crystal I has extended ([HSO4]−)n chains of hydrogen-bonded anions but crystal II has not. Raman spectra recorded at isothermal condition show the ultraslow dynamics of cold crystallization, solid–solid transition, and continuous melting of [C2C1im][HSO4]. A brief comparison is also provi...

The structure of choline salts containing the anions acetate, [Chol][Ac], and dihydrogen phosphate, [Chol][DHP], were investigated by infrared, Raman, and inelastic neutron scattering (INS). The chosen systems allow for the comparison of structural effects related to the bond acceptor characteristic of [Ac] and the simultaneous acceptor and donor characteristics of [DHP] in forming hydrogen bonds (H-bond) in salts of [Chol], which is itself prone to forming H-bonds. Different computational tools were used for the analysis of different spectral ranges. The calculation of the low-frequency range of Raman and INS spectra of the crystalline phases at low-temperatures by solid state DFPT (density functional perturbation theory) unveils the coupling between vibrations of the H-bonds and intramolecular modes. Changes observed in the spectral pattern of lattice and [DHP] modes upon heating crystalline [Chol][DHP] are analogous to the ferroelectric–paraelectric phase transition known in the potassium salt of [DHP]. The fingerprint region of the vibrational spectra provides information concerning the [Chol] conformation in the solid phase (gauche in [Chol][Ac] and anti in [Chol][DHP]) and in aqueous solution. DFT calculations of ionic pairs and ionic clusters unveil the interplay between [Chol] conformation and the [DHP] ability to form H-bonded dimers of anions. The high-frequency spectral range and the structures driven by H-bonds are discussed using classical molecular dynamics (MD) simulations. The MD simulations of aqueous solutions highlight the strong anion-cation H-bond in [Chol][Ac], in contrast to the strong anion–anion H-bond in [Chol][DHP] due to occurrence of dimers and larger clusters of [DHP].

A local order-disorder transition has been disclosed in the thermophysical behavior of the ionic liquid 1-benzyl-3-methylimidazolium dicyanamide, [Bzmim][N(CN)2], and its microscopic nature revealed by spectroscopic techniques. Differential scanning calorimetry and specific heat measurements show a thermal event of small enthalpy variation taking place in the range 250-260 K, which is not due to crystallization or melting. Molecular dynamic simulations and X-ray diffraction measurements have been used to discuss the segregation of domains in the liquid structure of [Bzmim][N(CN)2]. Raman and NMR spectroscopy measurements as a function of temperature indicate that the microscopic origin of the event observed in the calorimetric measurements comes from structural rearrangement involving the benzyl group. The results indicate that the characteristic structural heterogeneity allow for rearrangements within local domains implying the good glass-forming ability for the low viscosity ionic liquid [Bzmim][N(CN)2]. This work sheds light on our understanding of the microscopic origin behind complex thermal behavior of ionic liquids.

The vibrational spectra of two cyano-based ionic liquids, 1-ethyl-3-methylimidazolium dicyanamide (C 2 C 1 Im DCA) and 1-ethyl-3-methylimidazolium tricyanomethanide (C 2 C 1 Im TCM) are revisited experimentally and computationally using IR spectroscopy and ab initio molecular dynamics simulations, respectively. In the experimental spectrum of C 2 C 1 Im DCA, a number of interesting vibrational signatures are found. Aside from the expected symmetric and anti-symmetric stretching bands of the cyano groups, a Fermi resonance of a combination band and a CN stretching normal mode is identified. The assignment is confirmed by a normal mode analysis of the AIMD based IR spectrum. The AIMD does not only predict the existence of the combination band but also seems to capture the frequency shift and intensity change caused by Fermi resonance. The interpretation of the experimental C 2 C 1 Im TCM spectrum is more straightforward as no resonance effects are found. The combination of experimental spectroscopy and advanced AIMD simulations is a very promising approach to gain new insights into the behavior of room-temperature ionic liquids.

Vibrational spectroscopy has continued use as a powerful tool to characterize ionic liquids since the literature on room temperature molten salts experienced the rapid increase in number of publications in the 1990's. In the past years, infrared (IR) and Raman spectroscopies have provided insights on ionic interactions and the resulting liquid structure in ionic liquids. A large body of information is now available concerning vibrational spectra of ionic liquids made of many different combinations of anions and cations, but reviews on this literature are scarce. This review is an attempt at filling this gap. Some basic care needed while recording IR or Raman spectra of ionic liquids is explained. We have reviewed the conceptual basis of theoretical frameworks which have been used to interpret vibrational spectra of ionic liquids, helping the reader to distinguish the scope of application of different methods of calculation. Vibrational frequencies observed in IR and Raman spectra of ionic liquids based on different anions and cations are discussed and eventual disagreements between different sources are critically reviewed. The aim is that the reader can use this information while assigning vibrational spectra of an ionic liquid containing another particular combination of anions and cations. Different applications of IR and Raman spectroscopies are given for both pure ionic liquids and solutions. Further issues addressed in this review are the intermolecular vibrations that are more directly probed by the low-frequency range of IR and Raman spectra and the applications of vibrational spectroscopy in studying phase transitions of ionic liquids.

High energy X-ray diffraction has been combined with containerless techniques to determine the structure of a series of alkali and ammonium nitrate and nitrite liquids. The systems have been modelled using molecular dynamics simulation which allows for the flexibility of, and movement of charge within, the molecular anions. The model reproduces the experimentally-determined scattering functions in both the low- and high-Q regimes reflecting the inter- and intra-molecular length-scales. For ammonium nitrate the best fit to the diffraction data is obtained by assuming the NH4+ cation to have a radius closer to that for Cs+ rather than a smaller cation such as Rb+ as often previously assumed. The alkali nitrites show an emergent length scale, attributed to the nitrogen-nitrogen spatial correlations, that depends on both temperature and the identity of the alkali cation. The corresponding nitrates show a more subtle effect in the nitrogen-nitrogen correlations. As a result, the nature of this N-N length-scale appears different for the respective nitrites and nitrates.

The competition between Coulomb and van der Waals interactions brings forth unique dynamic features and broad applications to ionic liquids. Herein, we present a combined calorimetric, X-ray diffraction, incoherent elastic, and quasi-elastic neutron scattering study, over a wide temperature range (180-340 K), of the relaxational dynamics of the liquid, supercooled liquid, crystalline, glassy, and glacial states of two model ionic liquids: tributylmethylammonium (a good glass-former) and butyltrimethylammonium (a good crystal-former) cations and the bis(trifluoromethanesulfonyl)imide anion. In both systems, we observed two distinct relaxation processes. The Q-dependence of the respective relaxation time shows that the α-process is diffusive, while the β-process is modulated by the structure of the liquids.

X-ray diffraction and Raman scattering measurements of the ionic liquid 1-butyl-1-methylpyrrolidinium bis(trifluoromethanesufonyl)imide, [Pyrr1,4][NTf2], were performed in a wide range of temperature and pressure. Pressure dependence of glass transition Tg(p), cold-crystallization Tcc(p), and melting Tm(p) temperatures were obtained from atmospheric pressure up to ca. 2.0 GPa. The temperature dependence of Raman spectra within the Tcc

The frequency range below ∼100 cm-1 of the Raman spectrum of a glass-forming liquid exhibits two features that characterize the short-time (THz) dynamics: the quasi-elastic scattering (QES) tail and the boson peak (BP). In this work, we follow temperature and pressure effects on the intermolecular dynamics of a typical ionic liquid, 1-butyl-1-methylpiperidinium bis(trifluoromethanesulfonyl)imide, [Pip14][[NTf2]. The glass transition temperature of [Pip14][[NTf2] at atmospheric pressure is Tg = 198 K, and the pressure of glass transition at room temperature is Pg = 1.1 GPa. Raman spectra obtained while cooling the liquid or heating the glass exhibit hysteresis in QES and BP intensities, IQES and IBP. The dependence of IQES, IBP, and the BP frequency, ωBP, with pressure up to the glass transition is steeper than the temperature dependence due to the stronger pressure effect on density within the GPa range. The temperature and pressure behaviors of the parameters IQES, IBP, and ωBP obtained here for [Pip14][[NTf2] are discussed in light of known results for other glass-formers.

Melting of the ionic liquid choline acetate, [Chol][Ac], at ~335 K is manifest in the differential scanning calorimetry (DSC) curve as a broad band covering ~30 K of temperature range. The events taking place in the pre-melting of [Chol][Ac] are revealed by Raman spectroscopy and rheological measurements. The low-frequency range of the Raman spectrum exhibits changes in the intermolecular vibrational modes and the higher frequency range indicates conformational changes of the choline cation. Oscillatory rheological measurements show that the sample experiences a stiffening of its rheological characteristics within the temperature interval encompassing the melting process. Taking together the spectroscopic and rheological data, it is concluded that the sample experiences partial recrystallization during the pre-melting of [Chol][Ac].

Solubility parameters such as Hildebrand's solubility parameter or its square, the cohesive energy density ced are often not able to predict solubilities of organic compounds in ionic liquids accurately. It has been suggested that this is an effect of the structural heterogeneity that many ionic liquids exhibit due to the non-polar alkyl chains forming separate domains from the charged parts of the cation and the anion. We here calculated the partial volumes of the polar and non-polar domains in Molecular Dynamics simulations of several 1-alkyl-3-methylimidazolium nitrates and 1-octyl-3-methylimidazolium hexafluorophosphate. We used these partial volumes to calculate the ced of the polar and non-polar domains. For 1-octyl-3-methylimidazolium nitrate the internal pressures Pi of the domains were also calculated. Our results show that ced and Pi are indeed very different in the domains, and that the domains containing the hydrophobic alkyl chains have solvent parameters similar to alkanes. For the domains that contain the charged part of the ions, ced and Pi are much higher, and Pi is comparable to what is found for high temperature molten salts. The results provide a possible explanation why solubility parameters seem incorrect for many ionic liquids, and may be useful in estimating more useful values using computer simulations.