Advances in electrochemical biosensor design for the detection of the stress biomarker cortisol.

The monitoring of stress levels in humans has become increasingly relevant, given the recent incline of stress-related mental health disorders, lifestyle impacts, and chronic physiological diseases. Long-term exposure to stress can induce anxiety and depression, heart disease, and risky behaviors, such as drug and alcohol abuse. Biomarker molecules can be quantified in biological fluids to study human stress. Cortisol, specifically, is a hormone biomarker produced in the adrenal glands with biofluid concentrations that directly correlate to stress levels in humans. The rapid, real-time detection of cortisol is necessary for stress management and predicting the onset of psychological and physical ailments. Current methods, including mass spectrometry and immunoassays, are effective for sensitive cortisol quantification. However, these techniques provide only single measurements which pose challenges in the continuous monitoring of stress levels. Additionally, these analytical methods often require trained personnel to operate expensive instrumentation. Alternatively, low-cost electrochemical biosensors enable the real-time detection and continuous monitoring of cortisol levels while also providing adequate analytical figures of merit (e.g., sensitivity, selectivity, sensor response times, detection limits, and reproducibility) in a simple design platform. This review discusses the recent developments in electrochemical biosensor design for the detection of cortisol in human biofluids. Special emphasis is given to biosensor recognition elements, including antibodies, molecularly imprinted polymers (MIPs), and aptamers, as critical components of electrochemical biosensors for cortisol detection. Furthermore, the advantages and limiting factors of various electrochemical techniques and sensing in complex biofluid matrices are overviewed. Remarks on the current challenges and future perspectives regarding electrochemical biosensors for stress monitoring are provided, including matrix effects (pH dependence and biological interferences), wearability, and large-scale production.

The effect of differential mineral shrinkage on crack formation and network geometry.

Rock, concrete, and other engineered materials are often composed of several minerals that change volumetrically in response to variations in the moisture content of the local environment. Such differential shrinkage is caused by varying shrinkage rates between mineral compositions during dehydration. Using both 3D X-ray imaging of geo-architected samples and peridynamic (PD) numerical simulations, we show that the spatial distribution of the clay affects the crack network geometry with distributed clay particles yielding the most complex crack networks and percent damage (99.56%), along with a 60% reduction in material strength. We also demonstrate that crack formation, growth, coalescence, and distribution during dehydration, are controlled by the differential shrinkage rates between a highly shrinkable clay and a homogeneous mortar matrix. Sensitivity tests performed with the PD models show a clay shrinkage parameter of 0.4 yields considerable damage, and reductions in the parameter can result in a significant reduction in fracturing and an increase in material strength. Additionally, isolated clay inclusions induced localized fracturing predominantly due to debonding between the clay and matrix. These insights indicate differential shrinkage is a source of potential failure in natural and engineered barriers used to sequester anthropogenic waste.

Correlating structure and transport behavior in Li+ and O2 containing pyrrolidinium ionic liquids.

Ionic liquids are a unique class of materials with several potential applications in electrochemical energy storage. When used in electrolytes, these highly coordinating solvents can influence device performance through their high viscosities and strong solvation behaviors. In this work, we explore the effects of pyrrolidinium cation structure and Li+ concentration on transport processes in ionic liquid electrolytes. We present correlated experimental measurements and molecular simulations of Li+ mobility and O2 diffusivity, and connect these results to dynamic molecular structural information and device performance. In the context of Li-O2/Li-air battery chemistries, we find that Li+ mobility is largely influenced by Li+-anion coordination, but that both Li+ and O2 diffusion may be affected by variations of the pyrrolidinium cation and Li+ concentration.

Two-dimensional metal-organic frameworks with high thermoelectric efficiency through metal ion selection.

Two-dimensional (2D) materials have attracted much attention due to their novel properties. An exciting new class of 2D materials based on metal-organic frameworks (MOFs) has recently emerged, displaying high electrical conductivity, a rarity among organic nanoporous materials. The emergence of these materials raises intriguing questions about their fundamental electronic, optical, and thermal properties, but few studies exist in this regard. Here we present an atomistic study of the thermoelectric properties of crystalline 2D MOFs X3(HITP)2 with X = Ni, Pd or Pt, and HITP = 2,3,6,7,10,11-hexaiminotriphenylene, using both ab initio transport models and classical molecular dynamics simulations. We find that these materials have a high Seebeck coefficient and low thermal conductivity, making them promising for thermoelectric applications. Furthermore, we explore the dependence of thermoelectric transport properties on the atomic structure by comparing the calculated band structure, band alignment, and electronic density of states of the three 2D MOFs, and find that the thermoelectric transport properties strongly depend on both the interaction between the ligands and the metal ions, and the d orbital splitting of the metal ions induced by the ligands. This demonstrates that selection of the metal ion is a powerful approach to control and enhance the thermoelectric properties. Interestingly we reveal an unexpected effect where, unlike for electrons, the thermal and electrical current may not be equally carried by the holes, leading to a significant deviation from the Wiedemann-Franz law. The results of this work provide fundamental guidance to optimize the existing 2D MOFs, and to design and discover new families of MOF-like materials for thermoelectric applications.

Thermal boundary conductance between Al films and GaN nanowires investigated with molecular dynamics.

GaN nanowires are being pursued for optoelectronic and high-power applications. In either use, increases in operating temperature reduce both performance and reliability making it imperative to minimize thermal resistances. Since interfaces significantly influence the thermal response of nanosystems, the thermal boundary resistance between GaN nanowires and metal contacts has major significance. In response, we have performed systematic molecular dynamics simulations to study the thermal boundary conductance between GaN nanowires and Al films as a function of nanowire dimensions, packing density, and the depth the nanowire is embedded into the metal contact. At low packing densities, the apparent Kapitza conductance between GaN nanowires and an aluminum film is shown to be larger than when contact is made between films of these same materials. This enhancement decreases toward the film-film limit, however, as the packing density increases. For densely packed nanowires, maximizing the Kapitza conductance can be achieved by embedding the nanowires into the films, as the conductance is found to be proportional to the total contact area.

The application of an atomistic J-integral to a ductile crack.

In this work we apply a Lagrangian kernel-based estimator of continuum fields to atomic data to estimate the J-integral for the emission dislocations from a crack tip. Face-centered cubic (fcc) gold and body-centered cubic (bcc) iron modeled with embedded atom method (EAM) potentials are used as example systems. The results of a single crack with a K-loading compare well to an analytical solution from anisotropic linear elastic fracture mechanics. We also discovered that in the post-emission of dislocations from the crack tip there is a loop size-dependent contribution to the J-integral. For a system with a finite width crack loaded in simple tension, the finite size effects for the systems that were feasible to compute prevented precise agreement with theory. However, our results indicate that there is a trend towards convergence.

Adaptive Green-Kubo estimates of transport coefficients from molecular dynamics based on robust error analysis.

We present a rigorous Green-Kubo methodology for calculating transport coefficients based on on-the-fly estimates of: (a) statistical stationarity of the relevant process, and (b) error in the resulting coefficient. The methodology uses time samples efficiently across an ensemble of parallel replicas to yield accurate estimates, which is particularly useful for estimating the thermal conductivity of semi-conductors near their Debye temperatures where the characteristic decay times of the heat flux correlation functions are large. Employing and extending the error analysis of Zwanzig and Ailawadi [Phys. Rev. 182, 280 (1969)] and Frenkel [in Proceedings of the International School of Physics "Enrico Fermi", Course LXXV (North-Holland Publishing Company, Amsterdam, 1980)] to the integral of correlation, we are able to provide tight theoretical bounds for the error in the estimate of the transport coefficient. To demonstrate the performance of the method, four test cases of increasing computational cost and complexity are presented: the viscosity of Ar and water, and the thermal conductivity of Si and GaN. In addition to producing accurate estimates of the transport coefficients for these materials, this work demonstrates precise agreement of the computed variances in the estimates of the correlation and the transport coefficient with the extended theory based on the assumption that fluctuations follow a Gaussian process. The proposed algorithm in conjunction with the extended theory enables the calculation of transport coefficients with the Green-Kubo method accurately and efficiently.

A Long-Range Electric Field Solver for Molecular Dynamics Based on Atomistic-to-Continuum Modeling.

Understanding charge transport processes at a molecular level is currently hindered by a lack of appropriate models for incorporating nonperiodic, anisotropic electric fields in molecular dynamics (MD) simulations. In this work, we develop a model for including electric fields in MD using an atomistic-to-continuum framework. This framework provides the mathematical and the algorithmic infrastructure to couple finite element (FE) representations of continuous data with atomic data. Our model represents the electric potential on a FE mesh satisfying a Poisson equation with source terms determined by the distribution of the atomic charges. Boundary conditions can be imposed naturally using the FE description of the potential, which then propagate to each atom through modified forces. The method is verified using simulations where analytical solutions are known or comparisons can be made to existing techniques. In addition, a calculation of a salt water solution in a silicon nanochannel is performed to demonstrate the method in a target scientific application in which ions are attracted to charged surfaces in the presence of electric fields and interfering media.

A homogeneous nonequilibrium molecular dynamics method for calculating the heat transport coefficient of mixtures and alloys.

This work generalizes Evans' homogeneous nonequilibrium method for estimating heat transport coefficient to multispecies molecular systems described by general multibody potentials. The proposed method, in addition to being compatible with periodic boundary conditions, is shown to satisfy all the requirements of Evans' original method, namely, adiabatic incompressibility of phase space, equivalence of the dissipative and heat fluxes, and momentum preservation. The difference between the new equations of motion, suitable for mixtures and alloys, and those of Evans' original work are quantified by means of simulations for fluid Ar-Kr and solid GaN test systems.

Generalization of the homogeneous nonequilibrium molecular dynamics method for calculating thermal conductivity to multibody potentials.

This work provides a generalization of Evans' homogeneous nonequilibrium method for estimating thermal conductivity to molecular systems that are described by general multibody potentials. A perturbed form of the usual Nose-Hoover equations of motion is formally constructed and is shown to satisfy the requirements of Evans' original method. These include adiabatic incompressibility of phase space, equivalence of the dissipative and heat fluxes, and momentum preservation.

A homogeneous nonequilibrium molecular dynamics method for calculating thermal conductivity with a three-body potential.

In this work, Evans' homogeneous nonequilibrium molecular dynamics method for estimating thermal conductivity is extended to systems employing three-body potentials. This extension is put on a firm theoretical basis and applied to a silicon lattice modeled by the Stillinger-Weber potential. Two new methods are suggested for estimating the thermal conductivity based on a range of values of the fictitious force. Also, kinetic theory is used to estimate the linear range of the fictitious force necessary to bias the heat flow, thereby potentially reducing the number of simulations needed to estimate thermal conductivity.

Full-field deformation of bovine cornea under constrained inflation conditions.

The viscoelastic response of bovine corneas was characterized using in vitro inflation (bulge) experiments combined with spatially-resolved deformation mapping via digital image correlation. A complex fixture conforming to the limbal annulus was developed to hold the attached sclera rigid while allowing deformation only in the cornea. A statistical set of experiments was performed for a pressure range of 3.6-8 kPa (27-60 mmHg), representing nominal bovine intraocular pressure (IOP) to acute glaucoma conditions. A broader pressure range of 0-32 kPa (0-240 mmHg) was also examined to characterize the nonlinear finite deformation behavior of the tissue. Results showed that for pressures near and above IOP, the majority of the deformation was localized in the limbus and peripheral regions, which left the central cornea largely undeformed. This observation was consistent with the known preferred circumferential alignment of collagen fibrils outside of the central cornea. In general, the inflation experiments observed viscoelastic behavior in the form of rate-dependent hysteresis in the pressure-deformation response of the apex of the cornea, creep in the apex deformation at a constant inflation pressure, and relaxation in the pressure response at a constant inflation volume. The 3.6-8 kPa (27-60 mmHg) pressure range produced small viscoelastic deformations and a nearly linear pressure-deformation response, which suggests that for physiological pressure ranges, the cornea can be approximated as a linear viscoelastic or linear pseudo-elastic material.

Trace amine-associated receptor 1 displays species-dependent stereoselectivity for isomers of methamphetamine, amphetamine, and para-hydroxyamphetamine.

The synthetic amines methamphetamine (METH), amphetamine (AMPH), and their metabolite para-hydroxyamphetamine (POHA) are chemically and structurally related to the catecholamine neurotransmitters and a small group of endogenous biogenic amines collectively referred to as the trace amines (TAs). Recently, it was reported that METH, AMPH, POHA, and the TAs para-tyramine (TYR) and beta-phenylethylamine (PEA) stimulate cAMP production in human embryonic kidney (HEK)-293 cells expressing rat trace amine-associated receptor 1 (rTAAR1). The discovery that METH and AMPH activate the rTAAR1 motivated us to study the effect of these drugs on the mouse TAAR1 (mTAAR1) and a human-rat chimera (hrChTAAR1). Furthermore, because S-(+)-isomers of METH and AMPH are reported to be more potent and efficacious in vivo than R-(-), we determined the enantiomeric selectivity of all three species of TAAR1. In response to METH, AMPH, or POHA exposure, the accumulation of cAMP by HEK-293 cells stably expressing different species of TAAR1 was concentration- and isomer-dependent. EC50 values for S-(+)-METH were 0.89, 0.92, and 4.44 microM for rTAAR1, mTAAR1, and h-rChTAAR1, respectively. PEA was a potent and full agonist at each species of TAAR1, whereas TYR was a full agonist for the rodent TAAR1s but was a partial agonist at h-rChTAAR1. Interestingly, both isomers of METH were full agonists at mTAAR1 and h-rChTAAR1, whereas both were partial agonists at rTAAR1. Taken together, these in vitro results suggest that, in vivo, TAAR1 could be a novel mediator of the effects of these drugs.

Stable oxygen isotopes from theropod dinosaur tooth enamel: interlaboratory comparison of results and analytical interference by reference standards.

Although previous work has demonstrated that biological phosphates ('biophosphates') record significant changes in delta18O associated with variations in local climate and seasonality, the repeatability of these analyses between laboratories has not previously been tested. We serially sampled enamel on four Cretaceous dinosaur teeth for phosphate delta18O analysis at up to three different facilities. With the exception of one set of unprocessed enamel samples, the material supplied to each laboratory was chemically processed to silver phosphate. Each laboratory analyzed sample sets by pyrolysis (thermochemical decomposition) in a ThermoFinnigan TC/EA attached to a ThermoFinnigan Delta Plus mass spectrometer. Significant interference between phosphate samples and the NIST reference material 8557 barium sulfate (NBS 127) distorts some of the results. Samples analyzed immediately following NBS 127 may be depleted by 6 per thousand isotopically and in instrument peak amplitude response by 80%. Substantial interference can persist over the subsequent 20 silver phosphate samples, and can influence the instrument peak amplitude response from some organic standards. Experiments using reagent-grade silver phosphate link these effects to divalent cations, particularly Ca2+ and Ba2+, which linger in the reactor and scavenge oxygen evolved from pyrolysis of subsequent samples. Unprocessed enamel includes 40 wt% calcium and self-scavenges oxygen, disrupting the isotopic measurements for the first half of a set and depleting subsequent organic standards by up to 9 per thousand. In sets without NBS 127 or calcium, such interference did not occur and an interlaboratory comparison of results from enamel shows reproducible, significantly correlated peaked delta18O patterns with a 2-3 per thousand dynamic range, consistent with previous results from contemporaneous teeth. Whereas both unprocessed enamel and the NBS 127 barium sulfate should be applied to biological phosphate ('biophosphate') stable isotope research with caution, seasonal variations in enamel phosphate delta18O are a paleoecologically valuable, reproducible phenomenon in theropod dinosaur teeth.

Development of an intelligent polymerized crystalline colloidal array colorimetric reagent.

We have developed a novel colorimetric reagent for the determination of Pb2+, pH, and temperature. This colorimetric reagent consists of a dispersion of approximately 100-microm particles composed of an intelligent polymerized crystalline colloidal array (IPCCA). The IPCCA particles are composed of a hydrogel polymerized around a face-centered cubic (fcc) array of monodisperse, highly charged polystyrene colloidal particles. These IPCCA particles diffract visible light because the (111) planes of the fcc polystyrene colloidal particle array have an approximately 200-nm lattice constant. The IPCCA particles also contain a molecular recognition agent that actuates array volume changes as a result of changes in analyte concentration or temperature. This results in changes in the IPCCA lattice constants, which shifts the wavelength of light diffracted. We report here the use of these sensing materials in a liquid dispersion that can be poured into a sample solution. This diffraction measurement method is analogous to X-ray powder diffraction measurements. The diffraction wavelength is monitored at a defined angle relative to the incident light.

Three-dimensional dynamic MR hysterosalpingography: a preliminary report.

The aim of this study was to evaluate the feasibility of three-dimensional dynamic MR hysterosalpingography (3D MR HSG) for visualization of the cavum uteri and demonstration of bilateral fallopian tube patency as an alternative to conventional hysterosalpingography. Five infertile female patients underwent 3D dynamic MR HSG prior to conventional hysterosalpingography. The MR protocol consisted of axial T1-weighted spin-echo (SE), axial/coronal T2-weighted fast SE (FSE), and 3D MR angiography sequences before, during, and after injection of a diluted gadolinium solution into the cavum uteri via a balloon catheter. Positioning of the catheter was feasible in all patients. In one patient the catheter slipped out during MRI and in one patient the catheter was placed far in the cavum uteri. In three patients catheter position was optimal at the level of the cervical canal. Evaluation of pelvic anatomy, myometrium, and ovaries was possible in all patients on the basis of T1-weighted SE and T2-weighted FSE. Three-dimensional visualization of the dilated cavum uteri was possible in four patients. In these four patients 3D MR HSG also proved bilateral fallopian tube patency which was confirmed in each patient by conventional hysterosalpingography. Three-dimensional MR HSG is feasible and further research should be done to determine if this technique can evolve into an alternative technique to conventional hysterosalpingography with the advantages of no radiation and additional visualization of the uterus wall and ovaries.

Arterial first pass gadolinium-CM dynamics as a function of several intravenous saline flush and Gd volumes.

This study was performed to evaluate the dynamics of an arterial first pass gadolinium (Gd) contrast medium (CM) bolus at the descending aorta (DAo), depending on various saline flush and Gd volumes. Using an ultra-fast two- dimensional GE-sequence (Siemens Vision, 1.5-T), 200 sequential cross-sectional images of the addressed vessel (1 slice/s) were obtained. Several saline flush volumes (15 mL, 30 mL, and 60 mL) were applied following the administration of 10 mL Gd (single dose) to a group of 4 normal volunteers (body weight 50-55 kg) using a mechanical MR injector (injection rate = 3.0 mL/s). Additionally, when performing a second test series, the saline volume remained constant, while the Gd volumes were varied from half doses to triple doses (5, 10, 20, and 30 mL Gd were given to every volunteer of the group). The signal intensity versus time (SI/T) curve at a measured region of interest (ROI) within the DAo was calculated. The bolus arrival time (BAT), the maximal signal-to-noise ratio (SNR(max)), the bolus time length (BL; 75% and 80% maximum intensity duration), the slope of the SI/T curve, and the areas below the SI/T curve for both the 80% and 75% maximum intensity duration level (INT(80%) and INT(75%)) were calculated. The increase of saline flush volume from 30 to 60 mL caused significant bolus lengthening of approximately 50% (mean BL = 9.5 s, 10.3 s, and 15.4 s for 15 mL, 30 mL, and 60 mL saline flush volumes, respectively, measured as SI/T duration at the 75% SNR(max) level). Using saline flush volumes equal to or higher than 30 mL increased the slope of the SI/T curve. A continuous increase of INT(75%/80%) by using higher saline flush volumes was found. Different saline and Gd volumes did not affect the SNR(max) and the BAT. Only the low dose (0.05 mmol/kg Gd) showed a 17%-21.6% significantly lower SNR(max). The BL and the INT increased mainly by enlarging of applied Gd volume from single to double dose (BL(75%) and INT(75%) were 9.6 s and 1305, 12.3 s and 2121, 38.5 s and 6181, 37.8 s and 6613 for 5, 10, 20, and 30 mL applied Gd volume, respectively). The arterial bolus length benefits from increasing Gd and saline flush volumes due to increased venous bolus length and wash out effects of Gd within the injection site of the vein. Doses larger than a single dose are not needed to increase the SNR in contrast-enhanced magnetic resonance angiography images of the thoracic aorta.

Dynein, dynactin, and kinesin II's interaction with microtubules is regulated during bidirectional organelle transport.

The microtubule motors, cytoplasmic dynein and kinesin II, drive pigmented organelles in opposite directions in Xenopus melanophores, but the mechanism by which these or other motors are regulated to control the direction of organelle transport has not been previously elucidated. We find that cytoplasmic dynein, dynactin, and kinesin II remain on pigment granules during aggregation and dispersion in melanophores, indicating that control of direction is not mediated by a cyclic association of motors with these organelles. However, the ability of dynein, dynactin, and kinesin II to bind to microtubules varies as a function of the state of aggregation or dispersion of the pigment in the cells from which these molecules are isolated. Dynein and dynactin bind to microtubules when obtained from cells with aggregated pigment, whereas kinesin II binds to microtubules when obtained from cells with dispersed pigment. Moreover, the microtubule binding activity of these motors/dynactin can be reversed in vitro by the kinases and phosphatase that regulate the direction of pigment granule transport in vivo. These findings suggest that phosphorylation controls the direction of pigment granule transport by altering the ability of dynein, dynactin, and kinesin II to interact with microtubules.

Predictive validity of the New Zealand MacArthur Communicative Development Inventory: Words and Sentences.

This study assessed the long-term predictive validity of the MacArthur Communicative Development Inventories: Words and Sentences (CDI:WS; Fenson, Dale, Reznick, Thal, Bates, Hartung, Pethick & Reilly, 1993) for children's expressive and receptive vocabulary development. Sixty-one New Zealand children (31 females) were assessed with a New Zealand version of the CDI: WS at 1;7 and 2;1 and with the Expressive Vocabulary Test (Williams, 1997) and the Peabody Picture Vocabulary Test-III (Dunn & Dunn, 1997) at 2;8 and 3;4. Excellent reliability and good predictive validity was obtained for the NZ CDI:WS even over a 21-month delay. Predictive validity of the NZ CDI:WS for the PPVT-III was higher for children of mothers with less education. We discuss the implications of these results for use of the CDI:WS with children from a broad range of cultural and educational backgrounds.