The desire for designing efficient synthetic methods that lead to industrially important nanomaterials has led a desire to more fully understand the mechanism of growth and how modern synthetic techniques can be employed. Microwave (MW) synthesis is one such technique that has attracted attention as a green, sustainable method. The reports of enhancement of formation rates and improved quality for MW driven reactions are intriguing, but the lack of understanding of the reaction mechanism and how coupling to the MW field leads to these observations is concerning. In this manuscript, the growth of a metal nanoparticles (NPs) in a microwave cavity is spectroscopically analyzed and compared with the classical autocatalytic method of NP growth to elucidate the underpinnings for the observed enhanced growth behavior for metal NPs prepared in a MW field. The study illustrates that microwave synthesis of nickel and gold NPs below saturation conditions follows the Finke–Watzky mechanism of nucleation and growth. The enhancement of the reaction arises from the size-dependent increase in MW absorption cross section for the metal NPs. For Ni, the presence of oxides is considered via theoretical computations and compared to dielectric measurements of isolated nickel NPs. The study definitively shows that MW growth can be modeled by an autocatalytic mechanism that directly leads to the observed enhanced rates and improved quality widely reported in the nanomaterial community when MW irradiation is employed.Keywords: autocatalytic; core/shell; mechanism; microwave; nanoparticle; nickel; spectroscopy;

Systematic growth of a soft-magnet Co shell (0.6 to 2.7 nm thick) around a hard-magnet Fe0.65Pt0.35 core (5 nm in diameter) has been achieved in a one-pot microwave synthesis. This controlled growth led to a 4-fold enhancement in the energy product of the core–shell assembly as compared to the energy product of bare Fe0.65Pt0.35 nanoparticles. The simultaneous enhancement of coercivity and saturation moment reflects the onset of theoretically predicted exchange-spring behavior. The demonstration of nanoscale exchange-spring magnets can lead to improved high-performance magnet design for energy applications.

Optical ruler methods employing multiple fluorescent labels offer great potential for correlating distances among several sites, but are generally limited to interlabel distances under 10 nm and suffer from complications due to spectral overlap. Here we demonstrate a multicolor surface energy transfer (McSET) technique able to triangulate multiple points on a biopolymer, allowing for analysis of global structure in complex biomolecules. McSET couples the competitive energy transfer pathways of Förster Resonance Energy Transfer (FRET) with gold-nanoparticle mediated Surface Energy Transfer (SET) in order to correlate systematically labeled points on the structure at distances greater than 10 nm and with reduced spectral overlap. To demonstrate the McSET method, the structures of a linear B-DNA and a more complex folded RNA ribozyme were analyzed within the McSET mathematical framework. The improved multicolor optical ruler method takes advantage of the broad spectral range and distances achievable when using a gold nanoparticle as the lowest energy acceptor. The ability to report distance information simultaneously across multiple length scales, short-range (10–50 Å), mid-range (50–150 Å), and long-range (150–350 Å), distinguishes this approach from other multicolor energy transfer methods.Keywords: Förster resonance energy transfer; long-range optical molecular ruler; noble metal nanoparticles; nucleic acid structure modeling; surface resonance energy transfer;

This paper describes the synthesis of Eu(III)-doped ZnB2O4 (B = Al(III) or Ga(III)) nanospinels with Eu(III) concentrations varying between 1% and 15.6%. The synthesis was achieved through a microwave (MW) synthetic methodology producing 3 nm particles by the thermal decomposition of zinc undecylenate (UND) and a metal 2,4-pentanedionate (B(acac)3, B = Al3+ or Ga3+) in oleylamine (OAm). The nanospinels were then ligand exchanged with the β-diketonate, 2-thenoyltrifluoroacetone (tta). Using tta as a ligand on the surface of the particles resulted in soluble materials that could be embedded in lens mimics, such as poly(methyl methacrylate) (PMMA). Through a Dexter energy transfer mechanism, tta efficiently sensitized the Eu(III) doped within the nanospinels, resulting in red phosphors with intrinsic quantum efficiencies (QEs) and QEs in PMMA as high as 50% when excited in the UV. Optical measurements on the out of batch and tta-passivated nanospinels were done to obtain absorption, emission, and lifetime data. The structural properties of the nanospinels were evaluated by ICP-MS, pXRD, TEM, FT-IR, EXAFS, and XANES.

Microwave chemistry has revolutionized synthetic methodology for the preparation of organics, pharmaceuticals, materials, and peptides. The enhanced reaction rates commonly observed in a microwave have led to wide speculation about the function of molecular microwave absorption and whether the absorption leads to microwave specific effects and enhanced molecular heating. The comparison of theoretical modeling, reactor vessel design, and dielectric spectroscopy allows the nuance of the interaction to be directly understood. The study clearly shows an unaltered silicon carbide vessel allows measurable microwave penetration and therefore, molecular absorption of the microwave photons by the reactants within the reaction vessel cannot be ignored when discussing the role of molecular heating in enhanced molecular reactivity for microwave synthesis. The results of the study yield an improved microwave reactor vessel design that eliminates microwave leakage into the reaction volume by incorporating a noble metal surface layer onto a silicon carbide reaction vessel. The systematic study provides the necessary theory and measurements to better inform the arguments in the field.

Recent advances in cell transfection have suggested that delivery of a gene on a gold nanoparticle (AuNP) can enhance transfection efficiency. The mechanism of transfection is poorly understood, particularly when the gene is appended to a AuNP, as expression of the desired exogenous protein is dependent not only on the efficiency of the gene being taken into the cell but also on efficient endosomal escape and cellular processing of the nucleic acid. Design of a multicolor surface energy transfer (McSET) molecular beacon by independently dye labeling a linearized plasmid and short duplex DNA (sdDNA) appended to a AuNP allows spatiotemporal profiling of the transfection events, providing insight into package uptake, disassembly, and final plasmid expression. Delivery of the AuNP construct encapsulated in Lipofectamine2000 is monitored in Chinese hamster ovary cells using live-cell confocal microscopy. The McSET beacon signals the location and timing of the AuNP release and endosomal escape events for the plasmid and the sdDNA discretely, which are correlated with plasmid transcription by fluorescent protein expression within the cell. It is observed that delivery of the construct leads to endosomal release of the plasmid and sdDNA from the AuNP surface at different rates, prior to endosomal escape. Slow cytosolic diffusion of the nucleic acids is believed to be the limiting step for transfection, impacting the time-dependent expression of protein. The overall protein expression yield is enhanced when delivered on a AuNP, possibly due to better endosomal escape or lower degradation prior to endosomal escape.Keywords: energy transfer; gold nanoparticle; in vitro; molecular beacon; optical imaging; SET; transfection;

Mesenchymal stem cells (MSC) have been identified as having great potential as autologous cell therapeutics to treat traumatic brain injury and spinal injury as well as neuronal and cardiac ischemic events. All future clinical applications of MSC cell therapies must allow the MSC to be harvested, transfected, and induced to express a desired protein or selection of proteins to have medical benefit. For the full potential of MSC cell therapy to be realized, it is desirable to systematically alter the protein expression of therapeutically beneficial biomolecules in harvested MSC cells with high fidelity in a single transfection event. We have developed a delivery platform on the basis of the use of a solid gold nanoparticle that has been surface modified to produce a fusion containing a zwitterionic, pentapeptide designed from Bax inhibiting peptide (Ku70) to enhance cellular uptake and a linearized expression vector to induce enhanced expression of brain-derived neurotrophic factor (BDNF) in rat-derived MSCs. Ku70 is observed to effect >80% transfection following a single treatment of femur bone marrow isolated rat MSCs with efficiencies for the delivery of a 6.6 kbp gene on either a Au nanoparticle (NP) or CdSe/ZnS quantum dot (QD). Gene expression is observed within 4 d by optical measurements, and secretion is observed within 10 d by Western Blot analysis. The combination of being able to selectively engineer the NP, to colocalize biological agents, and to enhance the stability of those agents has provided the strong impetus to utilize this novel class of materials to engineer primary MSCs.

Single-stranded DNA sequences that are highly specific for a target ligand are called aptamers. While the incorporation of aptamer sequences into stem-loop molecular beacons has become an essential tool in optical biosensors, the design principles that determine the magnitude of binding affinity and its relationship to placement of the aptamer sequence in the stem-loop architecture are not well defined. By controlled placement of the aptamer along the loop region of the molecular beacon, it is observed that the binding affinity can be tuned over 4 orders of magnitude (1.3 nM – 203 μM) for the Huizenga and Szostak ATP DNA aptamer sequence. It is observed that the Kd is enhanced for the fully exposed sequence, with reduced binding affinity when the aptamer is part of the stem region of the beacon. Analysis of the ΔG values indicate a clear correlation between the aptamer hybridized length in the stem and its observed Kd. The use of a nanometal surface energy transfer probe method for monitoring ATP binding to the aptamer sequence allows the observation of negative cooperativity between the two ATP binding events. Maintenance of the high binding affinity of this ATP aptamer and the observation of two separate Kd’s for ATP binding indicate NSET as an effective, nonmanipulative, optical method for tracking biomolecular changes.

The interaction of a fluorescent molecule with a gold nanoparticle is complex and can lead to excited-state enhancement or quenching. Many attempts have been made to explain the observed interaction when in close proximity to the metal surface; yet no single model has been capable of explaining the observations. In this work, we show that by accurately describing the interaction in terms of an induced image dipole modified within the gold nanoparticle by the size-dependent changes in absorptivity and dielectric constant, the oscillator interaction can be fully described in terms of a surface-moderated interaction. Comparison of experimental and theoretical data confirms the validity of the model for a selected range of separation distances, nanoparticle radii, and fluorescent molecule selection. The results of the study illustrate the importance of nonradiative pathways for modifying the decay of a fluorescent molecule by coupling to the image dipole, thus providing a firm understanding of the reported variance in behavior for an emitting species in close proximity to nanometal surfaces. A more significant impact of the results is the ability to apply nanometal surface energy transfer methods as a molecular ruler to probe physical questions at much greater distances (>400 Å) than previously achievable.

The nature of the interfacial structure between the core and the arms of a tetrapod quantum dot (QD) formed during the heteroepitaxial growth of a ZnS arm onto a CdSe core is not well understood but can be analyzed through the use of high-frequency electron paramagnetic resonance (HF-EPR) spectroscopy. The spectroscopic resolution at high frequency allows the presence of unique crystal fields reflecting interfacial alloying to be analyzed by incorporating Mn(II) ions as a dopant into the QD to act as an intentional EPR active spectroscopic probe. In addition, the HF-EPR can spectroscopically observe the presence of ion vacancies that are anticipated to form at the heteroepitaxial interface to accommodate structural mismatch. The HF-EPR spectra for Mn(II) are extremely sensitive to perturbations of the microenvironment due to changes in the crystal field. The HF-EPR spectra of Mn(II) in a CdSe (core)/ZnS (arm) tetrapod exhibiting wurtzite symmetry for both core and interface of the tetrapod provide clear evidence of heteroalloying at the core–arm interface and formation of intrinsic dislocations at grain boundaries. The formation of the interfacial alloy and grain boundaries reflects short-range ion migration at the heteroepitaxial layer to reduce strain energy due to the 12% lattice mismatch between the wurtzite lattices of CdSe and ZnS.

Herein we report doping of ZnSe by Cr ions leads to formation of small ZnCr2Se4 spinel inclusions within the cubic sphalerite lattice of a 2.8 nm CrZnSe quantum dot (QD). The Cr ion incorporates as a pair of Cr(III) ions occupying edge-sharing tetragonal distorted octahedral sites generated by formation of three Zn ion vacancies in the sphalerite lattice in order to charge compensate the QD. The site is analogous to the formation of a subunit of the ZnCr2Se4 spinel phase known to form as inclusions during peritectoid crystal growth in the ternary CrZnSe solid-state compound. The oxidation state and site symmetry of the Cr ion is confirmed by X-ray absorption near edge spectroscopy (XANES), crystal field absorption spectroscopy, and electron paramagnetic resonance (EPR). Incorporation as the Cr(III) oxidation state is consistent with the thermodynamic preference for Cr to occupy an octahedral site within a II–VI semiconductor lattice with a half-filled t2g d-level. The measured crystal field splitting energy for the CrZnSe QD is 2.08 eV (2.07 eV form XANES), consistent with a spinel inclusion. Further evidence of a spinel inclusion is provided by analysis of the magnetic data, where antiferromagnetic (AFM) exchange, a Curie–Weiss (C–W) temperature of θ = −125 K, and a nearest-neighbor exchange coupling constant of JNN = −12.5 K are observed. The formation of stable spinel inclusions in a QD has not been previously reported.

A century ago Ostwald described the “Rule of Stages” after deducing that crystal formation must occur through a series of intermediate crystallographic phases prior to formation of the final thermodynamically stable structure. Direct evidence of the Rule of Stages is lacking, and the theory has not been implemented to allow isolation of a selected structural phase. Here we report the role of Ostwald’s Rule of Stages in the growth of CdSe quantum dots (QDs) from molecular precursors in the presence of hexadecylamine. It is observed that, by controlling the rate of growth through the reaction stoichiometry and therefore the probability of ion-packing errors in the growing QD, the initially formed zinc blende (ZB) critical nuclei representing the kinetic phase can be maintained at sizes >14 nm in diameter without phase transformation to the thermodynamic wurtzite (WZ) structure. An intermediate pseudo-ZB structure is observed to appear at intermediate reaction conditions, as predicted by Ostwald. The ZB and pseudo-ZB structures convert to the WZ lattice above a critical melting temperature. This study validates Ostwald’s Rule of Stages and provides a phase diagram for growth of CdSe QDs exhibiting a specific crystallographic motif.

A new advance in cell transfection protocol using a bimodal nanoparticle agent to selectively manipulate protein expression levels within mammalian cells is demonstrated. The nanoparticle based transfection approach functions by controlled release of gene regulatory elements from a 6 nm AuNP (gold nanoparticle) surface. The endosomal release of the regulatory elements from the nanoparticle surface results in endogenous protein knockdown simultaneously with exogenous protein expression for the first 48 h. The use of fluorescent proteins as the endogenous and exogenous signals for protein expression enables the efficiency of codelivery of siRNA (small interfering RNA) for GFP (green fluorescent protein) knockdown and a dsRed-express linearized plasmid for induction to be optically analyzed in CRL-2794, a human kidney cell line expressing an unstable green fluorescent protein. Delivery of the bimodal nanoparticle in cationic liposomes results in 20% GFP knockdown within 24 h of delivery and continues exhibiting knockdown for up to 48 h for the bimodal agent. Simultaneous dsRed expression is observed to initiate within the same time frame with expression levels reaching 34% after 25 days although cells have divided approximately 20 times, implying daughter cell transfection has occurred. Fluorescence cell sorting results in a stable colony, as demonstrated by Western blot analysis. The simultaneous delivery of siRNA and linearized plasmid DNA on the surface of a single nanocrystal provides a unique method for definitive genetic control within a single cell and leads to a very efficient cell transfection protocol.

The magnetic behavior for Mn:CdSe (0.6%) quantum dots (QDs) exhibits size-dependent magnetic exchange mediated by the concentration of intrinsic carriers, which arise from surface states. High temperature paramagnetic behavior that can be fit to a Brillouin function with weak low temperature antiferromagnetic (AFM) coupling is observed for the large Mn:CdSe (5.0 and 5.8 nm) QDs. The 2.8 and 4.0 nm Mn:CdSe QDs display a size-independent blocking temperature (TB) at 12 K, decreasing coercivity with increasing size, and a lowering of the activation barrier for spin relaxation as the QD is increased in size. The magnetic behavior is inconsistent with classical domain theory behavior for a superparamagnet (SPM) but can be accounted for in a carrier-mediated RKKY model. Fitting the susceptibility data reveals a Pauli-paramagnetic (PPM) component that is believed to arise from the presence of carriers. The carrier density is observed to scale with the surface to volume ratio in the QDs, indicating the carriers arise from surface states that are weakly localized resulting in the onset of long-distance carrier-mediated RKKY exchange inducing overall ferrimagnetism in the Mn:CdSe QDs when the carrier concentration is above a critical threshold.

Eu(III)-doped Y2O3 nanocrystals are prepared by microwave synthetic methods as spherical 6.4 ± 1.5 nm nanocrystals with a cubic crystal structure. The surface of the nanocrystal is passivated by acetylacetonate (acac) and HDA on the Y exposed facet of the nanocrystal. The presence of acac on the nanocrystal surface gives rise to a strong S0 → S1 (π → π*, acac) and acac → Ln3+ ligand to metal charge transfer (LMCT) transitions at 270 and 370 nm, respectively, in the Eu:Y2O3 nanocrystal. Excitation into the S0 → S1 (π → π*) or acac → Ln3+ LMCT transition leads to the production of white light emission arising from efficient intramolecular energy transfer to the Y2O3 oxygen vacancies and the Eu(III) Judd–Ofelt f–f transitions. The acac passivant is thermally stable below 400 °C, and its presence is evidenced by UV–vis absorption, FT-IR, and NMR measurements. The presence of the low-lying acac levels allows UV LED pumping of the solid phosphor, leading to high quantum efficiency (∼19%) when pumped at 370 nm, high-quality white light color rendering (CIE coordinates 0.33 and 0.35), a high scotopic-to-photopic ratio (S/P = 2.21), and thermal stability. In a LED lighting package luminosities of 100 lm W–1 were obtained, which are competitive with current commercial lighting technology. The use of the passivant to funnel energy to the lanthanide emitter via a molecular antenna effect represents a new paradigm for designing phosphors for LED-pumped white light.

A quantum dot (QD) contains a well-defined surface passivated by ligands and a bulklike core. The effect of surface passivation and lattice truncation on local structural and electronic microenvironments within a CdSe QD is an area of active research. Selectively probing the local microenvironments that exist at the surface and core of the QD is difficult but can be achieved by use of a Mn(II) impurity ion doped into a CdSe QD using electron paramagnetic resonance (EPR). By use of high frequency EPR (HF-EPR) spectroscopy, the site-dependent perturbation experienced for Mn(II) incorporated as a guest ion into CdSe QDs allows the distinguishing of two unique microenvironments within the QD, namely, an unperturbed core and an electronically distorted surface. Analysis of the Landé g-factor, hyperfine constant (A), and the distribution of g and D (Δg, ΔD) allows the local microenvironments within CdSe to be probed as a function of size, ligand passivation, and site of Mn(II) incorporation.

Nanometal surface energy transfer (NSET) is a molecular ruler technique that has been utilized to optically probe long distances in biomolecular structures. We investigate the useful spectral range of donor dyes and the importance of overlap between the localized surface plasmon resonance (LSPR) and the donor photoluminescence (520−780 nm) and provide a comprehensive study of the R0 values for the NSET processes from dyes to 2 nm Au NP (gold nanoparticle). The distance-dependent quenching results provide experimental evidence that the efficiency curve slope, R0 value, and distance of quenching is best modeled as a surface-mediated NSET process analogous to the predictions of Persson−Lang and Chance−Prock−Silbey (CPS). The results show that the LSPR plays a very important role in the observed quenching of excited-state donors at the surface of the nanometal, and the correlation to the NSET model allows a compilation of the necessary biophysical constants for application within the toolbox of biophysics.

Evidence of size-dependent reconstruction in quantum dots leading to changes in bonding is observed through analysis of the 77Se{1H} cross-polarization magic angle spinning and 77Se spin−echo solid-state NMR for Cd77Se quantum dots. The CP-MAS and spin−echo data indicate discrete surface and core 77Se sites exist with the QD, in which the surface is comprised of numerous reconstructed lattice planes. Due to the nearly 100% enrichment level for 77Se, efficient spin coupling is observed between the surface 77Se and sublayer 77Se sites due to spin diffusion in the Cd77Se quantum dots. The observed chemical shift for the discrete 77Se sites can be correlated to the effective mass approximation via the Ramsey expression, indicating a 1/r2 size dependence for the change in chemical shift with size, while a plot of chemical shift versus the inverse band gap is linear. The correlation of NMR shift for the discrete sites allows a valence bond theory interpretation of the size-dependent changes in bonding character within the reconstructed QD. The NMR results provide a structural model for the QDs in which global reconstruction occurs below 4 nm in diameter, while an apparent self-limiting reconstruction process occurs above 4 nm.

Through selective microwave absorption, we demonstrate the ability to activate TOPS as an efficient sulfur donor, allowing the rapid (18 m) growth of highly emissive (PLQY = 33%), Zn blende CdS quantum dots (QDs) passivated by TOP/TOPS in the 4−6 nm size regime (5% size dispersity). The CdS QDs exhibit sharp absorption features and bandedge photoluminescence even for the largest CdS sample. Addition of hexadecylamine restricts the growth rate by limiting the Cd monomer activity and lowers overall PLQY. The use of MW chemistry for QD formation allows a highly reproducible synthetic protocol that is fully adaptable to industrial applications.

Chemical transformations carried out under MW (microwave) irradiation often produce unexpected rate enhancements because of selective MW absorption by the reactants in the solution. We demonstrate unprecedented control over nucleation, growth, and Ostwald ripening in the formation of CdSe quantum dots (QDs), the quintessential quantum dot. The selectivity of the MW reactions is demonstrated by the ability to generate multiple, different sized QDs in the same reaction, where each QD component exhibits 6−7% size dispersity. The number of QDs in solution translates to color saturation (intensity), and the size of the QD translates to color index and is completely controlled by temperature and concentration in the MW reaction. The ability to repetitively generate nucleation and growth events in which a specific color index with defined color saturation is isolated from a single reaction offers potential for preparing mixed QD compositions for applications in optical bar-coding, white light emitting diodes (LEDs), and photovoltaics (PVs).

Whether assembling proteins onto nanoscale, mesoscopic, or macroscropic material surfaces, maintaining a protein’s structure and function when conjugated to a surface is complicated by the high propensity for electrostatic or hydrophobic surface interactions and the possibility of direct metal coordination of protein functional groups. In this study, the assembly of a 1.5 nm CAAKA passivated gold nanoparticle (AuNP) onto FGF1 (human acidic fibroblast growth factor) using an amino terminal His6 tag is analyzed. The impact of structure and time-dependent changes in the structural elements in FGF1and FGF1-heparin in the presence of the AuNP is probed by a molecular beacon fluorescence assay, circular dichroism, and NMR spectroscopy. Analysis of the results indicates that a time-dependent evolution of the protein structure without loss of FGF1 heparin binding occurs following the formation of the initial FGF1-AuNP complex. The time-dependent changes are believed to reflect protein sampling of the AuNP surface to minimize the free energy of the AuNP-FGF1 complex without impacting FGF1 function.

For biomolecular applications, potential interactions between newly developed dye molecules and the biomolecule of interest can dramatically influence the accuracy of optical ruler techniques. By utilizing nanometal surface energy transfer (NSET), an optical technique is developed that allows the nature of interactions between dyes and a biomolecule, namely DNA, to be directly assessed. To demonstrate the method, interactions between well-known molecular dyes based on carboxyfluorescein (FAM, noninteracting) and Cy5 (known intercalator) with DNA is probed. The results demonstrate that FAM exhibits no interactions with the DNA backbone and is adequately represented as a solvent exposed dye, while the commonly used near-IR dye Cy5 exhibits two discrete interactions that depend on the site of appendage and the length of the linker arm. The exact population and nature of Cy5 interaction with the DNA indicates a 37% ratio of intercalation for the internal C6, a 42% ratio for an internal C3 spacer length, and no evidence of interaction for terminal labeling. The results allow quantitative assignment of the site occupation of donors to be analyzed providing a powerful set of information for use of dyes in FRET based optical ruler technologies without the need of single molecule methods or the assumption of an averaged site occupation for the donor.

High quantum yield (47%) InP nanocrystals can be prepared without the need for post HF treatment by combining microwave methodologies with the presence of a fluorinated ionic liquid. Growing the InP nanocrystals in the presence of the ionic liquid 1-hexyl-3-methyl-imidazolium tetrafluoroborate (hmim BF4) allows in situ etching to be achieved. The optimization of the PL QY is achieved by balancing growth and etching rates in the reaction.

Microwave chemistry has revolutionized synthetic methodology for the preparation of organics, pharmaceuticals, materials, and peptides. The enhanced reaction rates commonly observed in a microwave have led to wide speculation about the function of molecular microwave absorption and whether the absorption leads to microwave specific effects and enhanced molecular heating. The comparison of theoretical modeling, reactor vessel design, and dielectric spectroscopy allows the nuance of the interaction to be directly understood. The study clearly shows an unaltered silicon carbide vessel allows measurable microwave penetration and therefore, molecular absorption of the microwave photons by the reactants within the reaction vessel cannot be ignored when discussing the role of molecular heating in enhanced molecular reactivity for microwave synthesis. The results of the study yield an improved microwave reactor vessel design that eliminates microwave leakage into the reaction volume by incorporating a noble metal surface layer onto a silicon carbide reaction vessel. The systematic study provides the necessary theory and measurements to better inform the arguments in the field.