Peak Asymmetry Research Articles

Ab-initio theory of photoionization via resonances.

We present an ab initio approach for computing the photoionization spectrum near autoionization resonances in multi-electron systems. While traditional (Hermitian) theories typically require computing the continuum states, which are difficult to obtain with high accuracy, our non-Hermitian approach requires only discrete bound and metastable states, which can be accurately computed with available quantum chemistry tools. We derive a simple formula for the absorption line shape near Fano resonances, which relates the asymmetry of the spectral peaks to the phase of the complex transition dipole moment. Additionally, we present a formula for the ionization spectrum of laser-driven targets and relate the "Autler-Townes" splitting of spectral lines to the existence of exceptional points in the Hamiltonian. We apply our formulas to compute the autoionization spectrum of helium, but our theory is also applicable for nontrivial multi-electron atoms and molecules.

Investigating the potential of Zernike polynomials to characterise spatial distribution of macular pigment.

It has been postulated that particular patterns of macular pigment (MP) distribution may be associated with the risk for eye diseases such as age-related macular degeneration (AMD). This work investigates the potential of Zernike polynomials (ZP) to characterise the level and distribution of MP, and their suitability as a representation for analysis of the effects of age and AMD on MP patterns. As the case study, MP distribution maps computed using an experimental method based on fundus reflectance (MRIA) were obtained for ninety volunteers representing three groups: under-fifty without AMD, fifty and over without AMD, and fifty and over with AMD. ZP with 105 coefficients were fitted to the maps using least-squares optimisation and found to represent MP maps accurately (RMSE<10−1). One-way MANOVA analysis carried out on ZP representations showed that the three subject groups have significantly different means (Wilk’s Lambda 0.125, p<0.0001). Linear discriminant analysis with leave-one-out scheme resulted in accuracy, sensitivity and specificity of classification according to, respectively, disease status regardless of age (81% all); disease status in the age-matched groups (87%, 88%, 86%); age irrespective of disease status (81%, 83%, 73%); and age for subjects without AMD (83%, 88%, 80%). Mean MP distributions computed from ZP coefficients for the three groups showed more elevated and more peaked MP for the healthy under-fifty group; more irregular and more elevated peripheral levels in over-fifty AMD group than in over-fifty non-AMD group; and moderate radial asymmetry in non-AMD over-50 group. The results suggest that ZP coefficients are capable of accurately representing MP in a way that captures certain spatial patterns of its distribution. Using the ZP representation MP maps could be classified according to both age and disease status with accuracy significantly greater than chance, with peak elevation, pattern irregularity and radial asymmetry identified as important features.

Quality by Design oriented development of hydrophilic interaction liquid chromatography method for the analysis of amitriptyline and its impurities

This paper presents integration of Quality by Design concept in the development of hydrophilic interactions liquid chromatographic methods for analysis of amitriptyline and its impurities (A, B, C, and F). This is the first time that HILIC method for amitriptyline and its impurities is developed. Using QbD concept, it is possible to design a robust method and incorporate quality directly into its development. QbD concept in combination of Design of Experiments methodology (DoE) enables creation of well-defined design space. In this study, for method optimization a Box-Behnken design was used to test the effect of acetonitrile content, buffer concentration and pH of water phase on critical system responses such as retention factor of impurity A, resolution between impurity B and impurity C, amitriptyline peak asymmetry factor and retention time of last eluted impurity F. The defined mathematical models and Monte Carlo simulations were used to identify the design space. For robustness testing, fractional factorial design was applied. Optimal chromatographic conditions were the analytical column ZORBAX NH2 (250 mm x 4.6 mm, 5 μm particle size); mobile phase consisted of acetonitrile-water phase (60 mM ammonium acetate, pH adjusted to 4.5 with glacial acetic acid) (92.5:7.5 v/v); column temperature 30 °C, mobile phase flow rate 1 mL min−1, wavelength of detection 254 nm. Finally, method was fully validated and applicability of the method in tablet analysis was confirmed.

Comparison of reversed-phase, anion-exchange, and hydrophilic interaction HPLC for the analysis of nucleotides involved in biological enzymatic pathways

Nucleotides and other phosphate-containing compounds are integral to enzymatic reactions such as those of the methylerythritol phosphate (MEP) pathway and glycolysis. Traditional chromatographic analysis of phosphates is often plagued by long run times and/or lack of MS compatibility. This study compares separation of five enzymatically-important nucleotides using ion-pair reversed phase (IP-RP), strong anion exchange (SAX), and hydrophilic interaction (HILIC) methods. These three methods were evaluated and compared based on separation parameters describing retention, resolution, efficiency, peak symmetry, selectivity, and inter- and intraday peak drift. Use of the FructoShell-N HILIC column led to separation of the five nucleotides isocratically with the shortest run time of all three methods tested. Additionally, the FructoShell HILIC method yielded a very low intraday variability and low peak asymmetry, issues that are often observed with HILIC separations on other stationary phases. To our knowledge, this column has not been applied to the separation of phosphates in biological samples and future work will focus on in vitro and in vivo analysis as well as broadening the applicability to other pathways. To this end, we have shown that the column will retain fructose bisphosphate, the substrate of the aldolase enzyme, under the same chromatographic conditions used for nucleotides.

Ballistic Dark Matter oscillates above ΛCDM

Dark matter may have been relativistic and collisional until relatively late times and become cold and collisionless after a phase transition before the matter-radiation equality of the standard ΛCDM cosmology. We show that such a dark matter has large peculiar velocities due to acoustic oscillations before the phase transition, and evolves ballistically after the phase transition in the collisionless phase until the initial acoustic velocities are redshifted away. We show that this Ballistic Dark Matter (BDM) results in new non-trivial interesting features in the cosmological observables. In particular, the linear matter power spectrum exhibits acoustic oscillations on scales smaller than the Hubble scale at the time of phase transition, and for fast transitions the power at the acoustic peaks in the matter power spectrum exceeds that in a ΛCDM cosmology. If BDM only forms a part of the total dark matter, an odd vs. even acoustic peak asymmetry becomes prominent. We give an approximate analytical treatment of the linear perturbations in BDM, explaining these features. We also discuss the possibility to constrain BDM using cosmic microwave background and large scale structure data.

Fast and direct determination of catechol-3, 6-bis(methyleiminodiacetic acid) prototype in beagle dog plasma using liquid chromatography tandem mass spectrometry: A simplified and high throughput in-vivo method for the metal chelator

It is usually somewhat difficult to analyze the metal chelators, especially in complex biological matrix, because of the interference of metal ions in both the matrix and analyzing system. In this study, an innovative and simple bioanalytical method was established and validated for the quantification of a newly developed uranium chelator catechol-3, 6-bis (methyleiminodiacetic acid) (CBMIDA) in beagle dog plasma. Different analytical columns and mobile phase were tested for effective chromatography resolution and sensitive and reproducible response of CBMIDA and the internal standard. An Agilent Zorbax SB AQ column was chosen. Excessive peak tailing, peak asymmetry, low recovery, and poor reproducibility, which are generally observed in chromatographic analysis of metal chelators, were overcome by the use of a pulse gradient method and addition of ethylene diamine tetraacetic acid (EDTA) to the mobile phase at 8 μg mL−1, enabling good peak shape, low matrix interference, high precision and good linearity for CBMIDA quantification in beagle dog plasma. Plasma sample pretreatment was performed by a simple, high throughput protein precipitation step with 2.5 mM EDTA methanol solution in a 96-well protein precipitation plate without complexing with the metal ions, and the sample was directly analyzed by electrospray ionization mass spectrometry. By shifting the analysis target from the metal complex to metal chelator itself, the method has an advantage over the existing method for determination of EDTA and diethylenetriaminepentaacetic acid owing to increased sample throughput and apparent simplicity. The assay was validated in accordance with the United States Food and Drug Administration guidelines and successfully applied to the pharmacokinetic study of CBMIDA in beagles after intramuscular injection of CBMIDA at different doses. The method was sensitive enough for the detection of CBMIDA concentration at 4 elimination half-times. The experimental strategies presented herein may be helpful for the measurement of other radionuclide chelators in biological matrices.

Definition of the interlayer interaction type in magnetic multilayers analyzing the shape of the ferromagnetic resonance peaks

We present a theoretical study of the ferromagnetic resonance in a system of two coupled magnetic layers. We show that an interaction between the layers leads to the occurrence of the so-called Fano resonance. The Fano resonance changes the shape of the ferromagnetic resonance peak. It introduces a peak asymmetry. The asymmetry type is defined by the sign of the interaction between the magnetic layers. Therefore, by studying the shape of the ferromagnetic resonance peaks, one can define the type of the interlayer coupling (ferromagnetic or antiferromagnetic).

Investigation of Chromatographic Parameters of a Capillary Column with Functionalized Poly(1-trimethylsilyl-1-propyne)

A comparative assessment of the chromatographic parameters of an Rt-Q-BOND commercial column and capillary columns 30 m × 0.32 mm with layers of functionalized poly(1-trimethylsilyl-1-propyne) (PTMSP/N2O) 0.5 and 0.8 μm thick is made with respect to the products (light (C1–C2) and aromatic hydrocarbons) of the catalytic reaction of ethylbenzene pyrolysis. It is shown that the peak resolution grows along with the thickness of the PTMSP/N2O layer grows. It is found that the measured retention parameters, resolution, and asymmetry of peaks of components on the column with the polymer layer 0.8 μm thick did not change after two years (~15 000 h) of column operation. This testifies to the stability of the PTMSP/N2O stationary phase. It is concluded that columns of the two investigated types selectively separate the products of the ethylbenzene pyrolysis. On the column with the functionalized polymer, the components elute at shorter retention times, and the shapes of the peaks are nearly Gaussian.

Chemical State Quantification of X-ray Auger Electron Spectrum with Top-Hat Filtering

The chemical state quantification of elements, especially transition metals and their compounds from X-ray Auger electron spectrum, is generally difficult due to the complexity of spectra resulting from peak asymmetries and overlapped binding energies. Moreover, background shape which contains information on surface contamination and roughness affects comparability of spectral fitting data on the element of interest. To promote practical use of spectral fitting for the chemical state quantification, the top-hat filtering (THF) was applied to Cu LMM Auger electron spectra. It was found that the THF suppressed the difference of background shapes derived from surface contamination and that oxidation states of Cu was quantified plausibly by least square fitting of standard spectra. Thus, it is suggested that the combination of the THF and least square fitting is a practical method for the chemical state quantification of X-ray Auger electron spectrum.

Factors affecting line shapes and intensities of Q3 and Q4 Raman bands of Cs silicate glasses

The Raman spectra of glasses containing 0 to 30 mol% Cs2O have been fit successfully with line shapes of dominantly Lorentzian character for the Q3 species, allowing quantification of Q3 and Q4 species intensities (Q represents a Si tetrahedron and the superscript indicates the number of bridging oxygen atoms, BOs, bonded to Si.) The intensity of the Q4 species A1 symmetric stretch is exceptionally weak in vitreous silica (v-SiO2) but it increases dramatically with addition of small amounts of Cs2O to the glass. We propose that Cs, where in close proximity to BO of Q4 species, promotes the polarizability of Q4 tetrahedra and these primed Q4 species (Q4-p) produce a strong Q4 signal. There are, therefore, two variants of the Q4 species, a Q4-p species which produces a strong signal, and an unprimed species (Q4-u) which yields a very weak signal. The increase in the abundance of the primed Q4 species (Q4-p) can be modelled as a function of alkali content using a simple, upper-bounded growth model:XQ4-p = (1 − e−kx)where XQ4-p is the fraction of polarizable Q4 species, k is a constant and x is the mol% counter oxide in the glass (here Cs2O). Comparison of calculated XQ4-p values with experimental results indicates that its cross-section is similar to that of the Q3 species.There is no evidence for a ~1050 cm−1 band in the 5 mol% Cs2O glass spectrum but in the 30 mol% Cs2O glass spectrum about 11% of spectral intensity is observed at about this frequency. The intensity likely results from development of asymmetry on the Q3 band, which increases with Cs2O content of the glass. The asymmetry results from weakened SiO force constants of some Q3 tetrahedra due to charge transfer via CsBO bonds. As evidence, Si 2p and O 1s X-ray Photoelectron Spectroscopic (XPS) studies demonstrate that the electron density over Si and BO atoms of Q4 species increases with Cs2O content. With charge transfer to tetrahedra, the negative charge accumulates preferentially on Si atoms thus decreasing SiO coulombic interactions, weakening SiO force constants, and shifting the Q3 A1 symmetric stretch vibrational frequencies to lower values (e.g., from ~1100 cm−1 to ~1050 cm−1). The fraction of affected Q3 species increases with alkali content, as does the Q3 peak asymmetry. The Raman shifts of the Q4 species are also affected by increased Cs2O contents.

Effect of the Mobile Phase Composition on Selectivity in Supercritical Fluid Chromatography in the Separation of Salbutamol Enantiomers

Three chiral chromatography stationary phases based on amylose and cellulose were tested for the supercritical fluid chromatography separation of antiasthmatic drug salbutamol enantiomers. A cellulose tris- 3-chloro-4-methylphenylcarbamate stationary phase provided the highest selectivity for this separation. The optimization of mobile phase composition allowed us to maximize the selectivity coefficient and to minimize the peak asymmetry factors. A successful salbutamol enantiomer separation is achieved at moderate modifier fraction (10–15 vol %) in the mobile phase on this column. Amine additives are necessary to suppress peak tailing. Among three tested amines isopropylamine gives the most symmetrical peaks along with the highest enantioselectivity.

Nanometer-Sized Crystalline Clusters of IGZO Films Determined from the Grazing Incidence X-ray Scattering and Anomalous X-ray Scattering Data Combined with Reverse Monte Carlo Simulations

Grazing incidence X-ray scattering measurements have been carried out on c-axis aligned crystalline-indium gallium zinc oxide (CAAC-IGZO) film and nanocrystalline category-indium gallium zinc oxide (NC-IGZO) film and the following results were obtained: (1) the characteristic layered structure of the IGZO crystal did not hold its shape and the X-ray scattering profile showed only a relatively sharp first peak at the wave vector (Q) = 21.8 for CAAC film and 23.1 nm−1 for NC film, respectively, and additional weak broad peaks were observed at a higher angle. (2) In the case of the CAAC film, tiny peaks were observed at Q = 7 and 14 nm−1, corresponding to the positions of the 003 and 006 reflections, respectively, of the IGZO crystal. Such tiny peaks were not detected in the case of NC film but the asymmetry of the first peak at the low angle side was clearly observed. (3) These structural features implied that more than three polyhedral units, such as InOx (x = 4–6), GaOy (y = 4–6), and ZnOz (z = 4–6), were likely to coexist. It is appropriate to call this structural feature as cluster-1. (4) A composite-type structure formed by combining these polyhedral units is also likely to exist and leads to middle-range ordering. This structure is called cluster-2. The size of such cluster-2 has been estimated to be 2.2 nm for CAAC film and 1.8 nm for NC film using the measured pair distribution function. To gain insights into the structural features of IGZO films, realistic atomic-scale models were obtained to fit not only the ordinary interference function of grazing incidence X-ray scattering but also the environmental interference function of the anomalous X-ray scattering (AXS) with Zn-absorption edge using reverse Monte Carlo (RMC) simulation. (5) The resultant models indicated the complex and irregular atomic arrangements of two types of IGZO films, which are well characterized by nanometer-sized crystalline clusters. This characteristic feature may be referred to as crystalline–cluster–composite (triple C) structure.

Investigation of the atomization mechanism of gold nanoparticles in graphite furnace atomic absorption spectrometry

Recently, graphite furnace atomic absorption spectrometry (GFAAS) has been introduced as a new tool to distinguish between silver ions and nanoparticles using graphite furnace atomic absorption spectrometry (GFAAS) by evaluation of the newly presented parameters atomization delay (tad) and atomization rate (kat). Moreover, sizing of NPs in aqueous suspensions by GFAAS measurement was shown by several authors. However, the atomization mechanism of NPs in GFAAS and possible differences to ionic salts introduced into the graphite furnace has not yet been investigated. In this work, therefore we study the newly introduced parameters and further peak characteristics, like full width at half maximum (FWHM), peak asymmetry and appearance time (tAP) and their concentration-dependent trends applying ionic gold Au(III) standards as well as 5- to 100-nm-sized gold nanoparticles (AuNPs), respectively. Interpretation of the data helps to enlighten the atomization mechanism and kinetic of the atom release process of AuNPs in comparison to ionic Au(III). Ionic Au(III) shows a rising trend in tad with increasing gold concentrations, whereas tad is nearly constant for AuNPs over this concentration range. On the other hand, AAS peaks of ionic Au(III) reveal constant tAP, while AuNPs show a shift in appearance time. Moreover, peak asymmetry differs for ionic Au(III) in comparison to AuNPs. These differences suggest different atomization mechanisms involved in the evaporation of gold atoms introduced into the graphite furnace as either ionic Au(III) solution or AuNP hydrosol.

Structural, electrical and relaxor properties of Sc-In solid solution in tetragonal tungsten bronze ceramics

The electrical properties of a family of tetragonal tungsten bronze (TTB) materials, Ba6Sc1-xInxNb9O30 (x = 0.25, 0.5, 0.75), which display relaxor properties were characterised using high- and low-temperature dielectric spectroscopy. All powders were synthesised at 1250 °C (24 h) + 1350 °C (6.5 h), while the pellets were further sintered at 1350 °C (12 h). At high temperature, the electrical conductivity in all samples is dominated by a single response, attributed to the bulk response, while the subtle asymmetry of the imaginary impedance peak suggests a minor contribution of the grain boundary response. In general, the Sc-In solid solutions samples exhibit similar electrical behaviour to the Sc compound, x = 1 reported previously (Ceram. Int. 2016, 42, 11810–11821). At low temperature all compounds exhibit frequency dependent relaxor behaviour. With increasing the content of In, the dielectric peaks are more asymmetric and the curves flatten more at temperatures above the transition temperature. The dipole freezing temperature, TVF, determined by Vogel-Fulcher (VF) analysis does not simply increase linearly as a function of M3+ (Sc3+,In3+) cation size, the extrapolation of VF-like curves results in considerably different values when compared to those found previously, since the acquired dielectric data are very sensitive to preparative conditions.

29Si NMR Chemical Shifts in Crystalline and Amorphous Silicon Nitrides.

We investigate 29Si nuclear magnetic resonance (NMR) chemical shifts, δiso, of silicon nitride. Our goal is to relate the local structure to the NMR signal and, thus, provide the means to extract more information from the experimental 29Si NMR spectra in this family of compounds. We apply structural modeling and the gauge-included projector augmented wave (GIPAW) method within density functional theory (DFT) calculations. Our models comprise known and hypothetical crystalline Si3N4, as well as amorphous Si3N4 structures. We find good agreement with available experimental 29Si NMR data for tetrahedral Si[4] and octahedral Si[6] in crystalline Si3N4, predict the chemical shift of a trigonal-bipyramidal Si[5] to be about −120 ppm, and quantify the impact of Si-N bond lengths on 29Si δiso. We show through computations that experimental 29Si NMR data indicates that silicon dicarbodiimide, Si(NCN)2 exhibits bent Si-N-C units with angles of about 143° in its structure. A detailed investigation of amorphous silicon nitride shows that an observed peak asymmetry relates to the proximity of a fifth N neighbor in non-bonding distance between 2.5 and 2.8 Å to Si. We reveal the impact of both Si-N(H)-Si bond angle and Si-N bond length on 29Si δiso in hydrogenated silicon nitride structure, silicon diimide Si(NH)2.

Evaluating nanocrystallite size distributions in doped and undoped nanocrystalline ceramics by X-ray diffractometry

Analytical expressions are formulated that enable the lognormal distribution of nanocrystallite sizes and the mean-squared crystal lattice microstrain in both doped and undoped nanocrystalline ceramics to be routinely determined by X-ray diffractometry. Importantly, these expressions, which are also applicable to most well-annealed nanocrystalline metals/alloys, are developed under the consideration that both the experimental and instrumental X-ray diffraction peaks are modeled by split Voigt functions to account for the (hitherto widely ignored) intrinsic peak asymmetry. The general analytical expressions of this new single-peak line-broadening method are then particularized to the case of small nanocrystallites with uniform composition for which a reasonable simplification (i.e., symmetrization of the experimental peak) can be made without compromising the accuracy of the results. Next, as an example of application the method developed is applied to the characterization of a nanocrystalline ceramic powder, and the nanocrystallite sizes so-determined are validated by transmission electron microscopy. The more complete and reliable microstructural information offered by this single-peak line-broadening method could contribute towards the accurate characterization of both doped and undoped nanocrystalline ceramics, and of most well-annealed nanocrystalline metals/alloys as well, a topic of particular research interest today.

Using Superficially Porous Particles and Ultrahigh Pressure Liquid Chromatography in Pharmacopeial Monograph Modernization of Common Analgesics

The higher pressures and flow rates needed to increase throughput in ultrahigh pressure liquid chromatography (UHPLC) can lead to thermal broadening due to viscous friction. The use of superficially porous particles and still air thermal environments can help reduce this broadening, but this has not yet been studied for applied, isocratic methods. Here, the use of five columns with varying lengths, diameters, and particle sizes were investigated for increased analytical throughput of pharmacopeial monograph methods for two over-the-counter analgesic drugs. System suitability parameters (resolution and peak asymmetry) and temperature changes across the axial length of the column were monitored at conditions near column or system pressure limits. Results from these investigations indicated that a 2.1 × 50-mm column packed with 2.6 µm particles provides the best opportunity for increased throughput, which was demonstrated with a 20-s cycle time method for the separation of four compounds (two active pharmaceutical ingredients, one impurity, and one internal standard) while maintaining a baseline resolution of 1.5 between all peaks.

Persistent geotropic positional nystagmus in unilateral cerebellar lesions.

To determine the prevalence of central lesions in persistent geotropic positional nystagmus, and characteristics and anatomical substrates of the nystagmus in cerebellar lesions. We prospectively recruited 58 patients with persistent geotropic positional nystagmus at the Dizziness Clinic of Pusan National University Hospital. Seven patients with unilateral cerebellar lesions were subjected to analysis of clinical characteristics, oculographic data, and MRI lesions. For comparison, we studied 37 cases of peripheral persistent geotropic positional nystagmus. The prevalence of central lesions in persistent geotropic positional nystagmus was 12% (7/58). Persistent geotropic positional nystagmus in cerebellar lesions was mostly asymmetrical. Horizontal nystagmus changed in direction during the bow-and-lean test with null positions. All patients showed impaired horizontal smooth pursuit bilaterally, and 3 of them also had positional downbeat nystagmus. The peak intensity and asymmetry of persistent geotropic positional nystagmus did not differ between central and peripheral groups (p > 0.05), while there was a difference in the maxima. Lesion overlays revealed that damage to the cerebellar tonsil was responsible for the generation of persistent geotropic positional nystagmus. Although persistent geotropic positional nystagmus in cerebellar lesions shares the characteristics of nystagmus measures with peripheral cases, accompanying central oculomotor signs can aid in differentiation. In tonsillar lesions, compensatory rotational feedback due to erroneous estimation of the direction of gravity may generate constant horizontal geotropic positional nystagmus.

Formation and identification of novel derivatives of primary amine and zwitterionic drugs

Gas chromatography-mass spectrometry (GC–MS) is a “workhorse” in the analysis of controlled substances in forensic laboratories. However, many drugs are not amenable to GC–MS due to thermal instability, non-ideal interactions in the column, or both. To improve the suitability of a molecule for analysis by GC–MS, derivatization can be employed. Derivatization replaces a labile hydrogen in the analyte molecule with a more stable functional group. In this paper, three different derivatization agents were tested for effectiveness with two classes of drugs: primary amines (i.e., amphetamine and 2C-I) and zwitterions (i.e., gabapentin, lorazepam, vigabatrin, pregabalin, and clorazepate). Trifluoroacetic anhydride (TFAA) was used as an acylating agent and N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) was used as a silylating agent. Dimethylformamide-dimethyl acetal (DMF-DMA), which has not been previously used for derivatization of drugs, was used as an alkylating agent. DMF-DMA was found to form dimethylaminomethylene derivatives with several primary amines and zwitterions. Amphetamine, 2C-I, gabapentin, and lorazepam were all detected in their underivatized form but generally suffered from peak asymmetry and band broadening. Derivatization resulted in drastic improvements in their chromatographic behavior. Vigabatrin, clorazepate and pregabalin were not detectable in their underivatized form. However, the trimethylsilyl (TMS) derivative of clorazepate was readily detected by GC–MS, as were the TMS and trifluoroacetyl (TFA) derivatives of vigabatrin. Derivatization of pregabalin was not successful, resulting in multiple chromatographic peaks with each derivatization agent. The mass spectra of several derivatives were not found in commercially available mass spectral databases. Hence, those spectra are reported here with interpretation of their fragmentation.

Precise implications for real-space pair distribution function modeling of effects intrinsic to modern time-of-flight neutron diffractometers.

Total scattering and pair distribution function (PDF) methods allow for detailed study of local atomic order and disorder, including materials for which Rietveld refinements are not traditionally possible (amorphous materials, liquids, glasses and nanoparticles). With the advent of modern neutron time-of-flight (TOF) instrumentation, total scattering studies are capable of producing PDFs with ranges upwards of 100-200 Å, covering the correlation length scales of interest for many materials under study. Despite this, the refinement and subsequent analysis of data are often limited by confounding factors that are not rigorously accounted for in conventional analysis programs. While many of these artifacts are known and recognized by experts in the field, their effects and any associated mitigation strategies largely exist as passed-down `tribal' knowledge in the community, and have not been concisely demonstrated and compared in a unified presentation. This article aims to explicitly demonstrate, through reviews of previous literature, simulated analysis and real-world case studies, the effects of resolution, binning, bounds, peak shape, peak asymmetry, inconsistent conversion of TOF to d spacing and merging of multiple banks in neutron TOF data as they directly relate to real-space PDF analysis. Suggestions for best practice in analysis of data from modern neutron TOF total scattering instruments when using conventional analysis programs are made, as well as recommendations for improved analysis methods and future instrument design.