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PubMed2026

Genomic and phenotypic characterization of Klebsiella pneumoniae phage KP Ø1: a novel lytic Slopekvirus targeting uropathogenic multidrug-resistant Klebsiella pneumoniae.

The rise of multidrug-resistant (MDR) uropathogenic gram-negative bacteria (GNB) necessitates the development of alternative therapeutic strategies. This study aimed to isolate, phenotypically characterize, and perform whole-genome sequencing of the bacteriophage demonstrating the broadest host range against MDR uropathogens. Fifty MDR GNB isolates were screened for lytic phages. The most promising candidate, Klebsiella pneumoniae phage KP Ø1, was characterized using plaque assay, Transmission Electron Microscopy (TEM), and pH/thermal stability testing. Genomic characterization was performed via whole-genome sequencing (WGS), with functional annotation and lifestyle prediction using PhaBOX and PhageScope software. Klebsiella pneumoniae was the most prevalent MDR uropathogen. Klebsiella pneumoniae phage KP Ø1 exhibited a 50% host range and high lytic titer (10⁸ PFU/mL). TEM revealed an icosahedral head and short contractile tail. Genomic characterization by WGS revealed that Klebsiella pneumoniae phage KP Ø1 possesses a 174,591 bp double-stranded deoxyribonucleic acid (dsDNA) genome containing 274 predicted open reading frames (ORFs). No lysogeny-related genes, toxins, or antibiotic resistance markers were detected, confirming its strictly lytic nature and supporting its potential as a candidate for phage therapy applications. The phage remained stable (10⁸ PFU/mL) across temperatures of - 20 °C to 50 °C; supporting its suitability for long-term biobanking and suggesting potential activity at physiological temperature, and across a pH range of 7-9. Klebsiella pneumoniae phage KP Ø1 is a novel, obligately lytic Slopekvirus whose genomic architecture, stability profile, and absence of lysogeny-associated, virulence, and antimicrobial resistance genes ( AMR) collectively support its candidacy for further preclinical evaluation as a phage therapy agent against uropathogenic MDR Klebsiella pneumoniae.

Klebsiella pneumoniae↗

PubMed2000

DC-ELF characterization of random mixtures of piecewise nonlinear media.

Biological tissues are ensembles of linear and nonlinear, symmetric and asymmetric constituents. As far as their electromagnetic characterization is concerned, they can be modeled as microscopic mixtures of the corresponding material media. Any medium volume can be properly discretized in a finite number of cells which can be modeled as an equivalent three dimensional network of lumped components, in order to characterize its electromagnetic behavior at wavelengths much longer than the relevant average linear size of the constitutive cells. Therefore, any mixture and the corresponding tissue can be characterized in terms of its effective conductance at extremely low frequency, with respect to a reference set of electrodes (ports of the equivalent network). When the above procedure is implemented for evaluating any of the aforesaid conductances, a resulting nonlinear characteristic should be expected. In reality, it may happen that the effect of the constitutive nonlinearities and the related asymmetries are smeared out by the randomness of the interconnections of the lumped components, leading at a macroscopic level to an isotropic constant equivalent conductance, i.e., to an isotropic constant equivalent conductivity of the mixture. The closed form analysis of a random network of nonlinear (piecewise linear) resistors offers a simple but clear cut example of such a property. This result, if extrapolated to biological media, suggests a new hint for explaining why there is no inconsistency between the typical electric characterization of biological tissues as almost linear macroscopic media, by means of their effective conductivity and permittivity, and the nonlinearities of the biochemical processes occurring in the tissue cells. In fact, the nonlinearities may not be observable by means of macroscopic electrical measurements because of the randomized spatial orientation and location of the processes.

Animals↗

PubMed2000

Molecular characterization of a highly heterogeneous mixture of glucosylceramides from a deep-water Mediterranean scleractinian coral Dendrophyllia cornigera.

We report here on the structural characterization of a highly heterogeneous mixture of glucosylceramides (GlcCers) isolated from a deep-water Mediterranian dendrophylliid coral, Dendrophyllia cornigera. The neutral glycosphingolipid (GSL) components of the coral were separated into three HPLC fractions which were structurally characterized by nuclear magnetic resonance (NMR) and mass spectrometry (MS). NMR analysis revealed a beta-glucosylpyranose, a methyl branched conjugated sphingadienine and alpha-hydroxy fatty acid moieties characteristic for the species. Molecular mass distributions of the HPLC fractions were monitored using single-stage MS. At least 17 different GlcCer constituents with variable long-chain base and fatty acid residues were observed based on the molecular ion peaks in the liquid secondary ion (LSI) survey spectra. Structures of the individual components were revealed by product ion spectra of the alkali-cationized molecules ([M + Cat](+)), which resulted in two characteristic fragment ions, F(F) and F(S). Tandem MS of the same fragment ions formed in the ion source showed that F(F) carries the hydoxy fatty acid, while F(S) carries the long-chain sphingoid base, thus providing complementary structural information for the characterization of ceramide composition. Based on the tandem mass spectra of the molecular ions [M + Na](+), 26 different GlcCers of the coral were identified. The ceramide moiety showed heterogeneity in both the sphingoid portion (d18:2, d19:2, d20:2 and d20:3) and the alpha-hydroxy fatty acid chain (h19-h24, either saturated or unsaturated), forming an extremely heterogeneous mixture. The method is generally applicable to the characterization of structurally heterogeneous GlcCer mixtures.

Animals↗

PubMed2000

Cell heterogeneity and subpopulations in solid tumors characterized by simultaneous immunophenotyping and DNA content analysis.

BACKGROUND: Heterogeneity in human malignant tumors is a well-described phenomenon and of interest with regard to subpopulations with differences in clonality, metastatic potential, and response to therapy under different treatment regimes. The aim of this study was the simultaneous characterization of surface markers and DNA content of solid tumors to identify tumor cell subpopulations and to study the association between the expression of antigens and DNA content. METHODS: In the present study, six different malignant tumors grown as xenografts in nude mice were characterized by five-parameter flow cytometry. Immunophenotyping was performed using a variety of direct fluorescence-conjugated antibodies. In all cases, simultaneous detection of DNA content was done after staining with 7-aminoactinomycin D. RESULTS: Tumor cells were characterized by light scatter properties, antigen expression, and DNA content. Tumor cell heterogeneity, subpopulations, and DNA content-dependent antigen expression were identified. CONCLUSIONS: This method offers the possibility of characterizing solid tumors according to their immunophenotype and DNA content. The results obtained can be used to identify changes in immunophenotypic and DNA profiles of tumor cell populations before and after therapy and might be useful to define parameters predictive for response to therapy.

Animals↗

PubMed2001

Synthesis and preliminary characterization of a high-affinity novel radioligand for the dopamine transporter.

In our effort to develop a novel radioligand selective for the dopamine transporter, compound 1b (O-972) was designed and characterized. The compound 1b was characterized for its binding both in monkey and rat striatum tissue, which demonstrated its high selectivity for the dopamine transporter (DAT) when its binding was compared with that at the serotonin transporter (SERT). The compound 5, which is a precursor for the tritiated radiolabel ligand [3H]O-972, was synthesized and biologically characterized. The preliminary characterization of this novel radioligand revealed its strong binding affinity for the DAT. Thus, the pharmacological profile of [3H]O-972 indicated that DAT inhibitors, which include GBR 12909, mazindol, CFT, and cocaine, could potently displace this novel radioligand from monkey brain striatum tissue. On the other hand, compounds known to be not selective for and potent at the DAT were very weak to do so. Initial binding results also indicate that [3H]O-972 may interact with the DAT in a manner that is not identical to that for GBR 12909 and tropane analogs.

Animals↗

PubMedDate not supplied

From gel filtration to biosensor technology: the development of chromatography for the characterization of protein interactions.

The objective of this review is to summarize the development of chromatographic techniques for the determination of reaction stoichiometries and equilibrium constants for solute interactions of biological importance. Gel chromatography is shown to offer a convenient means of characterizing solute self-association as well as solute-ligand interactions. Affinity chromatography is an even more versatile method of characterizing interactions between dissimilar reactants because the biospecificity incorporated into the design of the affinity matrix ensures applicability of the method regardless of the relative sizes of the two reactants. Adoption of different experimental strategies such as column chromatography, simple partition equilibrium experiments and biosensor technology has created a situation wherein affinity chromatography affords a means of characterizing the whole range of reaction affinities-from relatively weak interactions (binding constants less that 10(3)M (-1)) to tight interactions with binding constants greater than 10(9)M (-1). In addition to its established prowess as a means of solute separation and purification, chromatography thus also possesses considerable potential for investigation of the functional roles of the purified reactants-an endeavour that requires characterization as well as identification of the interactions responsible for a physiological phenomenon.

Biosensing Techniques↗

PubMed2002

Fine-tuned characterization at the solid/solution interface of organotin compounds grafted onto cross-linked polystyrene by using high-resolution MAS NMR spectroscopy.

The structural characterization of organotin compounds that are grafted onto insoluble cross-linked polymers has necessarily been limited to elemental analysis, infrared spectroscopy, and in a few instances, solid-state NMR spectroscopy. This important bottleneck in the development of such grafted systems has been addressed by using high-resolution magic angle spinning (hr-MAS) NMR spectroscopy. The great potential of this technique is demonstrated through the structural characterization of diphenylbutyl-(3,4) and dichlorobutylstannanes (5,6), grafted onto divinylbenzene cross-linked polystyrene by means of a suitable linker (1, 2). First, conditions suitable for the application of hr-MAS NMR spectroscopy were identified by characterizing the (1)H resonance line widths of the grafted organotin moiety following swelling of the functionalized beads in eight representative solvents. The presence of clearly identifiable tin coupling patterns in both the 1D (13)C and 2D (1)H-(13)C HSQC spectra, and the incorporation of (119)Sn chemical shift and connectivity information from hr-MAS 1D (119)Sn and 2D (1)H-(119)Sn HMQC spectra, provide an unprecedented level of characterization of grafted organotins directly at the solid/liquid interface. In addition, the use of hr-MAS (119)Sn NMR for reaction monitoring, impurity detection, and quantification and assessment of the extent of coordination reveals its promise as a novel tool for the investigation of polymer-grafted organotin compounds. The approach described here should be sufficiently general for extension to a variety of other nuclei of interest in polymer-supported organometallic chemistry.

Magnetic Resonance Spectroscopy↗

PubMed1995

Comment on "designing EMF experiments: what is required to characterize 'exposure'?".

Dr. Peter Valberg has written an excellent and clear paper describing our current understanding of the many facets of characterizing exposure to extremely-low-frequency (ELF) electric and magnetic fields. Dr. Valberg has directed his paper to the characterization of exposures used in laboratory experimentation. In this context, it seems to me that Valberg's program of exposure characterization can be accomplished with currently available instrumentation and with relatively modest effort. Thus, I have no fundamental problems with his recommendations and, really, have only a few minor comments to make. However, if one argues that Valberg's recommendations should be extended to the characterization of exposure in epidemiological research, I have serious reservations, which I will mention briefly at the end of this commentary.

Animals↗

PubMed2002

On-Line HPLC-UV-mass spectrometry and tandem mass spectrometry for the rapid delineation and characterization of differences in complex mixtures: a case study using toxic oil variants.

An integrated differential approach to the characterization of complex mixtures is presented which includes the targeting of liquid chromatography (LC) peaks for identification using characteristic UV adsorption of the LC peak, subsequent molecular weight and formula determination using accurate mass LC mass spectrometry (MS), and structure characterization using accurate mass LC-tandem mass spectrometry. The use of differential UV adsorption aids in narrowing the scope of the study to only specific peaks of interest. Accurate mass measurement of the molecular ion species provides molecular weight information as well as atomic composition information. The tandem MS (MS/MS) spectra provide fragmentation information which allows for structural characterization of each component. Accurate mass assignment of each of the fragment ions in the MS/MS spectrum provides atomic composition for each of the fragment ions and thus further aids in the structural characterization. These experiments are facilitated through the use of on-line LC-MS and LC-MS/MS with in-line UV detection. A synthetic toxic oil (STO) related to Toxic Oil Syndrome is studied with a focus on possible contaminants resulting from the interaction of aniline, used as a denaturant, with the normal components of the oil. A differential analysis between the STO and a control oil is performed. LC peaks were targeted using UV absorbance to indicate the possible presence of the aniline moiety. Further differential analysis was performed through the determination of the MS signals associated with each component separated on the LC. Finally, the MS/MS data was also used to determine if the fragmentation of the targeted components indicated the presence of aniline. The MS/MS and accurate mass data were used to assign the structures for the targeted components.

Chromatography, High Pressure Liquid↗

PubMed1992

Utility of the parent-neutral loss scan screening technique: partial characterization of urinary metabolites of U-78875 in monkey urine.

Metabolites of an antianxiety-sedative drug candidate (U-78875; 3-(5-cyclopropyl-1,2,4-oxadiazol-3-yl)-5-(1-methylethyl)-imidazo[1 ,5-alpha] quinoxalin-4(5H)-one (I)) present in the urine of monkeys were detected using tandem mass spectrometry (MS/MS) by application of parent ion scans and characterized or partially characterized by performing daughter ion scans of the pseudo-molecular ions of suspected metabolites. The use of liquid secondary ion mass spectrometry ionization of crude urinary extracts in combination with tandem quadrupole MS/MS analyses using parent ion scans of m/z 69 and subsequent daughter ion scans characterized unmetabolized I and N-dealkyl I (U-85466) and partially characterized aryl hydroxyl, aryl hydroxyl-N-dealkyl, aryl O-glucuronide, aryl O-glucuronide-N-dealkyl, aryl O-sulfate and aryl O-sulfate-N-dealkyl metabolites. From these data it was concluded that some of the metabolic pathways involved in the biotransformation of U-78875 include N-dealkylation, aryl hydroxylation and conjugation of aryl hydroxides. Several other metabolites of U-78875 not detected using this analytical approach were subsequently identified by alternative mass spectrometric approaches. These data clearly demonstrated both the utility and, just as important, the limitations of the parent-neutral loss scan screening technique in detecting drug metabolites in complex biological milieux.

Animals↗

PubMed1979

Intracellular marking with lucifer yellow CH and horseradish peroxidase of cells electrophysiologically characterized as glia in the cerebral cortex of the cat.

Intracellular microelectrodes filled with either Lucifer Yellow CH, a highly florescent dye, or horseradish peroxidase (HRP) were used to electrophysiologically characterize and mark cells in the cerebral cortex of cat. Fifty-eight cells, characterized electrophysiologically as glia, were marked with Lucifer Yellow CH. All were identified as protoplasmic astrocytes, and included cells in the glia limitans of the molecular layer. An additional 54 cells, similarly characterized as glia, were labeled with HRP. The results were the same; only protoplasmic astrocytes were labeled. The "staining quality" of the glia labeled with HRP was superior to that of cells injected with Lucifer Yellow; greater lengths of individual processes were revealed, and they could often be followed to blood vessels where they ended on the walls of vessels with expanded perivascular end-feet. The observations indicate that the many previously reported studies on presumed glial cells in the cat cerebral cortex have characterized the behavior of protoplasmic astrocytes. Neurons were also marked during these experiments. The "staining" quality of the Lucifer Yellow filled neurons was excellent; dendritic spines, axons, and axon collaterals were clearly visible. These fine neuronal details were not as well revealed after HRP labeling. High resting membrane potentials (RMP's) were not a prerequisite for obtaining well-marked neurons (mean RMP of Lucifer Yellow filled neurons was -33.6 mV; mean RMP of HRP filled neurons was 42.3 mV). In contrast, the mean RMPs of Lucifer Yellow and HRP marked glia was -68 Mv and -75 mV respectively, and the quality of "staining" appeared to be more closely related to the RMP.

Animals↗

PubMed2004

Characterization of novel antigens recognized by serum autoantibodies from anti-CD1 TCR-transgenic lupus mice.

In this study, we further characterize the humoral autoimmune response in the recently described anti-CD1 autoreactive T cell receptor-transgenic mouse lupus model (CD1 lupus model). We discovered and characterized novel autoantigens, comprising a protein of 105 kDa (p105) and a novel RNA molecule of 140 base pairs (bp) that is likely associated with p105, and several additional factors with distinct biochemical properties. In the CD1 lupus model, lethally irradiated BALB/c/nu/nu mice were injected intravenously with sorted bone marrow cells and sorted splenic T cells from donor BALB/c mice expressing TCR alpha and beta transgenes that encode autoreactivity for CD1d. Adoptive hosts injected with the single-positive (CD4(+) and CD8(+)) subset of transgenic cells developed anti-double-stranded DNA antibodies and a lupus-like illness. Sera were analyzed by Western blotting and immunoprecipitation. Antigens were characterized by biochemical and serological methods. Serum autoantibodies from 5 of 12 (42%) CD1 lupus mice immunoprecipitated a 105-kDa protein, termed p105. p105 was associated with a small RNA of approximately 140 bp. Anti-p105 autoantibodies appeared early in the course of disease. Serological and biochemical characterization suggested that p105 was distinct from known lupus autoantigens of similar molecular masses, indicating that p105 represents a novel autoantigen in lupus.

3T3 Cells↗

PubMed2005

Functional characterization of two-dimensional gel-separated proteins using sequential staining.

Proteins separated by two-dimensional (2-D) gel electrophoresis can be visualized using various protein staining methods. This is followed by downstream procedures, such as image analysis, gel spot cutting, protein digestion, and mass spectrometry (MS), to characterize protein expression profiles within cells, tissues, organisms, or body fluids. Characterizing specific post-translational modifications on proteins using MS of peptide fragments is difficult and labor-intensive. Recently, specific staining methods have been developed and merged into the 2-D gel platform so that not only general protein patterns but also patterns of phosphorylated and glycosylated proteins can be obtained. We used the new Pro-Q Diamond phosphoprotein dye technology for the fluorescent detection of phosphoproteins directly in 2-D gels of mouse leukocyte proteins, and Pro-Q Emerald 488 glycoprotein dye to detect glycoproteins. These two fluorescent stains are compatible with general protein stains, such as SYPRO Ruby stain. We devised a sequential procedure using Pro-Q Diamond (phosphoprotein), followed by Pro-Q Emerald 488 (glycoprotein), followed by SYPRO Ruby stain (general protein stain), and finally silver stain for total protein profile. This multiple staining of the proteins in a single gel provided parallel determination of protein expression and preliminary characterization of post-translational modifications of proteins in individual spots on 2-D gels. Although this method does not provide the same degree of certainty as traditional MS methods of characterizing post-translational modifications, it is much simpler, faster, and does not require sophisticated equipment and expertise in MS.

Animals↗

PubMed1992

Characterization of a complex chromosomal rearrangement maps the locus for in vitro complementation of xeroderma pigmentosum group D to human chromosome band 19q13.

Microcell-mediated chromosome transfer (MMCT) is a powerful genetic technique that permits the transfer of a single chromosome from one mammalian cell to another. The utility of MMCT for gene mapping strategies is critically dependent on the careful characterization of the chromosomes being transferred. We have recently reported the identification of a single rearranged human chromosome, designated Tneo, which corrects the UV sensitivity and excision repair defect of cells of xeroderma pigmentosum genetic complementation group D (XP-D) in culture (Flejter WL et al., Proc Natl Acad Sci USA 89:261-265, 1992). Additionally, those studies demonstrated a role for the excision repair cross-complementing 2 (ERCC2) gene in the observed phenotypic correction. We now report the results of detailed conventional and molecular cytogenetic characterization of the complementing Tneo chromosome. This analysis revealed a complex rearrangement involving material from human chromosomes 16, 17, and 19. Characterization of deletions of Tneo which retained or lost XP-D complementing ability mapped the gene responsible for phenotypic correction to a small region of the terminal q-arm of this chromosome. This region includes the previously described human DNA repair gene cluster located in the region 19q13.2-q13.3, a result consistent with the notion that the in vitro correction of XP-D cells by the Tneo chromosome is rendered by the ERCC2 locus. The data illustrate the potential value of detailed cytogenetic characterization of a human chromosome present in a somatic cell hybrid, even when that material involves complex rearrangements.

Cell Line↗

PubMed2005

Molecular characterization of a t(2;6) balanced translocation that is associated with a complex phenotype and leads to truncation of the TCBA1 gene.

The molecular characterization of balanced chromosomal rearrangements has often been a powerful tool for the positional identification of genes associated with specific diseases. In some instances, these rearrangements may be associated with a variety of different phenotypes, and thus establishing a genotype-phenotype correlation may be a complex process. However, molecular characterization of the rearrangement remains a useful tool for diagnoses or prognoses, or for identifying new genes and establishing a gene-to-function relationship. In this work we describe the characterization of a de novo balanced translocation t(2;6)(q24.3;q22.31) found in a patient with a complex phenotype. The major clinical finding was a severe neurological involvement. Thanks to the molecular characterization of this translocation we found that the rearrangement led to the truncation of the TCBA1 gene on chromosome 6q. We found that the gene is transcribed in different splice variants and is highly specific for the central nervous system. TCBA1 does not show any similarity with other known genes, and no information is available about its function. However, the gene appears to be well conserved among species, and we were able to infer the sequence of a putative mouse homolog of TCBA1. This allowed us to perform a more detailed expression study in mice, thus confirming its specificity for the nervous system. This finding is of particular interest because it suggests that TCBA1 may be correlated with the neurological phenotype of our patient, and possibly mutated in genetic diseases with a neurological phenotype.

Alternative Splicing↗

PubMed2001

Characterization of novel di- and tricarboxylic acids in fine tropical aerosols.

Three unknown di- and tricarboxylic acids were characterized in the fine size fraction of aerosols which were collected during the wet season in the Amazon basin (Rondonia, Brazil). For the structural characterization of the methyl esters of these unknown compounds, mass spectrometry with electron ionization (EI) and tandem mass spectral techniques combined with gas chromatographic (GC) separation were employed. Fragment and parent ion spectra were recorded during elution of the GC peaks by linked scanning of the B and E sectors in combination with high-energy collision-induced dissociation. The fragmentation patterns of significant ions in the first-order EI spectra were also obtained for nonanedioic acid, which was examined as a model compound. The compounds were tentatively identified as 4-acetyloxyheptanedioic acid and cis and trans isomers of 5-hexene-1,1,6-tricarboxylic acid. Since there were indications of biomass burning during the aerosol sampling the di- and tricarboxylic acids characterized in the present work could be markers for biomass burning. Furthermore, the characterization of di- and tricarboxylic acids in the fine size fraction of atmospheric aerosols may be important for assessing the effects of organic aerosols in cloud formation.

Aerosols↗

PubMed2006

Molecular detection and characterization of human enteroviruses directly from clinical samples using RT-PCR and DNA sequencing.

Enteroviruses are common human pathogens associated with a wide spectrum of symptoms ranging from asymptomatic infection to acute flaccid paralysis and neonatal multi-organ failure. Molecular methods that provide rapid diagnosis and increased sensitivity have been developed for the diagnosis of enterovirus infection using oligonucleotide primers complementary to conserved sequences located in the 5' untranslated region (UTR), but data generated from these regions are not sufficiently discriminatory for typing due to the lack of correlation between their nucleic acid sequence and serotype specificity. Sequences derived from the gene encoding the capsid VP1 correlate with serotype, and therefore provide the opportunity for the development of molecular typing methods consistent with present serogical methods. In this study, oligonucleotide primers that amplify a region of the 5'UTR to detect enterovirus RNA, and the region encoding the enterovirus VP1 N-terminus to characterize virus strains were used in nested and semi-nested RT-PCRs, respectively. The ability of the VP1 RT-PCR to amplify diverse viruses within genotypes and genogroups was confirmed by the correct identification of both prototype strains, and strains circulating currently of the same genotypes. The molecular methods proved their utility through the detection of enteroviruses that failed to grow in cell culture, their subsequent characterization and the characterization of strains that failed to serotype in neutralization assays. Molecular methods increased significantly the sensitivity of detection (P < 0.001) and of characterization (P < 0.01) of enteroviruses when compared to classical methods.

Amino Acid Sequence↗

PubMed1993

A method for production and characterization of metal prosthesis wear particles.

The wear of joint prostheses generates wear particles that produce an inflammatory response in the surrounding tissues and may contribute to bone resorption resulting in prosthetic loosening. Although the effects of particles produced from prosthetic materials have been studied extensively in vitro and in vivo, little attention has been paid to the standardisation of methods for the generation and characterization of these particles. This paper describes a reproducible method for generation of metal particles by the abrasive shaking of joint replacement components. Particular attention was given to the production of metal particles that closely resembled particles found around solid and loose human prostheses. To achieve this, particle size, size distribution, chemical composition, and shape were characterized. Particles that were 0.5-3.0 microns in diameter were isolated by differential sedimentation, and the distribution of particle sizes was determined with use of a Coulter Multisizer. Chemical composition was measured by atomic absorption spectrophotometry, and transmission electron microscopy was used to characterize particle shape. The techniques were shown to be reproducible, since there was little variation between batches over a lengthy time period. These or similar methods of particle production and characterization should be an essential part of future in vitro and in vivo studies of wear particles.

Alloys↗