Cystic echinococcosis in cattle and sheep caused by Echinococcus granulosus sensu stricto genotypes G1 and G3 in the USA.

BACKGROUND: Endemic domestic dog-ruminant cycles and human cystic echinococcosis caused by Echinococcus granulosus have been sporadically reported in the United States. However, there is a paucity of molecular data describing the genotypes and haplotypes of this important cestode in domestic ruminant hosts. METHODS: Ninety-four cysts from the lungs and/or livers of slaughtered beef cattle (76 samples), dairy cows (five samples) and sheep (13 samples) were collected from abattoirs in four states of the USA. Samples were genotyped at two mitochondrial loci, cox1 and nad5. Sequences were used to determine species, genotypes and haplotypes using median joining networks and Bayesian phylogenetic analyses. Cyst fertility was assessed in hematoxylin and eosin-stained sections. Additionally, previously reported autochthonous E. granulosus infections in the USA in various hosts were mapped. RESULTS: Based on cox1 sequences obtained from 94 cysts, 89 (94.7%) were identified as E. granulosus G1/G3, while five (5.3%) were Taenia hydatigena. Taenia hydatigena were only isolated from sheep. Based on nad5 sequences obtained from 89 hydatid cysts, 96.6% and 3.4% belonged to E. granulosus sensu stricto genotypes G1 and G3 respectively. Two haplotypes were found among E. granulosus cox1 sequences, neither of which was geographically unique. Six haplotypes were found among nad5 sequences in genotype G1, of which five were novel, while one haplotype was found in genotype G3. In the concatenated cox1-nad5 dataset, seven haplotypes were identified, of which six were geographically unique. All cysts from cattle were non-fertile. Four cysts from sheep were fertile. CONCLUSIONS: All genotyped samples belonged to E. granulosus s.s. This is the first study to our knowledge to confirm the presence of genotypes G1 and G3 in domestic cattle and sheep intermediate hosts in the USA and provide data for future diagnostic and epidemiological studies. Sequences have been deposited in GenBank (cox1 sequences: OR398494-OR398496, nad5 sequences: OR400695-OR400702).

Choclo virus (CHOV) recovered from deep metatranscriptomics of archived frozen tissues in natural history biorepositories.

BACKGROUND: Hantaviruses are negative-stranded RNA viruses that can sometimes cause severe disease in humans; however, they are maintained in mammalian host populations without causing harm. In Panama, sigmodontine rodents serve as hosts to transmissible hantaviruses. Due to natural and anthropogenic forces, these rodent populations are having increased contact with humans. METHODS: We extracted RNA and performed Illumina deep metatranscriptomic sequencing on Orthohantavirus seropositive museum tissues from rodents. We acquired sequence reads mapping to Choclo virus (CHOV, Orthohantavirus chocloense) from heart and kidney tissue of a two-decade old frozen museum sample from a Costa Rican pygmy rice rat (Oligoryzomys costaricensis) collected in Panama. Reads mapped to the CHOV reference were assembled and then validated by visualization of the mapped reads against the assembly. RESULTS: We recovered a 91% complete consensus sequence from a reference-guided assembly to CHOV with an average of 16X coverage. The S and M segments used in our phylogenetic analyses were nearly complete (98% and 99%, respectively). There were 1,199 ambiguous base calls of which 93% were present in the L segment. Our assembled genome varied 1.1% from the CHOV reference sequence resulting in eight nonsynonymous mutations. Further analysis of all publicly available partial S segment sequences support a clear relationship between CHOV clinical cases and O. costaricensis acquired strains. CONCLUSIONS: Viruses occurring at extremely low abundances can be recovered from deep metatranscriptomics of archival tissues housed in research natural history museum biorepositories. Our efforts resulted in the second CHOV genome publicly available. This genomic data is important for future surveillance and diagnostic tools as well as understanding the evolution and pathogenicity of CHOV.

A Genetic Locus in Elizabethkingia anophelis Associated with Elevated Vancomycin Resistance and Multiple Antibiotic Reduced Susceptibility.

The Gram-negative Elizabethkingia express multiple antibiotic resistance and cause severe opportunistic infections. Vancomycin is commonly used to treat Gram-positive infections and has also been used to treat Elizabethkingia infections, even though Gram-negative organisms possess a vancomycin permeability barrier. Elizabethkingia anophelis appeared relatively vancomycin-susceptible and challenge with this drug led to morphological changes indicating cell lysis. In stark contrast, vancomycin growth challenge revealed that E. anophelis populations refractory to vancomycin emerged. In addition, E. anophelis vancomycin-selected mutants arose at high frequencies and demonstrated elevated vancomycin resistance and reduced susceptibility to other antimicrobials. All mutants possessed a SNP in a gene (vsr1 = vancomycin-susceptibility regulator 1) encoding a PadR family transcriptional regulator located in the putative operon vsr1-ORF551, which is conserved in other Elizabethkingia spp as well. This is the first report linking a padR homologue (vsr1) to antimicrobial resistance in a Gram-negative organism. We provide evidence to support that vsr1 acts as a negative regulator of vsr1-ORF551 and that vsr1-ORF551 upregulation is observed in vancomycin-selected mutants. Vancomycin-selected mutants also demonstrated reduced cell length indicating that cell wall synthesis is affected. ORF551 is a membrane-spanning protein with a small phage shock protein conserved domain. We hypothesize that since vancomycin-resistance is a function of membrane permeability in Gram-negative organisms, it is likely that the antimicrobial resistance mechanism in the vancomycin-selected mutants involves altered drug permeability.

Genetic Determinants of Acinetobacter baumannii Serum-Associated Adaptive Efflux-Mediated Antibiotic Resistance.

Acinetobacter baumannii is a nosocomial pathogen of serious healthcare concern that is becoming increasingly difficult to treat due to antibiotic treatment failure. Recent studies have revealed that clinically defined antibiotic-susceptible strains upregulate the expression of a repertoire of putative drug efflux pumps during their growth under biologically relevant conditions, e.g., in human serum, resulting in efflux-associated resistance to physiologically achievable antibiotic levels within a patient. This phenomenon, termed Adaptive Efflux Mediated Resistance (AEMR), has been hypothesized to account for one mechanism by which antibiotic-susceptible A. baumannii fails to respond to antibiotic treatment. In the current study, we sought to identify genetic determinants that contribute to A. baumannii serum-associated AEMR by screening a transposon mutant library for members that display a loss of the AEMR phenotype. Results revealed that mutation of a putative pirin-like protein, YhaK, results in a loss of AEMR, a phenotype that could be complemented by a wild-type copy of the yhaK gene and was verified in a second strain background. Ethidium bromide efflux assays confirmed that the loss of AEMR phenotype due to pirin-like protein mutation correlated with reduced overarching efflux capacity. Further, flow cytometry and confocal microscopy measures of a fluorophore 7-(dimethylamino)-coumarin-4-acetic acid (DMACA)-tagged levofloxacin isomer, ofloxacin, further verified that YhaK mutation reduces AEMR-mediated antibiotic efflux. RNA-sequencing studies revealed that YhaK may be required for the expression of multiple efflux-associated systems, including MATE and ABC families of efflux pumps. Collectively, the data indicate that the A. baumannii YhaK pirin-like protein plays a role in modulating the organism's adaptive efflux-mediated resistance phenotype.

Staphylococcal Enterotoxins Promote Virulence in Bacterial Keratitis.

Purpose: Staphylococcus aureus is an important cause of corneal infections (keratitis). To better understand the virulence mechanisms mediating keratitis, a recent comparative genomics study revealed that a set of secreted enterotoxins were found with higher prevalence among ocular versus non-ocular S. aureus clinical infection isolates, suggesting a key role for these toxins in keratitis. Although well known to cause toxic shock syndrome and S. aureus food poisoning, enterotoxins have not yet been shown to mediate virulence in keratitis. Methods: A set of clinical isolate test strains, including a keratitis isolate that encodes five enterotoxins (sed, sej, sek, seq, ser), its corresponding enterotoxin deletion mutant and complementation strain, a keratitis isolate devoid of enterotoxins, and the non-ocular S. aureus strain USA300 along with its corresponding enterotoxin deletion and complementation strains, were evaluated for cellular adhesion, invasion and cytotoxicity in a primary corneal epithelial model as well as with microscopy. Additionally, strains were evaluated in an in vivo model of keratitis to quantify enterotoxin gene expression and measure disease severity. Results: We demonstrate that, although enterotoxins do not impact bacterial adhesion or invasion, they do elicit direct cytotoxicity in vitro toward corneal epithelial cells. In an in vivo model, sed, sej, sek, seq, ser were found to have variable gene expression across 72 hours of infection and test strains encoding enterotoxins resulted in increased bacterial burden as well as a reduced host cytokine response. Conclusions: Our results support a novel role for staphylococcal enterotoxins in promoting virulence in S. aureus keratitis.

Antimicrobial Drug-Drug Interactions in the Treatment of Infectious Keratitis.

PURPOSE: Infectious keratitis is a serious disease requiring immediate, intensive, and broad-spectrum empiric treatment to prevent vision loss. Given the diversity of organisms that can cause serious corneal disease, current guidelines recommend treatment with several antimicrobial agents simultaneously to provide adequate coverage while awaiting results of microbiology cultures. However, it is currently unknown how the use of multiple ophthalmic antimicrobial agents in combination may affect the efficacy of individual drugs. METHODS: Using a panel of 9 ophthalmic antibiotics, 3 antifungal agents, and 2 antiacanthamoeba therapeutics, fractional inhibitory concentration testing in the standard checkerboard format was used to study 36 antibiotic-antibiotic combinations, 27 antibiotic-antifungal combinations, and 18 antibiotic-antiacanthamoeba combinations against both Staphylococcus aureus and Pseudomonas aeruginosa for synergistic, additive, neutral, or antagonistic drug-drug interactions. RESULTS: We demonstrate that while most combinations resulted in no change in antimicrobial efficacy of individual components, the combination of erythromycin + polyhexamethylene biguanide was found to be antagonistic toward P. aeruginosa . Conversely, 18 combinations toward S. aureus and 15 combinations toward P. aeruginosa resulted in additive or synergistic activity, including 4 with improved activity toward both species. CONCLUSIONS: Understanding how drug-drug interactions may affect drug efficacy is critical to selecting the appropriate combination therapy and improving clinical outcomes of this blinding disease.

Assessment of Keratitis Severity Using Quantitative Image Analysis in an In Vivo Murine Model of Staphylococcus aureus Bacterial Keratitis.

Purpose: Bacterial keratitis (BK) severity in murine models has traditionally been measured by subjective clinical grading or quantification of ocular bacterial burden. This investigation explores an objective and repeatable quantification of slit lamp photography (SLP) images to measure BK severity. Methods: BALB/c strain mice underwent three parallel scratches of the right cornea with subsequent inoculation of 107Staphylococcus aureus cells. SLP imaging and clinical severity grading were performed at 48 hours post-infection. Stromal infiltrate (SI) area on SLP images were quantified. Bacterial burden was determined after enucleation and homogenization. Spearman rank correlations (rs) were used to estimate associations between SI area, clinical severity grades, and bacterial burden. Results: BALB/c strain mice (n = 14) were evaluated with an average SI area of 0.92 mm2 (standard deviation, SD = 0.65) and average bacterial burden of 3.16 × 105 colony forming units per milliliter (CFU/mL) (SD = 8.3 × 105). Clinical severity grade positively correlated with SI area (rs = 0.59, p = 0.0276) and bacterial burden (rs = 0.66, p = 0.0106). There was a trend towards positive association between SI area and bacterial burden (rs = 0.51, p = 0.0543). Conclusions: SLP annotation of SI area is correlated with clinical severity and may provide an objective, quantitative, and repeatable assessment of BK disease severity. Translational Relevance: SLP annotation of SI area is a novel quantitative method to evaluate bacterial keratitis severity longitudinally in mouse models which may be a powerful tool to better understand BK pathogenesis and response to treatments.

A comparison of Mini-FLOTAC and McMaster techniques, overdispersion and prevalence of parasites in naturally infected North American bison (Bison bison) in the USA.

Several quantitative diagnostic techniques are available to estimate gastrointestinal parasite counts in the feces of ruminants. Comparing egg and oocyst magnitudes in naturally infected samples has been a recommended approach to rank fecal techniques. In this study, we compared the Mini-FLOTAC (sensitivity of 5 eggs per gram (EPG)/oocysts per gram (OPG)) and different averaged replicates of the modified McMaster techniques (sensitivity of 33.33 EPG/OPG) in 387 fecal samples from 10 herds of naturally infected North American bison in the Central Great Plains region of the USA. Both techniques were performed with fecal slurries homogenized in a fill-FLOTAC device. In the study population, prevalence of strongyle eggs, Eimeria spp. oocysts, Moniezia spp. eggs and Trichuris spp. eggs was 81.4%, 73.9%, 7.5%, and 3.1%, respectively. Counts of strongyle eggs and Eimeria spp. oocysts obtained from 1 to 3 averaged technical replicates of the modified McMaster technique were compared to a single replicate of the Mini-FLOTAC. Correlation between the two techniques increased with an increase in the number of averaged technical replicates of the modified McMaster technique used to calculate EGP/OPG. The correlation for Moniezia spp. EPG when averaged triplicates of the modified McMaster technique were compared to a single replicate of the Mini-FLOTAC count was high; however, the correlation for Trichuris spp. eggs was low. Additionally, we used averaged counts from both techniques to show the overdispersion of parasites in bison herds.

The L-G phase transition in binary Cu-Zr metallic liquids.

The authors recently reported that undercooled liquid Ag and Ag-Cu alloys both exhibit a first order phase transition from the homogeneous liquid (L-phase) to a heterogeneous solid-like G-phase under isothermal evolution. Here, we report a similar L-G transition and heterogenous G-phase in simulations of liquid Cu-Zr bulk glass. The thermodynamic description and kinetic features (viscosity) of the L-G-phase transition in Cu-Zr simulations suggest it corresponds to experimentally reported liquid-liquid phase transitions in Vitreloy 1 (Vit1) and other Cu-Zr-bearing bulk glass forming alloys. The Cu-Zr G-phase has icosahedrally ordered cores versus fcc/hcp core structures in Ag and Ag-Cu with a notably smaller heterogeneity length scale Λ. We propose the L-G transition is a phenomenon in metallic liquids associated with the emergence of elastic rigidity. The heterogeneous core-shell nano-composite structure likely results from accommodating strain mismatch of stiff core regions by more compliant intervening liquid-like medium.

Genomics of Staphylococcus aureus ocular isolates.

Staphylococcus aureus is a major cause of ocular infections, often resulting in devastating vision loss. Despite the significant morbidity associated with these infections, little is yet known regarding the specific strain types that may have a predilection for ocular tissues nor the set of virulence factors that drive its pathogenicity in this specific biological niche. Whole genome sequencing (WGS) can provide valuable insight in this regard by providing a prospective, comprehensive assessment of the strain types and virulence factors driving disease among specific subsets of clinical isolates. As such, a set of 163-member S. aureus ocular clinical strains were sequenced and assessed for both common strain types (multilocus sequence type (MLST), spa, agr) associated with ocular infections as well as the presence/absence of 235 known virulence factors in a high throughput manner. This ocular strain set was then directly compared to a fully sequenced 116-member non-ocular S. aureus strain set curated from NCBI in order to identify key differences between ocular and non-ocular S. aureus isolates. The most common sequence types found among ocular S. aureus isolates were ST5, ST8 and ST30, generally reflecting circulating non-ocular pathogenic S. aureus strains. However, importantly, ocular isolates were found to be significantly enriched for a set of enterotoxins, suggesting a potential role for this class of virulence factors in promoting ocular disease. Further genomic analysis revealed that these enterotoxins are located on mobile pathogenicity islands, thus horizontal gene transfer may promote the acquisition of enterotoxins, potentially amplifying S. aureus virulence in ocular tissues.

Observation of an apparent first-order glass transition in ultrafragile Pt-Cu-P bulk metallic glasses.

An experimental study of the configurational thermodynamics for a series of near-eutectic Pt80-x Cu x P20 bulk metallic glass-forming alloys is reported where 14 < x < 27. The undercooled liquid alloys exhibit very high fragility that increases as x decreases, resulting in an increasingly sharp glass transition. With decreasing x, the extrapolated Kauzmann temperature of the liquid, T K , becomes indistinguishable from the conventionally defined glass transition temperature, T g For x < 17, the observed liquid configurational enthalpy vs. T displays a marked discontinuous drop or latent heat at a well-defined freezing temperature, T gm The entropy drop for this first-order liquid/glass transition is approximately two-thirds of the entropy of fusion of the crystallized eutectic alloy. Below T gm , the configurational entropy of the frozen glass continues to fall rapidly, approaching that of the crystallized eutectic solid in the low T limit. The so-called Kauzmann paradox, with negative liquid entropy (vs. the crystalline state), is averted and the liquid configurational entropy appears to comply with the third law of thermodynamics. Despite their ultrafragile character, the liquids at x = 14 and 16 are bulk glass formers, yielding fully glassy rods up to 2- and 3-mm diameter on water quenching in thin-wall silica tubes. The low Cu content alloys are definitive examples of glasses that exhibit first-order melting.

First-Order Phase Transition in Liquid Ag to the Heterogeneous G-Phase.

A molten metal is an atomic liquid that lacks directional bonding and is free from chemical ordering effects. Experimentally, liquid metals can be undercooled by up to ∼20% of their melting temperature but crystallize rapidly in subnanosecond time scales at deeper undercooling. To address this limited metastability with respect to crystallization, we employed molecular dynamics simulations to study the thermodynamics and kinetics of the glass transition and crystallization in deeply undercooled liquid Ag. We present direct evidence that undercooled liquid Ag undergoes a first-order configurational freezing transition from the high-temperature homogeneous disordered liquid phase (L) to a metastable, heterogeneous, configurationally ordered state that displays elastic rigidity with a persistent and finite shear modulus, µ. We designate this ordered state as the G-phase and conclude it is a metastable non-crystalline phase. We show that the L-G transition occurs by nucleation of the G-phase from the L-phase. Both the L- and G-phases are metastable because both ultimately crystallize. The observed first-order transition is reversible: the G-phase displays a first-order melting transition to the L-phase at a coexistence temperature, TG,M. We develop a thermodynamic description of the two phases and their coexistence boundary.

Pan-Genomic and Polymorphic Driven Prediction of Antibiotic Resistance in Elizabethkingia.

The Elizabethkingia are a genetically diverse genus of emerging pathogens that exhibit multidrug resistance to a range of common antibiotics. Two representative species, Elizabethkingia bruuniana and E. meningoseptica, were phenotypically tested to determine minimum inhibitory concentrations (MICs) for five antibiotics. Ultra-long read sequencing with Oxford Nanopore Technologies (ONT) and subsequent de novo assembly produced complete, gapless circular genomes for each strain. Alignment based annotation with Prokka identified 5,480 features in E. bruuniana and 5,203 features in E. meningoseptica, where none of these identified genes or gene combinations corresponded to observed phenotypic resistance values. Pan-genomic analysis, performed with an additional 19 Elizabethkingia strains, identified a core-genome size of 2,658,537 bp, 32 uniquely identifiable intrinsic chromosomal antibiotic resistance core-genes and 77 antibiotic resistance pan-genes. Using core-SNPs and pan-genes in combination with six machine learning (ML) algorithms, binary classification of clindamycin and vancomycin resistance achieved f1 scores of 0.94 and 0.84, respectively. Performance on the more challenging multiclass problem for fusidic acid, rifampin and ciprofloxacin resulted in f1 scores of 0.70, 0.75, and 0.54, respectively. By producing two sets of quality biological predictors, pan-genome genes and core-genome SNPs, from long-read sequence data and applying an ensemble of ML techniques, our results demonstrated that accurate phenotypic inference, at multiple AMR resolutions, can be achieved.

Transcriptional profiling and metabolomic analysis of Staphylococcus aureus grown on autoclaved chicken breast.

Although Staphylococcus aureus is a major cause of food poisoning, little is known about its response to growth on food. Utilizing a transcriptional profiling and metabolomics approach, we compared S. aureus grown on autoclaved chicken breast (ACB) to Luria broth agar. ACB cultures demonstrated increased expression of genes associated with protein synthesis, cofactors, secondary metabolites, nitrogen and nucleotide metabolism, amino acid transport, and reduced expression of general stress, lipid metabolism, and virulence genes. The ACB culture also displayed characteristics of catabolite de-repression and anaerobic growth, and increased expression of arginine biosynthesis genes (argFGH) and an arginine/ornithine antiporter gene (arcD). S. aureus synthesizes arginine from proline and the ACB culture exhibited increased expression of proline transport genes (opuBA, opuBB and putP) and increased proline accumulation. Amino acid and sugar content in the ACB grown culture increased, and this was attributed to the consumption of ACB, transport of amino acids, and gluconeogenesis. Genes involved with biotin biosynthesis and uptake were upregulated and biotin is required for amino acid catabolism. Genes encoding urease and urease activity were upregulated in ACB cultures, while urea levels were reduced. This research provides fundamental information on the response of S. aureus growing on chicken meat that could find application in future attempts to reduce the growth of S. aureus in food.

Designing color in metallic glass.

"Designing" metallic glasses to exhibit properties beyond those offered within the narrow composition ranges where glass formation is possible poses a formidable scientific challenge. This challenge may be tackled by forming composite structures comprising a metallic glass matrix and homogeneously precipitated dendrites, known as "metallic glass matrix composites" (MGMCs). In principle, MGMCs can be designed to exploit the attractive performance characteristics of the metallic glass while alleviating its negative undesirable attributes. In this work we introduce a MGMC development concept for designing color in metallic glass. MGMCs consisting of a white-gold metallic glass matrix with finely dispersed yellow-gold microdendrites are explored. A series of gold MGMCs is developed displaying uniform and visually-unresolved yellow colors over a broad range of chromaticity, along with high overall hardness. This design concept paves the way for the development of a new generation of metal alloys that combine advanced engineering performance with attractive cosmetic attributes.

Surface tension and viscosity of liquid Pd43Cu27Ni10P20 measured in a levitation device under microgravity.

Here we present measurements of surface tension and viscosity of the bulk glass-forming alloy Pd43Cu27Ni10P20 performed during containerless processing under reduced gravity. We applied the oscillating drop method in an electromagnetic levitation facility on board of parabolic flights. The measured viscosity exhibits a pronounced temperature dependence following an Arrhenius law over a temperature range from 1100 K to 1450 K. Together with literature values of viscosity at lower temperatures, the viscosity of Pd43Cu27Ni10P20 can be well described by a free volume model. X-ray diffraction analysis on the material retrieved after the parabolic flights confirm the glassy nature after vitrification of the bulk samples and thus the absence of crystallization during processing over a wide temperature range.

The draft genomes of Elizabethkingia anophelis of equine origin are genetically similar to three isolates from human clinical specimens.

We report the isolation and characterization of two Elizabethkingia anophelis strains (OSUVM-1 and OSUVM-2) isolated from sources associated with horses in Oklahoma. Both strains appeared susceptible to fluoroquinolones and demonstrated high MICs to all cell wall active antimicrobials including vancomycin, along with aminoglycosides, fusidic acid, chloramphenicol, and tetracycline. Typical of the Elizabethkingia, both draft genomes contained multiple copies of ß-lactamase genes as well as genes predicted to function in antimicrobial efflux. Phylogenetic analysis of the draft genomes revealed that OSUVM-1 and OSUVM-2 differ by only 6 SNPs and are in a clade with 3 strains of Elizabethkingia anophelis that were responsible for human infections. These findings therefore raise the possibility that Elizabethkingia might have the potential to move between humans and animals in a manner similar to known zoonotic pathogens.

Castable Bulk Metallic Glass Strain Wave Gears: Towards Decreasing the Cost of High-Performance Robotics.

The use of bulk metallic glasses (BMGs) as the flexspline in strain wave gears (SWGs), also known as harmonic drives, is presented. SWGs are unique, ultra-precision gearboxes that function through the elastic flexing of a thin-walled cup, called a flexspline. The current research demonstrates that BMGs can be cast at extremely low cost relative to machining and can be implemented into SWGs as an alternative to steel. This approach may significantly reduce the cost of SWGs, enabling lower-cost robotics. The attractive properties of BMGs, such as hardness, elastic limit and yield strength, may also be suitable for extreme environment applications in spacecraft.

Origin of embrittlement in metallic glasses.

Owing to their glassy nature, metallic glasses demonstrate a toughness that is extremely sensitive to the frozen-in configurational state. This sensitivity gives rise to "annealing embrittlement," which is often severe and in many respects limits the technological advancement of these materials. Here, equilibrium configurations (i.e., "inherent states") of a metallic glass are established around the glass transition, and the configurational properties along with the plane-strain fracture toughness are evaluated to associate the intrinsic glass toughness with the inherent state properties and identify the fundamental origin of embrittlement. The established correlations reveal a one-to-one correspondence between toughness and shear modulus continuous over a broad range of inherent states, suggesting that annealing embrittlement is controlled almost solely by an increasing resistance to shear flow. This annealing embrittlement sensitivity is shown to vary substantially between metallic glass compositions, and appears to correlate well with the fragility of the metallic glass.

How the toughness in metallic glasses depends on topological and chemical heterogeneity.

To gain insight into the large toughness variability observed between metallic glasses (MGs), we examine the origin of fracture toughness through bending experiments and molecular dynamics (MD) simulations for two binary MGs: Pd82Si18 and Cu46Zr54 The bending experiments show that Pd82Si18 is considerably tougher than Cu46Zr54, and the higher toughness of Pd82Si18 is attributed to an ability to deform plastically in the absence of crack nucleation through cavitation. The MD simulations study the initial stages of cavitation in both materials and extract the critical factors controlling cavitation. We find that for the tougher Pd82Si18, cavitation is governed by chemical inhomogeneity in addition to topological structures. In contrast, no such chemical correlations are observed in the more brittle Cu46Zr54, where topological low coordination number polyhedra are still observed around the critical cavity. As such, chemical inhomogeneity leads to more difficult cavitation initiation in Pd82Si18 than in Cu46Zr54, leading to a higher toughness. The absence of chemical separation during cavitation initiation in Cu46Zr54 decreases the energy barrier for a cavitation event, leading to lower toughness.