40 research outputs found
Bulk Metallic Glasses Deform via Slip Avalanches
Inelastic deformation of metallic glasses occurs via slip events with
avalanche dynamics similar to those of earthquakes. For the first time in these
materials, measurements have been obtained with sufficiently high temporal
resolution to extract both the exponents and the scaling functions that
describe the nature, statistics and dynamics of the slips according to a simple
mean-field model. These slips originate from localized deformation in shear
bands. The mean-field model describes the slip process as an avalanche of
rearrangements of atoms in shear transformation zones (STZs). Small slips show
the predicted power-law scaling and correspond to limited propagation of a
shear front, while large slips are associated with uniform shear on
unconstrained shear bands. The agreement between the model and data across
multiple independent measures of slip statistics and dynamics provides
compelling evidence for slip avalanches of STZs as the elementary mechanism of
inhomogeneous deformation in metallic glasses.Comment: Article: 11 pages, 4 figures, plus Supplementary Material: 16 pages,
8 figure
Universal Slip Dynamics in Metallic Glasses and Granular Matter – Linking Frictional Weakening with Inertial Effects
Slowly strained solids deform via intermittent slips that exhibit a material-independent critical size distribution. Here, by comparing two disparate systems - granular materials and bulk metallic glasses - we show evidence that not only the statistics of slips but also their dynamics are remarkably similar, i.e. independent of the microscopic details of the material. By resolving and comparing the full time evolution of avalanches in bulk metallic glasses and granular materials, we uncover a regime of universal deformation dynamics. We experimentally verify the predicted universal scaling functions for the dynamics of individual avalanches in both systems, and show that both the slip statistics and dynamics are independent of the scale and details of the material structure and interactions, thus settling a long-standing debate as to whether or not the claim of universality includes only the slip statistics or also the slip dynamics. The results imply that the frictional weakening in granular materials and the interplay of damping, weakening and inertial effects in bulk metallic glasses have strikingly similar effects on the slip dynamics. These results are important for transferring experimental results across scales and material structures in a single theory of deformation dynamics
Stimulating TAM-mediated anti-tumor immunity with mannose-decorated nanoparticles in ovarian cancer
BACKGROUND: Current cancer immunotherapies have made tremendous impacts but generally lack high response rates, especially in ovarian cancer. New therapies are needed to provide increased benefits. One understudied approach is to target the large population of immunosuppressive tumor-associated macrophages (TAMs). Using inducible transgenic mice, we recently reported that upregulating nuclear factor-kappaB (NF-κB) signaling in TAMs promotes the M1, anti-tumor phenotype and limits ovarian cancer progression. We also developed a mannose-decorated polymeric nanoparticle system (MnNPs) to preferentially deliver siRNA payloads to M2, pro-tumor macrophages in vitro. In this study, we tested a translational strategy to repolarize ovarian TAMs via MnNPs loaded with siRNA targeting the inhibitor of NF-κB alpha (IκBα) using mouse models of ovarian cancer.
METHODS: We evaluated treatment with MnNPs loaded with IκBα siRNA (IκBα-MnNPs) or scrambled siRNA in syngeneic ovarian cancer models. ID8 tumors in C57Bl/6 mice were used to evaluate consecutive-day treatment of late-stage disease while TBR5 tumors in FVB mice were used to evaluate repetitive treatments in a faster-developing disease model. MnNPs were evaluated for biodistribution and therapeutic efficacy in both models.
RESULTS: Stimulation of NF-κB activity and repolarization to an M1 phenotype via IκBα-MnNP treatment was confirmed using cultured luciferase-reporter macrophages. Delivery of MnNPs with fluorescent payloads (Cy5-MnNPs) to macrophages in the solid tumors and ascites was confirmed in both tumor models. A three consecutive-day treatment of IκBα-MnNPs in the ID8 model validated a shift towards M1 macrophage polarization in vivo. A clear therapeutic effect was observed with biweekly treatments over 2-3 weeks in the TBR5 model where significantly reduced tumor burden was accompanied by changes in immune cell composition, indicative of reduced immunosuppressive tumor microenvironment. No evidence of toxicity associated with MnNP treatment was observed in either model.
CONCLUSIONS: In mouse models of ovarian cancer, MnNPs were preferentially associated with macrophages in ascites fluid and solid tumors. Evidence of macrophage repolarization, increased inflammatory cues, and reduced tumor burden in IκBα-MnNP-treated mice indicate beneficial outcomes in models of established disease. We have provided evidence of a targeted, TAM-directed approach to increase anti-tumor immunity in ovarian cancer with strong translational potential for future clinical studies
Ultrafast Radiographic Imaging and Tracking: An overview of instruments, methods, data, and applications
Ultrafast radiographic imaging and tracking (U-RadIT) use state-of-the-art
ionizing particle and light sources to experimentally study sub-nanosecond
dynamic processes in physics, chemistry, biology, geology, materials science
and other fields. These processes, fundamental to nuclear fusion energy,
advanced manufacturing, green transportation and others, often involve one mole
or more atoms, and thus are challenging to compute by using the first
principles of quantum physics or other forward models. One of the central
problems in U-RadIT is to optimize information yield through, e.g.
high-luminosity X-ray and particle sources, efficient imaging and tracking
detectors, novel methods to collect data, and large-bandwidth online and
offline data processing, regulated by the underlying physics, statistics, and
computing power. We review and highlight recent progress in: a.) Detectors; b.)
U-RadIT modalities; c.) Data and algorithms; and d.) Applications.
Hardware-centric approaches to U-RadIT optimization are constrained by detector
material properties, low signal-to-noise ratio, high cost and long development
cycles of critical hardware components such as ASICs. Interpretation of
experimental data, including comparisons with forward models, is frequently
hindered by sparse measurements, model and measurement uncertainties, and
noise. Alternatively, U-RadIT makes increasing use of data science and machine
learning algorithms, including experimental implementations of compressed
sensing. Machine learning and artificial intelligence approaches, refined by
physics and materials information, may also contribute significantly to data
interpretation, uncertainty quantification and U-RadIT optimization.Comment: 51 pages, 31 figures; Overview of ultrafast radiographic imaging and
tracking as a part of ULITIMA 2023 conference, Mar. 13-16,2023, Menlo Park,
CA, US
Atomic structure of Mg-based metallic glasses from molecular dynamics and neutron diffraction
We use a combination of classical molecular dynamics simulation and neutron diffraction to identify the atomic structure of five different Mg–Zn–Ca bulk metallic glasses, covering a range of compositions with substantially different behaviour when implanted in vitro. There is very good agreement between the structures obtained from computer simulation and those found experimentally. Bond lengths and the total correlation function do not change significantly with composition. The zinc and calcium bonding shows differences between composition: the distribution of Zn–Ca bond lengths becomes narrower with increasing Zn content, and the preference for Zn and Ca to avoid bonding to themselves or each other becomes less strong, and, for Zn–Ca, transforms into a positive preference to bond to each other. This transition occurs at about the same Zn content at which the behaviour on implantation changes, hinting at a possible structural connection. A very broad distribution of Voronoi polyhedra are also found, and this distribution broadens with increasing Zn content. The efficient cluster packing model, which is often used to describe the structure of bulk metallic glasses, was found not to describe these systems well
Genetic Diversity among Enterococcus faecalis
Enterococcus faecalis, a ubiquitous member of mammalian gastrointestinal flora, is a leading cause of nosocomial infections and a growing public health concern. The enterococci responsible for these infections are often resistant to multiple antibiotics and have become notorious for their ability to acquire and disseminate antibiotic resistances. In the current study, we examined genetic relationships among 106 strains of E. faecalis isolated over the past 100 years, including strains identified for their diversity and used historically for serotyping, strains that have been adapted for laboratory use, and isolates from previously described E. faecalis infection outbreaks. This collection also includes isolates first characterized as having novel plasmids, virulence traits, antibiotic resistances, and pathogenicity island (PAI) components. We evaluated variation in factors contributing to pathogenicity, including toxin production, antibiotic resistance, polymorphism in the capsule (cps) operon, pathogenicity island (PAI) gene content, and other accessory factors. This information was correlated with multi-locus sequence typing (MLST) data, which was used to define genetic lineages. Our findings show that virulence and antibiotic resistance traits can be found within many diverse lineages of E. faecalis. However, lineages have emerged that have caused infection outbreaks globally, in which several new antibiotic resistances have entered the species, and in which virulence traits have converged. Comparing genomic hybridization profiles, using a microarray, of strains identified by MLST as spanning the diversity of the species, allowed us to identify the core E. faecalis genome as consisting of an estimated 2057 unique genes
Crack-tip strain field mapping and the toughness of metallic glasses.
We have used high-energy x-ray scattering to map the strain fields around crack tips in fracture specimens of a bulk metallic glass under load at room temperature and below. From the measured strain fields we can calculate the components of the stress tensor as a function of position and determine the size and shape of the plastic process zone around the crack tip. Specimens tested at room temperature develop substantial plastic zones and achieve high stress intensities ((K(If) = 76 MPa m(1/2)) prior to fracture. Specimens tested at cryogenic temperatures fail at reduced but still substantial stress intensities (K(If) = 39 MPa m(1/2)) and show only limited evidence of crack-tip plasticity. We propose that the difference in behavior is associated with changes in the flow stress and elastic constants, which influence the number density of shear bands in the plastic zone and thus the strain required to initiate fracture on an individual band. A secondary effect is a change in the triaxial state of stress around the crack tip due to the temperature dependence of Poisson's ratio. It is likely that this ability to map elastic strains on the microscale will be useful in other contexts, although interpreting shifts in the position of the scattering peaks in amorphous materials in terms of elastic strains must be done with caution
Overview No.144 - Mechanical behavior of amorphous alloys
The mechanical properties of amorphous alloys have proven both scientifically unique and of potential practical interest, although the underlying deformation physics of these materials remain less firmly established as compared with crystalline alloys. In this article, we review recent advances in understanding the mechanical behavior of metallic glasses, with particular emphasis on the deformation and fracture mechanisms. Atomistic as well as continuum modeling and experimental work on elasticity, plastic flow and localization, fracture and fatigue are all discussed, and theoretical developments are connected, where possible, with macroscopic experimental responses. The role of glass structure on mechanical properties, and conversely, the effect of deformation upon glass structure, are also described. The mechanical properties of metallic glass-derivative materials – including in situ and ex situ composites, foams and nanocrystal-reinforced glasses – are reviewed as well. Finally, we identify a number of important unresolved issues for the field
Elastic constants.
<p>Young's modulus and Poisson ratio used for the stress calculations. Room-temperature data are from Ref. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0083289#pone.0083289-ChoiYim1" target="_blank">[39]</a> and the temperature dependence is estimated from data in Ref. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0083289#pone.0083289-Wang1" target="_blank">[40]</a>.</p