Mounting evidence is pointing to some emerging novel behaviors of metals with ultrafine-grain (UFG) and/or nanocrystalline (NC) microstructures. One such novel behavior is related to the ...thermodynamic and kinetic aspects of plastic response in the UFG/NC regime. Two inter-related parameters, viz., the strain rate sensitivity (SRS) and the activation volumes of plastic deformation, are used as fingerprints for the thermodynamics and kinetics of plastic deformation. Changes of these parameters with grain size may indicate transition of plastic deformation mechanisms. Therefore, investigations of these phenomena may bring out new strategies for ingenious design and synthesis of UFG/NC materials with desirable properties. In this article, we present a critical review on the experimental results and theories associated with the SRS of UFG/NC metals with different lattice structures, and the influences on some constitutive responses.
Acoustic metamaterials offer great flexibility for manipulating sound waves and promise unprecedented functionality, ranging from transformation acoustics, super-resolution imaging to acoustic ...cloaking. However, the design of acoustic metamaterials with exciting functionality remains challenging with traditional approaches using classic acoustic elements such as Helmholtz resonators and membranes. Here we demonstrate an ultraslow-fluid-like particle with intense artificial Mie resonances for low-frequency airborne sound. Eigenstate analysis and effective parameter retrieval show two individual negative bands in the single-size unit cell, one of which exhibits a negative bulk modulus supported by the monopolar Mie resonance, whereas the other exhibits a negative mass density induced by the dipolar Mie resonance. The unique single-negative nature is used to develop an ultra-sparse subwavelength metasurface with high reflectance for low-frequency sound. We demonstrate a 0.15λ-thick, 15%-filling ratio metasurface with an insertion loss over 93.4%. The designed Mie resonators provide diverse routes to construct novel acoustic devices with versatile applications.
Nanoindentation was used to measure hardness before and after room temperature He ion implantation on sputter-deposited V/Ag multilayers of different layer thickness as well as pure Ag and V. The ...radiation-induced hardening was found to decrease with decreasing individual layer thickness. No change in hardness after implantation was measured in multilayers with a layer thickness of less than 10nm, which is of the order of the average spacing of He bubbles. The pure V films exhibit significant hardening due to a dense distribution of 0.8nm diameter He bubbles, but in the nanocrystalline pure Ag films bubbles grow to a diameter of approximately 20nm and become ineffective in causing hardening. A model describing layer-thickness-dependent radiation hardening in multilayers was developed by extending the Friedel model to take into account the layer thickness and the He bubble spacing.
Small membrane proteins represent a largely unexplored yet abundant class of proteins in pro- and eukaryotes. They essentially consist of a single transmembrane domain and are associated with stress ...response mechanisms in bacteria. How these proteins are inserted into the bacterial membrane is unknown. Our study revealed that in Escherichia coli, the 27-amino-acid-long model protein YohP is recognized by the signal recognition particle (SRP), as indicated by in vivo and in vitro site-directed cross-linking. Cross-links to SRP were also observed for a second small membrane protein, the 33-amino-acid-long YkgR. However, in contrast to the canonical cotranslational recognition by SRP, SRP was found to bind to YohP posttranslationally. In vitro protein transport assays in the presence of a SecY inhibitor and proteoliposome studies demonstrated that SRP and its receptor FtsY are essential for the posttranslational membrane insertion of YohP by either the SecYEG translocon or by the YidC insertase. Furthermore, our data showed that the yohP mRNA localized preferentially and translation-independently to the bacterial membrane in vivo. In summary, our data revealed that YohP engages an unique SRP-dependent posttranslational insertion pathway that is likely preceded by an mRNA targeting step. This further highlights the enormous plasticity of bacterial protein transport machineries.
One of the most important issues related to adiabatic shear failure is the correlation among temperature elevation, adiabatic shear band (ASB) formation and the loss of load capacity of the material. ...Our experimental results show direct evidence that ASB forms several microseconds after stress collapse and temperature rise reaches its maximum about 30 μs after ASB formation. This observation indicates that temperature rise cannot be the cause of ASB. Rather, it might be the result of adiabatic shear localization. As such, the traditional well-accepted thermal-softening mechanism of ASB needs to be reconsidered.
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•The adiabatic shear failure process of solids was investigated for the first time by dynamic tests synchronically combined with high-speed photography and infrared temperature measurement.•The key ...characteristics of ASB, such as temperature, critical strain, propagation speed and cooling rate were systematically studied.•The experimental results shows that the apparent temperature rise might have occurred after ASB initiation, indicating it might not be the causation but the consequences of ASB.•The discovery might help to clarify the causality of ASB and serve as the starting point for further physical, mechanistic and mathematic studies of ASB.
One of the most important issues related to dynamic shear localization is the correlation among the stress collapse, temperature elevation and adiabatic shear band (ASB) formation. In this work, the adiabatic shear failure process of pure titanium was investigated by dynamic shear-compression tests synchronically combined with high-speed photography and infrared temperature measurement. The time sequence of important events such as stress collapse, ASB initiation, temperature rise and crack formation was recorded. The key characteristics of ASB, such as width, critical strain, temperature, propagation speed and cooling rate were systematically studied. The maximum propagation velocity of ASB is found in this work to be about 1900 m/s, about 0.6Cs (Cs is the shear wave speed). The maximum temperature within ASB is in the range of 350–650 °C, while the material close to ASB is also heated. The cooling rate of ASB is on the order of 106 °C/s, indicating that it needs a few hundreds of microseconds for the ASB to cool down to the ambient temperature. One important observation is that the apparent temperature rise occurs after ASB initiation, which indicates that it might not be the causation but the consequences of ASB. Further efforts are called for confirmation of this notion because of its significance.
Cholangiocarcinoma (CCA), a deadly malignancy of the bile ducts, can be classified based on its anatomical location into either intrahepatic (iCCA) or extrahepatic (eCCA), each with different ...pathogenesis and clinical management. There is limited understanding of the molecular landscape of eCCA and no targeted therapy with clinical efficacy has been approved. We aimed to provide a molecular classification of eCCA and identify potential targets for molecular therapies.
An integrative genomic analysis of an international multicenter cohort of 189 eCCA cases was conducted. Genomic analysis included whole-genome expression, targeted DNA-sequencing and immunohistochemistry. Molecular findings were validated in an external set of 181 biliary tract tumors from the ICGC.
KRAS (36.7%), TP53 (34.7%), ARID1A (14%) and SMAD4 (10.7%) were the most prevalent mutations, with ∼25% of tumors having a putative actionable genomic alteration according to OncoKB. Transcriptome-based unsupervised clustering helped us define 4 molecular classes of eCCA. Tumors classified within the Metabolic class (19%) showed a hepatocyte-like phenotype with activation of the transcription factor HNF4A and enrichment in gene signatures related to bile acid metabolism. The Proliferation class (23%), more common in patients with distal CCA, was characterized by enrichment of MYC targets, ERBB2 mutations/amplifications and activation of mTOR signaling. The Mesenchymal class (47%) was defined by signatures of epithelial-mesenchymal transition, aberrant TGFβ signaling and poor overall survival. Finally, tumors in the Immune class (11%) had a higher lymphocyte infiltration, overexpression of PD-1/PD-L1 and molecular features associated with a better response to immune checkpoint inhibitors.
An integrative molecular characterization identified distinct subclasses of eCCA. Genomic traits of each class provide the rationale for exploring patient stratification and novel therapeutic approaches.
Targeted therapies have not been approved for the treatment of extrahepatic cholangiocarcinoma. We performed a multi-platform molecular characterization of this tumor in a cohort of 189 patients. These analyses revealed 4 novel transcriptome-based molecular classes of extrahepatic cholangiocarcinoma and identified ∼25% of tumors with actionable genomic alterations, which has potential prognostic and therapeutic implications.
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•Integrative molecular characterization of extrahepatic cholangiocarcinoma was performed.•Targeted DNA-sequencing and whole-genome expression was conducted.•∼25% of extrahepatic cholangiocarcinoma have a putative actionable genomic alteration.•Four distinct molecular classes of extrahepatic cholangiocarcinoma were identified.
Recent advancements in bioanalytical techniques have led to the development of novel and robust diagnostic approaches that hold promise for providing optimal patient treatment, guiding prevention ...programs and widening the scope of personalized medicine. However, these advanced diagnostic techniques are still complex, expensive and limited to centralized healthcare facilities or research laboratories. This significantly hinders the use of evidence‐based diagnostics for resource‐limited settings and the primary care, thus creating a gap between healthcare providers and patients, leaving these populations without access to precision and quality medicine. Smartphone‐based imaging and sensing platforms are emerging as promising alternatives for bridging this gap and decentralizing diagnostic tests offering practical features such as portability, cost‐effectiveness and connectivity. Moreover, towards simplifying and automating bioanalytical techniques, biosensors and lab‐on‐a‐chip technologies have become essential to interface and integrate these assays, bringing together the high precision and sensitivity of diagnostic techniques with the connectivity and computational power of smartphones. Here, we provide an overview of the emerging field of clinical smartphone diagnostics and its contributing technologies, as well as their wide range of areas of application, which span from haematology to digital pathology and rapid infectious disease diagnostics.
Single-file diffusion, prevalent in many processes, refers to the restricted motion of interacting particles in narrow micropores with the mutual passage excluded. A single-filing system was ...developed by confining colloidal spheres in one-dimensional circular channels of micrometer scale. Optical video microscopy study shows evidence that the particle self-diffusion is non-Fickian for long periods of time. In particular, the distribution of particle displacement is a Gaussian function.
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