Natural selection is commonly assumed to act on extensive standing genetic variation. Yet, accumulating evidence highlights the role of mutational processes creating this genetic variation: to become ...evolutionarily successful, adaptive mutants must not only reach fixation, but also emerge in the first place, i.e. have a high enough mutation rate. Here, we use numerical simulations to investigate how mutational biases impact our ability to observe rare mutational pathways in the laboratory and to predict outcomes in experimental evolution. We show that unevenness in the rates at which mutational pathways produce adaptive mutants means that most experimental studies lack power to directly observe the full range of adaptive mutations. Modelling mutation rates as a distribution, we show that a substantially larger target size ensures that a pathway mutates more commonly. Therefore, we predict that commonly mutated pathways are conserved between closely related species, but not rarely mutated pathways. This approach formalizes our proposal that most mutations have a lower mutation rate than the average mutation rate measured experimentally. We suggest that the extent of genetic variation is overestimated when based on the average mutation rate.
Single-layer transition-metal dichalcogenides (TMDs) receive significant attention due to their intriguing physical properties for both fundamental research and potential applications in electronics, ...optoelectronics, spintronics, catalysis, and so on. Here, we demonstrate the epitaxial growth of high-quality single-crystal, monolayer platinum diselenide (PtSe2), a new member of the layered TMDs family, by a single step of direct selenization of a Pt(111) substrate. A combination of atomic-resolution experimental characterizations and first-principle theoretic calculations reveals the atomic structure of the monolayer PtSe2/Pt(111). Angle-resolved photoemission spectroscopy measurements confirm for the first time the semiconducting electronic structure of monolayer PtSe2 (in contrast to its semimetallic bulk counterpart). The photocatalytic activity of monolayer PtSe2 film is evaluated by a methylene-blue photodegradation experiment, demonstrating its practical application as a promising photocatalyst. Moreover, circular polarization calculations predict that monolayer PtSe2 has also potential applications in valleytronics.
The prediction of the glass-forming ability (GFA) by varying the composition of alloys is a challenging problem in glass physics, as well as a problem for industry, with enormous financial ...ramifications. Although different empirical guides for the prediction of GFA were established over decades, a comprehensive model or approach that is able to deal with as many variables as possible simultaneously for efficiently predicting good glass formers is still highly desirable. Here, by applying the support vector classification method, we develop models for predicting the GFA of binary metallic alloys from random compositions. The effect of different input descriptors on GFA were evaluated, and the best prediction model was selected, which shows that the information related to liquidus temperatures plays a key role in the GFA of alloys. On the basis of this model, good glass formers can be predicted with high efficiency. The prediction efficiency can be further enhanced by improving larger database and refined input descriptor selection. Our findings suggest that machine learning is very powerful and efficient and has great potential for discovering new metallic glasses with good GFA.
In this work, a novel surface roughness prediction model, in which the kinematics, plastic side flow, material spring back and random factors are considered, is theoretically formulated to reveal the ...underlying mechanisms for the observed size effect of surface roughness in diamond turning. In this newly developed model, the copy effect of tool edge waviness is successively integrated into the kinematic component, and a yield stress and minimum undeformed chip thickness related function is constructed for calculating the material spring back. For the component of plastic side flow, the effects of minimum undeformed chip thickness, tool nose radius, feed rate as well as cutting width are took into account. Moreover, the component of random factors is assumed to follow a Gaussian distribution. Theoretical predictions and experimental validations show that the feed rate dependent size effect of surface roughness as observed on the fine grain substrate is derived from the decrement of the kinematic component being less than the increment of the plastic side flow component. For the coarse grain substrate, the large and hard inclusion inevitably appears in the matrix. Therefore, the size effect of surface roughness can be attributed to the formation of pit defect and deep groove on the finished surface at large feed rate and the protrusion of hard inclusion from the finished surface at low feed rate.
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•A new surface model is developed in theory to explain the size effect of surface roughness.•Tool edge waviness is considered in modeling the kinematic roughness.•Plastic side flow is a function of tool nose radius, edge radius, cutting width and feed rate.•On fine grain substrate, the size effect depends on the large increment of plastic side flow.•On coarse grain substrate, the size effect is derived from the hard inclusions.
Aromatic carbonyl derivative sulfide polymers (see figure and inside cover) are described as a novel organic positive‐electrode material for Li‐ion batteries. The excellent capacity and cycling ...stability performances, as well as many advantages including, amongst others, high safety, make them a possible replacement for conventional inorganic transition‐metal‐oxide‐based materials.
Negative refraction of elastic waves has been studied and experimentally demonstrated in three- and two-dimensional phononic crystals, but Bragg scattering is impractical for low-frequency wave ...control because of the need to scale the structures to manageable sizes. Here we present an elastic metamaterial with chiral microstructure made of a single-phase solid material that aims to achieve subwavelength negative refraction of elastic waves. Both negative effective mass density and modulus are observed owing to simultaneous translational and rotational resonances. We experimentally demonstrate negative refraction of the longitudinal elastic wave at the deep-subwavelength scale in the metamaterial fabricated in a stainless steel plate. The experimental measurements are in good agreement with numerical simulations. Moreover, wave mode conversion related with negative refraction is revealed and discussed. The proposed elastic metamaterial may thus be used as a flat lens for elastic wave focusing.
The heterogeneous breast cancers can be classified into different subtypes according to their histopathological characteristics and molecular signatures. Foxa1 expression is linked with luminal ...breast cancer (LBC) with good prognosis, whereas Twist1 expression is associated with basal-like breast cancer (BLBC) with poor prognosis owing to its role in promoting epithelial-to-mesenchymal transition (EMT), invasiveness and metastasis. However, the regulatory and functional relationships between Twist1 and Foxa1 in breast cancer progression are unknown. In this study, we demonstrate that in the estrogen receptor (ERα)-positive LBC cells Twist1 silences Foxa1 expression, which has an essential role in relieving Foxa1-arrested migration, invasion and metastasis of breast cancer cells. Mechanistically, Twist1 binds to Foxa1 proximal promoter and recruits the NuRD transcriptional repressor complex to de-acetylate H3K9 and repress RNA polymerase II recruitment. Twist1 also silences Foxa1 promoter by inhibiting AP-1 recruitment. Twist1 expression in MCF7 cells silenced Foxa1 expression, which was concurrent with the induction of EMT, migration, invasion and metastasis of these cells. Importantly, restored Foxa1 expression in these cells largely inhibited Twist1-promoted migration, invasion and metastasis. Restored Foxa1 expression did not change the Twist1-induced mesenchymal cellular morphology and the expression of Twist1-regulated E-cadherin, β-catenin, vimentin and Slug, but it partially rescued Twist1-silenced ERα and cytokeratin 8 expression and reduced Twist1-induced integrin α5, integrin β1 and MMP9 expression. In a xenografted mouse model, restored Foxa1 also increased Twist1-repressed LBC markers and decreased Twist1-induced BLBC markers. Furthermore, Twist1 expression is negatively correlated with Foxa1 in the human breast tumors. The tumors with high Twist1 and low Foxa1 expressions are associated with poor distant metastasis-free survival. These results demonstrate that Twist1's silencing effect on Foxa1 expression is largely responsible for Twist1-induced migration, invasion and metastasis, but less responsible for Twist1-induced mesenchymal morphogenesis and expression of certain EMT markers.
The RNS(®) System is the first commercially available device to provide closed-loop responsive brain stimulation. The system includes a cranially implanted neurostimulator that continually monitors ...the electrocorticogram through one or two depth and/or subdural cortical strip leads that are placed at the seizure focus. When abnormal electrographic activity is detected, the neurostimulator delivers brief pulses of electrical stimulation to the seizure focus through the implanted leads. In November 2013, the US FDA approved the RNS System as an adjunctive therapy for patients with drug resistant, partial onset seizures who have undergone diagnostic testing that localized no more than 2 epileptogenic foci. Safety and effectiveness of the RNS System for the indicated patient population was demonstrated in a multicenter, randomized, sham-stimulation controlled 2-year pivotal study. An ongoing, prospective, long-term treatment study is currently gathering an additional 7 years of prospective safety and effectiveness data of the RNS System.
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