Duplex Structure Research Articles

Structural dynamics of therapeutic nucleic acids with phosphorothioate backbone modifications.

Antisense oligonucleotides (ASOs) offer ground-breaking possibilities for selective pharmacological intervention for any gene product-related disease. Therapeutic ASOs contain extensive chemical modifications that improve stability to enzymatic cleavage and modulate binding affinity relative to natural RNA/DNA. Molecular dynamics (MD) simulation can provide valuable insights into how such modifications affect ASO conformational sampling and target binding. However, force field parameters for chemically modified nucleic acids (NAs) are still underdeveloped. To bridge this gap, we developed parameters to allow simulations of ASOs with the widely applied phosphorothioate (PS) backbone modification, and validated these in extensive all-atom MD simulations of relevant PS-modified NA systems representing B-DNA, RNA, and DNA/RNA hybrid duplex structures. Compared to the corresponding natural NAs, single PS substitutions had marginal effects on the ordered DNA/RNA duplex, whereas substantial effects of phosphorothioation were observed in single-stranded RNA and B-DNA, corroborated by the experimentally derived structure data. We find that PS-modified NAs shift between high and low twist states, which could affect target recognition and protein interactions for phosphorothioated oligonucleotides. Furthermore, conformational sampling was markedly altered in the PS-modified ssRNA system compared to that of the natural oligonucleotide, indicating sequence-dependent effects on conformational preference that may in turn influence duplex formation.

Abnormal grain growth of tetragonal tungsten bronze structured ferroelectric ceramics

Microstructures of tetragonal tungsten bronze-structured ferroelectric ceramics vary owing to abnormal grain growth. Control of the grain microstructure stability is a critical aspect in the electrical properties. In this study, the grain growth behavior was meticulously explored through a combination of experiments and numerical simulations. Effects of the liquid phase and initial particle-size distribution on the microstructural evolution were investigated under different grain boundary energy anisotropy conditions. The grain area and edge number were calculated to investigate the grain growth kinetics and shape variation. The results revealed that the presence of a large amount of the liquid phase contributed to rapid grain growth and a duplex structure formation. The grain-size inhomogeneity can be eliminated by using initial particles with a bimodal particle-size distribution. The grain shape was mainly determined by the degree of anisotropy of the grain boundary energy and was nearly unaffected by the process parameters. The findings of this study afford theoretical guidance for microstructure regulation and stable preparation of high-performance ferroelectric ceramics.

Construction of a fluorescent and colorimetric multi-mode aptasensor for label-free and sensitive detection of ochratoxin A in agricultural products

Ochratoxin A (OTA) can induce a serious danger to human beings, and it is crucial to develop a sensitive and simple strategy for visual detection of OTA. Herein, we construct a fluorescent and colorimetric multi-mode aptasensor for label-free and sensitive detection of OTA on the basis of target-initiated assembly of functional G-quadruplex (G4) DNAzyme nanostructures. When OTA is present, it specifically recognizes the aptamer and disintegrates the aptamer-cDNA duplex structure, resulting in the liberation of intact cDNA and the subsequent initiation of terminal deoxynucleotidyl transferase (TdT) assisted-extension reaction. The resultant G4 DNAzyme nanostructures can light up Thioflavin T (ThT) to produce a high fluorescence signal. Meanwhile, the addition of hemin can trigger the self-assembly of hemin/G4 DNAzymes that can catalyze the 3,3′,5,5′-tetramethylbenzidine/hydrogen peroxide (TMB/H2O2) system to generate a distinct colorimetric signal. Consequently, the introduction of G4 DNAzyme/ThT and hemin/G4 DNAzyme can efficiently transduce the OTA signal into both a fluorescence signal and a colorimetric signal. The further utilization of a smartphone facilitates the development of a simple method based on red-green-blue (RGB) digital analysis for OTA assay. The proposed multi-mode aptasensor displays ultrahigh sensitivity with a detection limit of 2 pg/mL for the fluorescent mode, 25 pg/mL for the colorimetric mode, and 6 pg/mL for the RGB mode. Moreover, this multi-mode aptasensor can be applied to accurately detect OTA in real samples, providing a new platform for on-site monitoring of OTA in agricultural products.

Label-Free, Sensitive, and Versatile Colorimetric Method for Molecule Detection via the G-Quadruplex-Based Signal Quenching Strategy.

Signal amplification strategies have emerged as a prominent tool in the field of improving the detection sensitivity of small extracellular vesicles (sEVs). It is important to highlight that the utilization of signal quenching strategies is not commonly implemented. A detection technique for sEVs was established based on the unwinding of G-quadruplex using Klenow fragment polymerase (KF), which served as an inspiration for this study. This system is characterized by its simplicity and lack of labeling, making it an efficient approach for signal quenching. In the presence of sEVs, the CD63 aptamer in the capture@sMBs complex binds with the CD63 protein on the surface of sEVs to release trigger sequences, which were employed as a primer to mediate the DNA polymerase/endonuclease-assisted signal recycling. The signal recycling process produces numerous single-stranded DNA sequences that can bind to the toehold section of the G-quadruplex. This leads to the rupture of the G-quadruplex structure and the subsequent deactivation of a DNAzyme generated by the G-quadruplex structure and hemin, thereby inhibiting its biological catalytic function. Consequently, the G-quadruplex structure would undergo a transformation to a duplex structure, leading to the emergence of a discernible differential signal that can be noticed in a majority of instances, even without the aid of magnification devices. The decrease in the prominent signal allows for the efficient analysis of target sEVs, which exhibit a notably low detection limit. In addition to the detection of sEVs, the approach has also been utilized for the investigation of miRNA-21. The approach demonstrates a high level of selectivity and robustness in its capacity to differentiate between target miRNA and base-mismatched miRNA as well as other miRNA families. This statement suggests that the assay holds significant promise for use in biochemical research and clinical diagnosis.

Microstructure and mechanical properties of high relative density Ti-48Al-1Fe alloy using irregular blend powder

Conventional pressing and sintering methods provide difficulties in achieving high density for PM TiAl alloys. The Ti-48Al-1Fe alloy was prepared via vacuum pressure-less sintering, and the microstructure evolution and mechanical properties during the sintering densification process of the mixed powder system were investigated. The results shows that the density of the mixed powder reached 98.3 ± 0.14% after pressure-less sintering for 3 hours under high vacuum conditions at 1300°C. The microstructure of the as-sintered alloy is a fine duplex structure composed of α2/γ lamellar colonies and the composite structure. The ultimate tensile strength (UTS) of the as-sintered alloy at room temperature is 315 MPa. The density of the as-sintered alloy reach more than 99.9% after non-capsule hot isostatic pressing (HIP). The as-HIPed alloy exhibits an UTS of 332 MPa at room temperature. At high temperatures, it maintains high strength, with an UTS of 408 MPa and yield strength of 386 MPa at 900°C, which is comparable to that of forged TiAl alloy. Furthermore, the elongation of the sample at 900°C is 20.0%. This process offers a novel method for sintering PM TiAl with high density and mechanical properties at a low cost and near-net shape.

DNA Cryogels with Anisotropic Mechanical and Responsive Properties for Specific Cell Capture and Release.

Due to their programmable stimuli-responsiveness, excellent biocompatibility, and water-rich and soft structures similar to biological tissues, smart DNA hydrogels hold great promise for biosensing and biomedical applications. However, most DNA hydrogels developed to date are composed of randomly oriented and isotropic polymer networks, and the resulting slow response to biotargets and lack of anisotropic properties similar to those of biological tissues have limited their extensive applications. Herein, anisotropic DNA hydrogels consisting of unidirectional void channels internally oriented up to macroscopic length scales were constructed by a directional cryopolymerization method, as exemplified by a DNA-incorporated covalently cross-linked DNA cryogel and a DNA duplex structure noncovalently cross-linked DNA cryogel. Results showed that the formation of unidirectional channels significantly improved the responsiveness of the gel matrix to biomacromolecular substances and further endowed the DNA cryogels with anisotropic properties, including anisotropic mechanical properties, anisotropic swelling/shrinking behaviors, and anisotropic responsiveness to specific biotargets. Moreover, the abundant oriented and long macroporous channels in the gel matrix facilitated the migration of cells, and through the introduction of aptamer structures and thermosensitive polymers, an anisotropic DNA cryogel-based platform was further constructed to achieve the highly efficient capture and release of specific cells. These anisotropic DNA hydrogels may provide new opportunities for the development of anisotropic separation and biosensing systems.

Effect of trace Nb element on the performance of Fe82-xB10P7.5Cu0.5Nbx amorphous/nanocrystalline ribbons by one-step melt spinning method

The amorphous/nanocrystalline duplex structure is a stable structure with excellent soft magnetic properties, but there is still very little research on the amorphous/nanocrystalline alloy obtained by one-step melt spinning method. In this work, Fe82-xB10P7.5Cu0.5Nbx (x = 0, 0.5, 1.0, & 1.5 at%) alloys whose performance can surpass Fe-Si-B alloy was prepared, and the effect of trace Nb element replacing Fe element on the structural characteristics, thermal properties, mechanical properties and soft magnetic properties of the alloys were studied. With the increase of Nb content, the saturation magnetic flux density of the alloys gradually increases. The Fe81.5B10P7.5Cu0.5Nb0.5 shows a saturation magnetic flux density of 1.68 T and a coercivity of 5.56 A/m, together with stable thermal properties and good mechanical properties, which provides a promising candidate for amorphous/nanocrystalline alloys with both excellent soft magnetic properties and satisfactory processing properties.

Mechanical properties and corrosion behavior of electron beam cold hearth melting high strength and high corrosion resistant Ti-0.3Mo-0.8Ni alloy with different states

In this study, a large size Ti-0.3Mo-0.8Ni (TA10) alloy ingot melted by electron beam cold hearth melting (EBCHM) technology was investigated. The microstructure, mechanical properties, and corrosion behavior of as-cast, hot-rolled, and annealed TA10 alloys were investigated. The results show that different states of TA10 alloys have different microstructure and properties. The microstructure of the as-cast TA10 alloy exhibits the Widmanstätten α phase, and the hot-rolled TA10 sheet shows a fibrous structure with an obvious rolling streamline. After 650 °C annealing, the intergranular β phase decreases, and most of the strip α phase changes to the equiaxed α phase. With the annealing temperature increasing to 840 °C, the microstructure gradually changed from an equiaxed structure to a duplex structure. The mechanical properties of the TA10 alloy were enhanced after hot-rolling with an increase in ultimate tensile strength from 386.5 MPa to 610 MPa. Additionally, the elongation increased from 15.6 % to 23.3 %. Upon annealing at varying temperatures, it was observed that the strength decreased, reaching to 423.5 MPa at 650 °C and 478.2 MPa at 840 °C, while the plasticity increased significantly, reaching to 26.5 % at 650 °C and 28.6 % at 840 °C. The improved strength was attributed to the better grain boundary slip of the equiaxed structure. The corrosion resistance of titanium alloys is closely connected with their microstructure. The results of the immersion corrosion test indicate that the samples in various states exhibit similar corrosion behavior. Additionally, the hot-rolled TA10 alloy shows the highest corrosion resistance, with a lower corrosion rate of 0.34459 mm/year. The as-cast TA10 alloy shows the lowest corrosion resistance, with a lower corrosion rate of 1.37559 mm/year.

Controllable Assembly of a Quantum Dot-Based Aptasensor Guided by CRISPR/Cas12a for Direct Measurement of Circulating Tumor Cells in Human Blood.

Accurate and sensitive analysis of circulating tumor cells (CTCs) in human blood provides a non-invasive approach for the evaluation of cancer metastasis and early cancer diagnosis. Herein, we demonstrate the controllable assembly of a quantum dot (QD)-based aptasensor guided by CRISPR/Cas12a for direct measurement of CTCs in human blood. We introduce a magnetic bead@activator/recognizer duplex core-shell structure to construct a multifunctional platform for the capture and direct detection of CTCs in human blood, without the need for additional CTC release and re-identification steps. Notably, the introduction of magnetic separation ensures that only a target-induced free activator can initiate the downstream catalysis, efficiently avoiding the undesired catalysis triggered by inappropriate recognition of the activator/recognizer duplex structure by crRNAs. This aptasensor achieves high CTC-capture efficiency (82.72%) and sensitive detection of CTCs with a limit of detection of 2 cells mL-1 in human blood, holding great promise for the liquid biopsy of cancers.

Distinguishing G-Quadruplexes Stabilizer and Chaperone for c-MYC Promoter G-Quadruplexes through Single-Molecule Manipulation.

G-quadruplex (G4) selective stabilizing ligands can regulate c-MYC gene expression, but the kinetic basis remains unclear. Determining the effects of ligands on c-MYC promoter G4s' folding/unfolding kinetics is challenging due to the polymorphic nature of G4s and the high energy barrier to unfold c-MYC promoter G4s. Here, we used single-molecule magnetic tweezers to manipulate a duplex hairpin containing a c-MYC promoter sequence to mimic the transiently denatured duplex during transcription. We measured the effects of six commonly used G4s binding ligands on the competition between quadruplex and duplex structures, as well as the folding/unfolding kinetics of G4s. Our results revealed two distinct roles for G4s selective stabilization: CX-5461 is mainly acting as c-MYC G4s stabilizer, reducing the unfolding rate (ku) of c-MYC G4s, whereas PDS and 360A also act as G4s chaperone, accelerating the folding rates (kf) of c-MYC G4s. qRT-PCR results obtained from CA46 and Raji cell lines demonstrated that G4s stabilizing ligands can downregulate c-MYC expression, while G4s stabilizer CX-5461 exhibited the strongest c-MYC gene suppression. These results shed light on the potential of manipulating G4s' folding/unfolding kinetics by ligands for precise regulation of promoter G4-associated biological activities.

XGBoost algorithm-assisted prediction of amorphous formability of Fe-based nanocrystalline precursor

The completely amorphous structure in the precursor is a significantly important prerequisite for obtaining the perfect amorphous-nanocrystalline duplex structure and the excellent soft magnetic properties of Fe-based nanocrystalline alloy ribbons (FNR). However, the correlation between the amorphous formability (AFA) and the key parameters of FNR precursors is not clear. Herein, a data-preprocessed dataset was established, consisting of 158 FNR samples with amorphous and crystallized precursors. This dataset includes features such as elements, thermal parameters, and calculated parameters. Pearson correlation analysis was performed to assess the linear correlation between any two features, resulting in the removal of eight features. Then the features importance was ranked by random forest (RF) algorithm, and top five key features (e.g., ΔT, VEC1, VEC, P, and B) were retained. A classification predictive model in that the structure of FNR precursors is amorphous or crystalline was constructed based on XGBoost algorithm. The accuracy of the classification model by confusion matrix analysis is up to 97.9 %. Furthermore, SHAP (SHapley Additive exPlanations) results reveal that crystallization temperature intervals (ΔT), valence electron concentration without Fe, Ni, and Co elements (VEC1), as well as valence electron concentration (VEC) play an important role in affecting AFA of FNR precursors. When ΔT > 142 °C, VEC1 > 0.69, and VEC >7.27, the FNR precursors readily obtain a fully amorphous structure. The outstanding classification accuracy and the elucidated correlation between the key features and AFA could guide the discovery of novel fully amorphous FNR precursors.

Triplet Excimer Formation in a DNA Duplex with Silver Ion-Mediated Base Pairs.

The dynamics of excited electronic states in self-assembled structures formed between silver(I) ions and cytosine-containing DNA strands or monomeric cytosine derivatives were investigated by time-resolved infrared (TRIR) spectroscopy and quantum mechanical calculations. The steady-state and time-resolved spectra depend sensitively on the underlying structures, which change with pH and the nucleobase and silver ion concentrations. At pH ∼ 4 and low dC20 strand concentration, an intramolecularly folded i-motif is observed, in which protons, and not silver ions, mediate C-C base pairing. However, at the higher strand concentrations used in the TRIR measurements, dC20 strands associate pairwise to yield duplex structures containing C-Ag+-C base pairs with a high degree of propeller twisting. UV excitation of the silver ion-mediated duplex produces a long-lived excited state, which we assign to a triplet excimer state localized on a pair of stacked cytosines. The computational results indicate that the propeller-twisted motifs induced by metal-ion binding are responsible for the enhanced intersystem crossing that populates the triplet state and not a generic heavy atom effect. Although triplet excimer states have been discussed frequently as intermediates in the formation of cyclobutane pyrimidine dimers, we find neither computational nor experimental evidence for cytosine-cytosine photoproduct formation in the systems studied. These findings provide a rare demonstration of a long-lived triplet excited state that is formed in a significant yield in a DNA duplex, demonstrating that supramolecular structural changes induced by metal ion binding profoundly affect DNA photophysics.

RNA-based liposomes for oral cancer: From biophysical characterization to biological evaluation

Oral cancer incidence and mortality are increasing over time. The most common therapies for oral cancers are surgery and radiotherapy, either used alone or combined, and immunotherapy can be also an option. Although there are several therapeutic options, none of them are completely effective, and in addition, there are numerous associated side effects. To overcome these limitations, researchers have been trying to reduce these drawbacks by using drug delivery systems that carry drugs for specific delivery to cancer cells. For that purpose, RNA-coated liposomes to selectively deliver the ligands C8 (acridine orange derivative) and dexamethasone to oral cancer cells were produced, characterized, and biologically evaluated.Firstly, the RNA structure and binding interaction with ligands (C8 and dexamethasone) were evaluated by circular dichroism (CD), thermal difference spectroscopy (TDS), nuclear magnetic resonance (NMR) and fluorescence titrations. The biophysical assays evidenced the formation of an RNA hairpin and duplex structure. Moreover, steady-state and time-resolved fluorescence intensity and anisotropy experiments show that C8 forms a complex with RNA and adopts an open conformation upon RNA binding.Then, RNA-coated liposomes were characterized by dynamic light scattering, and diameters near 160 nm were observed. Time-resolved anisotropy measurements of C8 loaded in RNA-functionalized liposomes indicate the co-existence of free C8 in solution (inside the liposome) and C8 bound to RNA at the external liposome surface. The RNA-functionalized liposomes loaded with C8 or dexamethasone mediated a significant reduction in the cell viability of malignant UPCI-SCC-154 cells while maintaining viable non-malignant NHDF cells. Additionally, the liposomes were able to internalize the cells, with higher uptake by the malignant cell line.Overall, the results obtained in this work can contribute to the development of new drug delivery systems based on RNA-coated liposomes.

Iridium(III)-based minor groove binding complexes as DNA photocleavage agents.

Transition metal complexes containing the qtpy ligand (2':4,4'':4',4'''-quaterpyridyl) are known to be DNA intercalators or minor groove binders. In this study, new tricationic iridium(III) complexes of qtpy are reported. Both [Ir(bpy)2(qtpy)]3+1 and [Ir(phen)2(qtpy)]3+2 display good water solubility as chloride salts. The complexes possess high-energy excited states, which are quenched in the presence of duplex DNA and even by the mononucleotides guanosine monophosphate and adenosine monophosphate. Further studies reveal that although the complexes bind to quadruplex DNA, they display a preference for duplex structures, which are bound with an order of magnitude higher affinities than their isostructural dicationic RuII-analogues. Detailed molecular dynamics simulations confirm that the complexes are groove binders through the insertion of, predominantly, the qtpy ligand into the minor groove. Photoirradiation of 1 in the presence of plasmid DNA confirms that this class of complexes can function as synthetic photonucleases by cleaving DNA.

Structural Analysis and Petrography of High-Grade Gneisses and Associated Mafic / Ultramafic Dikes Around Salem, Southern India

Southern Granulite Terrane (SGT) of India preserves extensive high-grade granulite facies rocks of Archaean and Proterozoic age. The SGT is divided into number of blocks by several suture/shear zone. Structural investigations on the basement gneisses and younger mafic/ultramafic dikes have been carried out within the Salem block which is part of Northern Granulite Block (NGB), north of the Cauvery Suture Zone (CSZ). The present work emphasizes various scale fold styles and other structural patterns of the area, which includes regionally metamorphosed high-grade rocks as basement for the multiple ultramafic intrusions to the north of Cauvery Suture Zone (CSZ) which highlights the finite strain geometry, complex deformation pattern and high-grade metamorphism. Structural map of the study area is prepared showing two generations of folding, namely F1 whose axial trend is NE-SW, subparallel with general trend of gneissic foliation and are tight isoclinal folds while F2 which are open folds with axial trend NW-SE.E-W structural cross section across the foliation planes, characterizes antiformal and synformal fold patterns of the basement due to varying dip directions which also reflects type-3 interference pattern of folding. Mesoscopic scale shear zones of dextral kinematics in response to E-W collision during Paleo-Meso Archean time, delta type porphyroclasts, S-C fabrics with the dextral movement of CSZ system, Riedel shear, thrust imbricates implying duplex structures, rotation of mafic boudins along shear zones are the most prominent ductile structural features of this area. Brittle structures like different sets of cross cutting joints and faults indicate younger deformation as well. Petrography of major lithologies has classified them into amphibolite gneiss, migmatite gneiss, charnockites, granulites and mylonites as basement rocks to the younger pyroxenite intrusions. Typical textures like, perthite, granulose, reaction rims, sieve textures and microstructures like S-C fabrics, kink bands, rotated porphyroclasts, etc are observed within the basement rocks. Coarse grained textures with fractured porphyroclasts of garnets indicating the water interactions and retrogradations within the granulite facies rocks. Reaction rims observed in charnockites and granulites are indicative of retrogression during shearing. The coarse grained cummulate nature of pyroxenites neither represent deformation nor metamorphism. Keywords: Southern Granulite Terrane, Salem, Structural Analysis, Mafic/Ultramafics, Dikes, Petrography

Label-free and ultrasensitive electrochemical detection of nucleic acids based on an exonuclease III-assisted target recycling amplification strategy using a heated gold disk electrode.

The present work demonstrates a label-free, rapid and ultrasensitive electrochemical sensor for specific DNA detection with an exonuclease III (Exo III)-assisted target recycling amplification strategy and elevated electrode temperature at a heated gold disk electrode (HAuDE). The proposed electrochemical DNA (E-DNA) sensor was designed such that in the presence of the target DNA, the electrode self-assembled capture probe hybridizes with the target DNA to form a duplex structure, which triggers Exo III to specifically recognize this structure and selectively digest the capture probe, while the released target DNA underwent recycling to hybridize with a new capture probe, leading to the gradual digestion of a large amount of capture probes. It was found that during the digestion period, the activity of Exo III could be significantly improved by elevating electrode temperature, thus promoting the digestion reaction and improving the sensitivity for target DNA detection. Furthermore, an electrochemical indicator ([Ru(NH3)6]3+) was electrostatically bound to the capture probe, leading to a significant square wave voltammetry (SWV) response, which directly related to the amount and length of the capture probes remaining in the electrode and provided a quantitative measure for target DNA detection. The proposed strategy realized the highly sensitive detection of the target DNA with a detection limit of 26 aM (S/N = 3) at an electrode temperature of 40 °C during the digestion period, which was about two magnitudes lower than that at 24 °C.

Double-enzyme active MnO2@BSA mediated lab-on-paper dual-modality aptasensor for di(2-ethylhexyl)phthalate

Di(2-ethylhexyl)phthalate (DEHP), as an environmental endocrine disruptor, has adverse effects on eco-environments and health. Thus, it is crucial to highly sensitive on-site detect DEHP. Herein, a double-enzyme active MnO2@BSA mediated dual-modality photoelectrochemical (PEC)/colorimetric aptasensing platform with the cascaded sensitization structures of ZnIn2S4 and TiO2 as signal generators was engineered for rapid and ultrasensitive detection of DEHP using an all-in-one lab-on-paper analytical device. Benefitting from cascaded sensitization effect, the ZnIn2S4/TiO2 photosensitive structures-assembled polypyrrole paper electrode gave an enhanced photocurrent signal. The MnO2@BSA nanoparticles (NPs) with peroxidase-mimic and oxidase-mimic double-enzymatic activity induced multiple signal quenching effects and catalyzed color development. Specifically, the MnO2@BSA NPs acted as peroxidase mimetics to generate catalytic precipitates, which not only obstructed interfacial electron transfer but also served as electron acceptors to accept photogenerated electrons. Besides, the steric hindrance effect from MnO2@BSA NPs-loaded branchy polymeric DNA duplex structures further decreased photocurrent signal. The target recycling reaction caused the detachment of MnO2@BSA NPs to increase PEC signal, realizing the ultrasensitive detection of DEHP with a low detection limit of 27 fM. Ingeniously, the freed MnO2@BSA NPs flowed to colorimetric zone with the aid of fluid channels and acted as oxidase mimetics to induce color intensity enhancement, resulting in the rapid visual detection of DEHP. This work provided a prospective paradigm to develop field-based paper analytical tool for DEHP detection in aqueous environment.

Enhanced strength-ductility synergy of Al/Zn/Al laminated composite with unique interface and multi-modal heterogeneous microstructure

Laminated bimetal composites have become an important strategy for designing and manufacturing desirable metallic components. Here, Al/Zn/Al laminated composite was fabricated by porthole die co-extrusion (PDCE) process, offering excellent mechanical performance. An obvious transition zone with a dispersed duplex structure (α and η phases) instead of intermetallic compounds was formed in Al/Zn interface due to element inter-diffusion and eutectoid transformation. The α/η phase interface showed a 3D characteristic with compositional and structural gradients. Moreover, Al/Zn/Al composite displayed a multi-modal heterogenous structure including the typical macroscopic hierarchical structure by alternately stacking Al and Zn layers with different microstructures, the gradient structure from Al/Zn interface to the center of Al or Zn layer, and the bimodal structure formed either near Al/Zn interface or in the layer center. As a result, Al/Zn/Al composite exhibits superior mechanical performance compared with the individual component (Al or Zn) and a satisfactory balance between strength and ductility.

New Insights Into the Active Tectonics of the Northern Canadian Cordillera From an Enhanced Earthquake Catalog

AbstractSeismic activity in the Northern Canadian Cordillera is characterized by diffuse earthquakes that extend hundreds of km northwest from the Yakutat collision zone. We use 25 months of broadband seismic data from Mackenzie Mountain Earthscope Project (MMEP), USArray Transportable Array (TA), and permanent Canadian National Seismic Network stations to present a local earthquake catalog with high sensitivity to small regional events. Deep learning techniques are adopted for both seismic phase detection and association. Event relocations are performed to provide well constrained estimates of earthquake depth distributions. Clusters of seismicity spanning the upper crust are located in the central Richardson Mountains, along the Tintina fault, and in the northeast Selwyn Basin. These clusters suggest that the core of the Richardson Anticlinorium is tectonically active and that the Tintina fault is a locus for low levels of active deformation. We interpret seismicity in the northeast Selwyn Basin as primarily occurring in the hanging wall of the Plateau thrust fault and suggest that some combination of localized duplex structures and lithological strength contrasts both within the Selwyn Basin and between abutting Paleozoic shelf sequences may be responsible for seismicity in the Mackenzie Mountain foreland.

Molecular wrench activity of DNA helicases: Keys to modulation of rapid kinetics in DNA repair.

DNA helicase activity is essential for the vital DNA metabolic processes of recombination, replication, transcription, translation, and repair. Recently, an unexpected, rapid exponential ATP-stimulated DNA unwinding rate was observed from an Archaeoglobus fulgidus helicase (AfXPB) as compared to the slower conventional helicases from Sulfolobus tokodaii, StXPB1 and StXPB2. This unusual rapid activity suggests a "molecular wrench" mechanism arising from the torque applied by AfXPB on the duplex structure in transitioning from open to closed conformations. However, much remains to be understood. Here, we investigate the concentration dependence of DNA helicase binding and ATP-stimulated kinetics of StXPB2 and AfXPB, as well as their binding and activity in Bax1 complexes, via an electrochemical assay with redox-active DNA monolayers. StXPB2 ATP-stimulated activity is concentration-independent from 8 to 200 nM. Unexpectedly, AfXPB activity is concentration-dependent in this range, with exponential rate constants varying from seconds at concentrations greater than 20 nM to thousands of seconds at lower concentrations. At 20 nM, rapid exponential signal decay ensues, linearly reverses, and resumes with a slower exponential decay. This change in AfXPB activity as a function of its concentration is rationalized as the crossover between the fast molecular wrench and slower conventional helicase modes. AfXPB-Bax1 inhibits rapid activity, whereas the StXPB2-Bax1 complex induces rapid kinetics at higher concentrations. This activity is rationalized with the crystal structures of these complexes. These findings illuminate the different physical models governing molecular wrench activity for improved biological insight into a key factor in DNA repair.