Parallel Folding Research Articles

The beginning and the end: flanking nucleotides induce a parallel G-quadruplex topology.

Genomic sequences susceptible to form G-quadruplexes (G4s) are always flanked by other nucleotides, but G4 formation in vitro is generally studied with short synthetic DNA or RNA oligonucleotides, for which bases adjacent to the G4 core are often omitted. Herein, we systematically studied the effects of flanking nucleotides on structural polymorphism of 371 different oligodeoxynucleotides that adopt intramolecular G4 structures. We found out that the addition of nucleotides favors the formation of a parallel fold, defined as the ‘flanking effect’ in this work. This ‘flanking effect’ was more pronounced when nucleotides were added at the 5′-end, and depended on loop arrangement. NMR experiments and molecular dynamics simulations revealed that flanking sequences at the 5′-end abolish a strong syn-specific hydrogen bond commonly found in non-parallel conformations, thus favoring a parallel topology. These analyses pave a new way for more accurate prediction of DNA G4 folding in a physiological context.

Three-dimensional study of the lingual papillae and their connective tissue cores in the Nile fox (Vulpes vulpes aegyptica) (Linnaeus, 1758).

The Nile fox (Vulpes vulpes aegyptica) is the largest Egyptian fox being distributed in different geographical regions in Egypt. The current study aims to investigate the three-dimensional features of the lingual papillae and their connective tissue cores (CTCs) in the Nile fox by using scanning electron microscopy. Five types of lingual papillae were present on the dorsal aspect of the tongue: filiform, conical, fungiform, vallate, and foliate. Generally, the filiform papilla consisted of a main papilla and several accessory processes emerged from its basal part. Filiform papillae differed in their length, shape, and number of accessory processes according to the region of the tongue. Two types of filiform CTCs were present; either conical-shaped or consisted of a main core and several accessory cores. Two types of conical papillae and two types of conical CTCs were demonstrated; elongated triangular-shaped and large conical-shaped. In addition, two types of fungiform papillae were demonstrated; rounded-shaped and elongated fungiform papillae. The fungiform CTCs were thick columnar in shape with several parallel vertical folds. Six vallate papillae were present, they were surrounded by a groove and either conical papillae or an annular pad. The surface of the vallate CTCs and their surrounding pad had small protrusions. The foliate papillae were represented by 5-6 laminae separated by grooves. The foliate CTCs appeared as oval grooves limited by laminar projections. Regional variations of the filiform papillae and the presence of three types of gustatory papillae suggest specialization of the Nile foxes' tongue to their omnivorous diet.

Structural basis for the exolytic activity of polysaccharide lyase family 6 alginate lyase BcAlyPL6 from human gut microbe Bacteroides clarus

Alginate is the structural polysaccharide of the cell wall of brown algae, which is an important carbon source for marine life. The depolymerization of alginate is dependent on alginate lyases. Recent studies showed that the alginate utilization ability had been obtained by human gut microbes. In contrast to the great number of studies on alginate lyases from marine/soil organisms, studies on alginate lyases from gut microbes are still limited. Here, the structure of a polysaccharide lyase family 6 (PL6) alginate lyase from human gut microbe Bacteroides clarus was solved by X-ray crystallography, which represents the cluster of two-domain PL6 alginate lyases from Bacteroidetes. Similar with the two-domain alginate lyase AlyGC originated from marine bacterium, both the N terminal domain (NTD) and C terminal domain (CTD) of BcAlyPL6 show right-handed parallel β-helix fold. However, unlike AlyGC, which forms a homodimer, BcAlyPL6 functions as a monomer. Biochemical analysis indicates that the substrate binding affinity is mainly contributed by the NTD while the CTD of BcAlyPL6 is involved in the formation of −1 subsite, which is essential for substrate turnover rate. Furthermore, CTD is involved in shaping a closed catalytic pocket, and deletion of it leads to increased activity towards highly polymerized substrate. Structure comparison of PL6 family alginate lyases implies that the linkers of two-domain alginate lyases might have evolutionary relationship with the N/C terminal extension of single-domain lyases.

Structural and geochemical evidence for a failed rift crustal evolution model in Western Dharwar Craton, South India

Detailed geological mapping along with structural and geochemical analysis were carried out in the Kibbanahalli Schist Belt (KSB) of the Bababudan Group in the Western Dharwar Craton (WDC). Repeated sequences of sedimentary rocks and volcanic rocks with conformable contact relations are the major lithological association in KSB. Sedimentary structures and field relations indicate that the Bababudan Group begins with basal conglomerate composed of debris (talus) and alluvial fan deposits or fluvial deposits. Volcanic rocks preserve features of explosive volcanism in an aqueous environment.Based on the field and microstructural observations five stages of deformations (D0, D1, D2, D3, and D4) are characterized from the study area. Among these deformation events, D2 is the major regional-scale event. East dipping NW–SE trending thrust faults and F2 parallel folds that are upright and isoclinal mark the D2 event. These F2 folds are sandwiched between D2 thrust faults. D2 structures suggest the temporal evolution of a fold-and-thrust belt by inversion of an intracratonic basin.Trace element geochemical analysis of the mafic to intermediate rocks from KSB and Chitradurga Schist Belt (CSB) shows three types of patterns. Type 1 has Nb–Ta negative anomalies, Type 2 is relatively flat trend and Type 3 has Zr–Hf positive anomalies. Type 1 has slightly enriched LREE trend while relatively flat LREE trend in Type 2 and 3. HREE trend is relatively flat in all samples, except for one sample from Type 3. The geochemical variations are related to the degree of crustal contamination experienced during their eruption in connection with the intracratonic extension.A pair of thrust faults and folded sequences of volcanic, volcanoclastic and sedimentary rocks summarize the major structural association in the study area. This association is identical to an inverted failed rift structure. Geochemical evidence also points to an intracratonic mafic to intermediate volcanism. Our study thus provides a well-preserved example of Archean failed rift. We thus propose the post-3.0 Ga crustal growth throughout the Western Dharwar Craton is therefore initiated by similar failed rifting events.

A tetrahedral DNA nanorobot with conformational change in response to molecular trigger.

Dynamic DNA origami nanostructures that respond to external stimuli are promising platforms for cargo delivery and nanoscale sensing. However, the low stability of such nanostructures under physiological conditions presents a major obstacle for their use in biomedical applications. This article describes a stable tetrahedral DNA nanorobot (TDN) programmed to undergo a controlled conformational change in response to epithelial cell adhesion molecule (EpCAM), a molecular biomarker specifically expressed on the circulating tumor cells. Multiresolution molecular dynamics simulations verified the overall stability of the folded TDN design and characterized local distortions in the folded structure. Atomic force microscopy and gel electrophoresis results showed that tetragonal structures are more stable than unfolded DNA origami sheets. Live cell experiments demonstrated the low cytotoxicity and target specificity of TDN. In summary, the proposed TDN can not only effectively resist nuclease catalysis but also has the potential to monitor EpCAM-positive cells precisely.

Forward kinematic modeling of fault-bend folding

We present a forward numerical modeling approach for fault-bend folding based on a velocity description of deformation. The approach incorporates algorithms capable of modeling multiple fault bends of different geometries (e. g. fault bends not stepping up from a detachment), imbricates, and variable velocity-boundary orientations, with corresponding varying slip ratios. When modeling contraction, the approach is capable of reproducing rounded-hinges and parallel folds with localized bed thinning or thickening commonly observed in natural structures. Extensional fault-bend folds can be modeled using the same set of equations, with the minor modification that velocity boundary orientations are defined independently of the fault shape. The modeled structures conserve area, and commonly observed features of extensional fault-bend folds, such as rollover structures with growth, are produced. Thus, we present a unified inclined-shear and flexural-slip general transformation associated with displacement over bends in faults, describing the theoretical framework which we have implemented in the associated program, fbfFor. We show the utility of this kinematic approach by matching seismic reflection examples, analog models, and mechanical models of fault-bend folds to create progressive, balanced kinematic interpretations and gain further insight into the formation of these structures.

Triassic two-stage intra-continental orogensis of the South China Block, driven by Paleotethyan closure and interactions with adjoining blocks

The South China Block (SCB) is tectonically bounded by the Tethyan and Pacific subduction zones and the Qinling-Dabie HP-UHP metamorphic zone. Triassic tectonic activity was a key phase in the tectonic history of the SCB and in creating the fundamental framework of East Asia. The geometry and kinematics of the Triassic deformation sheds light on the mechanism driving intra-continental orogenesis in the SCB. Our new field- and mapped- based structural analysis, along with thermo-chronological dating results, reveal two-stage distinct Triassic deformations in the southern SCB involving top-to-north dextral thrusting at ~250–225 Ma and NE-trending sinistral transpression at ~230–190 Ma. Early Triassic dextral transpression is marked by WNW-trending high-strain zones and thrust nappes/sheets, which might have been rooted beneath the Hainan-Yunkai basement along a low angle, middle-upper crustal basal detachment. It transformed from a thick-skinned fold-and-thrust belt to thin-skinned Jura-like patterns with northerly-propagating deformation. Late Triassic NE-trending sinistral transpression was accompanied by a series of the parallel folds and thrusts in the SCB interior, resulting in the development of the regional positive-flower geometry and reactivation of the pre-existing structures. Such signatures, in combination with the available geological, geochronological, and paleogeographic observations, suggest two-stage (early-middle and late Triassic) intra-continental orogenesis in the SCB, were controlled by the clockwise scissor-like closure of the Paleotethyan Ocean and its interactions with the adjoining blocks including deep-subduction beneath the North China Block and limited lateral extrusion due to the obstructing paleo-Pacific plate.

The structure of a family 110 glycoside hydrolase provides insight into the hydrolysis of α-1,3-galactosidic linkages in λ-carrageenan and blood group antigens

α-Linked galactose is a common carbohydrate motif in nature that is processed by a variety of glycoside hydrolases from different families. Terminal Galα1–3Gal motifs are found as a defining feature of different blood group and tissue antigens, as well as the building block of the marine algal galactan λ-carrageenan. The blood group B antigen and linear α-Gal epitope can be processed by glycoside hydrolases in family GH110, whereas the presence of genes encoding GH110 enzymes in polysaccharide utilization loci from marine bacteria suggests a role in processing λ-carrageenan. However, the structure–function relationships underpinning the α-1,3-galactosidase activity within family GH110 remain unknown. Here we focus on a GH110 enzyme (PdGH110B) from the carrageenolytic marine bacterium Pseudoalteromonas distincta U2A. We showed that the enzyme was active on Galα1–3Gal but not the blood group B antigen. X-ray crystal structures in complex with galactose and unhydrolyzed Galα1–3Gal revealed the parallel β-helix fold of the enzyme and the structural basis of its inverting catalytic mechanism. Moreover, an examination of the active site reveals likely adaptations that allow accommodation of fucose in blood group B active GH110 enzymes or, in the case of PdGH110, accommodation of the sulfate groups found on λ-carrageenan. Overall, this work provides insight into the first member of a predominantly marine clade of GH110 enzymes while also illuminating the structural basis of α-1,3-galactoside processing by the family as a whole.

Geometry of folded and boudinaged pegmatite veins emplaced within a strike-slip shear zone: A case study from the Caledonian orogen, northern Scotland

The deformation of sheet-like igneous intrusions in multiple orientations can give detailed insights into the kinematics of ductile flow in shear zones. Using the Torrisdale Vein Complex in the northern Scottish Caledonides as a case study, we examine the relationships between folded and boudinaged pegmatitic intrusions deformed by strike-slip dominated shear. Within the shear zone, intrusions that trend clockwise of the adjacent regional foliation were commonly (75%) folded, whereas >80% of pegmatites at anticlockwise angles were asymmetrically boudinaged, giving dextral senses of shear parallel to the dominant and gently-plunging mineral lineations. Pegmatite fold trains at high angles to foliation (Sn) display the greatest % shortening, marked by steeply plunging ‘Z’ shaped folds when viewed down plunge. Pegmatites typically form Class 1C folds and were therefore more competent than their host gneisses at the time of deformation, i.e. they were not in the magmatic state. Such fold geometries are consistent with flattened parallel folds and suggest that up to 0.5 homogenous flattening was superimposed on the folds. Fold styles also indicate viscosity contrasts between the pegmatites and host gneisses of between 50 and 250 at the time of folding. Fold hinges are dispersed about an arc within the steeply-dipping foliation, suggesting a component of hinge rotation towards the mineral lineation during non-coaxial deformation. Folded pegmatites may also display boudinage on their limbs indicating that fold limbs had rotated into the extensional field during progressive deformation. Pegmatite boudin trains are typically developed <45° anticlockwise of Sn and display the greatest % extension when trending sub-parallel to the shear zone foliation. Within such trains, individual shearband boudins are more anticlockwise than the overall train and show right-stepping relative to neighbouring bodies. More equant boudins have rotated less than elongate boudins (aspect ratios >3) and preserve the largest anticlockwise angles with the overall boudin train. Conversely, domino boudins are clockwise of overall boudin trains and have undergone clockwise rotation marked by left-stepping of adjacent boudins. Domino boudins display flanking folds which progressively open as the deformable boudin rotates towards the foliation and margins of the boudin lozenges locally become clockwise of flow. This ‘unfolding’ of deflected foliation, together with local reversals in the sense of shear around rotating boudins, is consistent with a clockwise vorticity associated with bulk dextral shear. These observations collectively indicate that bulk dextral shear with an additional component of pure shear operated across the shear zone and provides further insights into the kinematics of mid-crustal deformation.

Cartographic pattern of terminations of simple, parallel fault-bend folds, fault-propagation folds and detachment folds

The maps of terminations of fault-bend folds, fault-propagation folds and detachment folds formed by hinge migration, limb rotation or a combination of both exhibit some differences. In this work, a set of maps has been constructed for simple structures with constant thickness and kink band geometry, and the main differences that allow diagnosing one or another type of structure have been established. Fundamentally, two criteria have been taken into account: geometric differences and differences in the strain distribution on map view. Fault-bend folds and detachment folds formed solely by limb rotation are easily distinguishable, while fault-propagation folds and detachment folds in which hinge migration intervenes are practically identical.

One Terminal Guanosine Flip of Intramolecular Parallel G-Quadruplex: Catalytic Enhancement of G-Quadruplex/Hemin DNAzymes.

Numerous studies have shown compelling evidence that incorporation of an inversion of polarity site (IPS) in G-rich sequences can affect the topological and structural characteristics of G-quadruplexes (G4s). Herein, the influence of IPS on the formation of a previously studied intramolecular parallel G4 of d(G3 TG3 TG3 TG3 ) (TTT) and its stacked higher-order structures is explored. Insertion of 3'-3' or 5'-5' IPS did not change the parallel folding pattern of TTT. However, both the species and position of the IPS in TTT have a significant impact on the G4 stability and end-stacking through the alteration of G4-G4 interfaces properties. The data demonstrate that one base flip in each terminal G-tetrad can stabilize parallel G4s and facilitate intermolecular packing of monomeric G4s. Such modifications can also enhance the fluorescence and enzymatic performances by promoting interactions between parallel G4s with N-methyl mesoporphyrin IX (NMM) and hemin, respectively.

Multiply deformed Paleoproterozoic foreland fold and thrust belt in northern Fennoscandia – The peripheral Kuusamo belt as a key example

The Central Lapland belt (CLB), Peräpohja belt (PB), and Kuusamo belt (KB) form an important part of northern Fennoscandia and record ca. 700 Ma (2.5–1.8 Ga) of Precambrian tectonic processes. The 2.5–2.1 Ga sedimentary-volcanic successions in these belts form a basin-wide surfaces with a wide lateral continuum. Tidal influenced shallow epeiric sea setting dominated at 2.4–2.1 Ga followed by a continental breakup and subsequent formation of a passive margin at 2.1 Ga. The collisional evolution (1.93–1.76 Ga) started with an E-W, locally NW-SE and NE-SW, compressional phase (D1; 1.93–1.90 Ga) that resulted in at least 600 km long and in part over 300 km wide E-vergent Lapland foreland fold and thrust belt (FTB). The KB is the best preserved example of this FTB and shows E-vergent imbricated structures in the east and E-vergent out of sequence thrusting in the west. The southern part of the KB has been affected by N-S shortening (D2) seen as upright to slightly inclined open to tight F2 folds and as oval-shaped dome and basin structures. The D3 overprinting causes folding with NW-SE trending spaced foliation in less competent rocks and parallel folds and faults in orthoquartzites. The D4 NE-SW trending overprinting deformation is characteristic for the high grade areas of the KB and is seen in outcrop to map scale tight folding. In general, the easternmost peripheral part of the E-vergent Lapland foreland FTB, formed upon non-stretched Archean basement, is only moderately affected by the later deformation events. In the stretched part of the Archean basement the earlier rift structures have facilitated the N-S shortening and the D2 structures dominate the map pattern. The D3, due to a SW-NE shortening, shows strong strain partitioning and localized deformation. After prolonged heating the Archean basement started to act ductile and long wavelength crustal-scale NE-SW trending D4 folds formed. The metamorphic zonation in the KB from greenschist facies in the south to medium pressure amphibolite facies in the north is explained by a major D4 anticlinorium (wavelength 70–100 km).

Quantification of the Intraglottal Pressure Induced by Flow Separation Vortices Using Large Eddy Simulation

The greatest rate of change in the glottal flow rate during phonation is a rapid decrease that occurs during the latter part of the glottal closing. Previous works showed that intraglottal flow separation vortices form in a divergent glottis, produce negative gauge pressures (below atmospheric) during closing. It is hypothesized here that flow separation vortices contribute to the rapid closing mechanism of the true vocal folds during phonation. Four idealized static models (M5) of the human larynx were investigated using large eddy simulation: 2 models featured parallel folds that did not enable flow separation in the glottis and 2 models involved a divergent glottis. The influence of the ventricular gap (narrow/wide) is evaluated. An unsteady pressure inlet representing a voicing cycle was applied to the sub-glottal region to mimic the time-varying glottal flow. Intraglottal vortex structures formed downstream of the separation point in a divergent glottis. Their existence caused a higher closing force that was applied onto the vocal folds. A narrow ventricular gap strengthens this effect. Strength of the intraglottal vortices increased with the maximum flow declination rate. Therefore, a more divergent shape of the glottis during glottal closing will be one of the main contributors to the voice quality.

Substituted Naphthalenediimide Compounds Bind Selectively to Two Human Quadruplex Structures with Parallel Topology.

Interactions are reported of three representative naphthalenediimide derivatives with three quadruplex targets, from the promoter region of the telomerase (hTERT) gene, a human telomeric DNA quadruplex, and a telomeric RNA quadruplex (TERRA). Thermal melting studies showed that these compounds strongly stabilize the quadruplexes, with weak stabilization of a duplex DNA. Binding studies by surface plasmon resonance and fluorescence spectroscopy found that the compounds bind to the quadruplexes with nanomolar equilibrium dissociation constants. Plausible topologies for the quadruplex complexes were deduced from CD spectra, which together with the surface plasmon resonance data indicate that the quadruplexes with parallel quadruplex folds are preferred by two compounds, which was confirmed by qualitative molecular modeling.

Folding intermediate states of the parallel human telomeric G-quadruplex DNA explored using Well-Tempered Metadynamics

An increasingly comprehension of the folding intermediate states of DNA G-quadruplexes (G4s) is currently an important scientific challenge, especially for the human telomeric (h-tel) G4s-forming sequences, characterized by a highly polymorphic nature. Despite the G-triplex conformation was proposed as one of the possible folding intermediates for the antiparallel and hybrid h-tel G4s, for the parallel h-tel topology with an all-anti guanine orientation, a vertical strand-slippage involving the G-triplets was proposed in previous works through microseconds-long standard molecular dynamics simulations (MDs). Here, in order to get further insights into the vertical strand-slippage and the folding intermediate states of the parallel h-tel G4s, we have carried out a Well-Tempered Metadynamics simulation (WT-MetaD), which allowed us to retrieve an ensemble of six G4s having two/G-tetrad conformations derived by the G-triplets vertical slippage. The insights highlighted in this work are aimed at rationalizing the mechanistic characterisation of the parallel h-tel G4 folding process.

Temporal variations in the dynamic evolution of an overriding plate: Evidence from the Wulong area in the eastern North China Craton, China

Abstract The evolution of overriding-plate deformation, and the mechanisms responsible for this deformation, are debated. One area where these processes can be investigated is the eastern North China Craton (NCC) in China, which was situated in an overriding-plate position relative to the subducting Paleo-Pacific Plate during the Jurassic and Cretaceous. Here we constrain the structural evolution of the Jurassic and Cretaceous using new structural, stress field, and geochronological data from the Wulong area. The results show that the first phase of deformation (D1) produced a series of SE-dipping reverse shear zones and parallel folds in response to NW-SE shortening at 157–146 Ma (Late Jurassic). Based on microscopic observations and quartz c-axis analysis, it is suggested that the temperature during D1 deformation was 500 ± 50 °C. A second phase of contractional deformation (D2) at 146–132 Ma (earliest Early Cretaceous) gave rise to numerous NE-SW–striking sinistral faults and shear zones. The majority of D2 structures display ductile fabrics in the southwest of the Wulong area and brittle deformational features in the northeast, thus indicating enhanced exhumation in the former area. Microstructures of D2 sinistral shear zones indicate deformation temperatures of 300–400 °C. Inversion of fault slip data from the sinistral faults demonstrate that N-S compression was responsible for the D2 structures. The third phase of deformation (D3) was related to WNW-ESE extension during the middle to late Early Cretaceous (132–100 Ma). This extensional phase produced a series of NE-SW–striking normal faults and reactivated pre-existing structures. Dikes and plutons were emplaced during the D3 deformation, synchronous with the peak destruction of the NCC. Our results indicate that the eastern NCC showed temporal variations in stress and strain during the Jurassic and Cretaceous. Consistent with the slab-driven model, we suggest that this behavior represents the response of the overriding-plate to changes in subduction kinematics.

Does Raman spectroscopy recognize different G‐quadruplex arrangements?

AbstractIn this work, we demonstrate the underused potential of Raman spectroscopy in detecting formation of DNA G‐quadruplex (G4) and differentiating between various G4‐folding topologies. As model structures, we used a 22‐mer human telomere fragment AG3(TTAG3)3 (denoted here as wt) and its two variants with adenine abasic lesions at the position 19 (ap19) or at the positions 7, 13, and 19 (ap7‐13‐19), the structures of which were previously characterized. These oligonucleotides adopt three basic G4‐folds: a basket‐type form for wt in Na+, a (3+1) hybrid form for ap19 in K+, and a parallel G4 for ap7‐13‐19 in K+, the last one furthermore stabilized at increased temperatures. We show that although wt and ap7‐13‐19 in Na+ adopt predominately antiparallel G4‐folds, these oligonucleotides in K+ display several Raman features of parallel G4 folds. Interestingly, ap19 has a Raman spectrum with some features of parallel G4 folds in both Na+ and K+ solutions. Raman signals indicative of parallel G4 are most obvious with ap7‐13‐19 in K+. The population of ap7‐13‐19 guanosines (unlike of wt and ap19 in K+) in the C2'‐endo/anti geometry gradually increases with increasing temperature, reaching its maximum at ~50°C, where an all‐parallel topology is observed. In summary, Raman spectroscopy has been proven to distinguish between different conformational properties of G4‐DNA structures, with reliability comparable with circular dichroism spectra, and with the potential to provide additional structural information.

Thermodynamics and folding landscapes of large proteins from a statistical mechanical model.

Statistical mechanical models that afford an intermediate resolution between macroscopic chemical models and all-atom simulations have been successful in capturing folding behaviors of many small single-domain proteins. However, the applicability of one such successful approach, the Wako-Saitô-Muñoz-Eaton (WSME) model, is limited by the size of the protein as the number of conformations grows exponentially with protein length. In this work, we surmount this size limitation by introducing a novel approximation that treats stretches of 3 or 4 residues as blocks, thus reducing the phase space by nearly three orders of magnitude. The performance of the ‘bWSME’ model is validated by comparing the predictions for a globular enzyme (RNase H) and a repeat protein (IκBα), against experimental observables and the model without block approximation. Finally, as a proof of concept, we predict the free-energy surface of the 370-residue, multi-domain maltose binding protein and identify an intermediate in good agreement with single-molecule force-spectroscopy measurements. The bWSME model can thus be employed as a quantitative predictive tool to explore the conformational landscapes of large proteins, extract the structural features of putative intermediates, identify parallel folding paths, and thus aid in the interpretation of both ensemble and single-molecule experiments.

Analysis of the Fatigue Crack Evolution of Corrugated Web Girders

Based on linear elastic fracture mechanics (LEFM), the fatigue crack evolution process and behavior of corrugated web girders were studied. The global finite element analysis (FEA) model of corrugated web girders was first developed and the equivalent structural stress method was used to reveal the dangerous locations along the weld under the bending load. The weld toe between the tension flange and the web weld, which is near the intersection of the inclined fold and the parallel fold, was determined as the fatigue crack easy-initiating location. Then a small region containing the crack-prone site was extracted as the sub-model for a crack propagating simulation. A semi-circle initial crack with 0.1 mm radius was inserted at the crack easy-initiating location. The stress intensity factors (SIFs; KI, KII, and KIII) of some discrete points along the crack front were calculated by the M-integral method. Based on Nasgro law, the geometry of the new crack front with a given extension length was obtained. Finally, the complete evolution process of the crack propagation was simulated. Results showed that the dominant crack propagating mode is open type (Mode I) and KI is the most important propagating driving force. According to the crack front shape evolution, the whole propagating process was divided into 6 stages. An obvious kink of the crack was found in stage 1, which covered only a very short time. The stages 3, 4 and 5 accounted for the majority of life, among which the stage 3 accounted for as high as 81% of the total life. Therefore, the cycles of the weld toe crack propagating from 0.1 mm to the thickness of the flange can be defined as the prediction life of this kind of structures.

Adlayer-Free Large-Area Single Crystal Graphene Grown on a Cu(111) Foil.

To date, thousands of publications have reported chemical vapor deposition growth of "single layer" graphene, but none of them has described truly single layer graphene over large area because a fraction of the area has adlayers. It is found that the amount of subsurface carbon (leading to additional nuclei) in Cu foils directly correlates with the extent of adlayer growth. Annealing in hydrogen gas atmosphere depletes the subsurface carbon in the Cu foil. Adlayer-free single crystal and polycrystalline single layer graphene films are grown on Cu(111) and polycrystalline Cu foils containing no subsurface carbon, respectively. This single crystal graphene contains parallel, centimeter-long ≈100 nm wide "folds," separated by 20 to 50 µm, while folds (and wrinkles) are distributed quasi-randomly in the polycrystalline graphene film. High-performance field-effect transistors are readily fabricated in the large regions between adjacent parallel folds in the adlayer-free single crystal graphene film.