Stress Concentration Factors for Non-Load-Carrying Welded Cruciform Joints Subjected to Tension, Bending, and Shear.

This paper deals with the problem of stress concentration at the weld toe of non-load-carrying-type plate cruciform joints under tension, bending, and shear. Theoretical stress concentration factors were derived using the finite element method. Five of the most important geometrical parameters: the thickness of the main plate and the attachments, the weld throat thickness, the weld toe radius, and the weld face inclination angle were treated as independent variables. For each loading mode-tension, bending, and shear-parametric expression of high accuracy was obtained, covering the range used in real structures for cruciform connections. The maximum percentage error was lower than 2.5% as compared to numerical values. The presented solutions proved to be valid for the toe radius ρ tending to zero.

Genomic Frequencies of Dynamic DNA Sequences and Mammalian Lifespan.

BACKGROUND/AIM: Dynamic DNA sequences (i.e. sequences capable of forming hairpins, G-quadruplexes, i-motifs, and triple helices) can cause replication stress and associated mutations. One example of such a sequence occurs in the RACK7 gene in human DNA. Since this sequence forms i-motif structures at neutral pH that cause replication stress and result in spontaneous deletions in prostate cancer cells, our initial aim was to determine its potential utility as a biomarker of prostate cancer. MATERIALS AND METHODS: We cloned and sequenced the region in RACK7 where i-motif deletions often occur in DNA obtained from eight individuals. Expressed prostatic secretions were obtained from three individuals with a positive biopsy for prostate cancer and two with individuals with a negative biopsy for prostate cancer. Peripheral blood specimens were obtained from two control healthy bone marrow donors and a marrow specimen was obtained from a third healthy marrow donor. Follow-up computer searches of the genomes of 74 mammalian species available at the NCBI ftp site or frequencies of 6 dynamic sequences known to produce mutations or replication stress using a program written in Mathematica were subsequently performed. RESULTS: Deletions were found in RACK7 in specimens from both older normal adults, as well as specimens from older patients with cancer, but not in the youngest normal adult. The deletions appeared to show a weak trend to increasing frequency with patient age. This suggested that endogenous mutations associated with dynamic sequences might accumulate during aging and might serve as biomarkers of biological age rather than direct biomarkers of cancer. To test that hypothesis, we asked whether or not the genomic frequencies of several dynamic sequences known to produce replication stress or mutations in human DNA were inversely correlated with maximum lifespan in mammals. CONCLUSION: Our results confirm this correlation for six dynamic sequences in 74 mammalian genomes studied, thereby suggesting that spontaneously induced replication stress and mutations linked to dynamic sequence frequency may limit lifespan by limiting genome stability.

What is new in flexor tendon pulleys and the gaps between them in triphalangeal fingers of the hand?

The flexor tendon pulleys in the fingers of the hand are fibrous structures of variable size, shape, and thickness that cover the synovial sheath of these tendons. Despite their clinical relevance, their arrangement and configuration in each of the triphalangeal fingers have been little studied and with small sample sizes. 192 triphalangeal fingers belonging to 48 fresh body donors' hands were dissected. Multivariate analysis was carried out. Twenty-five cases (52%) were left hands, and 26 of the 48 hands belonged to female donors (54.2%). The results were analyzed by fingers for each of the 5 annular pulleys, the 3 cruciform pulleys and the gaps between them. In addition, the most and least frequent configurations of the pulleys in each of the fingers were studied, observing that the classic pattern with all the pulleys appeared only in 3 fingers (1.56%), while the most frequent pattern was A1-A2-C1-A3-A4, which was seen in 35 fingers (18.22%). CONCLUSIONS: The flexor pulleys in the triphalangeal fingers of the hand have shown enormous variability in arrangement and shape, and also rarely appear all in the same finger. This peculiar anatomical arrangement can help the different professionals who perform their clinical work in this region.

Delineating the mechanism of fragility at BCL6 breakpoint region associated with translocations in diffuse large B cell lymphoma.

BCL6 translocation is one of the most common chromosomal translocations in cancer and results in its enhanced expression in germinal center B cells. It involves the fusion of BCL6 with any of its twenty-six Ig and non-Ig translocation partners associated with diffuse large B cell lymphoma (DLBCL). Despite being discovered long back, the mechanism of BCL6 fragility is largely unknown. Analysis of the translocation breakpoints in 5' UTR of BCL6 reveals the clustering of most of the breakpoints around a region termed Cluster II. In silico analysis of the breakpoint cluster sequence identified sequence motifs that could potentially fold into non-B DNA. Results revealed that the Cluster II sequence folded into overlapping hairpin structures and identified sequences that undergo base pairing at the stem region. Further, the formation of cruciform DNA blocked DNA replication. The sodium bisulfite modification assay revealed the single-strandedness of the region corresponding to hairpin DNA in both strands of the genome. Further, we report the formation of intramolecular parallel G4 and triplex DNA, at Cluster II. Taken together, our studies reveal that multiple non-canonical DNA structures exist at the BCL6 cluster II breakpoint region and contribute to the fragility leading to BCL6 translocation in DLBCL patients.

WRN Is a Promising Synthetic Lethal Target for Cancers with Microsatellite Instability (MSI).

Microsatellite instability (MSI), a type of genetic hypermutability arising from impaired DNA mismatch repair (MMR), is observed in approximately 3% of all cancers. Preclinical work has identified the RecQ helicase WRN as a promising synthetic lethal target for patients with MSI cancers. WRN depletion substantially impairs the viability of MSI, but not microsatellite stable (MSS), cells. Experimental evidence suggests that this synthetic lethal phenotype is driven by numerous TA dinucleotide repeats that undergo expansion mutations in the setting of long-standing MMR deficiency. The lengthening of TA repeats increases their propensity to form secondary DNA structures that require WRN to resolve. In the absence of WRN helicase activity, these unresolved DNA secondary structures stall DNA replication forks and induce catastrophic DNA damage.

Fatigue Analysis of Welded Joints Using a Thin-Walled Al/Fe Explosive Welded Transition Joints.

The study presents an analysis of S355J2+N steel and AA5083 aluminum alloy welded structural joints using explosion welded transition joints of reduced thickness. The transition joint thickness reduction significantly hinders the welding of the joints due to the risk of damage to the Al/steel interface as a result of the high temperatures during welding. In the previous article, the strength of the transition joint was analyzed but ship structures, apart from static loads, are subjected to many different cyclical loads. Welded structural joints are analyzed to determine the welding influence on the fatigue life and fracture type of the transition joints. The results of the fatigue tests show that the fatigue damage in the specimens occurs in the aluminum welded joint, and not in the explosively welded joint. The damage obtained was characteristic of cruciform welded joint specimens and both types of root and toe damage occurred. Based on the obtained results, fatigue curves for the joint were determined and compared to the fatigue curves for the AA5083 base material. The experimental fatigue curve was also compared with the design curve for welded aluminum structures from Eurocode. The conducted analysis showed the possibility of using Al/steel explosion welded transition joints of reduced thickness to transfer cyclical loads.

Computational analysis on the dissemination of non-B DNA structural motifs in promoter regions of 1180 cellular genomes.

The promoter regions of gene regulation are under evolutionary constraints and earlier studies uncovered that they are characterized by enrichment of functional non-B DNA structural signatures like curved DNA, cruciform DNA, G-quadruplex, triple-helical DNA, slipped DNA structures, and Z-DNA. However, these studies are restricted to a few model organisms, single non-B DNA motif types, or whole genomic sequences, and their comparative accumulation in promoter regions of different domains of life has not been reported comprehensively. In this study, for the first time, we investigated the preponderance of non-B DNA-prone motifs in promoter regions in 1180 genomes belonging to 28 taxonomic groups using the non-B DNA Motif Search Tool (nBMST). The trends suggest that they are predominant in promoters compared to the upstream and downstream regions of all three domains of life and variably linked to taxonomic groups. Cruciform DNA motif is the most abundant form of non-B DNA, spanning from archaea to lower eukaryotes. Curved DNA motifs are prominent in host-associated bacteria, and suppressed in mammals. Triplex-DNA and slipped DNA structure repeats are discretely dispersed in all lineages. G-quadruplex motifs are significantly enriched in mammals. We also observed that the unique enrichment of non-B DNA in promoters is strongly linked to genome GC, size, evolutionary time divergence, and ecological adaptations. Overall, our work systematically reports the unique non-B DNA structural landscape of cellular organisms from the perspective of the cis-regulatory code of genomes.

CGBO-Net: Cruciform structure guided and boundary-optimized lymphoma segmentation network.

Lymphoma segmentation plays an important role in the diagnosis and treatment of lymphocytic tumor. Most current existing automatic segmentation methods are difficult to give precise tumor boundary and location. Semi-automatic methods are usually combined with manually added features such as bounding box or points to locate the tumor. Inspired by this, we propose a cruciform structure guided and boundary-optimized lymphoma segmentation network(CGBS-Net). The method uses a cruciform structure extracted based on PET images as an additional input to the network, while using a boundary gradient loss function to optimize the boundary of the tumor. Our method is divided into two main stages: In the first stage, we use the proposed axial context-based cruciform structure extraction (CCE) method to extract the cruciform structures of all tumor slices. In the second stage, we use PET/CT and the corresponding cruciform structure as input in the designed network (CGBO-Net) to extract tumor structure and boundary information. The Dice, Precision, Recall, IOU and RVD are 90.7%, 89.4%, 92.5%, 83.1% and 4.5%, respectively. Validate on the lymphoma dataset and publicly available head and neck data, our proposed approach is better than the other state-of-the-art semi-segmentation methods, which produces promising segmentation results.

Temporal frequency dependence of the polarity inversion between upper and lower visual field in the pattern-onset steady-state visual evoked potential.

PURPOSE: According to the cruciform model, the upper and lower halves of the visual field representation in the primary visual cortex are located mainly on the opposite sides of the calcarine sulcus. Such a shape would have consequences for the surface-recorded visual evoked potential (VEP), as V1 responses to stimulation of the upper and lower hemifield manifest with opposite polarity (i.e., polarity inversion). However, the steady-state VEP results from a complex superposition of response components from different cortical sources, which can obscure the inversion of polarity. The present study assesses the issue for different stimulation frequencies which result in different patterns of superposition in the steady-state response. METHODS: Sequences of brief pattern-onset stimuli were presented at different stimulation rates ranging from 2 Hz (transient VEP) to 13 Hz (steady-state VEP). The upper and lower hemifields were tested separately and simultaneously. The data were assessed both in the time domain and in the frequency domain. RESULTS: Comparing the responses to the stimulation of upper and lower hemifield, polarity inversion was present within a limited time interval following individual stimulus onsets. With increasing frequency, this resulted in an approximate inversion of the full steady-state response and consequently in a phase shift of approximately 180° in the time-domain response. Polarity inversion was more prominent at electrode Pz, also for transient responses. Our data also demonstrated that the sum of the hemifield responses is a good approximation of the full-field response. CONCLUSION: While the basic phenomenon of polarity inversion occurs irrespective of the stimulus frequency, its relative impact on the steady-state response as a whole is the largest for high stimulation rates. We propose that this is because longer-lasting response components from other visual areas are not well represented in the steady-state VEP at higher frequencies.

The 'Cruciform Test': A diagnostic tool to detect pectoralis major rupture.

Introduction: Pectoralis major (PM) rupture is a severe injury that untreated can lead to a profound functional deficit. Early surgical repair can greatly improve outcomes and give a more predictable timetable for recovery, making this the goal of current treatment. Surgical intervention is also essential to return professional athletes to their previous level of competition. However, there is no single, reliable and easily reproducible test that can be used to establish the diagnosis. We describe 'The Cruciform Test'; a method of identifying PM rupture that can be used for initial diagnosis either in clinic or a pitch-side environment, or to assess restoration of normal anatomy and function post-operatively. Methods: We studied a series of 14 patients who underwent open PM repair in order to evaluate this method of assessment. Results: All patients had a positive test pre-operatively. 5 were formally tested at post-operative follow-up and all had a negative result. Discussion: The Cruciform Test is a simple and reproducible diagnostic tool that has potential as a clinical indicator of both PM rupture and successful repair. It can therefore contribute to earlier diagnosis, prompt surgical intervention and facilitate return to play at the earliest opportunity.

Non-canonical DNA structures: Diversity and disease association.

A complete understanding of DNA double-helical structure discovered by James Watson and Francis Crick in 1953, unveil the importance and significance of DNA. For the last seven decades, this has been a leading light in the course of the development of modern biology and biomedical science. Apart from the predominant B-form, experimental shreds of evidence have revealed the existence of a sequence-dependent structural diversity, unusual non-canonical structures like hairpin, cruciform, Z-DNA, multistranded structures such as DNA triplex, G-quadruplex, i-motif forms, etc. The diversity in the DNA structure depends on various factors such as base sequence, ions, superhelical stress, and ligands. In response to these various factors, the polymorphism of DNA regulates various genes via different processes like replication, transcription, translation, and recombination. However, altered levels of gene expression are associated with many human genetic diseases including neurological disorders and cancer. These non-B-DNA structures are expected to play a key role in determining genetic stability, DNA damage and repair etc. The present review is a modest attempt to summarize the available literature, illustrating the occurrence of non-canonical structures at the molecular level in response to the environment and interaction with ligands and proteins. This would provide an insight to understand the biological functions of these unusual DNA structures and their recognition as potential therapeutic targets for diverse genetic diseases.

An Investigation into a Miniature Saltless Solar Pond.

A simple, miniature saltless Solar Pond (SP) was designed and constructed in the present work. It consisted of a Plexiglas container with a square cross-section, within which cruciform baffles were suspended in the upper half of the pond, and copper coil tubing was fitted in the middle of the lower zone to function as a heat exchanger without disturbing the pond's inertia. Different variables' effect on the water's temperature rise at various vertical locations within the pond were investigated. These variables included the presence of the cruciform baffles, the inclination of a mirror fixed to the top rim of the pond, a glass transparent cover (GC), and the presence or absence of a gel thickening material to increase the water viscosity inside the SP, the climatic conditions, and the presence of glass wool (GW) in the lower section of the SP. For an experiment, an estimated energy balance was performed, and the thermal storage efficiency was calculated. The best obtained thermal storage efficiency was 32.58% in the presence of the cruciform baffles, a 45° inclination of a mirror fixed to the top rim of the SP, at an ambient temperature of 30 °C on a calm, sunny day with a wind speed of 7 km/h.

A Cruciform Petal-like (ZIF-8) with Bactericidal Activity against Foodborne Gram-Positive Bacteria for Antibacterial Food Packaging.

Most antibacterial nanomaterials used in food packaging act by releasing reactive oxygen species (ROS), which cannot efficiently have an inhibitory effect by penetrating the cell wall of Gram-positive Staphylococcus aureus. In this work, we used the cruciform petal-like zeolite imidazole framework-8 (ZIF-8) synthesized in the water phase which can release active Zn compounds in aqueous solution and exert a stronger inhibitory effect on S. aureus. The experimental results demonstrated that the aqueous cruciform petal-like ZIF-8 has the same photocatalytic activity as traditional ZIF-8 and can be applied in photocatalytic bacterial inactivation. The cruciform petal-like ZIF-8 was also shown to release active Zn compounds in aqueous solution with a better antibacterial effect against S. aureus, reaching 95% inactivation efficiency. The antibacterial effect was therefore 70% higher than that of traditional ZIF-8. Based on its excellent antibacterial properties, we loaded petal-like ZIF-8, PDA and PVA onto ordinary fibers to prepare ZIF-8-Film. The results further showed that ZIF-8-Film has a high filtration capacity, which can be used in antibacterial packaging material with the required air permeability. Moreover, ZIF-8-Flim can clean the surface on its own and can maintain a sterile environment. It is different from other disposable materials on the market in that it can be reused and has a self-disinfection function.

Quantifying Alignment Deviations for the In-Plane Biaxial Test System via a Shape-Optimised Cruciform Specimen.

The loading coaxiality of an in-plane biaxial test system and the structure of a cruciform specimen markedly affect the test results. However, due to the lack of methods for correcting the loading coaxiality and designing the cruciform specimen, the data scatter of the test results of the in-plane biaxial test systems varies from the laboratory to different tests. To quantify the loading coaxiality of the in-plane biaxial test system, we first developed a model to calculate alignment deviations with strain distribution of the shape-optimised cruciform specimen with Automated Machine Learning (AutoML). Our results demonstrated that 99.2% (54,536 of 54,976) of the quantified errors are less than 5%. Quantifying alignment deviations for an in-plane biaxial test system has been solved. The quantified method of alignment deviations could enhance the reliability of test data, improve assembly efficiency, and aid in constructing failure criteria of materials under biaxial stress.

Designing a Cruciform Specimen via Topology and Shape Optimisations under Equal Biaxial Tension Using Elastic Simulations.

Stress uniformity within the gauge zone of a cruciform specimen significantly affects materials' in-plane biaxial mechanical properties in material testing. The stress uniformity depends on the load transmission of the cruciform specimen from the fixtures to the gauge zone. Previous studies failed to alter the nature of the load transmission of the geometric features using parametric optimisations. To improve stress uniformity in the gauge zone, we optimised the cross-arms to design a centre-reduced cruciform specimen with topology and shape optimisations. The simulations show that the optimised specimen obtains significantly less stress variation and range in the gauge zone than the optimised specimen under different observed areas, directions, and load ratios of von Mises, S11, S22, and S12. In the quantified gauge zone, a more uniform stress distribution could be generated by optimizing specimen geometry, whose value should be estimated indirectly each time through simulations. We found that topology and shape optimisations could markedly improve stress uniformity in the gauge zone, and stress concentration at the cross-arms intersection. We first optimised the cruciform specimen structure by combining topology and shape optimisations, which provided a cost-effective way to improve stress uniformity in the gauge zone and reduce stress concentration at the cross-arms intersection, helping obtain reliable data to perform large strains in the in-plane biaxial tensile test.

A highly sensitive fluorescent aptasensor for detection of prostate specific antigen based on the integration of a DNA structure and CRISPR-Cas12a.

Herein, a facile fluorescent CRISPR-Cas12a-based sensing strategy is presented for prostate specific antigen (PSA), as a prostate cancer biomarker, with the assistance of a cruciform DNA nanostructure and PicoGreen (PG) as a fluorochrome. Highly sensitive recognition of PSA is one of the virtues of the proposed method which comes from the use of unique features of both CRISPR-Cas12a and DNA structure in the design of the aptasensor. The presence of PSA creates a cruciform DNA nanostructure in the sample which can be loaded by PG and make sharp fluorescence emission. While, when there is no PSA, the CRISPR-Cas12a digests sequences 1 and 3 as single-stranded DNAs, causing no DNA structure and a negligible fluorescence is detected after addition of PG. This aptasensor presents a sensitive recognition performance with detection limit of 4 pg/mL and a practical use for determination of PSA in serum samples. So, this analytical strategy introduces a convenient and highly sensitive approach for detection of disease biomarkers.

Interaction of Proteins with Inverted Repeats and Cruciform Structures in Nucleic Acids.

Cruciforms occur when inverted repeat sequences in double-stranded DNA adopt intra-strand hairpins on opposing strands. Biophysical and molecular studies of these structures confirm their characterization as four-way junctions and have demonstrated that several factors influence their stability, including overall chromatin structure and DNA supercoiling. Here, we review our understanding of processes that influence the formation and stability of cruciforms in genomes, covering the range of sequences shown to have biological significance. It is challenging to accurately sequence repetitive DNA sequences, but recent advances in sequencing methods have deepened understanding about the amounts of inverted repeats in genomes from all forms of life. We highlight that, in the majority of genomes, inverted repeats are present in higher numbers than is expected from a random occurrence. It is, therefore, becoming clear that inverted repeats play important roles in regulating many aspects of DNA metabolism, including replication, gene expression, and recombination. Cruciforms are targets for many architectural and regulatory proteins, including topoisomerases, p53, Rif1, and others. Notably, some of these proteins can induce the formation of cruciform structures when they bind to DNA. Inverted repeat sequences also influence the evolution of genomes, and growing evidence highlights their significance in several human diseases, suggesting that the inverted repeat sequences and/or DNA cruciforms could be useful therapeutic targets in some cases.

Cruciform DNA Structures Act as Legible Templates for Accelerating Homologous Recombination in Transgenic Animals.

Inverted repeat (IR) DNA sequences compose cruciform structures. Some genetic disorders are the result of genome inversion or translocation by cruciform DNA structures. The present study examined whether exogenous DNA integration into the chromosomes of transgenic animals was related to cruciform DNA structures. Large imperfect cruciform structures were frequently predicted around predestinated transgene integration sites in host genomes of microinjection-based transgenic (Tg) animals (αLA-LPH Tg goat, Akr1A1eGFP/eGFP Tg mouse, and NFκB-Luc Tg mouse) or CRISPR/Cas9 gene-editing (GE) animals (αLA-AP1 GE mouse). Transgene cassettes were imperfectly matched with their predestinated sequences. According to the analyzed data, we proposed a putative model in which the flexible cruciform DNA structures acted as a legible template for DNA integration into linear DNAs or double-strand break (DSB) alleles. To demonstrate this model, artificial inverted repeat knock-in (KI) reporter plasmids were created to analyze the KI rate using the CRISPR/Cas9 system in NIH3T3 cells. Notably, the KI rate of the 5' homologous arm inverted repeat donor plasmid (5'IR) with the ROSA gRNA group (31.5%) was significantly higher than the knock-in reporter donor plasmid (KIR) with the ROSA gRNA group (21.3%, p < 0.05). However, the KI rate of the 3' inverted terminal repeat/inverted repeat donor plasmid (3'ITRIR) group was not different from the KIR group (23.0% vs. 22.0%). These results demonstrated that the legibility of the sequence with the cruciform DNA existing in the transgene promoted homologous recombination (HR) with a higher KI rate. Our findings suggest that flexible cruciform DNAs folded by IR sequences improve the legibility and accelerate DNA 3'-overhang integration into the host genome via homologous recombination machinery.

Advances in Cruciform Biaxial Testing of Fibre-Reinforced Polymers.

The heterogeneity and anisotropy of fibre-reinforced polymer matrix composites results in a highly complex mechanical response and failure under multiaxial loading states. Among the different biaxial testing techniques, tests with cruciform specimens have been a preferred option, although nowadays, they continue to raise a lack of consensus. It is therefore necessary to review the state of the art of this testing methodology applied to fibre-reinforced polymers. In this context, aspects such as the specific constituents, the geometric design of the specimen or the application of different tensile/compressive load ratios must be analysed in detail before being able to establish a suitable testing procedure. In addition, the most significant results obtained in terms of the analytical, numerical and experimental analyses of the biaxial tests with cruciform specimens are collected. Finally, significant modifications proposed in literature are detailed, which can lead to variants or adaptations of the tests with cruciform specimens, increasing their scope.

Organoplatinum(II) Cruciform: A Versatile Building Block to Fabricate 2D Microcrystals with Full-Color and White Phosphorescence and Anisotropic Photon Transport.

Conventional square-planar platinum complexes typically form one-dimensional assemblies as a result of unidirectional metallophilic and/or π⋅⋅⋅π intermolecular interactions. Organoplatinum(II) complexes with a cruciform shape are presented herein to construct two-dimensional (2D) microcrystals with full-color and white phosphorescence. These 2D crystals show unique monocomponent π⋅⋅⋅π stacking, from either the cyclometalating or noncyclometalating ligand, and the bicomponent alternate π⋅⋅⋅π stacking from both ligands along different facet directions. Anisotropic tri-directional waveguiding is further implemented on a single hexagonal microcrystal. These results demonstrate the great capability of the organoplatinum(II) cruciform as a general platform to fabricate 2D phosphorescent micro-/nanocrystals for advanced photonic applications.