Micromechanical finite element analyses of fire retardant woven fabric composites at elevated temperatures using unit cells at multiple length scales

This paper presents a micromechanical Finite Element (FE) model developed to predict the effective mechanical properties of glass fibre-reinforced (woven fabric) polymer composites with/without fire retardant particulate additives at elevated temperatures. The elevated mechanical properties of glass fibre-reinforced epoxy composites with/without fire retardants were predicted using three unit cells of varying length scales in micromechanical FE analysis. Theoretically predictions of flexural behaviour of these fibre-reinforced polymer composites at elevated temperatures were satisfactorily validated against experimentally measured data. The numerical model developed herein was then used for the prediction of other mechanical properties of fibre-reinforced polymer composites that would have been difficult to collect at elevated temperatures. Micromechanical FE models such as the one contained in this paper are useful to architectural engineers as they can be used to guide the design and qualification of new engineering composites that satisfy stringent Building codes in fire prone engineering applications

Fastcloning: A Highly Simplified Purification-Free Sequence- And Ligation-Independent Pcr Cloning Method

Background: Although a variety of methods and expensive kits are available, molecular cloning can be a timeconsuming and frustrating process. Results: Here we report a highly simplified, reliable, and efficient PCR-based cloning technique to insert any DNA fragment into a plasmid vector or into a gene (cDNA) in a vector at any desired position. With this method, the vector and insert are PCR amplified separately, with only 18 cycles, using a high fidelity DNA polymerase. The amplified insert has the ends with ~16-base overlapping with the ends of the amplified vector. After DpnI digestion of the mixture of the amplified vector and insert to eliminate the DNA templates used in PCR reactions, the mixture is directly transformed into competent E. coli cells to obtain the desired clones. This technique has many advantages over other cloning methods. First, it does not need gel purification of the PCR product or linearized vector. Second, there is no need of any cloning kit or specialized enzyme for cloning. Furthermore, with reduced number of PCR cycles, it also decreases the chance of random mutations. In addition, this method is highly effective and reproducible. Finally, since this cloning method is also sequence independent, we demonstrated that it can be used for chimera construction, insertion, and multiple mutations spanning a stretch of DNA up to 120 bp. Conclusion: Our FastCloning technique provides a very simple, effective, reliable, and versatile tool for molecular cloning, chimera construction, insertion of any DNA sequences of interest and also for multiple mutations in a short stretch of a cDNA

Disturbance of the OPG/RANK/RANKL pathway and systemic inflammation in COPD patients with emphysema and osteoporosis

<p>Abstract</p> <p>Background</p> <p>Osteoporosis is one of the systemic features of COPD. A correlation between the emphysema phenotype of COPD and reduced bone mineral density (BMD) is suggested by some studies, however, the mechanisms underlying this relationship are unclear. Experimental studies indicate that IL-1β, IL-6 and TNF-α may play important roles in the etiology of both osteoporosis and emphysema. The OPG/RANK/RANKL system is an important regulator of bone metabolism, and participates in the development of post-menopausal osteoporosis. Whether the OPG/RANK/RANKL pathway is involved in the pathogenesis of osteoporosis in COPD has not been studied.</p> <p>Methods</p> <p>Eighty male patients (current or former smokers) completed a chest CT scan, pulmonary function test, dual x-ray absorptiometry measurements and questionnaires. Among these subjects, thirty patients with normal BMD and thirty patients with low BMD were selected randomly for measurement of IL-1β, IL-6, TNF-α (flow cytometry) and OPG/RANK/RANKL (ELISA). Twenty age-matched healthy volunteers were recruited as controls.</p> <p>Results</p> <p>Among these eighty patients, thirty-six had normal BMD and forty-four had low BMD. Age, BMI and CAT score showed significant differences between these two COPD groups (<it>p </it>< 0.05). The low-attenuation area (LAA%) in the lungs of COPD patients was negatively correlated with lumbar vertebral BMD (r = 0.741; <it>p </it>< 0.0001). Forward logistic regression analysis showed that only LAA% (<it>p </it>= 0.005) and BMI (<it>p </it>= 0.009) were selected as explanatory variables. The level of IL-1β was significantly higher in the COPD patients as compared to the normal controls (<it>p </it>< 0.05), but the difference between the two COPD groups did not reach significance. The levels of IL-6 and TNF-α among the three groups were significantly different (<it>p </it>< 0.05). The level of RANKL and the RANKL/OPG ratio were significantly higher in COPD patients with low BMD compared to those with normal BMD and the normal controls (<it>p </it>< 0.05), and correlated negatively with lumbar vertebral BMD, but positively with LAA%.</p> <p>Conclusions</p> <p>Radiographic emphysema is correlated with low BMD in current and former smokers with COPD. IL-1β, IL-6, TNF-α, and the osteoporosis-related protein system OPG/RANK/RANKL may have some synergetic effects on emphysema and bone loss in COPD.</p

Desensitization Of α7 Nicotinic Receptor Is Governed By Coupling Strength Relative To Gate Tightness

Binding of a neurotransmitter to its membrane receptor opens an integral ion conducting pore. However, prolonged exposure to the neurotransmitter drives the receptor to a refractory state termed desensitization, which plays an important role in shaping synaptic transmission. Despite intensive research in the past, the structural mechanism of desensitization is still elusive. Using mutagenesis and voltage clamp in an oocyte expression system, we provide several lines of evidence supporting a novel hypothesis that uncoupling between binding and gating machinery is the underlying mechanism for α7 nicotinic receptor (nAChR) desensitization. First, the decrease in gate tightness was highly correlated to the reduced desensitization. Second, nonfunctional mutants in three important coupling loops (loop 2, loop 7, and the M2-M3 linker) could be rescued by a gating mutant. Furthermore, the decrease in coupling strength in these rescued coupling loop mutants reversed the gating effect on desensitization. Finally, coupling between M1 and hinge region of the M2-M3 linker also influenced the receptor desensitization. Thus, the uncoupling between N-terminal domain and transmembrane domain, governed by the balance of coupling strength and gate tightness, underlies the mechanism of desensitization for the α7 nAChR. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc

DEM Investigation of Particle-Scale Mechanical Properties of Frozen Soil Based on the Nonlinear Microcontact Model Incorporating Rolling Resistance

Although frozen soil is in nature the discrete material, it is generally treated as the continuum material. The mechanical properties of frozen soil are so complex to describe adequately by conventional continuum mechanics method. In this study, the nonlinear microcontact model incorporating rolling resistance is proposed to investigate the particle-scale mechanical properties of frozen soil. The failure mechanism of frozen soil is explicated based on the evolution of contact force chains and propagation of microcracks. In addition, the effects of contact stiffness ratio and friction coefficient on stress-strain curve and energy evolution are evaluated. The results show that the nonlinear microcontact model incorporating rolling resistance can better describe the experimental data. At a higher axial strain, the contact force chains near shear band which can give rise to the soil arch effect rotate away from the shear band inclination but not so much as to become perpendicular to it. The propagation of microcracks can be divided into two phases. The stress-strain curve is strongly influenced by contact stiffness ratio. In addition, friction coefficient does not significantly affect the initial tangential modulus. Compared with frictional coefficient, the effect of contact stiffness ratio on stress-strain curve and energy evolution is greater

Clinical evaluation on automatic segmentation results of convolutional neural networks in rectal cancer radiotherapy

PurposeImage segmentation can be time-consuming and lacks consistency between different oncologists, which is essential in conformal radiotherapy techniques. We aimed to evaluate automatic delineation results generated by convolutional neural networks (CNNs) from geometry and dosimetry perspectives and explore the reliability of these segmentation tools in rectal cancer.MethodsForty-seven rectal cancer cases treated from February 2018 to April 2019 were randomly collected retrospectively in our cancer center. The oncologists delineated regions of interest (ROIs) on planning CT images as the ground truth, including clinical target volume (CTV), bladder, small intestine, and femoral heads. The corresponding automatic segmentation results were generated by DeepLabv3+ and ResUNet, and we also used Atlas-Based Autosegmentation (ABAS) software for comparison. The geometry evaluation was carried out using the volumetric Dice similarity coefficient (DSC) and surface DSC, and critical dose parameters were assessed based on replanning optimized by clinically approved or automatically generated CTVs and organs at risk (OARs), i.e., the Planref and Plantest. Pearson test was used to explore the correlation between geometric metrics and dose parameters.ResultsIn geometric evaluation, DeepLabv3+ performed better in DCS metrics for the CTV (volumetric DSC, mean = 0.96, P&lt; 0.01; surface DSC, mean = 0.78, P&lt; 0.01) and small intestine (volumetric DSC, mean = 0.91, P&lt; 0.01; surface DSC, mean = 0.62, P&lt; 0.01), ResUNet had advantages in volumetric DSC of the bladder (mean = 0.97, P&lt; 0.05). For critical dose parameters analysis between Planref and Plantest, there was a significant difference for target volumes (P&lt; 0.01), and no significant difference was found for the ResUNet-generated small intestine (P &gt; 0.05). For the correlation test, a negative correlation was found between DSC metrics (volumetric, surface DSC) and dosimetric parameters (δD95, δD95, HI, CI) for target volumes (P&lt; 0.05), and no significant correlation was found for most tests of OARs (P &gt; 0.05).ConclusionsCNNs show remarkable repeatability and time-saving in automatic segmentation, and their accuracy also has a certain potential in clinical practice. Meanwhile, clinical aspects, such as dose distribution, may need to be considered when comparing the performance of auto-segmentation methods

Engineering Escherichia coli for autoinducible production of n-butanol

Background: Escherichia coli does not produce n-butanol naturally, but can be butanologenic when related enzymes were expressed using inducible elements on plasmids. In this study we attempted to confer E. coli strain capability of automatic excretion of the chemical by employing a native anaerobic promoter. Also, a novel DNA kit was designed for PCR preparation of linear DNA fragments to perform strain modification. The kit is primarily composed of two mother vectors, co-transformation of linear DNAs into E. coli can simultaneously introduce two butanol synthetic operons into the chromosome and create two in-frame gene deletions at targeted native loci. Results: E. coli strain Bw2V carries plasmid pCNA-PHC and pENA-TA, both utilizes native anaerobic promoter Phya for the expression of butanol synthetic enzymes. When Bw2V was subjected in anaerobic fermentation using medium containing extra glucose, the accumulated n-butanol in the broth was up to 2.8 g/L in bioreactor; as the genetic element expressing the same pathway was introduced into the genome, the titer of butanol was 1.4 g/L. Conclusions: The expression systemusing Phya is effective in applications that involve expression plasmids as also applicable in ectopic expression as single copy on the chromosome. Results imply that Phya can be subjected for broader application in bioproduction of more feedstock chemicals

Extrachromosomal DNA (ecDNA) in cancer: mechanisms, functions, and clinical implications

Extrachromosomal DNA (ecDNA) is circular DNA that plays an important role in the development and heterogeneity of cancer. The rapid evolution of methods to detect ecDNA, including microscopic and sequencing approaches, has greatly enhanced our knowledge of the role of ecDNA in cancer development and evolution. Here, we review the molecular characteristics, functions, mechanisms of formation, and detection methods of ecDNA, with a focus on the potential clinical implications of ecDNA in cancer. Specifically, we consider the role of ecDNA in acquired drug resistance, as a diagnostic and prognostic biomarker, and as a therapeutic target in the context of cancer. As the pathological and clinical significance of ecDNA continues to be explored, it is anticipated that ecDNA will have broad applications in the diagnosis, prognosis, and treatment of patients with cancer