Search

Objective: Survival and reconstruction in osteosarcoma is quite challenging. The study aimed to investigate the prognosis in patients treated with neoadjuvant chemotherapy and determine the clinical outcomes of expandable endoprosthesis reconstruction in children. Methods: From January 2009 to December 2014, we retrospectively analyzed 29 skeletally immature children (mean age, 10.5 years; range, 6–15 years) with osteosarcoma around the knee. Of the 29 patients who underwent neoadjuvant chemotherapy and limb salvage surgery, an expandable prosthesis was implanted for reconstruction. No patients were missed during follow‐up. The evaluation index involved follow‐up time, complication, functional results, and lengthening procedures. The survivorship and recurrence were assessed by GraphPad Software, and the function was evaluated by the Musculoskeletal Tumor Society (MSTS) scoring system. Results: A mean follow‐up time was 8.9 years (range, 6–12 years), and the overall 5‐year survival was 89.1% based on Kaplan–Meier analysis. Three patients suffered a relapse and one underwent amputation. Lung metastasis developed in one patient. At 6 months after the operation, patients had a mean MSTS score of 27 points (range, 24–29). Two patients underwent revision surgery, one for implant infection and one for aseptic loosening. Prognosis is correlated with alkaline phosphatase change after treatment. Conclusions: Chemotherapy scheme and limb salvage can achieve high survival rates. This expandable prosthesis was associated with good function and low complication rates. The character of expandability could be a method to overcome discrepancies in the growth period. [ABSTRACT FROM AUTHOR]

A hybrid structure constructed by replacing external steel beams and columns in the steel frame (SF) to precast concrete shear walls with insulation (PCSWs) and precast concrete cladding panels (PCCPs, SFPCSW) is proposed in this paper to avoid the problem of columns protruding from walls and PCCPs directly connected with SF. Numerical models of the SF and SFPCSW structures are established in ETABS software based on an 18‐story assembled steel residential building to investigate the seismic performance and collapse resistance capacity of SFPCSW. Time history analysis results show that the SFPCSW exhibits bending‐shearing lateral deformation and has more uniform interstory drift ratios than the SF. Under major earthquakes (i.e., probability of exceedance of 2% in 50 years), the damage of SF is concentrated in stories 1–6; for SFPCSW, the plastic hinges mainly appear in the concrete beams between PCSWs at each story, and the damage in PCSWs and the internal frame is small. Using pinned connections between the steel beam and PCSW reduces the structural lateral stiffness and increases the earthquake load carried by the internal frame. The incremental dynamic analysis results show that the SF and SFPCSW have similar collapse resistance capacities. [ABSTRACT FROM AUTHOR]

Back diffusion of contaminants from secondary sources may hamper site remediation if it is not properly addressed in the remedial design. A review of all reported technologies and strategies that have been or could be applied to address plume persistence due to back diffusion as published in the peer‐reviewed literature is provided. We classify these into four major categories. The first category consists of those approaches that do not include active measures to specifically address contamination in the low permeable zones (LPZs) and can therefore be considered passive LPZ management approaches. A disadvantage of these approaches is the long duration that may be required to meet acceptable endpoints; however, this allows degradation to potentially play a significant part even at modest rates. The remaining three categories all use approaches to specifically address contaminants in the LPZ. The second category consists of strategies that promote contaminant destruction through the forward diffusion of amendments into the LPZ. A variety of laboratory tests indicate concentration or flux reductions range from no improvement, to reductions as high as four orders‐of‐magnitude depending on the evaluation metric. The third category consists of strategies that alter physical characteristics of the secondary source, and includes viscosity modification, fracturing, and soil mixing. Each of these offer unique advantages and are often used to deliver one or more amendments for contaminant treatment. The final category consists of thermal and electrokinetic remediation, both less susceptible to permeability contrast limitations. However, they are not routinely used for secondary‐source treatment. Article impact statement: Back diffusion of contaminants from secondary sources may hamper site remediation if it is not properly addressed in the remedial design. A review of all reported technologies and strategies that have been or could be applied to address plume persistence due to back diffusion as published in the peer‐reviewed literature was conducted and is intended to provide a state‐of‐the‐science resource to assist in evaluating treatment options. [ABSTRACT FROM AUTHOR]

This paper proposed a new lateral joint to connect precast concrete hollow‐core slabs (PCHSs) and increase their structural assembly efficiency. The main sensitive parameters are the longitudinal ribs and the number of proposed joints. Out‐of‐plane bending performance tests were conducted on four PCHSs with lateral joints (PCHS‐LJs) to study the effects of the main sensitive parameters on the mechanical properties and failure modes of the PCHS‐LJs. The test results showed that there is no obvious relative slip in the joints between the precast bottom slab and the upper post‐pouring concrete before PCHS‐LJs reaching the ultimate load. The transverse directions of PCHS‐LJs are the main force bearing directions and the cracks are mainly occurred in the longitudinal direction of the specimens, which is similar to the stress characteristics of one‐way slabs. Moreover, the vertical bearing capacities of PCHS‐LJs are increased when decreasing the number of proposed joints or when adding the longitudinal ribs. For the specimens without the longitudinal ribs, a wide transverse crack appears near the first transverse ribs, whereas the specimens with the longitudinal ribs do not exhibit this phenomenon. Thus, longitudinal ribs should be added to optimize the PCHS‐LJ failure modes. Finally, solid finite element (FE) models of the test specimens were established in MSC. MARC. The analysis results are basically consistent with the experimental results. [ABSTRACT FROM AUTHOR]

Small molecular PD‐1 inhibitors are lacking in current immuno‐oncology clinic. PD‐1/PD‐L1 antibody inhibitors currently approved for clinical usage block interaction between PD‐L1 and PD‐1 to enhance cytotoxicity of CD8+ cytotoxic T lymphocyte (CTL). Whether other steps along the PD‐1 signaling pathway can be targeted remains to be determined. Here, we report that methylene blue (MB), an FDA‐approved chemical for treating methemoglobinemia, potently inhibits PD‐1 signaling. MB enhances the cytotoxicity, activation, cell proliferation, and cytokine‐secreting activity of CTL inhibited by PD‐1. Mechanistically, MB blocks interaction between Y248‐phosphorylated immunoreceptor tyrosine‐based switch motif (ITSM) of human PD‐1 and SHP2. MB enables activated CTL to shrink PD‐L1 expressing tumor allografts and autochthonous lung cancers in a transgenic mouse model. MB also effectively counteracts the PD‐1 signaling on human T cells isolated from peripheral blood of healthy donors. Thus, we identify an FDA‐approved chemical capable of potently inhibiting the function of PD‐1. Equally important, our work sheds light on a novel strategy to develop inhibitors targeting PD‐1 signaling axis. Synopsis: PD‐1 inhibitors that are currently used in the clinic exhibit toxicity and limited patient response rate. This study identifies methylene blue (MB), an FDA‐approved chemical for treating methemoglobinemia, as a new potent PD‐1 inhibitor. MB activates T‐cell functions through inhibiting the recruitment of SHP2 to PD‐1.MB treatment effectively shrinks tumors in both an allograft mouse model and an autochthonous mouse model for lung cancer.MB activates human CD8+ T cells that are otherwise suppressed by PD‐1 signaling. [ABSTRACT FROM AUTHOR]

This study presents frequency upscaling as a technique for developing error resilient arithmetic designs in approximate computing whereby the input signal frequency of the circuit is upscaled beyond its largest operating value in generating errors in the arithmetic operation while speeding up the computational throughput. This study initially presents the mathematical modelling of frequency upscaling for both exact and inexact full adders. An exhaustive simulation and evaluation of 4 and 8 bits subtraction followed by addition of two images and approximate discrete cosine transform (DCT) is pursued using exact and inexact circuits when subjected to the proposed technique. The results estimated using the proposed model show good agreement with the simulation results. The normalised mean error distance of subtraction using an inexact circuit is close to the exact value for different technology nodes. The peak signal‐to‐noise ratio (PSNR) results for the addition of two images show that the inexact full adder achieves a higher output image quality than the exact circuit when the frequency is scaled up. Also, in an approximate DCT, the input frequency of an inexact full adder can be scaled up significantly higher than an exact full adder without a significant decrease in PSNR value. [ABSTRACT FROM AUTHOR]

Tumor necrosis factor α (TNFα), an important inflammatory cytokine, is associated with dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS), a severe pathological manifestation of dengue virus (DENV) infection. However, the regulatory mechanism of microRNA on TNFα is currently unknown. Our study showed that the TNFα expression increased immediately and then later decreased, while a marked increase for the miRNA let‐7e was detected in dengue virus type 2 (DENV2)‐infected peripheral blood mononuclear cells (PBMCs). From this study, we found that let‐7e was able to inhibit TNFα expression, but bioinformatics analysis showed that the enhancer of zeste homolog 2 (EZH2) was the potential direct target of let‐7e instead of TNFα. EZH2 methyl transferase can produce H3K27me3 and has a negative regulatory role. Using a dual‐luciferase reporter assay and Western blotting, we confirmed that EZH2 was a direct target of let‐7e and found that siEZH2 could inhibit TNFα expression. In the further study of the regulatory mechanism of EZH2 on TNFα expression, we showed that siEZH2 promoted EZH1 and H3K4me3 expression and inhibited H3K27me3 expression. More importantly, we revealed that siEZH2 down‐regulated NF‐κB p65 within the nucleus. These findings indicate that the let‐7e/EZH2/H3K27me3/NF‐κB p65 pathway is a novel regulatory axis of TNFα expression. In addition, we determined the protein differences between siEZH2 and siEZH2‐NC by iTRAQ and found a number of proteins that might be associated with TNFα. [ABSTRACT FROM AUTHOR]

A three-dimensional mathematical model that describes transport of contaminant in a horizontal aquifer with simultaneous diffusion into a fractured clay formation is proposed. A group of semianalytical solutions is derived based on specific initial and boundary conditions as well as various source functions. The analytical model solutions are evaluated by numerical Laplace inverse transformation and analytical Fourier inverse transformation. The model solutions can be used to study the fate and transport in a three-dimensional spatial domain in which a nonaqueous phase liquid exists as a pool atop a fractured low-permeability clay layer. The nonaqueous phase liquid gradually dissolves into the groundwater flowing past the pool, while simultaneously diffusing into the fractured clay formation below the aquifer. Mass transfer of the contaminant into the clay formation is demonstrated to be significantly enhanced by the existence of the fractures, even though the volume of fractures is relatively small compared to the volume of the clay matrix. The model solution is a useful tool in assessing contaminant attenuation processes in a confined aquifer underlain by a fractured clay formation. [ABSTRACT FROM AUTHOR]

A one-dimensional diffusion model was used to investigate the effects of dense nonaqueous phase liquid (DNAPL) source zone dissolution and remediation on the storage and release of contaminants from aquitards. Source zone dissolution was represented by a power law source depletion model, which served as a time variable boundary condition to the diffusion equation used to describe mass transport in the aquitard. Two key variables were used to assess source zone dissolution behavior on aquitard mass storage and release: the power law exponential term &b. Gamma;, which reflects the influence of the source zone architecture, and a new variable defined herein as the source to aquitard mass transfer coefficient &bgr;, which reflects the influences of both the source characteristics and the aquitard media properties. As &b.Gamma; increased or as &bgr; increased because of more rapid source dissolution, the aquitard concentrations, depth of penetration, and long-term back-diffusion flux decreased. However, when &bgr; increased because of increased sorption, concentrations and back diffusion increased but penetration decreased. The duration of aquitard mass loading was found to be significantly less than the duration of mass release. Moreover, the mass per unit area stored in the aquitard was 3 or more orders of magnitude less than the initial DNAPL source zone mass per unit area, and the back diffusion flux from the aquitard was typically 4 or more orders of magnitude less than the initial source zone flux. Additionally, the effects of partial source zone remediation were investigated, and the results suggest that source remediation can have a favorable effect on long-term back-diffusion risk. [ABSTRACT FROM AUTHOR]

The hallmark of the dengue hemorrhagic fever/dengue shock syndrome is hematologic abnormality. The pathogenesis of dengue hemorrhagic fever/dengue shock syndrome remains unknown. Our work showed that the dengue virus serotype-2 induced apoptosis in human umbilical vein endothelial cells. Fas (CD95), Tumor Necrosis Factor receptors, and Tumor Necrosis Factor-related apoptosis-inducing ligand receptors are the most common death receptors, which can induce apoptosis. Compared with the untreated human umbilical vein endothelial cells, Fas expression was increased both in the mRNA level and on the surface of infected human umbilical vein endothelial cells. FasL was expressed at similar levels on human umbilical vein endothelial cells over a course of dengue virus serotype-2 infection, but the expression in mRNA level was increased in infected human umbilical vein endothelial cells. It is possible that there is soluble FasL secreted from human umbilical vein endothelial cells in the supernatant. Tumor Necrosis Factor-related apoptosis-inducing ligand receptor 1 and Tumor Necrosis Factor receptors 1-2 were constantly very low, whereas Tumor Necrosis Factor-related apoptosis-inducing ligand receptors 2-4 decreased after dengue virus serotype-2 infection. This result suggested that dengue virus serotype-2 may inhibit Tumor Necrosis Factor-related apoptosis-inducing ligand receptors-induced apoptosis. The apoptotic rates in human umbilical vein endothelial cells were decreased upon the addition of caspase family inhibitors. In addition, activated caspase 8 and caspase 3 were also observed by Western blot following dengue virus serotype-2 infection. Thus, it is shown that the Fas/FasL pathway may participate in dengue virus-induced apoptosis of vascular endothelial cells in vitro. J. Med. Virol. 82:1392-1399, 2010. © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Single-well push-pull tracer tests have been used to characterize the extent, fate, and transport of subsurface contamination. Analytical solutions provide one alternative for interpreting test results. In this work, an exact analytical solution to two-dimensional equations describing the governing processes acting on a dissolved compound during a modified push-pull test (advection, longitudinal and transverse dispersion, first-order decay, and rate-limited sorption/partitioning in steady, divergent, and convergent flow fields) is developed. The coupling of this solution with inverse modeling to estimate aquifer parameters provides an efficient methodology for subsurface characterization. Synthetic data for single-well push-pull tests are employed to demonstrate the utility of the solution for determining (1) estimates of aquifer longitudinal and transverse dispersivities, (2) sorption distribution coefficients and rate constants, and (3) non-aqueous phase liquid (NAPL) saturations. Employment of the solution to estimate NAPL saturations based on partitioning and non-partitioning tracers is designed to overcome limitations of previous efforts by including rate-limited mass transfer. This solution provides a new tool for use by practitioners when interpreting single-well push-pull test results. [ABSTRACT FROM AUTHOR]

The article presents research on a modified solution-diffusion model for the pervaporation separation of alkane and thiophenes mixtures with poly-dimethylsiloxane (PDMS) membrane. In this study, the proposed model introduced the group contribution method to calculate the activity of penetrants in the polymer membrane. It was found that the model can be used to predict the flux and separation factor of polymer membrane systems by adjusting the group interaction parameters.