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The use of plastic in vehicle development has increased. In particular, a design trend has resulted in chromiumplated plastics being used in exterior panels. Recently, as the appearance has become more important in design, the plastic radiator grille has become larger, to where it can become the primary member when a front collision happens. The radiator grille should be designed with considerations of the geometric structure, such as delamination, and material characteristics, when plastics are plated with chromium. The enlarged grille has to pass regulations like FMVSS Part 581. Although the material property of plastic has been studied before, what seems to be lacking is study on the crashworthiness of plastic radiator grilles that are plated using chromium. In this paper, in order to evaluate the crashworthiness, tensile test and front collision analysis using finite element method are performed. Tensile test is conducted with 4 types of materials, and then material properties of chromium-plated plastics are obtained. Meanwhile radiator grille’s crashworthiness is evaluated using finite element analysis method. Analysis result is evaluated according to failure criterion. Through this study, method of the assessment of plastic radiator grille’s crashworthiness considered material properties of chromium plated plastics is proposed, and it can be predicted the delamination and the failure point of radiator grille at the design step.

Most types of cancers are made up of heterogeneous mixtures of genetically distinct subclones. In particular, acute myeloid leukemia (AML) has been shown to undergo substantial clonal evolution over the course of the disease. AML tends to harbor fewer mutations than solid tumors, making it challenging to infer clonal structure. Here, we present a 9-year, whole-exome sequencing study of a single case at 12 time points, from the initial diagnosis until a fourth relapse, including 6 remission samples in between. To the best of our knowledge, it covers the longest time span of any data set of its kind. We used these time series data to track the hierarchy and order of variant acquisition, and subsequently analyzed the evolution of somatic variants to infer clonal structure. From this, we postulate the development and extinction of subclones, as well as their anticorrelated expansion via varying drug responses. In particular, we show that new subclones started appearing after the first complete remission. The presence and absence of different subclones during remission and relapses implies differing drug responses among subclones. Our study shows that time series analysis contrasting remission and relapse periods provides a much more comprehensive view of clonal structure and evolution.

The histone variant, macroH2A1, has an important role in embryonic stem cell differentiation and tumor progression in various types of tumors. However, the regulatory roles of macroH2A1 on bladder cancer progression have not been fully elucidated. Here, we show that macroH2A1 knockdown promotes stem-like properties of bladder cancer cells. The knockdown of macroH2A1 in bladder cancer cells increased tumorigenicity, radioresistance, degeneration of reactive oxygen species, increased sphere formation capability and an increase in the proportion of side populations. We found that macroH2A1 is required for the suppression of Lin28B identified as a novel downstream target of macroH2A1 in bladder cancer. Loss of macroH2A1 expression significantly correlated with the elevated levels of Lin28B expression and subsequently inhibited the mature let-7 microRNA expression. Furthermore, the stable overexpression of Lin28B enhances the several phenotypes, including tumorigenicity and sphere-forming ability, which are induced by macroH2A1 depletion. Importantly, Lin28B expression was regulated by macroH2A1-mediated reciprocal binding of p300 and EZH2/SUV39H1. Our results suggest that Lin28B/let-7 pathway is tightly regulated by macroH2A1 and its cofactors, and have a pivotal role in the bladder tumor progression and the regulation of stem-like characteristics of bladder cancer cells.

The hybrid flow shop (HFS) scheduling, typically found in a variety of real-world industries, is an NP-hard combinatorial optimisation problem. Consideration of uncertainties hugely aggravates its complexity. This paper considers makespan minimisation of dynamic HFS scheduling problems under machine breakdown and stochastic processing times. It presents a novel cluster-based scheduling model (CBSM) that combines the good features of the shortest processing time (SPT) algorithm and the simulated annealing (SA) heuristic to synergise HFS scheduling under uncertainties. In this model, a neighbouring agglomerative hierarchical clustering algorithm is firstly developed. This algorithm decomposes an HFS into an appropriate number of machine clusters with different stochastic natures. The CBSM then performs a decision-tree-based assignment procedure using the classification and regression trees to determine an appropriate approach, either SPT or SA, for each machine cluster. Finally, the machine clusters are scheduled by their assigned approaches. To validate the effectiveness of the CBSM, a discrete-event simulator is conducted to evaluate its performance. The simulation results show that the CBSM outperforms all the compared algorithms in solving the dynamic HFS scheduling problems.

In multi-criteria decision-making problems, ordinal data themselves provide a convenient instrument for articulating preferences but they impose some difficulty on the aggregation process since ambiguity prevails in the preference structure inherent in the ordinal data. One of the key concerns in the aggregation of ordinal data is to differentiate among the rank positions by reflecting decision-maker’s preferences. Since individual attitude is fairly different, it is presumable that each ranking position has different importance. In other words, the quantification schemes among the rank positions could vary depending on the individual preference structure. We find that, among others, the ordered weighted averaging (OWA) operator can help to take this concept into effect on several reasons. First, the OWA operator provides a means to take into account a discriminating factor by introducing the measure of attitudinal character. Second, it can produce appropriate ranking weights corresponding to each rank position by solving a mathematical program subject to the constraint of attitudinal character. To better understand the attitudinal character playing a role as a discriminating factor, we develop centered ranking weights from ordinal weak relations among the ranking positions and then investigate their properties to relate them with the OWA operator weights having the maximum entropy. Finally, we present a method for generating the OWA operator weights via rank-based weighting functions.

The quality of an injection molded part is largely affected by the mold cooling. Consequently, this makes it necessary to optimize the mold cooling circuit when designing the part but prior to designing the mold. Various approaches of optimizing the mold cooling circuit have been proposed previously. In this work, optimization of the mold cooling circuit was automated by a commercial process integration and design optimization tool called Process Integration, Automation and Optimization (PIAnO), which is often used for large automotive parts such as bumpers and instrument panels. The cooling channels and baffle tubes were located on the offset profile equidistant from the part surface. The locations of the cooling channels and the baffle tubes were automatically generated and input into the mold cooling computer-aided engineering program, Autodesk Moldflow Insight 2010. The objective function was the deviation of the mold surface temperature from a given design temperature. Design variables in the optimization were the depths, distances and diameters of the cooling channels and the baffle tubes. For a more practical analysis, the pressure drop and temperature drop were considered the limited values. Optimization was performed using the progressive quadratic response surface method. The optimization resulted in a more uniform temperature distribution when compared to the initial design, and utilizing the proposed optimization method, a satisfactory solution could be made at a lower cost.

Background: This study aims to evaluate the effectiveness of adenosine triphosphate-based chemotherapy response assay (ATP-CRA)-guided neoadjuvant chemotherapy for increasing resectability in patients with unresectable colorectal liver metastasis. Patients and methods: Patients were randomised into two groups: Group A was treated by conventional chemotherapy regimen and Group B was treated by chemotherapy regimen according to the ATP-CRA. Three chemotherapeutic agents (5-fluorouracil, oxaliplatin and irinotecan) were tested by ATP-CRA and more sensitive agents were selected. Either FOLFOX or FOLFIRI was administered. Between Group A and B, treatment response and resectability were compared. Results: Between November 2008 and October 2010, a total 63 patients were randomised to Group A (N=32) or Group B (N=31). FOLFOX was more preferred in Group A than in Group B (26 out of 32 (81.3%) vs 20 out of 31 (64.5%)). Group B showed better treatment response than Group A (48.4% vs 21.9%, P=0.027). The resectability of hepatic lesion was higher in Group B (35.5% vs 12.5%, P=0.032). Mean duration from chemotherapy onset to the time of liver resection was 11 cycles (range 4–12) in Group A and 8 cycles (range 8–16) in Group B. Conclusion: This study showed that tailored-chemotherapy based on ATP-CRA could improve the treatment response and resectability in initially unresectable colorectal liver metastasis.

Diabetes is characterized by insulin resistance and a reduction in insulin secretion, leading to progressive β-cell failure and loss of β-cell mass. Its central therapeutic issues are how to restore glucose responsiveness of β-cells to normal and counteract defects in insulin secretion. Native glucagon-like peptide-1 (GLP-1), which makes β-cells competent and diabetic β-cells specifically more sensitive to glucose, has a major drawback of rapid inactivation. In this study, we describe the construction and analysis of a GLP-1 plasmid and double-stranded, adeno-associated viral (dsAAV) expression vector to overcome both the rapid degradation of native GLP-1 and limitations of gene therapy using standard single-stranded AAV. Our study results demonstrate that fasting blood glucose levels of db/db obese mice decreased significantly up to 4 months after a single injection of dsAAV GLP-1, and both insulin and circulating GLP-1 levels increased in dsAAV GLP-1-infected mice. These results demonstrate that dsAAV GLP-1 has long-term, efficient transgene expression with minimal toxicity and cellular immune responses. This study suggests that GLP-1 produced by dsAAV may be an alternative to the continuous infusions required for GLP-1 peptide therapy or daily injections of GLP-1.

Interleukin-12 (IL-12) plays a key role in promoting T helper 1 (Th1) responses and subsequent cell-mediated immunity. Given the role of cytokines in the pathogenesis of psychiatric disorders, the dysregulation of IL-12 in these illnesses would be expected. We measured the plasma levels of IL-12 in 102 psychiatric patients (43 schizophrenia, 34 major depression and 25 bipolar disorder) and 85 normal controls. In addition, IL-12 levels of the patients were measured after an 8-week treatment to assess whether the levels were affected by medication. The IL-12 levels of the patient group with major depression were significantly higher than that of the control group, whereas no differences were found among the other groups. IL-12 values of the three patient groups decreased significantly after 8 weeks of treatment. These findings support the hypothesis that activation of the inflammatory response system and in particular of Th-1-like cells, is involved in the pathophysiology of major depression and that repeated administration of antidepressive and antipsychotic drugs may suppress IL-12 plasma concentrations in psychiatric patients.

A single-frame 3-D PTV algorithm was constructed to measure 3-D high-speed flows with NTSC cameras. The measurement system consists of three NTSC cameras, an optical instrument called AOM, a digital image grabber and a hosting computer. The tracking algorithm of particles' pair is based on a concept of a spatial match probability. The measurement system is used to probe the turbulent properties of the backward-facing step flow. A preliminary test of the measurement system is also made on the measurement of 3-D vectors of 36 targets on a rotating table to verify its validity. The measurement uncertainty of the system is systematically evaluated through the preliminary test. A set of virtual images is constructed by using the vectors selected randomly from the grid vectors that had been obtained by the experiment on the backward-facing step flow with the system. A performance test is made on the vector recovery using the virtual images and it is validated.

A ball bearing is generally assumed as a linear spring in rotor dynamic analysis. In real case, the force equilibrium of the bearing is changed as the relative position, of each ball with respect to the direction of radial force. So, the stiffness of the bearing is also changed and is a function of time and position. In this study, the nonlinear characteristics of a ball bearing are considered in analyzing the vibration response of a rotating shaft due to an unbalance force. A finite element method is used to analyze the vibration characteristics of a rotor-bearing system and a direct numerical integration is performed to calculate the transient response of the rotor system. The responses are converted to the frequency domain and the effects of the parametric excitation due to a ball bearing are examined. The test rig for the investigation of the effect of a ball bearing on the rotor vibration is set up and the results are compared with those of numerical calculation. The calculation results show that the amplitudes of the nonlinear model are larger than those of the linear one. The frequencies of the calculations can be matched to the measured frequencies.

This paper studied the applicability of the method of caustics to anisotropic materials under Mode I and mixed-mode static-loading conditions and introduced the procedure to obtain stress-intensity factors (SIF) in anisotropic materials by the method of caustics.

Corrigendum: Comparative analysis of chimpanzee and human Y chromosomes unveils complex evolutionary pathway

Inheritance of resistance to a soybean isolate of peanut stripe virus (PStV-strain PN) was studied in three soybean varieties, AGS 129, Ankur, and PI 230971. Genetic analysis was based on necrotic, mosaic and symptomless reactions in inoculated soybeans. A single incompletely dominant gene in AGS 129 was found to confer the resistance to PStV and was tentatively designated as Pst. The homozygous parent AGS 129, possessing the genotype Pst Pst, was immune while Ankur and PI 230971, with a genotype of pst pst, were susceptible showing mosaic symptoms. The heterozygous genotype Pst pst resulting from the cross of either Ankur or PI 230971 with AGS 129 reacted with necrosis, distinctly different from either of the homozygous genotypes. This genotypic effect was confirmed through the phenotypic segregation in BC, F2, and F3.