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The nanoscale elastic-plastic response of single crystal 4H-SiC has been investigated by nanoindentationwith a Berkovich tip. The hardness (H) and elastic modulus (E) determined in the load-independent region were 36±2GPa and 413±8GPa, respectively. The indentation size effect (ISE) of hardness within an indentation depth of 60nm was systematically analyzed by the Nix-Gao model. Pop-in events occurring at a depth of ~23nm with indentation loads of 0.60-0.65mN were confirmed to indicate the elastic-plastic transition of the crystal, on the basis of the Hertzian contact theory and Johnson's cavity model. Theoritically calculated maximum tensile strength (13.5GPa) and cleavage strength (33GPa) also affirms the deformation due to the first pop-in rather than tensile stresses. Further analyses of deformation behavior across the indent was done in 4H-SiC by a combined technique of focused ion beam and transmission electron microscope, revealing that slippage occurred in the (0001) plane after indentation., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

What kinds of amino acid sequences could possibly be protein sequences? From all existing databases that we can find, known proteins are only a small fraction of all possible combinations of amino acids. Beginning with Sanger's first detailed determination of a protein sequence in 1952, previous studies have focused on describing the structure of existing protein sequences in order to construct the protein universe. No one, however, has developed a criteria for determining whether an arbitrary amino acid sequence can be a protein. Here we show that when the collection of arbitrary amino acid sequences is viewed in an appropriate geometric context, the protein sequences cluster together. This leads to a new computational test, described here, that has proved to be remarkably accurate at determining whether an arbitrary amino acid sequence can be a protein. Even more, if the results of this test indicate that the sequence can be a protein, and it is indeed a protein sequence, then its identity as a protein sequence is uniquely defined. We anticipate our computational test will be useful for those who are attempting to complete the job of discovering all proteins, or constructing the protein universe.

Genomic imprinting is a genetic phenomenon in which certain alleles are differentially expressed in a parent-of-origin-specific manner, and plays an important role in the study of complex traits. For a diallelic marker locus in human, the parentalasymmetry tests Q-PAT(c) with any constant c were developed to detect parent-of-origin effects for quantitative traits. However, these methods can only be applied to deal with nuclear families and thus are not suitable for extended pedigrees. In this study, by making no assumption about the distribution of the quantitative trait, we first propose the pedigree parentalasymmetry tests Q-PPAT(c) with any constant c for quantitative traits to test for parent-of-origin effects based on nuclear families with complete information from general pedigree data, in the presence of association between marker alleles under study and quantitative traits. When there are any genotypes missing in pedigrees, we utilize Monte Carlo (MC) sampling and estimation and develop the Q-MCPPAT(c) statistics to test for parent-of-origin effects. Various simulation studies are conducted to assess the performance of the proposed methods, for different sample sizes, genotype missing rates, degrees of imprinting effects and population models. Simulation results show that the proposed methods control the size well under the null hypothesis of no parent-of-origin effects and Q-PPAT(c) are robust to population stratification. In addition, the power comparison demonstrates that Q-PPAT(c) and Q-MCPPAT(c) for pedigree data are much more powerful than Q-PAT(c) only using two-generation nuclear families selected from extended pedigrees.

Recently, there have been many case-control studies proposed to test for association between haplotypes and disease, which require the Hardy-Weinberg equilibrium (HWE) assumption of haplotype frequencies. As such, haplotype inference of unphased genotypes and development of haplotype-based HWE tests are crucial prior to fine mapping. The goodness-of-fit test is a frequently-used method to test for HWE for multiple tightly-linked loci. However, its degrees of freedom dramatically increase with the increase of the number of loci, which may lack the test power. Therefore, in this paper, to improve the test power for haplotype-based HWE, we first write out two likelihood functions of the observed data based on the Niu's model (NM) and inbreeding model (IM), respectively, which can cause the departure from HWE. Then, we use two expectation-maximization algorithms and one expectation-conditional-maximization algorithm to estimate the model parameters under the HWE, IM and NM models, respectively. Finally, we propose the likelihood ratio tests LRT[Formula: see text] and LRT[Formula: see text] for haplotype-based HWE under the NM and IM models, respectively. We simulate the HWE, Niu's, inbreeding and population stratification models to assess the validity and compare the performance of these two LRT tests. The simulation results show that both of the tests control the type I error rates well in testing for haplotype-based HWE. If the NM model is true, then LRT[Formula: see text] is more powerful. While, if the true model is the IM model, then LRT[Formula: see text] has better performance in power. Under the population stratification model, LRT[Formula: see text] is still more powerful. To this end, LRT[Formula: see text] is generally recommended. Application of the proposed methods to a rheumatoid arthritis data set further illustrates their utility for real data analysis.

Genomic imprinting is an important epigenetic phenomenon in studying complex traits and has generally been examined by detecting parent-of-origin effects of alleles. The parental-asymmetry test (PAT) based on nuclear families with both parents and its extensions to deal with missing parental genotypes is simple and powerful for such a task. However, these methods only use case (affected) children in nuclear families and thus do not make full use of information on control (unaffected) children, if available, in these families. In this article, we propose a novel parent-of-origin effects test C-PATu (the combined test of PATu and 1-PATu) by using both the control and case children in nuclear families with one or both parents. C-PATu is essentially a weighted framework, in which the test based on all the control children and their parents and that based on all the case children and their parents are weighted according to the population disease prevalence. Simulation results demonstrate that the proposed tests control the size well under no parent-of-origin effects and using additional information from control children improves the power of the tests under the imprinting alternative. Application of C-PATu to a Framingham Heart Study data set further shows the feasibility in practical application of the test.

The muskmelon variety 'Xiholuotuo' was used as a test material in order to study the combined effects of substrate moisture and light intensity on growth, development and ecophysiological characteristics of muskmelon seedings in greenhouse. The results showed that the different substrate moisture and light intensity remarkably influenced the growth and development of muskmelon seedlings. With reduction of substrate moisture, chl a, chl b and chl a + b increased, while relative water content (RWC) of leaf and specific leaf area (SLA) declined. Under 60%-80% water-holding capacity of substrate, net photosynthetic rate was the highest. With the decrease of light intensity, chl a, chl b, chl a+b, RWC, SLA and intercellular CO2 concentration (Ci) went up, while chl a/b and net photosynthetic rate reduced. Among all the treatments, muskmelon seedlings with 80% water-holding capacity of substrate and 100% light density in greenhouse presented the most strong growth vigor, the highest healthy index and net photosynthetic rate.

1. All-trans retinoic acid (ATRA) is known to inhibit cellular proliferation and induce differentiation and apoptosis. It usually activates gene expression by binding to a nuclear receptor that interacts with retinoic acid-response elements (RARE) and then activates the mitogen-activated protein kinase signal pathway. JWA, a newly identified ATRA-responsive gene, has recently been proposed as an important molecule for cellular differentiation induced by some chemicals, including ATRA. 2. To investigate the possible involvement of JWA in the inhibition of cellular proliferation and induction of apoptosis by ATRA, HeLa cells were stably transfected with sense or antisense JWA to establish cell lines that overexpressed or were deficient in JWA; ATRA (0.05-10 micromol/L) was used to induce cellular differentiation and apoptosis. 3. Western blot analysis revealed that ATRA caused increased expression of JWA in HeLa cells in a dose- and time-dependent manner, accompanied by activation of extracellular signal-regulated kinase (ERK) 1/2 phosphorylation. However, ERK1/2 phosphorylation induced by ATRA was inhibited in JWA-deficient HeLa cells. In JWA-overexpressing HeLa cells, ATRA showed more significant antiproliferative effects and induced more apoptosis. 4. The reporter gene assay showed that ATRA (5 mmol/L) enhanced the transcriptional activity of JWA by interacting with its promoter in the region from -194 to +107 bp (P < 0.01). Bioinformatic analysis indicated that the JWA promoter did not contain RARE, but did contain two CCAAT boxes in this fragment spanning -194 to +107 bp, which may be responsive to the ATRA-activated nuclear transcription factor CCAAT/enhancer binding proteins (C/EBP) or interacting proteins. Therefore, ATRA-inhibited cellular proliferation and -induced apoptosis in HeLa cells may be dependent on JWA transactivation via its C/EBP-binding motifs. 5. These data indicate that the inhibition of proliferation and the induction of apoptosis by ATRA are dependent on JWA expression in HeLa cells. The findings may represent a novel mechanism by which the effects of ATRA in regulating cellular proliferation and apoptosis are mediated, at least in part, by JWA expression.

JWA (AF070523) was originally identified as a novel all-trans retinoic acid (ATRA) responsible gene in primary human tracheal bronchial epithelial cells. For the notable performance achieved by ATRA in the differentiation induction therapy, we investigated the role of JWA in ATRA-mediated differentiation of the human myeloid leukemia HL-60 cells. We found that concomitant with the progressive cell differentiation, JWA expression was up-regulated by ATRA in a dose- and time-dependent manner. Inhibition of JWA expression by RNA interference partially blocked ATRA-induced differentiation and growth inhibition of HL-60 cells. Pre-treatment of phorbol-12-myristate-13-acetate (TPA), a PKC activator, decreased ATRA-mediated differentiation, companied with the down-regulation of JWA expression. Arsenic trioxide (As(2)O(3), 0.5 microM) enhanced the cellular differentiation induced by 0.01 microM ATRA, but had no noticeable effect on the differentiation induced by 0.1 microM ATRA. Concurrent with the enhancement, JWA expression was up-regulated. All the data suggest that up-regulation of JWA expression is essential for ATRA-induced differentiation of HL-60 cells. And JWA, associated with PKC, is involved in its signal pathways. Ideal therapeutic efficacy with low toxicity may be obtained if low doses of ATRA (0.01 microM) and As(2)O(3) (0.5 microM) are combined. These findings may present a novel mechanism that cellular differentiation and growth inhibition induced by ATRA are mediated at least in part through regulation of JWA expression. JWA may be a novel molecular marker for ATRA-induced HL-60 cell differentiation. ATRA up-regulates JWA expression by stimulating the transcriptional activity of JWA gene promoter.

Dysregulation of hematopoietic cellular differentiation contributes to leukemogenesis. Unfortunately, relatively little is known about how cell differentiation is regulated. JWA (AF070523) is a novel all-trans retinoic acid (ATRA) responsible gene that initially isolated from ATRA-treated primary human tracheal bronchial epithelial cells. For the notable performance achieved by ATRA in the differentiation induction therapy, we investigated the role of JWA in the induction of differentiation of human myeloid leukemia cells. Our results showed that JWA was not only regulated by ATRA but also by several other differentiation inducers such as phorbol-12-myristate-13-acetate (TPA), arabinoside (Ara-C), and hemin, involved in the mechanisms of differentiation along different lineages of myeloid leukemia cells arrested at different stages of development. Generally, JWA was up-regulated by these inducers in a time-dependent manner. Inhibition of JWA by RNA interference decreased the induced cellular differentiation. However, in NB4 cells treated with ATRA, dissimilar with others, the expression of JWA was down-regulated, and the induced cellular differentiation could be enhanced by silencing of JWA. Collectively, JWA works as a potential critical molecule, associated with multi-directional differentiation of human myeloid leukemia cells. In NB4 cells, JWA may function as a lineage-restricted gene during differentiation along the monocyte/macrophage-like or granulocytic pathway.

Objective: To study how the combined effects of various differentiation inducers and heat stress on the expression of JWA protein in K562 cell, the relationship between JWA and Hsp70 expression, and the signal regulation mechanism possibly involved., Methods: The experimental model was established in K562 cells. Various directional differentiation inducers (TPA, Ara-C, hemin, adriamycin, ATRA and As(2)O(3)) were used alone or combined with heat shock treatment (42 degrees C, 2 h). Western blot was used for detecting expressions of JWA, Hsp70, heat stress factor 1 (HSF1) and HSF2., Results: (1) The expressions of both JWA protein and Hsp70 were significantly up-regulated after K562 cells treated by TPA (100, 200 ng/ml) or adriamycin (4 x 10(-8) mol/L) 48 h, and followed by heat shock (42 degrees C, 2 h). However, the opposite effects were observed when the cells treated by hemin (3 x 10(-5) mol/L, 48 h), Ara-C (80 ng/ml, 48 h) and As(2)O(3) (1 x 10(-6) mol/L, 48 h) followed by 2 h heat shock. No obvious changes were found when the cells treated by ATRA (1 x 10(-6) mol/L, 48 h) alone or followed by heat shock. (2) Both the heat shock transcriptional factors HSF1 and HSF2 did not show any significant changes when K562 cells were treated with various differentiation inducers and followed by heat stress., Conclusion: JWA not only takes part in the regulation of K562 cellular differentiation, but also of heat stress, it might be the co-target gene of several differentiation inducers and heat stress. The expression of Hsp70 seems not mediated by both HSF1 and HSF2 in K562 cells undergoing directional differentiation or heat stress treatment. JWA is likely to be a new signal molecule similar to Hsp70 signal pathways. The results show that JWA takes part in the mechanism of K562 cell response to heat stress.

Objective: To study the expression of JWA protein and heat shock protein (Hsp70), and to explore these relationship and the possible mechanism of JWA gene involved in induced differentiation and heat stress (42 degrees C) of K562 cells., Methods: The models of differentiation and heat stress of K562 cells were established. Western blot was used for detecting expressed proteins of JWA gene, Hsp70, heat shock factor (HSF1 and HSF2)., Results: (1) Under the condition of differentiations induced by TPA (100 ng/ml), hemin (3 x 10(-5) mol/L), Ara-C (80 ng/ml), adriamycin (4 x 10(-8) mol/L), ATRA (1 x 10(-6) mol/L) and As(2)O(3) (1 x 10(-6) mol/L) for 48 h respectively, the expression of JWA protein and Hsp70 were more significantly increased than control; the level of HSF2 protein was increased by inductions of hemin, Ara-C and adriamycin, respectively. (2) After heat exposure to 42 degrees C for 10, 20, 30, 45, 60, 90 min, and heat exposure to 39 degrees C, 42 degrees C, 45 degrees C, the trend of changing in expression of Hsp70 was similar to that of JWA protein, and HSF1 was expressed in earlier stage., Conclusion: The expression of JWA protein and Hsp70 were upregulated in induced differentiation and in heat stress, and the change of expression of JWA protein were similar to that of Hsp70, but the intracellular transduction signal pathways involved may be various. JWA might not be specifically related with both HSF1 and HSF2.