The involvement of decomposition and composition processes in restructuring during problem solving.

Decomposition of chunks has been widely accepted as a critical proxy of restructuring, but the role of composition in forming new representations has been largely neglected. This study aims to investigate the roles of both decomposition and composition processes in chunk restructuring, as well as their relationships with "aha" experiences during problem-solving. Participants were asked to move a part of a character to another character to create two new characters. Across three experiments, the characters to be decomposed or composed were varied in terms of tight or loose chunks. The results showed that decomposition or composition of tight chunks led to lower success rates, longer response times, and significantly stronger "Aha!" emotional experiences (mainly in terms of surprise and suddenness). This study provides evidence for the contribution of both decomposition and composition processes to restructuring in creative insight.

The Bombyx mori G protein ß subunit 1 (BmGNß1) gene inhibits BmNPV infection.

G protein ß subunit 1 (GNß1) has several functions, including cell growth regulation, the control of second messenger levels, and ion channel switching. Previous transcriptome analyses in our laboratory have shown that BmGNß1 transcription is reduced following infection with Bombyx mori nucleopolyhedrovirus (BmNPV), but it is unknown what role this gene may have in the host response to BmNPV infection. In this study, the BmGNß1 gene was cloned using the RACE method. After BmNPV infection, BmGNß1 was downregulated in Baiyu strains in tissues such as the hemolymph and midgut. Indirect immunofluorescence showed that BmGNß1 was localized to the cytoplasm. We further constructed a BmGNß1-pIZ/V5-His-mCherry overexpression plasmid and designed siRNA to evaluate the role of BmGNß1 in host response to infection. The results showed that BmGNß1 overexpression inhibited BmNPV proliferation, while knockdown of BmGNß1 was correlated with increased BmNPV proliferation. The siRNA-mediated reduction of BmGNß1 was correlated with an increase in BmNPV infection of BmN cells, increased BmNPV vp39 transcription, and reduced survival time of BmNPV-infected B. mori. Overexpression of BmGNß1 in BmN cells was also correlated with apoptosis and a modification in transcript levels of genes involved in host response to BmNPV infection (PI3K, AKT, Bmp53, BmFOXO, Caspase-1, Bmp21, BmPKN and BmCREB), suggesting that BmGNß1 may influence the apoptotic host response of infected B. mori through the PI3K-AKT pathway. This study provides potential targets and theoretical support for breeding BmNPV-resistant silkworm varieties.

An RFID Indoor Positioning Algorithm Based on Bayesian Probability and K-Nearest Neighbor.

The Global Positioning System (GPS) is widely used in outdoor environmental positioning. However, GPS cannot support indoor positioning because there is no signal for positioning in an indoor environment. Nowadays, there are many situations which require indoor positioning, such as searching for a book in a library, looking for luggage in an airport, emergence navigation for fire alarms, robot location, etc. Many technologies, such as ultrasonic, sensors, Bluetooth, WiFi, magnetic field, Radio Frequency Identification (RFID), etc., are used to perform indoor positioning. Compared with other technologies, RFID used in indoor positioning is more cost and energy efficient. The Traditional RFID indoor positioning algorithm LANDMARC utilizes a Received Signal Strength (RSS) indicator to track objects. However, the RSS value is easily affected by environmental noise and other interference. In this paper, our purpose is to reduce the location fluctuation and error caused by multipath and environmental interference in LANDMARC. We propose a novel indoor positioning algorithm based on Bayesian probability and K-Nearest Neighbor (BKNN). The experimental results show that the Gaussian filter can filter some abnormal RSS values. The proposed BKNN algorithm has the smallest location error compared with the Gaussian-based algorithm, LANDMARC and an improved KNN algorithm. The average error in location estimation is about 15 cm using our method.

DNA templated Click Chemistry via 5-vinyl-2'-deoxyuridine and an acridine-tetrazine conjugate induces DNA damage and apoptosis in cancer cells.

AIMS: Click Chemistry is providing valuable tools to biomedical research, but its direct use in therapies remains nearly unexplored. For cancer treatment, nucleoside analogues (NA) such as 5-vinyl-2'-deoxyuridine (VdU) can be metabolically incorporated into cancer cell DNA and subsequently "clicked" to form a toxic product. The inverse electron-demand Diels-Alder (IEDDA) reaction between VdU and an acridine-tetrazine conjugate (PINK) has previously been used to label cell nuclei of cultured cells. Here, we report tandem usage of VdU and PINK to induce cytotoxicity. MAIN METHODS: Cell lines were subsequently treated with VdU and PINK, and cell viability was measured via well confluency and 3D tumor spheroid assays. DNA damage and apoptosis were evaluated using Western Blotting and cell cycle analysis by flow cytometry. Double stranded DNA break (DSB) formation was measured using the comet assay. Apoptosis was assessed by fluorescent detection of externalized phosphatidylserine residues. KEY FINDINGS: We report that the combination of VdU and PINK synergistically induces cytotoxicity in cultured human cells. The combination of VdU and PINK strongly reduced cell viability in 2D and 3D cultured cancer cells. Mechanistically, the compounds induced DNA damage through DSB formation, which leads to S-phase accumulation and apoptosis. SIGNIFICANCE: The combination of VdU and PINK represents a novel and promising DNA-templated "click" approach for cancer treatment via selective induction of DNA damage.

Design, Manufacture, and Characterization of Auxetic Yarns with Multiple Core/Wrap Structure by Braiding Method.

Auxetic textiles with a negative Poisson's ratio show significant energy absorption and synclastic curvature characteristics and potential application value in sportsmen protection material. The stability and reliability of the structure and properties of auxetic textiles is also an important factor to assess and promote the application. Thus, auxetic yarns with multiple core/wrap structure were prepared by a 16-spindle braiding machine. It mainly focused on the axial stretching behavior and the relationship between the structure and auxetic effect of yarn samples. The maximum Poisson's ratio of auxetic yarns was -3.26. The experimental results also showed that the complex yarns still presented an auxetic effect during 30 repeats of cycle stretching. According to the study about the repeatable stretchability and auxetic effect of complex yarns, it could be expected to provide more comfortable, safer, and smarter protective textiles.

[The relationship between anaphylatoxin C3a and benign prostatic hyperplasia with inflammation].

OBJECTIVE: To study the relationship of anaphylatoxin C3a level in expressed prostatic secretions (EPS) with prostate tissue inflammation in BPH. METHODS: This study included 40 BPH patients receiving TURP operational therapy in West China Hospital during September, 2009 to March, 2010. For each patient, IPSS and NIH-CPSI were evaluated, serum PSA levels, prostatic volume and urine WBC were measured. EPS was collected before operation for the test of C3a level, while EPS also was obtained from 10 healthy men as normal control. Prostatic tissue was collected by the operation and histological inflammation was investigated by histopathological study. RESULTS: C3a levels in EPS of the BPH patients: severe inflammation group > mild inflammation group > normal control group (all P < 0.01). C3a levels in the EPS could be used to determine whether BPH combined inflammation, sensitivity : 0.97, specificity: 0.70. C3a levels in EPS was not relevant with PSA, fPSA levels, age, BMI, prostate volume or urine WBC levels; but NIH-CPSI was correlated (r = 0.495, P < 0.01). C3a in EPS of retained catheter group was more than non-catheter group significantly (P < 0.05). CONCLUSION: C3a is an ideal criteria to diagnose prostatic histological inflammation in BPH patients. There is no convincing evidence to correlate C3a in EPS with serum PSA levels, BMI, age, prostatic volume and urine's WBC. Excessively high C3a levels and the NIH-CPSI, indwelling have correlations.

Research on Concrete Columns Reinforced with New Developed High-Strength Steel under Eccentric Loading.

The use of new developed high-strength steel in concrete members can reduce steel bar congestion and construction costs. This research aims to study the behavior of concrete columns reinforced with new developed high-strength steel under eccentric loading. Ten reinforced concrete columns were fabricated and tested. The test variables were the transverse reinforcement amount and yield strength, eccentricity, and longitudinal reinforcement yield strength. The failure patterns were compression and tensile failure for columns subjected to small eccentricity and large eccentricity, respectively. The same level of post-peak deformability and ductility could only be obtained with a lower amount of transverse reinforcement when high-strength transverse reinforcements were used in columns subjected to small eccentricity. The high-strength longitudinal reinforcement improved the bearing capacity and post-peak deformability of the concrete columns. Furthermore, three different equivalent rectangular stress block (ERSB) parameters for predicting the bearing capacity of columns with high-strength steel are discussed based on test and simulated results. It is concluded that the China Code GB 50010-2010 overestimates the bearing capacity of columns with high-strength steel, whereas the bearing capacities computed using the America Code ACI 318-14 and Canada Code CSA A23.3-04 agree well with the test results.

Inhibition of MAPKAPK2/MK2 facilitates DNA replication upon cancer cell treatment with gemcitabine but not cisplatin.

The signaling pathway driven by p38 and MAPKAPK2 alias MK2 is activated as part of stress responses, and these kinases represent attractive drug targets for cancer therapy. However, seemingly conflicting results were obtained when assessing the role of MK2 in chemotherapy. MK2 inhibitors were reported to either enhance or diminish the chemosensitivity of cancer cells. Here we show that this strongly depends on the particular chemotherapeutic drug. Two different MK2 inhibitors increased the proliferating fraction of pancreatic cancer-derived cells upon treatment with gemcitabine, whereas no consistent protection against cisplatin was observed. Both drugs enhanced, rather than attenuated, the toxicity of another DNA crosslinking agent, mitomycin C. Gemcitabine and cisplatin were each capable of activating MK2, and we did not observe differences in the intracellular localization of MK2 upon treatment. However, DNA replication fork progression, as determined by fiber assays, was restored by MK2 inhibition upon treatment with gemcitabine, but not when cisplatin was used. Thus, MK2 is required for the reduction in DNA replication in response to gemcitabine but not to cisplatin. These observations raise the need to carefully evaluate synergisms and antagonisms with conventional chemotherapeutics when taking MK2 inhibitors to the clinics.

Membrane fouling mitigation in a moving bed membrane bioreactor combined with anoxic biofilter for treatment of saline wastewater from mariculture.

Membrane fouling mitigation in a novel AF-MBMBR system (moving bed membrane bioreactor (10L) coupled with anoxic biofilter (4L)) under high salinity condition (35‰) was systematically investigated. Pre-positioned AF served as a pretreatment induced significant decrease of suspended biomass by 85% and dissolved organic matters by 51.7% in subsequent MBR, which resulted in a reduction of cake layer formation. Based on this, sponge bio-carriers in MBMBR further alleviated the fouling propensity by modifying extracellular polymeric substances (EPS) properties. The protein component in EPS decreased from 181.4 to 116.5mg/g MLSS, with a decline of protein/carbohydrate ratio from 4.6 to 3.4. In particular, elimination of hydrophobic groups like aromatic protein-like substance in EPS was detected. These caused the less biomass deposition on membrane surface, thereby alleviating membrane fouling. In summary, mitigation of membrane fouling in AF-MBMBR should be attributed to contributions from both pre-positioned AF and sponge bio-carriers.

Cooperation of Nutlin-3a and a Wip1 inhibitor to induce p53 activity.

Targeting the Mdm2 oncoprotein by drugs has the potential of re-establishing p53 function and tumor suppression. However, Mdm2-antagonizing drug candidates, e. g. Nutlin-3a, often fail to abolish cancer cell growth sustainably. To overcome these limitations, we inhibited Mdm2 and simultaneously a second negative regulator of p53, the phosphatase Wip1/PPM1D. When combining Nutlin-3a with the Wip1 inhibitor GSK2830371 in the treatment of p53-proficient but not p53-deficient cells, we observed enhanced phosphorylation (Ser 15) and acetylation (Lys 382) of p53, increased expression of p53 target gene products, and synergistic inhibition of cell proliferation. Surprisingly, when testing the two compounds individually, largely distinct sets of genes were induced, as revealed by deep sequencing analysis of RNA. In contrast, the combination of both drugs led to an expression signature that largely comprised that of Nutlin-3a alone. Moreover, the combination of drugs, or the combination of Nutlin-3a with Wip1-depletion by siRNA, activated p53-responsive genes to a greater extent than either of the compounds alone. Simultaneous inhibition of Mdm2 and Wip1 enhanced cell senescence and G2/M accumulation. Taken together, the inhibition of Wip1 might fortify p53-mediated tumor suppression by Mdm2 antagonists.

p53 Activity Results in DNA Replication Fork Processivity.

p53 induces cell death upon DNA damage, but this may not confer all of its tumor suppressor activity. We report that p53 activation enhances the processivity of DNA replication, as monitored by multi-label fiber assays, whereas removal of p53 reduces fork progression. This is observed in tumor-derived U2OS cells but also in murine embryonic fibroblasts with heterozygous or homozygous p53 deletion and in freshly isolated thymocytes from mice with differential p53 status. Mdm2, a p53-inducible gene product, similarly supports DNA replication even in p53-deficient cells, suggesting that sustained Mdm2-expression is at least one of the mechanisms allowing p53 to prevent replicative stress. Thus, p53 helps to protect the genome during S phase, by preventing the occurrence of stalled or collapsed replication forks. These results expand p53's tumor-suppressive functions, adding to the ex-post model (elimination of damaged cells) an ex-ante activity; i.e., the prevention of DNA damage during replication.

Wee1 is required to sustain ATR/Chk1 signaling upon replicative stress.

The therapeutic efficacy of nucleoside analogues, e.g. gemcitabine, against cancer cells can be augmented by inhibitors of checkpoint kinases, including Wee1, ATR, and Chk1. We have compared the chemosensitizing effect of these inhibitors in cells derived from pancreatic cancer, a tumor entity where gemcitabine is part of the first-line therapeutic regimens, and in osteosarcoma-derived cells. As expected, all three inhibitors rendered cancer cells more sensitive to gemcitabine, but Wee1 inhibition proved to be particularly efficient in this context. Investigating the reasons for this potent sensitizing effect, we found that Wee1 inhibition or knockdown not only blocked Wee1 activity, but also reduced the activation of ATR/Chk1 in gemcitabine-treated cells. Combination of several inhibitors revealed that Wee1 inhibition requires Cyclin-dependent kinases 1 and 2 (Cdk1/2) and Polo-like kinase 1 (Plk1) to reduce ATR/Chk1 activity. Through activation of Cdks and Plk1, Wee1 inhibition reduces Claspin and CtIP levels, explaining the impairment in ATR/Chk1 activity. Taken together, these results confer a consistent signaling pathway reaching from Wee1 inhibition to impaired Chk1 activity, mechanistically dissecting how Wee1 inhibitors not only dysregulate cell cycle progression, but also enhance replicative stress and chemosensitivity towards nucleoside analogues.

Mdm2 inhibition confers protection of p53-proficient cells from the cytotoxic effects of Wee1 inhibitors.

Pharmacological inhibition of the cell cycle regulatory kinase Wee1 represents a promising strategy to eliminate cancer cells. Wee1 inhibitors cooperate with chemotherapeutics, e. g. nucleoside analogues, pushing malignant cells from S phase towards premature mitosis and death. However, considerable toxicities are observed in preclinical and clinical trials. A high proportion of tumor cells can be distinguished from all other cells of a patient's body by inactivating mutations in the tumor suppressor p53. Here we set out to develop an approach for the selective protection of p53-proficient cells against the cytotoxic effects of Wee1 inhibitors. We pretreated such cells with Nutlin-3a, a prototype inhibitor of the p53-antagonist Mdm2. The resulting transient cell cycle arrest effectively increased the survival of cells that were subsequently treated with combinations of the Wee1 inhibitor MK-1775 and/or the nucleoside analogue gemcitabine. In this constellation, Nutlin-3a reduced caspase activation and diminished the phosphorylation of Histone 2AX, an indicator of the DNA damage response. Both effects were strictly dependent on the presence of p53. Moreover, Nutlin pre-treatment reduced the fraction of cells that were undergoing premature mitosis in response to Wee1 inhibition. We conclude that the pre-activation of p53 through Mdm2 antagonists serves as a viable option to selectively protect p53-proficient cells against the cytotoxic effects of Wee1 inhibitors, especially when combined with a nucleoside analogue. Thus, Mdm2 antagonists might prove useful to avoid unwanted side effects of Wee1 inhibitors. On the other hand, when a tumor contains wild type p53, care should be taken not to induce its activity before applying Wee1 inhibitors.

Regulation of polyp-to-jellyfish transition in Aurelia aurita.

BACKGROUND: The life cycle of scyphozoan cnidarians alternates between sessile asexual polyps and pelagic medusa. Transition from one life form to another is triggered by environmental signals, but the molecular cascades involved in the drastic morphological and physiological changes remain unknown. RESULTS: We show in the moon jelly Aurelia aurita that the molecular machinery controlling transition of the sessile polyp into a free-swimming jellyfish consists of two parts. One is conserved and relies on retinoic acid signaling. The second, novel part is based on secreted proteins that are strongly upregulated prior to metamorphosis in response to the seasonal temperature changes. One of these proteins functions as a temperature-sensitive "timer" and encodes the precursor of the strobilation hormone of Aurelia. CONCLUSIONS: Our findings uncover the molecule framework controlling the polyp-to-jellyfish transition in a basal metazoan and provide insights into the evolution of complex life cycles in the animal kingdom.