A novel fluorescent probe involving a graphene quantum dot-enzyme hybrid system for the analysis of hydroquinone in the presence of toxic resorcinol and catechol

An efficient method for the analysis of hydroquinone at trace levels in water samples has been developed in the form of a fluorescent probe based on graphene quantum dots (GQDs). The analytical variable, fluorescence quenching, was generated from the formation of benzoquinone intermediates, which formed during the catalytic oxidation of hydroquinone by horseradish peroxidase (HRP). In general, the reaction mechanism involved hydroquinone, as an electron acceptor, which affected the surface state of GQDs via an electron transfer effect. The water-soluble GQDs were directly prepared by the pyrolysis of citric acid and with the use of the mentioned hybrid enzyme system, the detection limit for hydroquinone was as low as 8.4 × 10−8 M. Furthermore, this analysis was almost unaffected by other phenol and quinine compounds, such as phenol, resorcinol and other quinines, and therefore, the developed GQD method produced satisfactory results for the analysis of hydroquinone in several different lake water samples.

Hybrid metaheuristic techniques for optimising sugarcane rail operations

Mixed integer programming and parallel-machine job shop scheduling are used to solve the sugarcane rail transport scheduling problem. Constructive heuristics and metaheuristics were developed to produce a more efficient scheduling system and so reduce operating costs. The solutions were tested on small and large size problems. High-quality solutions and improved CPU time are the result of developing new hybrid techniques which consist of different ways of integrating simulated annealing and Tabu search techniques.

Multipurpose nanoporous alumina-carbon nanowall bi-dimensional nano-hybrid platform via catalyzed and catalyst-free plasma CVD

Simple, rapid, plasma-assisted synthesis of large-area arrays of vertically-aligned carbon nanowalls on highly-porous, transparent bare and gold-coated alumina membranes with the two pore sizes is reported. It is demonstrated that the complex patterns of vertically aligned nanowalls can nucleate and form different morphologies in the low-temperature plasmas. The process is stable, and the twofold change in the gas flow (10 and 20 sccm) does not noticeably influence the morphology of the nanowall pattern. Application of a thin (5 nm) gold layer to nanoporous membrane prior to the nanowall growth allows controlling the network morphology.

A germline polymorphism of thymine DNA glycosylase induces genomic instability and cellular transformation

Thymine DNA glycosylase (TDG) functions in base excision repair, a DNA repair pathway that acts in a lesion-specific manner to correct individual damaged or altered bases. TDG preferentially catalyzes the removal of thymine and uracil paired with guanine, and is also active on 5-fluorouracil (5-FU) paired with adenine or guanine. The rs4135113 single nucleotide polymorphism (SNP) of TDG is found in 10% of the global population. This coding SNP results in the alteration of Gly199 to Ser. Gly199 is part of a loop responsible for stabilizing the flipped abasic nucleotide in the active site pocket. Biochemical analyses indicate that G199S exhibits tighter binding to both its substrate and abasic product. The persistent accumulation of abasic sites in cells expressing G199S leads to the induction of double-strand breaks (DSBs). Cells expressing the G199S variant also activate a DNA damage response. When expressed in cells, G199S induces genomic instability and cellular transformation. Together, these results suggest that individuals harboring the G199S variant may have increased risk for developing cancer.

Tumor-associated mutations inO6-methylguanine DNA-methyltransferase (MGMT) reduce DNA repair functionality

MGMT is the primary vehicle for cellular removal of alkyl lesions from the O-6 position of guanine and the O-4 position of thymine. While key to the maintenance of genomic integrity, MGMT also removes damage induced by alkylating chemotherapies, inhibiting the efficacy of cancer treatment. Germline variants of human MGMT are well-characterized, but somatic variants found in tumors were, prior to this work, uncharacterized. We found that MGMT G132R, from a human esophageal tumor, and MGMT G156C, from a human colorectal cancer cell line, are unable to rescue methyltransferase-deficient Escherichia coli as well as wild type (WT) human MGMT after treatment with a methylating agent. Using pre-steady state kinetics, we biochemically characterized these variants as having a reduced rate constant. G132R binds DNA containing an O6-methylguanine lesion half as tightly as WT MGMT, while G156C has a 40-fold decrease in binding affinity for the same damaged DNA versus WT. Mammalian cells expressing either G132R or G156C are more sensitive to methylating agents than mammalian cells expressing WT MGMT. G132R is slightly resistant to O6-benzylguanine, an inhibitor of MGMT in clinical trials, while G156C is almost completely resistant to this inhibitor. The impared functionality of expressed variants G132R and G156C suggests that the presence of somatic variants of MGMT in a tumor could impact chemotherapeutic outcomes.

The ascidian natural product eusynstyelamide B is a novel topoisomerase II poison that induces DNA damage and growth arrest in prostate and breast cancer cells

As part of an anti-cancer natural product drug discovery program, we recently identified eusynstyelamide B (EB), which displayed cytotoxicity against MDA-MB-231 breast cancer cells (IC50 = 5 μM) and induced apoptosis. Here, we investigated the mechanism of action of EB in cancer cell lines of the prostate (LNCaP) and breast (MDA-MB-231). EB inhibited cell growth (IC50 = 5 μM) and induced a G2 cell cycle arrest, as shown by a significant increase in the G2/M cell population in the absence of elevated levels of the mitotic marker phospho-histone H3. In contrast to MDA-MB-231 cells, EB did not induce cell death in LNCaP cells when treated for up to 10 days. Transcript profiling and Ingenuity Pathway Analysis suggested that EB activated DNA damage pathways in LNCaP cells. Consistent with this, CHK2 phosphorylation was increased, p21CIP1/WAF1 was up-regulated and CDC2 expression strongly reduced by EB. Importantly, EB caused DNA double-strand breaks, yet did not directly interact with DNA. Analysis of topoisomerase II-mediated decatenation discovered that EB is a novel topoisomerase II poison.

Hashtag as hybrid forum: The case of #agchatoz

This chapter imports Michel Callon’s model of the ‘hybrid forum’ (Callon et al, 2009, p. 18) into social media research, arguing that certain kinds of hashtag publics can be mapped onto this model. It explores this idea of the hashtag as hybrid forum through the worked example of #agchatoz—a hashtag used as both ‘meetup’ organizer for Australian farmers and other stakeholders in Australian agriculture, and as a topic marker for general discussion of related issues. Applying the principles and techniques of digital methods (Rogers, 2013), we employ a standard suite of analytics to a longitudinal dataset of #agchatoz tweets. The results are used not only to describe various elements and dynamics of this hashtag, but also to experiment with the articulation of such approaches with the theoretical model of the hybrid forum, as well as exploring the ways that controversies animate and transform such forums as part of the emergence and cross-pollination of issue publics.

A three-dimensional hybrid smoothed finite element method (H-SFEM) for nonlinear solid mechanics problems

This paper presents a novel three-dimensional hybrid smoothed finite element method (H-SFEM) for solid mechanics problems. In 3D H-SFEM, the strain field is assumed to be the weighted average between compatible strains from the finite element method (FEM) and smoothed strains from the node-based smoothed FEM with a parameter α equipped into H-SFEM. By adjusting α, the upper and lower bound solutions in the strain energy norm and eigenfrequencies can always be obtained. The optimized α value in 3D H-SFEM using a tetrahedron mesh possesses a close-to-exact stiffness of the continuous system, and produces ultra-accurate solutions in terms of displacement, strain energy and eigenfrequencies in the linear and nonlinear problems. The novel domain-based selective scheme is proposed leading to a combined selective H-SFEM model that is immune from volumetric locking and hence works well for nearly incompressible materials. The proposed 3D H-SFEM is an innovative and unique numerical method with its distinct features, which has great potential in the successful application for solid mechanics problems.

A hybrid cellular automata model of multicellular tumour spheroid growth in hypoxic microenvironment

A three-dimensional hybrid cellular automata (CA) model is developed to study the dynamic process of multicellular tumour spheroid (MTS) growth by introducing hypoxia as an important microenvironment factor which influences cell migration and cell phenotype expression. The model enables us to examine the effects of different hypoxic environments on the growth history of the MTS and to study the dynamic interactions between MTS growth and chemical environments. The results include the spatial distribution of different phenotypes of tumour cells and associated oxygen concentration distributions under hypoxic conditions. The discussion of the model system responses to the varied hypoxic conditions reveals that the improvement of the resistance of tumour cells to a hypoxic environment may be important in the tumour normalization therapy.

Arsenic trioxide promotes mitochondrial DNA mutation and cell apoptosis in primary APL cells and NB4 cell line

This study aimed to investigate the effects of arsenic trioxide (As2O3) on the mitochondrial DNA (mtDNA) of acute promyelocytic leukemia (APL) cells. The NB4 cell line was treated with 2.0 μmol/L As2O3in vitro, and the primary APL cells were treated with 2.0 μmol/L As2O3in vitro and 0.16 mg kg-1 d-1 As2O3in vivo. The mitochondrial DNA of all the cells above was amplified by PCR, directly sequenced and analyzed by Sequence Navigatore and Factura software. The apoptosis rates were assayed by flow cytometry. Mitochondrial DNA mutation in the D-loop region was found in NB4 and APL cells before As2O3 use, but the mutation spots were remarkably increased after As2O3 treatment, which was positively correlated to the rates of cellular apoptosis, the correlation coefficient: rNB4-As2O3=0.973818, and rAPL-As2O3=0.934703. The mutation types include transition, transversion, codon insertion or deletion, and the mutation spots in all samples were not constant and regular. It is revealed that As2O3 aggravates mtDNA mutation in the D-loop region of acute promyelocytic leukemia cells both in vitro and in vivo. Mitochondrial DNA might be one of the targets of As2O3 in APL treatment.

Rapid assessment of genotype-by-environment interactions and heritability for growth rate in aquaculture species using in vitro fertilisation and DNA tagging

Commercial environments may receive only a fraction of expected genetic gains for growth rate as predicted from the selection environment This fraction is the result of undesirable genotype-by-environment interactions (G x E) and measured by the genetic correlation (r(g)) of growth between environments. Rapid estimates of genetic correlation achieved in one generation are notoriously difficult to estimate with precision. A new design is proposed where genetic correlations can be estimated by utilising artificial mating from cryopreserved semen and unfertilised eggs stripped from a single female. We compare a traditional phenotype analysis of growth to a threshold model where only the largest fish are genotyped for sire identification. The threshold model was robust to differences in family mortality differing up to 30%. The design is unique as it negates potential re-ranking of families caused by an interaction between common maternal environmental effects and growing environment. The design is suitable for rapid assessment of G x E over one generation with a true 0.70 genetic correlation yielding standard errors as low as 0.07. Different design scenarios were tested for bias and accuracy with a range of heritability values, number of half-sib families created, number of progeny within each full-sib family, number of fish genotyped, number of fish stocked, differing family survival rates and at various simulated genetic correlation levels

Efficient parameter estimation in longitudinal data analysis using a hybrid GEE method

The method of generalized estimating equations (GEEs) provides consistent estimates of the regression parameters in a marginal regression model for longitudinal data, even when the working correlation model is misspecified (Liang and Zeger, 1986). However, the efficiency of a GEE estimate can be seriously affected by the choice of the working correlation model. This study addresses this problem by proposing a hybrid method that combines multiple GEEs based on different working correlation models, using the empirical likelihood method (Qin and Lawless, 1994). Analyses show that this hybrid method is more efficient than a GEE using a misspecified working correlation model. Furthermore, if one of the working correlation structures correctly models the within-subject correlations, then this hybrid method provides the most efficient parameter estimates. In simulations, the hybrid method's finite-sample performance is superior to a GEE under any of the commonly used working correlation models and is almost fully efficient in all scenarios studied. The hybrid method is illustrated using data from a longitudinal study of the respiratory infection rates in 275 Indonesian children.

Hybrid game strategies for MO problems in aerospace design

Game strategies have been developed in past decades and used in the field of economics, engineering, computer science and biology due to their efficiency in solving design optimisation problems. In addition, research on Multi-Objective (MO) and Multidisciplinary Design Optimisation (MDO) has focused on developing robust and efficient optimisation method to produce quality solutions with less computational time. In this paper, a new optimisation method Hybrid Game Strategy for MO problems is introduced and compared to CMA-ES based optimisation approach. Numerical results obtained from both optimisation methods are compared in terms of computational expense and model quality. The benefits of using Game-strategies are demonstrated.

Fusion of worlds?: Consumers' self-narrative in a hybrid digital/physical world

As the Internet becomes deeply embedded in consumers' life and continuously accessed through mobile devices, the boundary between the digital and the physical becomes less defined. This thesis investigates how this blurring boundary impacts on consumers' construction of their self-narrative and found that consumers' narrative is paradoxically coherent and fragmented and depicts a heroic story of the self. Prior studies show consumers achieve their desired life story through meaningful consumption, however, the notion of fragmented lives are challenged. Further, extensive digital leisure consumption is often viewed in a less positive light. Nevertheless, consumers, who significantly consume digital leisure, do not disregard their physical world or favour one space over the other. Rather, they negotiate key aspects from their digital and physical lives and fluidly move between these two worlds, creating a hybrid narrative that saves their self and others.

Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways

To newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural menopause (at P < 5 x 10(-8)). Candidate genes located at these newly associated loci include genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG and PRIM1) and immune function (IL11, NLRP11 and PRRC2A (also known as BAT2)). Gene-set enrichment pathway analyses using the full GWAS data set identified exoDNase, NF-kappaB signaling and mitochondrial dysfunction as biological processes related to timing of menopause.