Highly accurate detection of ovarian cancer using CA125 but limited improvement with serum matrix-assisted laser desorption/ionization time-of-flight mass spectrometry profiling

Objectives: Our objective was to test the performance of CA125 in classifying serum samples from a cohort of malignant and benign ovarian cancers and age-matched healthy controls and to assess whether combining information from matrix-assisted laser desorption/ionization (MALDI) time-of-flight profiling could improve diagnostic performance. Materials and Methods: Serum samples from women with ovarian neoplasms and healthy volunteers were subjected to CA125 assay and MALDI time-of-flight mass spectrometry (MS) profiling. Models were built from training data sets using discriminatory MALDI MS peaks in combination with CA125 values and tested their ability to classify blinded test samples. These were compared with models using CA125 threshold levels from 193 patients with ovarian cancer, 290 with benign neoplasm, and 2236 postmenopausal healthy controls. Results: Using a CA125 cutoff of 30 U/mL, an overall sensitivity of 94.8% (96.6% specificity) was obtained when comparing malignancies versus healthy postmenopausal controls, whereas a cutoff of 65 U/mL provided a sensitivity of 83.9% (99.6% specificity). High classification accuracies were obtained for early-stage cancers (93.5% sensitivity). Reasons for high accuracies include recruitment bias, restriction to postmenopausal women, and inclusion of only primary invasive epithelial ovarian cancer cases. The combination of MS profiling information with CA125 did not significantly improve the specificity/accuracy compared with classifications on the basis of CA125 alone. Conclusions: We report unexpectedly good performance of serum CA125 using threshold classification in discriminating healthy controls and women with benign masses from those with invasive ovarian cancer. This highlights the dependence of diagnostic tests on the characteristics of the study population and the crucial need for authors to provide sufficient relevant details to allow comparison. Our study also shows that MS profiling information adds little to diagnostic accuracy. This finding is in contrast with other reports and shows the limitations of serum MS profiling for biomarker discovery and as a diagnostic tool

Hydrogen-bond assisted stabilization of the less favored conformation of a tridentate Schiff base ligand in dinuclear nickel(II) complex: an experimental and theoretical study

The Schiff base ligand, HL (2-[1-(3-methylamino-propylimino)-ethyl]-phenol), the 1:1 condensation product of 2-hydroxy acetophenone and N-methyl-1,3-diaminopropane, has been synthesized and characterized by X-ray crystallography as the perchlorate salt [H2L]ClO4 (1). The structure consists of discrete [H2L](+) cations and perchlorate anions. Two dinuclear Ni-II complexes, [Ni2L2(NO2)(2)] (2), [Ni2L2(NO3)(2)] (3) have been synthesized using this ligand and characterized by single crystal X-ray analyses. Complexes 2 and 3 are centrosymmetric dimers in which the Ni-II ions are in distorted fac- and mer-octahedral environments, respectively, bridged by two mu(2)-phenolate ions of deprotonated ligand, L. The plane of the phenyl rings and the Ni2O2 basal plane are nearly coplanar in 2 but almost perpendicular in 3. We have studied and explained this different behavior using high level DFT calculations (RI-BP86/def2-TZVP level of theory). The conformation observed in 3, which is energetically less favorable, is stabilized via intermolecular non-covalent interactions. Under the excitation of ultraviolet light, characteristic fluorescence of compound 1 was observed; by comparison fluorescence intensity decreases in case of compound 3 and completely quenched in compound 2.

Adaptive modelling with tunable RBF network using multi-innovation RLS algorithm assisted by swarm intelligence

In this paper, we propose a new on-line learning algorithm for the non-linear system identification: the swarm intelligence aided multi-innovation recursive least squares (SI-MRLS) algorithm. The SI-MRLS algorithm applies the particle swarm optimization (PSO) to construct a flexible radial basis function (RBF) model so that both the model structure and output weights can be adapted. By replacing an insignificant RBF node with a new one based on the increment of error variance criterion at every iteration, the model remains at a limited size. The multi-innovation RLS algorithm is used to update the RBF output weights which are known to have better accuracy than the classic RLS. The proposed method can produces a parsimonious model with good performance. Simulation result are also shown to verify the SI-MRLS algorithm.

Climate change and the risks associated with delayed breeding in a tropical wild bird population

There is growing evidence of changes in the timing of important ecological events, such as flowering in plants and reproduction in animals, in response to climate change, with implications for population decline and biodiversity loss. Recent work has shown that the timing of breeding in wild birds is changing in response to climate change partly because individuals are remarkably flexible in their timing of breeding. Despite this work, our understanding of these processes in wild populations remains very limited and biased towards species from temperate regions. Here, we report the response to changing climate in a tropical wild bird population using a long-term dataset on a formerly critically endangered island endemic, the Mauritius kestrel. We show that the frequency of spring rainfall affects the timing of breeding, with birds breeding later in wetter springs. Delays in breeding have consequences in terms of reduced reproductive success as birds get exposed to risks associated with adverse climatic conditions later on in the breeding season, which reduce nesting success. These results, combined with the fact that frequency of spring rainfall has increased by about 60 per cent in our study area since 1962, imply that climate change is exposing birds to the stochastic risks of late reproduction by causing them to start breeding relatively late in the season.

Microwave-assisted hydrogel synthesis: a new method for crosslinking polymers in aqueous solutions

It has been found that hydrogels may be formed by microwave irradiation of aqueous solutions containing appropriate combinations of polymers. This new method of hydrogel synthesis yields sterile hydrogels without the use of monomers, eliminating the need for the removal of unreacted species from the final product. Results for two particularly successful combinations, poly(vinyl alcohol) with either poly(acrylic acid) or poly(methylvinylether-alt-maleic anhydride), are presented. Irradiation using temperatures of 100–150 °C was found to yield hydrogels with large equilibrium swelling degrees of 500–1000 g g−1. Material leached from both types of hydrogel shows little cytotoxicity towards HT29 cells.

Assisted remote viewing of a teleoperation work cell

Intelligent viewing systems are required if efficient and productive teleoperation is to be applied to dynamic manufacturing environments. These systems must automatically provide remote views to an operator which assist in the completion of the task. This assistance increases the productivity of the teleoperation task if the robot controller is responsive to the unpredictable dynamic evolution of the workcell. Behavioral controllers can be utilized to give reactive 'intelligence.' The inherent complex structure of current systems, however, places considerable time overheads on any redesign of the emergent behavior. In industry, where the remote environment and task frequently change, this continual redesign process becomes inefficient. We introduce a novel behavioral controller, based on an 'ego-behavior' architecture, to command an active camera (a camera mounted on a robot) within a remote workcell. Using this ego-behavioral architecture the responses from individual behaviors are rapidly combined to produce an 'intelligent' responsive viewing system. The architecture is single-layered, each behavior being autonomous with no explicit knowledge of the number, description or activity of other behaviors present (if any). This lack of imposed structure decreases the development time as it allows each behavior to be designed and tested independently before insertion into the architecture. The fusion mechanism for the behaviors provides the ability for each behavior to compete and/or co-operate with other behaviors for full or partial control of the viewing active camera. Each behavior continually reassesses this degree of competition or co-operation by measuring its own success in controlling the active camera against pre-defined constraints. The ego-behavioral architecture is demonstrated through simulation and experimentation.

PSO assisted NURB Neural Network Identification

A system identification algorithm is introduced for Hammerstein systems that are modelled using a non-uniform rational B-spline (NURB) neural network. The proposed algorithm consists of two successive stages. First the shaping parameters in NURB network are estimated using a particle swarm optimization (PSO) procedure. Then the remaining parameters are estimated by the method of the singular value decomposition (SVD). Numerical examples are utilized to demonstrate the efficacy of the proposed approach.

Transcriptional regulators of the GAD acid stress island are carried by effector protein-encoding prophages and indirectly control type III secretion in enterohemorrhagic Escherichia coli O157:H7

P>Type III secretion (T3S) plays a pivotal role in the colonization of ruminant hosts by Enterohemorrhagic Escherichia coli (EHEC). The T3S system translocates effector proteins into host cells to promote bacterial attachment and persistence. The repertoire and variation in prophage regions underpins differences in the pathogenesis and epidemiology of EHEC strains. In this study, we have used a collection of deletions in cryptic prophages and EHEC O157 O-islands to screen for novel regulators of T3S. Using this approach we have identified a family of homologous AraC-like regulators that indirectly repress T3S. These prophage-encoded secretion regulator genes (psr) are found exclusively on prophages and are associated with effector loci and the T3S activating Pch family of regulators. Transcriptional profiling, mutagenesis and DNA binding studies were used to show that these regulators usurp the conserved GAD acid stress resistance system to regulate T3S by increasing the expression of GadE (YhiE) and YhiF and that this regulation follows attachment to bovine epithelial cells. We further demonstrate that PsrA and effectors encoded within cryptic prophage CP933-N are required for persistence in a ruminant model of colonization.

Role of NleH, a Type III Secreted Effector from Attaching and Effacing Pathogens, in Colonization of the Bovine, Ovine, and Murine Gut

The human pathogen enterohemorrhagic Escherichia coli (EHEC) O157:H7 colonizes human and animal gut via formation of attaching and effacing lesions. EHEC strains use a type III secretion system to translocate a battery of effector proteins into the mammalian host cell, which subvert diverse signal transduction pathways implicated in actin dynamics, phagocytosis, and innate immunity. The genomes of sequenced EHEC O157: H7 strains contain two copies of the effector protein gene nleH, which share 49% sequence similarity with the gene for the Shigella effector OspG, recently implicated in inhibition of migration of the transcriptional regulator NF-kappa B to the nucleus. In this study we investigated the role of NleH during EHEC O157: H7 infection of calves and lambs. We found that while EHEC Delta nleH colonized the bovine gut more efficiently than the wild-type strain, in lambs the wild-type strain exhibited a competitive advantage over the mutant during mixed infection. Using the mouse pathogen Citrobacter rodentium, which shares many virulence factors with EHEC O157: H7, including NleH, we observed that the wild-type strain exhibited a competitive advantage over the mutant during mixed infection. We found no measurable differences in T-cell infiltration or hyperplasia in colons of mice inoculated with the wild-type or the nleH mutant strain. Using NF-kappa B reporter mice carrying a transgene containing a luciferase reporter driven by three NF-kappa B response elements, we found that NleH causes an increase in NF-kappa B activity in the colonic mucosa. Consistent with this, we found that the nleH mutant triggered a significantly lower tumor necrosis factor alpha response than the wild-type strain.

EU enlargement and consequences for FDI-assisted industrial development

Many of the new member states as well as candidate and accession countries of the EU are confident that membership will result in substantially increased inward foreign direct investment (FDI) in manufacturing. This paper discusses the policy issues and challenges that cohesion and accession countries face, applying lessons that by now have become mainstream in the parallel discussion of FDI-assisted development in the developing economies. We argue that globalisation has attenuated the benefits that accrue from EU membership for latecomers, and they must now compete for FDI not just with other European countries but also with non- EU emerging economies. We posit that they should not base their industrial development strategy on mere passive reliance of FDI flows without considering how to concatenate their industrial development and the nature of the MNE activities they attract.