Cellular model systems to study the tumor biological role of kallikrein-related peptidases in ovarian and prostate cancer

Since the identification of the gene family of kallikrein related peptidases (KLKs), their function has been robustly studied at the biochemical level. In vitro biochemical studies have shown that KLK proteases are involved in a number of extracellular processes that initiate intracellular signaling pathways by hydrolysis, as reviewed in Chapters 8, 9, and 15, Volume 1. These events have been associated with more invasive phenotypes of ovarian, prostate, and other cancers. Concomitantly, aberrant expression of KLKs has been associated with poor prognosis of patients with ovarian and prostate cancer (Borgoño and Diamandis, 2004; Clements et al., 2004; Yousef and Diamandis, 2009), with prostate-specific antigen (PSA, KLK3) being a long standing, clinically employed biomarker for prostate cancer (Lilja et al., 2008). Data generated from patient samples in clinical studies, alongwith biochemical activity, suggests that KLKs function in the development and progression of these diseases. To bridge the gap between their function at the molecular level and the clinical need for efficacious treatment and prognostic biomarkers, functional assessment at the in vitro cellular level, using various culture models, is increasing, particularly in a three-dimensional (3D) context (Abbott, 2003; Bissell and Radisky, 2001; Pampaloni et al., 2007; Yamada and Cukierman, 2007).

Optimal power system stabilizer tuning in multi-machine system via an improved differential evolution

Power system stabilizer (PSS) is one of the most important controllers in modern power systems for damping low frequency oscillations. Many efforts have been dedicated to design the tuning methodologies and allocation techniques to obtain optimal damping behaviors of the system. Traditionally, it is tuned mostly for local damping performance, however, in order to obtain a globally optimal performance, the tuning of PSS needs to be done considering more variables. Furthermore, with the enhancement of system interconnection and the increase of system complexity, new tools are required to achieve global tuning and coordination of PSS to achieve optimal solution in a global meaning. Differential evolution (DE) is a recognized as a simple and powerful global optimum technique, which can gain fast convergence speed as well as high computational efficiency. However, as many other evolutionary algorithms (EA), the premature of population restricts optimization capacity of DE. In this paper, a modified DE is proposed and applied for optimal PSS tuning of 39-Bus New-England system. New operators are introduced to reduce the probability of getting premature. To investigate the impact of system conditions on PSS tuning, multiple operating points will be studied. Simulation result is compared with standard DE and particle swarm optimization (PSO).

Cometary evolution : Clues from chondritic interplanetary dust particles

Cometary and interplanetary dust particles (IDP) are compared, and the mineralogical evolution of comet nuclei is discussed. Chondritic IDP have properties consistent with properties expected for cometary dust. The complex and varied mineralogy of these particles may indicate mineral alteration processes that occur in comet nuclei. Depending on the thermal budget of a comet, the upper few meters of nucleus material may maintain temperatures within regimes of hydrocryogenic (200 to 237K) and low-temperature aqueous (274 to 400K) alteration. Thus, layer silicates, carbonates, and sulfates may be important components of cometary dust and, correspondingly are common constituents of chondritic IDPs. Alteration of comet starting materials may be a common occurrence, and depends on the specific physical and chemical properties of each individual comet.

Visualizing the evolution of knowledge management capability in construction firms

A firm, as a dynamic, evolving, and quasi-autonomous system of knowledge production and application, develops knowledge management capability (KMC) through strategic learning in order to sustain competitive advantages in a dynamic environment. Knowledge governance mechanisms and knowledge processes connect and interact with each other forming learning mechanisms, which carry out double loop learning that drives genesis and evolution of KMC to modify operating routines that effect desired performance. This paper reports a study that was carried out within a context of construction contractors, a type of project-based firms, operating within the dynamic Hong Kong construction market. A multiple-case design was used to incorporate evidence from the literature and interviews, with the help of system dynamics modeling, to visualize the evolution of KMC. The study demonstrates the feasibility to visualize how a firm's KMC matches its operating environment over time. The findings imply that knowledge management (KM) applications can be better planned and controlled through evaluation of KM performance over time from a capability perspective.

Smartphone malware evolution revisited : Android next target?

Smartphones started being targets for malware in June 2004 while malware count increased steadily until the introduction of a mandatory application signing mechanism for Symbian OS in 2006. From this point on, only few news could be read on this topic. Even despite of new emerging smartphone platforms, e.g. android and iPhone, malware writers seemed to lose interest in writing malware for smartphones giving users an unappropriate feeling of safety. In this paper, we revisit smartphone malware evolution for completing the appearance list until end of 2008. For contributing to smartphone malware research, we continue this list by adding descriptions on possible techniques for creating the first malware(s) for Android platform. Our approach involves usage of undocumented Android functions enabling us to execute native Linux application even on retail Android devices. This can be exploited to create malicious Linux applications and daemons using various methods to attack a device. In this manner, we also show that it is possible to bypass the Android permission system by using native Linux applications.

Paleomagnetic data support Early Permian age for the Abor Volcanics in the lower Siang Valley, NE India; significance for Gondwana-related break-up models

Confusion exists as to the age of the Abor Volcanics of NE India. Some consider the unit to have been emplaced in the Early Permian, others the Early Eocene, a difference of ∼230 million years. The divergence in opinion is significant because fundamentally different models explaining the geotectonic evolution of India depend on the age designation of the unit. Paleomagnetic data reported here from several exposures in the type locality of the formation in the lower Siang Valley indicate that steep dipping primary magnetizations (mean = 72.7 ± 6.2°, equating to a paleo-latitude of 58.1°) are recorded in the formation. These are only consistent with the unit being of Permian age, possibly Artinskian based on a magnetostratigraphic argument. Plate tectonic models for this time consistently show the NE corner of the sub-continent >50°S; in the Early Eocene it was just north of the equator, which would have resulted in the unit recording shallow directions. The mean declination is counter-clockwise rotated by ∼94°, around half of which can be related to the motion of the Indian block; the remainder is likely due local Himalayan-age thrusting in the Eastern Syntaxis. Several workers have correlated the Abor Volcanics with broadly coeval mafic volcanic suites in Oman, NE Pakistan–NW India and southern Tibet–Nepal, which developed in response to the Cimmerian block peeling-off eastern Gondwana in the Early-Middle Permian, but we believe there are problems with this model. Instead, we suggest that the Abor basalts relate to India–Antarctica/India–Australia extension that was happening at about the same time. Such an explanation best accommodates the relevant stratigraphical and structural data (present-day position within the Himalayan thrust stack), as well as the plate tectonic model for Permian eastern Gondwana.

Large igneous provinces and silicic large igneous provinces : progress in our understanding over the last 25 years

Large Igneous Provinces are exceptional intraplate igneous events throughout Earth’s history. Their significance and potential global impact is related to the total volume of magma intruded and released during these geologically brief events (peak eruptions are often within 1-5 Myrs duration) where millions to tens of millions of cubic kilometers of magma are produced. In some cases, at least 1% of the Earth’s surface has been directly covered in volcanic rock, being equivalent to the size of small continents with comparable crustal thicknesses. Large Igneous Provinces are thus important, albeit episodic episodes of new crust addition. However, most magmatism is basaltic so that contributions to crustal growth will not always be picked up in zircon geochronology studies that better trace major episodes of extension-related silicic magmatism and the silicic Large Igneous Provinces. Much headway has been made on our understanding of these anomalous igneous events over the last 25 years, driving many new ideas and models. This includes their: 1) global spatial and temporal distribution, with a long-term average of one event approximately every 20 Myrs, but a clear clustering of events at times of supercontinent break-up – Large Igneous Provinces are thus an integral part of the Wilson cycle and are becoming an increasingly important tool in reconnecting dispersed continental fragments; 2) compositional diversity that in part reflects their crustal setting of ocean basins, and continental interiors and margins where in the latter setting, LIP magmatism can be silicicdominant; 3) mineral and energy resources with major PGE and precious metal resources being hosted in these provinces, as well as magmatism impacting on the hydrocarbon potential of volcanic basins and rifted margins through enhancing source rock maturation, providing fluid migration pathways, and trap formation; 4) biospheric, hydrospheric and atmospheric impacts, with Large Igneous Provinces now widely regarded as a key trigger mechanism for mass extinctions, although the exact kill mechanism(s) are still being resolved; 5) role in mantle geodynamics and thermal evolution of the Earth, by potentially recording the transport of material from the lower mantle or core-mantle boundary to the Earth's surface and being a fundamental component in whole mantle convection models; and 6) recognition on the inner planets where the lack of plate tectonics and erosional processes and planetary antiquity means that the very earliest record of LIP events during planetary evolution may be better preserved than on Earth.

How do supercontinents break up? — assessing the continental large igneous province (LIP) record of the break-up of Pangea

LIP emplacement is linked to the timing and evolution of supercontinental break-up. LIP-related break-up produces volcanic rifted margins, new and large (up to 108 km2) ocean basins, and new, smaller continents that undergo dispersal and potentially reassembly (e.g., India). However, not all continental LIPs lead to continental rupture. We analysed the <330 Ma continental LIP record(following final assembly of Pangea) to find relationships between LIP event attributes (e.g., igneous volume, extent, distance from pre-existing continental margin) and ocean basin attributes (e.g., length of new ocean basin/rifted margin) and how these varied during the progressive break up of Pangea. No correlation exists between LIP magnitude and size of the subsequent ocean basin or rifted margin. Our review suggests a three-phased break-up history of Pangea: 1) “Preconditioning” phase (∼330–200 Ma): LIP events (n=7) occurred largely around the supercontinental margin clustering today in Asia, with a low (<20%) rifting success rate. The Panjal Traps at ∼280 Ma may represent the first continental rupturing event of Pangea, resulting in continental ribboning along the Tethyan margin; 2) “Main Break-up” phase (∼200–100 Ma): numerous large LIP events(n=10) in the supercontinent interior, resulting in highly successful fragmentation (90%) and large, new ocean basins(e.g., Central/South Atlantic, Indian, >3000 km long); 3) “Waning” phase (∼100–0 Ma): Declining LIP magnitudes (n=6), greater proximity to continental margins (e.g., Madagascar, North Atlantic, Afro-Arabia, Sierra Madre) producing smaller ocean basins (<2600 km long). How Pangea broke up may thus have implications for earlier supercontinent reconstructions and LIP record.

Prediction of IBD based on population history for fine gene mapping

A novel multiple regression method (RM) is developed to predict identity-by-descent probabilities at a locus L (IBDL), among individuals without pedigree, given information on surrounding markers and population history. These IBDL probabilities are a function of the increase in linkage disequilibrium (LD) generated by drift in a homogeneous population over generations. Three parameters are sufficient to describe population history: effective population size (Ne), number of generations since foundation (T), and marker allele frequencies among founders (p). IBD L are used in a simulation study to map a quantitative trait locus (QTL) via variance component estimation. RM is compared to a coalescent method (CM) in terms of power and robustness of QTL detection. Differences between RM and CM are small but significant. For example, RM is more powerful than CM in dioecious populations, but not in monoecious populations. Moreover, RM is more robust than CM when marker phases are unknown or when there is complete LD among founders or Ne is wrong, and less robust when p is wrong. CM utilises all marker haplotype information, whereas RM utilises information contained in each individual marker and all possible marker pairs but not in higher order interactions. RM consists of a family of models encompassing four different population structures, and two ways of using marker information, which contrasts with the single model that must cater for all possible evolutionary scenarios in CM.

Functional monoecy due to delayed anther dehiscence : a novel mechanism in pseuduvaria mulgraveana (annonaceae)

Unlike most genera in the early-divergent angiosperm family Annonaceae, Pseuduvaria exhibits a diversity of floral sex expression. Most species are structurally andromonoecious (or possibly androdioecious), although the hermaphroditic flowers have been inferred to be functionally pistillate, with sterile staminodes. Pseuduvaria presents an ideal model for investigating the evolution of floral sex in early-divergent angiosperms, although detailed empirical studies are currently lacking. The phenology and pollination ecology of the Australian endemic species Pseuduvaria mulgraveana are studied in detail, including evaluations of floral scent chemistry, pollen viability, and floral visitors. Results showed that the flowers are pollinated by small diurnal nitidulid beetles and are protogynous. Pollen from both hermaphroditic and staminate flowers are shown to be equally viable. The structurally hermaphroditic flowers are nevertheless functionally pistillate as anther dehiscence is delayed until after petal abscission and hence after the departure of pollinators. This mechanism to achieve functional unisexuality of flowers has not previously been reported in angiosperms. It is known that protogyny is widespread amongst early-divergent angiosperms, including the Annonaceae, and is effective in preventing autogamy. Delayed anther dehiscence represents a further elaboration of this, and is effective in preventing geitonogamy since very few sexually mature flowers occur simultaneously in an individual. We highlight the necessity for field-based empirical interpretations of functional floral sex expression prior to evaluations of evolutionary processes.

The rise of birds and mammals: are microevolutionary processes sufficient for macroevolution?

It is a basis of darwinian evolution that the microevolutionary mechanisms that can be studied in the present are sufficient to account for macroevolution. However, this idea needs to be tested explicitly, as highlighted here by the example of the superceding of dinosaurs and pterosaurs by birds and placental mammals that occurred near the Cretaceous/Tertiary boundary approximately 65 million years ago. A major problem for testing the sufficiency of microevolutionary processes is that independent ideas (such as the existence of an extraterrestrial impact, and the extinction of dinosaurs) were linked without the evidence for each idea being evaluated separately. Here, we suggest and discuss five testable models for the times and divergences of modern mammals and birds. Determination of the model that best represents these events will enable the role of microevolutionary mechanisms to be evaluated. The question of the sufficiency of microevolutionary processes for macroevolution is solvable, and available evidence supports an important role for biological processes in the initial decline of dinosaurs and pterosaurs.

Genome-scale phylogeny and the detection of systematic biases

Phylogenetic inference from sequences can be misled by both sampling (stochastic) error and systematic error (nonhistorical signals where reality differs from our simplified models). A recent study of eight yeast species using 106 concatenated genes from complete genomes showed that even small internal edges of a tree received 100% bootstrap support. This effective negation of stochastic error from large data sets is important, but longer sequences exacerbate the potential for biases (systematic error) to be positively misleading. Indeed, when we analyzed the same data set using minimum evolution optimality criteria, an alternative tree received 100% bootstrap support. We identified a compositional bias as responsible for this inconsistency and showed that it is reduced effectively by coding the nucleotides as purines and pyrimidines (RY-coding), reinforcing the original tree. Thus, a comprehensive exploration of potential systematic biases is still required, even though genome-scale data sets greatly reduce sampling error.

Four new avian mitochondrial genomes help get to basic evolutionary questions in the late cretaceous

Good phylogenetic trees are required to test hypotheses about evolutionary processes. We report four new avian mitochondrial genomes, which together with an improved method of phylogenetic analysis for vertebrate mt genomes give results for three questions in avian evolution. The new mt genomes are: magpie goose (Anseranas semipalmata), an owl (morepork, Ninox novaeseelandiae); a basal passerine (rifleman, or New Zealand wren, Acanthisitta chloris); and a parrot (kakapo or owl-parrot, Strigops habroptilus). The magpie goose provides an important new calibration point for avian evolution because the well-studied Presbyornis fossils are on the lineage to ducks and geese, after the separation of the magpie goose. We find, as with other animal mitochondrial genomes, that RY-coding is helpful in adjusting for biases between pyrimidines and between purines. When RY-coding is used at third positions of the codon, the root occurs between paleognath and neognath birds (as expected from morphological and nuclear data). In addition, passerines form a relatively old group in Neoaves, and many modern avian lineages diverged during the Cretaceous. Although many aspects of the avian tree are stable, additional taxon sampling is required.

Anisotropic damage mechanics as a novel approach to improve pre-and post-failure borehole stability analysis

Anisotropic damage distribution and evolution have a profound effect on borehole stress concentrations. Damage evolution is an irreversible process that is not adequately described within classical equilibrium thermodynamics. Therefore, we propose a constitutive model, based on non-equilibrium thermodynamics, that accounts for anisotropic damage distribution, anisotropic damage threshold and anisotropic damage evolution. We implemented this constitutive model numerically, using the finite element method, to calculate stress–strain curves and borehole stresses. The resulting stress–strain curves are distinctively different from linear elastic-brittle and linear elastic-ideal plastic constitutive models and realistically model experimental responses of brittle rocks. We show that the onset of damage evolution leads to an inhomogeneous redistribution of material properties and stresses along the borehole wall. The classical linear elastic-brittle approach to borehole stability analysis systematically overestimates the stress concentrations on the borehole wall, because dissipative strain-softening is underestimated. The proposed damage mechanics approach explicitly models dissipative behaviour and leads to non-conservative mud window estimations. Furthermore, anisotropic rocks with preferential planes of failure, like shales, can be addressed with our model.

Simplified method for including spatial correlations in mean-field approximations

Biological systems involving proliferation, migration and death are observed across all scales. For example, they govern cellular processes such as wound-healing, as well as the population dynamics of groups of organisms. In this paper, we provide a simplified method for correcting mean-field approximations of volume-excluding birth-death-movement processes on a regular lattice. An initially uniform distribution of agents on the lattice may give rise to spatial heterogeneity, depending on the relative rates of proliferation, migration and death. Many frameworks chosen to model these systems neglect spatial correlations, which can lead to inaccurate predictions of their behaviour. For example, the logistic model is frequently chosen, which is the mean-field approximation in this case. This mean-field description can be corrected by including a system of ordinary differential equations for pair-wise correlations between lattice site occupancies at various lattice distances. In this work we discuss difficulties with this method and provide a simplication, in the form of a partial differential equation description for the evolution of pair-wise spatial correlations over time. We test our simplified model against the more complex corrected mean-field model, finding excellent agreement. We show how our model successfully predicts system behaviour in regions where the mean-field approximation shows large discrepancies. Additionally, we investigate regions of parameter space where migration is reduced relative to proliferation, which has not been examined in detail before, and our method is successful at correcting the deviations observed in the mean-field model in these parameter regimes.