An androgen receptor mutation in the MDA-MB-453 cell line model of molecular apocrine breast cancer compromises receptor activity

Recent evidence indicates that the estrogen receptor-a-negative, androgen receptor (AR)- positive molecular apocrine subtype of breast cancer is driven by AR signaling. The MDA-MB-453 cell line is the prototypical model of this breast cancer subtype; its proliferation is stimulated by androgens such as 5a-dihydrotestosterone (DHT) but inhibited by the progestin medroxyprogesterone acetate (MPA) via AR-mediated mechanisms. We report here that the AR gene in MDAMB- 453 cells contains a G-T transversion in exon 7, resulting in a receptor variant with a glutamine to histidine substitution at amino acid 865 (Q865H) in the ligand binding domain. Compared with wild-type AR, the Q865H variant exhibited reduced sensitivity to DHT and MPA in transactivation assays in MDA-MB-453 and PC-3 cells but did not respond to non-androgenic ligands or receptor antagonists. Ligand binding, molecular modeling, mammalian two-hybrid and immunoblot assays revealed effects of the Q865H mutation on ligand dissociation, AR intramolecular interactions, and receptor stability. Microarray expression profiling demonstrated that DHT and MPA regulate distinct transcriptional programs in MDA-MB-453 cells. Gene Set Enrichment Analysis revealed that DHT- but not MPA-regulated genes were associated with estrogen-responsive transcriptomes from MCF-7 cells and the Wnt signaling pathway. These findings suggest that the divergent proliferative responses of MDA-MB-453 cells to DHT and MPA result from the different genetic programs elicited by these two ligands through the AR-Q865H variant. This work highlights the necessity to characterize additional models of molecular apocrine breast cancer to determine the precise role of AR signaling in this breast cancer subtype. Endocrine-Related Cancer (2012) 19 599–613

Identification and estimation of equivalent area parameters using synchronised phasor measurements

A new approach is proposed for obtaining a non-linear area-based equivalent model of power systems to express the inter-area oscillations using synchronised phasor measurements. The generators that remain coherent for inter-area disturbances over a wide range of operating conditions define the areas, and the reduced model is obtained by representing each area by an equivalent machine. The parameters of the reduced system are identified by processing the obtained measurements, and a non-linear Kalman estimator is then designed for the estimation of equivalent area angles and frequencies. The simulation of the approach on a two-area system shows substantial reduction of non-inter-area modes in the estimated angles. The proposed methods are also applied to a ten-machine system to illustrate the feasibility of the approach on larger and meshed networks.

Did you see that? Dissociating advanced visual information and ball flight constrains perception and action processes during one-handed catching

The integration of separate, yet complimentary, cortical pathways appears to play a role in visual perception and action when intercepting objects. The ventral system is responsible for object recognition and identification, while the dorsal system facilitates continuous regulation of action. This dual-system model implies that empirically manipulating different visual information sources during performance of an interceptive action might lead to the emergence of distinct gaze and movement pattern profiles. To test this idea, we recorded hand kinematics and eye movements of participants as they attempted to catch balls projected from a novel apparatus that synchronised or de-synchronised accompanying video images of a throwing action and ball trajectory. Results revealed that ball catching performance was less successful when patterns of hand movements and gaze behaviours were constrained by the absence of advanced perceptual information from the thrower's actions. Under these task constraints, participants began tracking the ball later, followed less of its trajectory, and adapted their actions by initiating movements later and moving the hand faster. There were no performance differences when the throwing action image and ball speed were synchronised or de-synchronised since hand movements were closely linked to information from ball trajectory. Results are interpreted relative to the two-visual system hypothesis, demonstrating that accurate interception requires integration of advanced visual information from kinematics of the throwing action and from ball flight trajectory.

Multivariate statistical analysis of hydrochemical data to assess alluvial aquifer–stream connectivity during drought and flood : Cressbrook Creek, southeast Queensland, Australia

A catchment-scale multivariate statistical analysis of hydrochemistry enabled assessment of interactions between alluvial groundwater and Cressbrook Creek, an intermittent drainage system in southeast Queensland, Australia. Hierarchical cluster analyses and principal component analysis were applied to time-series data to evaluate the hydrochemical evolution of groundwater during periods of extreme drought and severe flooding. A simple three-dimensional geological model was developed to conceptualise the catchment morphology and the stratigraphic framework of the alluvium. The alluvium forms a two-layer system with a basal coarse-grained layer overlain by a clay-rich low-permeability unit. In the upper and middle catchment, alluvial groundwater is chemically similar to streamwater, particularly near the creek (reflected by high HCO3/Cl and K/Na ratios and low salinities), indicating a high degree of connectivity. In the lower catchment, groundwater is more saline with lower HCO3/Cl and K/Na ratios, notably during dry periods. Groundwater salinity substantially decreased following severe flooding in 2011, notably in the lower catchment, confirming that flooding is an important mechanism for both recharge and maintaining groundwater quality. The integrated approach used in this study enabled effective interpretation of hydrological processes and can be applied to a variety of hydrological settings to synthesise and evaluate large hydrochemical datasets.

Current control in the magnetron systems for nanofabrication : a comparison

A cylindrical magnetron system and a hybrid inductively coupled plasma-assisted magnetron deposition system were examined experimentally in light of their discharge characteristics with a view to stress the enhanced controllability of the hybrid system. The comparative study has shown that the hybrid magnetron + the inductively coupled plasma system is a flexible, powerful, and convenient tool that has certain advantages as compared with the cylindrical dc magnetrons. In particular, the hybrid system features more linear current-voltage characteristics and the possibility of a bias-independent control of the discharge current.

Reversible Conversion of Dominant Polarity in Ambipolar Polymer/Graphene Oxide Hybrids

The possibility to selectively modulate the charge carrier transport in semiconducting materials is extremely challenging for the development of high performance and low-power consuming logic circuits. Systematical control over the polarity (electrons and holes) in transistor based on solution processed layer by layer polymer/graphene oxide hybrid system has been demonstrated. The conversion degree of the polarity is well controlled and reversible by trapping the opposite carriers. Basically, an electron device is switched to be a hole only device or vice versa. Finally, a hybrid layer ambipolar inverter is demonstrated in which almost no leakage of opposite carrier is found. This hybrid material has wide range of applications in planar p-n junctions and logic circuits for high-throughput manufacturing of printed electronic circuits.

Genus i östra Nyland : från dialektutjämning till dialektmarkör

Gender in eastern Nyland – from dialect levelling to identity marking The study of dialect leveling in eastern Nyland focuses on variation and change in the Swedish dialects of Nyland (Fi. Uusimaa) on the south coast of Finland. During the last century the grammatical gender system of the dialects in the area has been reduced from a three-gender system to a two-gender system (cf. Corbett 1991). The present study is based on five linguistic variables in the gender system: the anaphoric pronouns (han, hon, den) when used for inanimates; the neuter pronouns he(t) and de(t) – when used anaphorically or as expletives; and three different types of morphological postposed definite articles. For all these variables, both dialect variants and standard variants are used in the dialects. Within the study of processes of variation and change, the work focuses on the mechanisms of leveling, simplification and reallocation; cf. Trudgill (1986) and Hinskens, Auer Kerswill (2005). With regard to the reductions of the gender system, the possibility that some of these variables might have turned into becoming dialect markers (Labov 1972) in the modern varieties of eastern Nyland is given special attention. The primary data consist of tape recordings with 25 informants done in the 1960s and 1970s. The informants were born in 1881–1913. In addition, recent changes were investigated in detail in tape recordings from 2005–2008 with 15 informants, who were born in the period 1927–1947 or 1976–1988. The study combines quantitative and qualitative methods in the systematic analysis of the data. Theoretically and methodologically the study relies on methods and results from variation studies and socio-dialectology, as well as on methods and results from traditional dialectology; cf. Ahlbäck (1946) and the dictionary of Swedish dialects, Ordbok över Finlands svenska folkmål, (1976–). The results show that there are different strategies among the informants in their use of the features studied. In the modern varieties of the dialects, most of the informants use only two genders, uter and neuter. Of the variables, the masculine pronoun for inanimates, the traditional neuter pronoun he(t) and some variants of the traditional definite articles have received a new function as dialect markers in my data. These changes first affect the gender distinctions, and the function of marking gender is lost; gradually the features then get new functions as dialect markers through processes of dialect leveling and reallocation. These processes are connected to changes taking place in the communities in eastern Nyland because of urbanization. When the dialect speakers experience that the traditional values of both the dialects and the culture are threatened, they begin to mark their dialectal identity by using dialect markers in their speech.

Reciprocal and advanced generation hybrids between Corymbia citriodora and C-torelliana: forestry breeding and the risk of gene flow

Corymbia F1 hybrids have high potential for plantation forestry; however, little is known of their reproductive biology and potential for genetic pollution of native Corymbia populations. This study aims to quantify the influence of reproductive isolating barriers on the success of novel reciprocal and advanced generation Corymbia hybrids. Two maternal taxa, Corymbia citriodora subsp. citriodora and Corymbia torelliana, were pollinated using five paternal taxa, C. citriodora subsp. citriodora, C. torelliana, one C. torelliana x C. citriodora subsp. citriodora hybrid and two C. torelliana x C. citriodora subsp. variegata hybrids. Pollen tube, embryo and seed development were assessed. Reciprocal hybridisation between C. citriodora subsp. citriodora and C. torelliana was successful. Advanced generation hybrids were also created when C. citriodora subsp. citriodora or C. torelliana females were backcrossed with F1 hybrid taxa. Prezygotic reproductive isolation was identified via reduced pollen tube numbers in the style and reduced numbers of ovules penetrated by pollen tubes. Reproductive isolation was weakest within the C. citriodora subsp. citriodora maternal taxon, with two hybrid backcrosses producing equivalent capsule and seed yields to the intraspecific cross. High hybridising potential was identified between all Corymbia species and F1 taxa studied. This provides opportunities for advanced generation hybrid breeding, allowing desirable traits to be amplified. It also indicates risks of gene flow between plantation and native Corymbia populations.

Visual detection of occluded crop: For automated harvesting

This paper presents a novel crop detection system applied to the challenging task of field sweet pepper (capsicum) detection. The field-grown sweet pepper crop presents several challenges for robotic systems such as the high degree of occlusion and the fact that the crop can have a similar colour to the background (green on green). To overcome these issues, we propose a two-stage system that performs per-pixel segmentation followed by region detection. The output of the segmentation is used to search for highly probable regions and declares these to be sweet pepper. We propose the novel use of the local binary pattern (LBP) to perform crop segmentation. This feature improves the accuracy of crop segmentation from an AUC of 0.10, for previously proposed features, to 0.56. Using the LBP feature as the basis for our two-stage algorithm, we are able to detect 69.2% of field grown sweet peppers in three sites. This is an impressive result given that the average detection accuracy of people viewing the same colour imagery is 66.8%.

The Structure and Functions of Hantavirus Nucleocapsid Protein

Hantaviruses, members of the genus Hantavirus in the Bunyaviridae family, are enveloped single-stranded RNA viruses with tri-segmented genome of negative polarity. In humans, hantaviruses cause two diseases, hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS), which vary in severity depending on the causative agent. Each hantavirus is carried by a specific rodent host and is transmitted to humans through excreta of infected rodents. The genome of hantaviruses encodes four structural proteins: the nucleocapsid protein (N), the glycoproteins (Gn and Gc), and the polymerase (L) and also the nonstructural protein (NSs). This thesis deals with the functional characterization of hantavirus N protein with regard to its structure. Structural studies of the N protein have progressed slowly and the crystal structure of the whole protein is still not available, therefore biochemical assays coupled with bioinformatical modeling proved essential for studying N protein structure and functions. Presumably, during RNA encapsidation, the N protein first forms intermediate trimers and then oligomers. First, we investigated the role of N-terminal domain in the N protein oligomerization. The results suggested that the N-terminal region of the N protein forms a coiled-coil, in which two antiparallel alpha helices interact via their hydrophobic seams. Hydrophobic residues L4, I11, L18, L25 and V32 in the first helix and L44, V51, L58 and L65 in the second helix were crucial for stabilizing the structure. The results were consistent with the head-to-head, tail-to-tail model for hantavirus N protein trimerization. We demonstrated that an intact coiled-coil structure of the N terminus is crucial for the oligomerization capacity of the N protein. We also added new details to the head-to-head, tail-to-tail model of trimerization by suggesting that the initial step is based on interaction(s) between intact intra-molecular coiled-coils of the monomers. We further analyzed the importance of charged aa residues located within the coiled-coil for the N protein oligomerization. To predict the interacting surfaces of the monomers we used an upgraded in silico model of the coiled-coil domain that was docked into a trimer. Next the predicted target residues were mutated. The results obtained using the mammalian two-hybrid assay suggested that conserved charged aa residues within the coiled-coil make a substantial contribution to the N protein oligomerization. This contribution probably involves the formation of interacting surfaces of the N monomers and also stabilization of the coiled-coil via intramolecular ionic bridging. We proposed that the tips of the coiled-coils are the first to come into direct contact and thus initiate tight packing of the three monomers into a compact structure. This was in agreement with the previous results showing that an increase in ionic strength abolished the interaction between N protein molecules. We also showed that residues having the strongest effect on the N protein oligomerization are not scattered randomly throughout the coiled-coil 3D model structure, but form clusters. Next we found evidence for the hantaviral N protein interaction with the cytoplasmic tail of the glycoprotein Gn. In order to study this interaction we used the GST pull-down assay in combination with mutagenesis technique. The results demonstrated that intact, properly folded zinc fingers of the Gn protein cytoplasmic tail as well as the middle domain of the N protein (that includes aa residues 80 248 and supposedly carries the RNA-binding domain) are essential for the interaction. Since hantaviruses do not have a matrix protein that mediates the packaging of the viral RNA in other negatve stranded viruses (NSRV), hantaviral RNPs should be involved in a direct interaction with the intraviral domains of the envelope-embedded glycoproteins. By showing the N-Gn interaction we provided the evidence for one of the crucial steps in the virus replication at which RNPs are directed to the site of the virus assembly. Finally we started analysis of the N protein RNA-binding region, which is supposedly located in the middle domain of the N protein molecule. We developed a model for the initial step of RNA-binding by the hantaviral N protein. We hypothesized that the hantaviral N protein possesses two secondary structure elements that initiate the RNA encapsidation. The results suggest that amino acid residues (172-176) presumably act as a hook to catch vRNA and that the positively charged interaction surface (aa residues 144-160) enhances the initial N-RNA interacation. In conclusion, we elucidated new functions of hantavirus N protein. Using in silico modeling we predicted the domain structure of the protein and using experimental techniques showed that each domain is responsible for executing certain function(s). We showed that intact N terminal coiled-coil domain is crucial for oligomerization and charged residues located on its surface form a interaction surface for the N monomers. The middle domain is essential for interaction with the cytoplasmic tail of the Gn protein and RNA binding.

A soluble random-matrix model for relaxation in quantum systems

We study the relaxation of a degenerate two-level system interacting with a heat bath, assuming a random-matrix model for the system-bath interaction. For times larger than the duration of a collision and smaller than the Poincaré recurrence time, the survival probability of still finding the system at timet in the same state in which it was prepared att=0 is exactly calculated.

Friction-formed liquid droplets

The formation of nanoscale liquid droplets by friction of a solid is observed in real-time. This is achieved using a newly developed in situ transmission electron microscope (TEM) triboprobe capable of applying multiple reciprocating wear cycles to a nanoscale surface. Dynamical imaging of the nanoscale cyclic rubbing of a focused-ion-beam (FIB) processed Al alloy by diamond shows that the generation of nanoscale wear particles is followed by a phase separation to form liquid Ga nanodroplets and liquid bridges. The transformation of a two-body system to a four-body solid-liquid system within the reciprocating wear track significantly alters the local dynamical friction and wear processes. Moving liquid bridges are observed in situ to play a key role at the sliding nanocontact, interacting strongly with the highly mobile nanoparticle debris. In situ imaging demonstrates that both static and moving liquid droplets exhibit asymmetric menisci due to nanoscale surface roughness. Nanodroplet kinetics are furthermore dependent on local frictional temperature, with solid-like surface nanofilaments forming on cooling. TEM nanotribology opens up new avenues for the real-time quantification of cyclic friction, wear and dynamic solid-liquid nanomechanics, which will have widespread applications in many areas of nanoscience and nanotechnology.

Magnetization properties of some quantum spin ladders

The experimental realization of various spin ladder systems has prompted their detailed theoretical investigations. Hen we study the evolution of ground-state magnetization with an external magnetic field for two different antiferromagnetic systems: a three-legged spin-1/2 ladder, and a two-legged spin-1/2 ladder with an additional diagonal interaction. The finite system density-matrix renormalization-group method is employed for numerical studies of the three-chain system, and an effective low-energy Hamiltonian is used in the limit of strong interchain coupling to study the two- and three-chain systems. The three-chain system has a magnetization plateau at one-third of the saturation magnetization. The two-chain system has a plateau at zero magnetization due to a gap above the singlet ground state. It also has a plateau at half of the saturation magnetization for a certain range of values of the couplings. We study the regions of transitions between plateaus numerically and analytically, and find that they are described, at first order in a strong-coupling expansion, by an XXZ spin-1/2 chain in a magnetic field; the second-order terms give corrections to the XXZ model, We also study numerically some low-temperature properties of the three-chain system, such as the magnetization, magnetic susceptibility and specific heat. [S0163-1829(99)303001-5].

Stability of degenerate diffusions with state-dependent switching

This paper deals with the ergodic properties of hybrid systems modelled by diffusion processes with state-dependent switching. We investigate the sufficient conditions expressed in terms of the parameters of the underlying process which would ensure the existence of a unique invariant probability and stability in distribution of the flow. It turns out that the conditions would depend on certain averaging mechanisms over the states of the discrete component of the hybrid system. (C) 1999 Academic Press.

The steady state nuclear Overhauser effect revisited

The steady state of a two spin system coupled to an isotropic environment and to each other through a dipolar interaction and under irradiation by a monochromatic, circularly polarized radio frequency field is determined ab initio using thermodynamic arguments. This steady state is used to describe the well known nuclear Overhauser effect in liquids. The steady state is also derived from the Solomon-Bloch set of equations used to describe the driven spin. It is shown that in the limit of weak driving, the two solutions coincide. (C) 1999 American Institute of Physics. [S0021-9606(99)71210-9].