ATP7B expression in human breast epithelial cells is mediated by lactational hormones

A role for the copper transporter, ATP7B, in secretion of copper from the human breast into milk has previously not been reported, although it is known that the murine ortholog of ATP7B facilitates copper secretion in the mouse mammary gland. We show here that ATP7B is expressed in luminal epithelial cells in both the resting and lactating human breast, where it has a perinuclear localization in resting epithelial cells and a diffuse location in lactating tissue. ATP7B protein was present in a different subset of vesicles from those containing milk proteins and did not overlap with Menkes ATPase, ATP-7A, except in the perinuclear region of cells. In the cultured human mammary line, PMC42-LA, treatment with lactational hormones induced a redistribution of ATP7B from a perinuclear region to a region adjacent, but not coincident with, the apical plasma membrane. Trafficking of ATP7B was copper dependent, suggesting that the hormone-induced redistribution of ATP7A was mediated through an increase in intracellular copper. Radioactive copper (⁶⁴Cu) studies using polarized PMC42-LA cells that overexpressed mAtp7B protein showed that this transporter facilitates copper efflux from the apical surface of the cells. In summary, our results are consistent with an important function of ATP7B in the secretion of copper from the human mammary gland.

Exploiting geometry for improved hybrid AOA/TDOA-based localization

In this paper we examine the geometrically constrained optimization approach to localization with hybrid bearing (angle of arrival, AOA) and time difference of  arrival (TDOA) sensors. In particular, we formulate a constraint on the measurement errors which is then used along with constraint-based optimization tools in order to estimate the maximum likelihood values of the errors given an appropriate cost function. In particular we focus on deriving a localization algorithm for stationary target localization in the so-called adverse localization geometries where the relative positioning of the sensors and the target do not readily permit accurate or convergent localization using traditional approaches. We illustrate this point via simulation and we compare our approach to a number of different techniques that are discussed in the literature.

Optimal range-difference-based localization considering geometrical constraints

This paper proposes a new type of algorithm aimed at finding the traditional maximum-likelihood (TML) estimate of the position of a target given time-difference-of-arrival (TDOA) information, contaminated by noise. The novelty lies in the fact that a performance index, akin to but not identical with that in maximum likelihood (ML), is a minimized subject to a number of constraints, which flow from geometric constraints inherent in the underlying problem. The minimization is in a higher dimensional space than for TML, and has the advantage that the algorithm can be very straightforwardly and systematically initialized. Simulation evidence shows that failure to converge to a solution of the localization problem near the true value is less likely to occur with this new algorithm than with TML. This makes it attractive to use in adverse geometric situations.

Localization of mobile transmitters by means of linear state estimation using RSS measurements

This paper investigates the problem of estimating the location and velocity of a mobile agent using the received signal strength (RSS) measurements. Typical power measurements are inherently nonlinear and in this approach we derive a linear measurement scheme using an analytical measurement conversion technique which can readily be used with RSS measuring sensors. Power measurements are hence used in our robust version of a linear Kalman filter to estimate the dynamic parameters of the moving transmitter.

TDOA based transmitter localization with minimum number of teceivers and power measurements

This paper investigates the problem of localizing a wireless transmitter using a minimum number of receivers and other readily available means in a time difference of arrival (TDOA) setting. Using the necessary and sufficient conditions for unique solution, we use power measurements to compensate for the reduced number of receivers. In other words, if the transmitter is not located in the unique solution area, we provides a technique to find the true location via the measured received signal power. Our approach neither requires the knowledge of the transmission power nor the path loss exponent.

Application of the strain localization CAFE model to investigate extrusion with various die shapes

Multi scale CAFE model for the prediction of initiation and propagation of the micro shear bands and shear bands in metallic materials subjected to plastic deformation is presented. The CAFE approach is the combination of the Cellular Automata (CA) and the Finite Element (FE) methods. The application of the developed CAFE model to analyze material flow during extrusion is the objective of the present work. The proposed CAFE approach is applied in this work to simulation of the extrusion with flat face and convex dies and to investigate differences in the material flow. The initial FE meshes with the set of the CA point are generated for the numerical tests and the results of the metal flow predicted by the CAFE method are presented in the paper.

Co-localization and distribution of corticotrophin-releasing hormone, arginine vasopressin and enkephalin in the paraventricular nucleus of sheep : a sex comparison

The paraventricular nucleus (PVN) is integral to regulation of the hypothalamo-pituitary-adrenal (HPA) axis and contains cells producing corticotrophin-releasing hormone (CRH), arginine vasopressin (AVP) and enkephalin. We used immunohistochemistry to map these peptides and to resolve the extent of co-localization within PVN cells in intact and gonadectomized male and female sheep. Immunoreactive (ir) CRH, AVP and enkephalin cells were mapped in two rams and two ewes at 180 μm intervals throughout the rostro-caudal extent of the PVN. Similar distributions of AVP-ir cells occurred in both sexes whereas CRH-ir and enkephalin-ir cells extended more rostrally in rams. In groups (n=4) of intact and gonadectomized sheep of both sexes, co-localization and distribution of neuropeptides was influenced by sex and gonadectomy. Males had more AVP and CRH cells than females. Intact animals had more AVP cells than gonadectomized animals. There were no differences between groups in the number or percentage of cells that stained for both CRH and AVP or in the number of cells that stained for both CRH and enkephalin. Differences were observed in the percentage of enkephalin cells that contained CRH with males having a greater percentage of co-localized cells than did females. Differences were also observed in the number and percentage of cells that stained for both enkephalin and AVP; the number of cells that stained for both neuropeptides was greater in males than in females and greater in intact animals than in gonadectomized animals. Differences were observed in the percentage of AVP cells that contained enkephalin, and in the percentage of enkephalin cells that contained AVP with males having a greater percentage of co-localized cells than did females. We conclude that sex and gonadal status affect peptide distribution in the PVN of the sheep which may provide an anatomical basis for sex differences in HPA axis

Epidermal growth factor-induced ovarian carcinoma cell migration is associated with JAK2/STAT3 signals and changes in the abundance and localization of α6β1 integrin

Peritoneal dissemination of ovarian carcinoma is mediated by epithelial–mesenchymal interconversions leading to the disruption of cell–cell contact and modulation of cell–extracellular matrix (ECM) interactions. The present study was designed to evaluate the effects of epidermal growth factor (EGF) as a modulator of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) signalling and changes in integrin expression during the process similar to EMT. A fibroblastic morphology with reduced intercellular cell contacts and increased cell motility was observed in ovarian cancer cell lines in response to EGF and was concomitant with the up regulation of EMT-associated N-cadherin and vimentin expression. These changes were accompanied by an increase in α2, α6 and β1 integrin subunits and activation of JAK2 and STAT3 signalling which was suppressed by a specific JAK2 inhibitor. Consistent with the suppression of STAT3 activity, N-cadherin and vimentin expression were abrogated and was coherent with the loss of cell motility and the expression of α6 and β1 integrin subunits. Neutralizing antibodies against α6 and β1 subunits inhibited cancer cell migration. A strong correlation between the expression of N-cadherin, vimentin and JAK2/STAT3 levels were detected in high-grade ovarian tumors and was consistent with the previously reported enhanced expression of α6 integrin subunit in advanced tumors [Ahmed N, Riley C, Oliva K, Rice G, Quinn M. Ascites induces modulation of α6β1 integrin and urokinase plasminogen activator receptor expression and associated functions in ovarian carcinoma. British Journal of Cancer 2005;92:1475–85]. Our data incorporating the clinical samples and the cancer cell lines is the first to demonstrate that JAK2/STAT3 pathway may be one of the downstream events in EMT-like process and α6β1 integrin-mediated signalling in ovarian carcinomas.

Monaural sound localization : mechanisms and processes

A review of the literature established that localization acuity measured during monaural listening conditions was directly related to various methodological considerations. These included method of attenuation, segment of auditory space where monaural localization was measured, and the presence or absence of head movements. An extensive measurement of monaural localization was made with due consideration of these factors, allowing a more comprehensive evaluation of monaural acuity and the underlying processes that were involved. Establishing a monaural condition is dependent both on the attenuation level of the occluded ear and the signal level, both of which are clearly inter-related since the attenuation level of the occluded ear sets the maximum level of die stimulus. In a series of experiments it was established that there was a minimum signal level for accurate localization. Testing on both sides of the head revealed that there were three regions of monaural localization acuity. The first was about the interaural axis on the ipsilateral ear where monaural localization was relatively accurate, the second a region either side of the MSP where there was some loss of localization, and a third about the interaural axis on the ipsilateral side where virtually no monaural localization ability existed. In the final series of experiments it was established that head-movements allowed subjects to extend the accuracy of the first region by minimizing the distance between the sound and the ipsilateral interaural axis, thus compensating for the loss of localization ability in the second and third regions. This was determined from changes recorded in the error data, and also the extent and direction of measured head-movements. The results of this series of experiments demonstrated the relationship between spectral cues and monaural localization. Firstly, monaural localization was not possible in the absence of accurate spectral information. Thus large errors were observed in the third region where there was blockage of the high-frequencies by the head, and in all regions during the presentation of low signal levels where the high-frequencies fell below threshold. Secondly, the inaccuracy of the second region due to the loss of information from the second pinna suggested that there was a binaural component with relation to pinna cues. It seems that for sounds in this region the spectral modifications from both pinnae are processed to determine a sound's location in space.

Development of the multi-scale analysis model to simulate strain localization occurring during material processing

Abstract A detailed description of possibilities given by the developed Cellular Automata—Finite Element (CAFE) multi scale model for prediction of the initiation and propagation of micro shear bands and shear bands in metallic materials subjected to plastic deformation is presented in the work. Particular emphasis in defining the criterion for initiation of micro shear and shear bands, as well as in defining the transition rules for the cellular automata, is put on accounting for the physical aspects of these phenomena occurring in two different scales in the material. The proposed approach led to the creation of the real multi scale model of strain localization phenomena. This model predicts material behavior in various thermo-mechanical processes. Selected examples of applications of the developed model to simulations of metal forming processes, which involve strain localization, are presented in the work. An approach based on the Smoothed Particle Hydrodynamic, which allows to overcome difficulties with remeshing in the traditional CAFE method, is a subject of this work as well. In the developed model remeshing becomes possible and difficulties limiting application of the CAFE method to simple deformation processes are solved. Obtained results of numerical simulaA detailed description of possibilities given by the developed Cellular Automata—Finite Element (CAFE) multi scale model for prediction of the initiation and propagation of micro shear bands and shear bands in metallic materials subjected to plastic deformation is presented in the work. Particular emphasis in defining the criterion for initiation of micro shear and shear bands, as well as in defining the transition rules for the cellular automata, is put on accounting for the physical aspects of these phenomena occurring in two different scales in the material. The proposed approach led to the creation of the real multi scale model of strain localization phenomena. This model predicts material behavior in various thermo-mechanical processes. Selected examples of applications of the developed model to simulations of metal forming processes, which involve strain localization, are presented in the work. An approach based on the Smoothed Particle Hydrodynamic, which allows to overcome difficulties with remeshing in the traditional CAFE method, is a subject of this work as well. In the developed model remeshing becomes possible and difficulties limiting application of the CAFE method to simple deformation processes are solved. Obtained results of numerical simulations are compared with the experimental results of cold rolling process to show good predicative capabilities of the developed model.tions are compared with the experimental results of cold rolling process to show good predicative capabilities of the developed model.

On the geometry of localization, tracking and navigation

The thesis characterizes the geometry of certain localization, tracking and navigation problems. For instance, the potential localization performance of certain multi-sensor systems is measurably linked to the relative sensor-target geometry. Additionally, several optimal and robust algorithms for localization and tracking are designed which exploit the underlying geometry of the problem considered.

Bearing-only localization using geometrically constrained optimization

We examine the problem of optimal bearing-only localization of a single target using synchronous measurements from multiple sensors. We approach the problem by forming geometric relationships between the measured parameters and their corresponding errors in the relevant emitter localization scenarios. Specifically, we derive a geometric constraint equation on the measurement errors in such a scenario. Using this constraint, we formulate the localization task as a constrained optimization problem that can be performed on the measurements in order to provide the optimal values such that the solution is consistent with the underlying geometry. We illustrate and confirm the advantages of our approach through simulation, offering detailed comparison with traditional maximum likelihood (TML) estimation.

Towards haptic microrobotic intracellular injection

This paper proposes a system providing the operator with an intuitive method for controlling a micromanipulator during intracellular injection. A low-cost haptic device is utilised and 3D position-to-position kinematic mapping allows the operator to control the micropipette using a similar method to handheld needle insertion. The workspaces of the haptic device and micromanipulator are analysed and the importance of appropriate scaling to positioning resolution and tracking performance is investigated. The control issues integral to achieving adequate control of the micromanipulator using the Phantom Omni haptic device are addressed. Aside from offering an intuitive method for controlling the micropipette, this work lays the foundation for real-time haptic assistance in the cell injection task.