5,381 research outputs found
MECHANISMS OF THE DOWNREGULATION OF PROLACTIN RECEPTOR AND THEIR ROLE IN CELL PROLIFERATION
Cells react to diverse stimuli by expressing specific receptors that recognize these stimuli and initiate specific signaling pathways that enable a cell to change with the environment. Downregulation of these signaling receptors represents the most direct method for limiting the magnitude and duration of downstream signal transduction. For cell surface transmembrane receptors, ligand-stimulated endocytosis is a major mechanism by which the ability of a cell to react to a ligand is restricted. In order to investigate the downregulation of the prolactin receptor (PRLr), we investigated the mechanism and key determinants in the endocytosis and downregulation of PRLr. In Chapter 2, we show that the endocytosis of PRLr is a ligand-induced process which requires the catalytic activity of the constitutively bound Janus kinase Jak2. In Chapter 3, we show that PRLr is internalized by a clathrin-dependent mechanism which requires phosphorylation of the conserved phosphodegron motif (DS349GRGS) at Ser 349 and an active SCF╬▓-TrCP E3 ligase complex. Optimal PRLr endocytosis is shown to be achieved via K63-linked polyubiquitination of the receptor. In Chapter 4, we show that PRL signaling promotes cell growth in 2-D and 3-D culture systems where PRLr levels are increased/stabilized. In Chapter 5, we identify pyruvate kinase M2 (PKM2), a glycolytic enzyme whose role in tumorigenesis has been described, to be a novel interactor of PRLr. We show that prolactin (PRL) signaling works to inhibit PKM2 activity by the propagation of tyrosine-phosphorylated proteins. This inhibition of PKM2 prevents progression through glycolysis and allows PKM2 to take a pro-tumorigenic role. We show that the interaction between PRL signaling and PKM2 is required for optimal prolactin-dependent cell growth. In this thesis (model shown in Model 1), we show that there is a defined mechanism of PRLr downregulation which works to limit PRL signaling. If this mode of receptor downregulation is not properly executed, it can result in aberrant signaling whereby prolactin-mediated inhibition of pyruvate kinase M2 mediates the pro-tumorigenic effect of prolactin
Roadway-Embedded Transmitters and Multi-Pad Receivers for High Power Dynamic Wireless Power Transfer
Electric vehicles (EVs) offer considerable economic and environmental benefits to society. Despite the decreasing vehicle costs and increasing range of newer EVs, the problem of range anxiety still exists. Range anxiety, at its core, is an issue of charging speeds rather than a concern about the driving range. Dynamic wireless charging of EVs is seen as a potential solution to this issue of range anxiety. Further, wireless charging technology also helps the push towards level 5 autonomy and opens new opportunities for how an EV can be utilized.
Dynamic wireless power transfer (DWPT) systems typically require a high initial investment due to the scale of deployment needed and require a certain level of EV adoption before they become economically viable. The challenges facing DWPT technologies are broadly categorized into development, deployment and operation challenges. To address the deployment challenges, this dissertation presents the pavement integration of DWPT systems, and the design and validation of concrete-embedded wireless charging pads. To improve infrastructure utilization and address the operation challenge, different vehicle classes need to recharge from the same charging infrastructure. This is made possible by the use of multi-pad receivers, which allow different vehicle classes to receive different power levels using the same charging infrastructure. This work presents a scaled-down version of a multi-pad receiver system to demonstrate the operation and scalability of these modular receivers.
To help further reduce the cost of development and implementation of DWPT systems, finite element method (FEM) and circuit simulation models are presented. The time-domain simulations can be used to develop and validate various control and communication schemes without the need for expensive hardware implementation. Finally, leakage magnetic field reduction to ensure safety and compliance for DWPT systems is discussed, and an example system is analyzed using FEM simulations
Land, labour and migrations : understanding Kerala's economic modernity
This paper seeks to map out the historical trajectory leading to a
series of migrations in and from the erstwhile princely state of Travancore
during 1900-70 in order to acquire and bring land under cultivation. It
argues that these migrations undertaken with a moralistic and paternal
mission of reclaiming тАШemptyтАЩ spaces into productive locations were a
result of a specific form of economic modernity in Kerala as beckoned
by colonialism and appropriated by a resolute local agency through a
process of translation. The attempt is to disentangle the intertwining
history of colonialism, capital and тАШnativeтАЩ agency and thereby to capture
the complex circumstances that unleashed a new discourse of
development with land and hard work at the centre of its scheme. The
transition was facilitated by a conforming social imaginary that not
only dissented radically with the idea of leaving landscape empty and
being idle but also advocated passionately the idea of using the opulent
natural resources for the development of the self and the nation. Leading
the transition the Syrian Christians were successful in wielding a new
subjectivity of development with a specific authority over the modernity
of Kerala as purogamana karshakar (forward-looking peasants).
Key words: Economic modernity, translation, objectification, social
imaginary, migration, modernisation, development
discourse.
JEL Classification: N5, P16, O13, O1
Model based methodology development for energy recovery in ash heat exchange systems
Flash tank evaporation combined with a condensing heat exchanger can be used when heat exchange is required between two streams and where at least one of these streams is difficult to handle (in terms of solid particles content, viscosity, pH, consistency etc.). To increase the efficiency of heat exchange, a cascade of these units in series can be used. Heat transfer relationships in such a cascade are very complex due to their interconnectivity, thus the impact of any changes proposed is difficult to predict. In this report, a mathematical model of a single unit ash tank evaporator combined with a condensing heat exchanger unit is proposed. This model is then developed for a chain of the units. The purpose of this model is to allow an accurate evaluation of the effect and result of an alteration to the system. The resulting model
is applied to the RUSAL Aughinish Alumina digester area
Transition to the ultimate regime in two-dimensional Rayleigh-B\'enard convection
The possible transition to the so-called ultimate regime, wherein both the
bulk and the boundary layers are turbulent, has been an outstanding issue in
thermal convection, since the seminal work by Kraichnan [Phys. Fluids 5, 1374
(1962)]. Yet, when this transition takes place and how the local flow induces
it is not fully understood. Here, by performing two-dimensional simulations of
Rayleigh-B\'enard turbulence covering six decades in Rayleigh number Ra up to
for Prandtl number Pr , for the first time in numerical
simulations we find the transition to the ultimate regime, namely at
. We reveal how the emission of thermal plumes enhances
the global heat transport, leading to a steeper increase of the Nusselt number
than the classical Malkus scaling [Proc.
R. Soc. London A 225, 196 (1954)]. Beyond the transition, the mean velocity
profiles are logarithmic throughout, indicating turbulent boundary layers. In
contrast, the temperature profiles are only locally logarithmic, namely within
the regions where plumes are emitted, and where the local Nusselt number has an
effective scaling , corresponding to the
effective scaling in the ultimate regime.Comment: 6 pages, 4figure
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