Outside-in signaling through integrins and cadherins: a central mechanism to control epidermal growth and differentiation?

The process of epidermal renewal persists throughout the entire life of an organism. It begins when a keratinocyte progenitor leaves the stem cell compartment, undergoes a limited number of mitotic divisions, exits the cell cycle, and commits to terminal differentiation. At the end of this phase, the postmitotic keratinocytes detach from the basement membrane to build up the overlaying stratified epithelium. Although highly coordinated, this sequence of events is endowed with a remarkable versatility, which enables the quiescent keratinocyte to reintegrate into the cell cycle and become migratory when necessary, for example after wounding. It is this versatility that represents the Achilles heel of epithelial cells allowing for the development of severe pathologies. Over the past decade, compelling evidence has been provided that epithelial cancer cells achieve uncontrolled proliferation following hijacking of a "survival program" with PI3K/Akt and a "proliferation program" with growth factor receptor signaling at its core. Recent insights into adhesion receptor signaling now propose that integrins, but also cadherins, can centrally control these programs. It is suggested that the two types of adhesion receptors act as sensors to transmit extracellular stimuli in an outside-in mode, to inversely modulate epidermal growth factor receptor signaling and ensure cell survival. Hence, cell-matrix and cell-cell adhesion receptors likely play a more powerful and wide-ranging role than initially anticipated. This Perspective article discusses the relevance of this emerging field for epidermal growth and differentiation, which can be of importance for severe pathologies such as tumorigenesis and invasive metastasis, as well as psoriasis and Pemphigus vulgaris.

Cardiovascular risk factor control and outcomes in peripheral artery disease patients in the Reduction of Atherothrombosis for Continued Health (REACH) Registry

OBJECTIVES: To examine differences in risk factor (RF) management between peripheral artery disease (PAD) and coronary artery (CAD) or cerebrovascular disease (CVD), as well as the impact of RF control on major 1-year cardiovascular (CV) event rates. METHODS: The REACH Registry recruited >68000 outpatients aged >/=45 years with established atherothrombotic disease or >/=3 RFs for atherothrombosis. The predictors of RF control that were evaluated included: (1) patient demographics, (2) mode of PAD diagnosis, and (3) concomitant CAD and/or CVD. RESULTS: RF control was less frequent in patients with PAD (n=8322), compared with those with CAD or CVD (but no PAD, n=47492) [blood pressure; glycemia; total cholesterol; smoking cessation (each P<0.001)]. Factors independently associated with optimal RF control in patients with PAD were male gender (OR=1.9); residence in North America (OR=3.5), Japan (OR=2.5) or Latin America (OR=1.5); previous coronary revascularization (OR=1.3); and statin use (OR=1.4); whereas prior leg amputation was a negative predictor (OR=0.7) (P<0.001). Optimal RF control was associated with fewer 1-year CV ischemic symptoms or events. CONCLUSIONS: Patients with PAD do not achieve RF control as frequently as individuals with CAD or CVD. Improved RF control is associated with a positive impact on 1-year CV event rates.

Dynamic modeling, simulation and control design of a parafoil-payload system for ship launched aerial delivery system (SLADS)

The objective of this research was to develop a high-fidelity dynamic model of a parafoilpayload system with respect to its application for the Ship Launched Aerial Delivery System (SLADS). SLADS is a concept in which cargo can be transfered from ship to shore using a parafoil-payload system. It is accomplished in two phases: An initial towing phase when the glider follows the towing vessel in a passive lift mode and an autonomous gliding phase when the system is guided to the desired point. While many previous researchers have analyzed the parafoil-payload system when it is released from another airborne vehicle, limited work has been done in the area of towing up the system from ground or sea. One of the main contributions of this research was the development of a nonlinear dynamic model of a towed parafoil-payload system. After performing an extensive literature review of the existing methods of modeling a parafoil-payload system, a five degree-of-freedom model was developed. The inertial and geometric properties of the system were investigated to predict accurate results in the simulation environment. Since extensive research has been done in determining the aerodynamic characteristics of a paraglider, an existing aerodynamic model was chosen to incorporate the effects of air flow around the flexible paraglider wing. During the towing phase, it is essential that the parafoil-payload system follow the line of the towing vessel path to prevent an unstable flight condition called ‘lockout’. A detailed study of the causes of lockout, its mathematical representation and the flight conditions and the parameters related to lockout, constitute another contribution of this work. A linearized model of the parafoil-payload system was developed and used to analyze the stability of the system about equilibrium conditions. The relationship between the control surface inputs and the stability was investigated. In addition to stability of flight, one more important objective of SLADS is to tow up the parafoil-payload system as fast as possible. The tension in the tow cable is directly proportional to the rate of ascent of the parafoil-payload system. Lockout instability is more favorable when tow tensions are large. Thus there is a tradeoff between susceptibility to lockout and rapid deployment. Control strategies were also developed for optimal tow up and to maintain stability in the event of disturbances.

Optimal current control for sub-unity power factor correction

Switching mode power supplies (SMPS) are subject to low power factor and high harmonic distortions. Active power-factor correction (APFC) is a technique to improve the power factor and to reduce the harmonic distortion of SMPSs. However, this technique results in double frequency output voltage variation which can be reduced by using a large output capacitance. Using large capacitors increases the cost and size of the converter. Furthermore, the capacitors are subject to frequent failures mainly caused by evaporation of the electrolytic solution which reduce the converter reliability. This thesis presents an optimal control method for the input current of a boost converter to reduce the size of the output capacitor. The optimum current waveform as a function of weighing factor is found by using the Euler Lagrange equation. A set of simulations are performed to determine the ideal weighing which gives the lowest possible output voltage variation as the converter still meets the IEC-61000-3-2 class-A harmonics requirements with a power factor of 0.8 or higher. The proposed method is verified by the experimental work. A boost converter is designed and it is run for different power levels, 100 W, 200 W and 400 W. The desired output voltage ripple is 10 V peak to peak for the output voltage of 200 Vdc. This ripple value corresponds to a ± 2.5% output voltage ripple. The experimental and the simulation results are found to be quite matching. A significant reduction in capacitor size, as high as 50%, is accomplished by using the proposed method.

Optimal game theoretic distributed control methodologies in small scale power systems

This dissertation presents the competitive control methodologies for small-scale power system (SSPS). A SSPS is a collection of sources and loads that shares a common network which can be isolated during terrestrial disturbances. Micro-grids, naval ship electric power systems (NSEPS), aircraft power systems and telecommunication system power systems are typical examples of SSPS. The analysis and development of control systems for small-scale power systems (SSPS) lacks a defined slack bus. In addition, a change of a load or source will influence the real time system parameters of the system. Therefore, the control system should provide the required flexibility, to ensure operation as a single aggregated system. In most of the cases of a SSPS the sources and loads must be equipped with power electronic interfaces which can be modeled as a dynamic controllable quantity. The mathematical formulation of the micro-grid is carried out with the help of game theory, optimal control and fundamental theory of electrical power systems. Then the micro-grid can be viewed as a dynamical multi-objective optimization problem with nonlinear objectives and variables. Basically detailed analysis was done with optimal solutions with regards to start up transient modeling, bus selection modeling and level of communication within the micro-grids. In each approach a detail mathematical model is formed to observe the system response. The differential game theoretic approach was also used for modeling and optimization of startup transients. The startup transient controller was implemented with open loop, PI and feedback control methodologies. Then the hardware implementation was carried out to validate the theoretical results. The proposed game theoretic controller shows higher performances over traditional the PI controller during startup. In addition, the optimal transient surface is necessary while implementing the feedback controller for startup transient. Further, the experimental results are in agreement with the theoretical simulation. The bus selection and team communication was modeled with discrete and continuous game theory models. Although players have multiple choices, this controller is capable of choosing the optimum bus. Next the team communication structures are able to optimize the players’ Nash equilibrium point. All mathematical models are based on the local information of the load or source. As a result, these models are the keys to developing accurate distributed controllers.

Supersymmetric Mode Converters

Originally developed in the context of quantum field theory, the concept of supersymmetry can be used to systematically design a new class of optical structures. In this work, we demonstrate how key features arising from optical supersymmetry can be exploited to control the flow of light for mode division multiplexing applications. Superpartner configurations are experimentally realized in coupled optical networks, and the corresponding light dynamics in such systems are directly observed. We show that supersymmetry can be judiciously utilized to remove the fundamental mode of a multimode optical structure, while establishing global phase matching conditions for the remaining set of modes. Along these lines, supersymmetry may serve as a promising platform for versatile optical components with desirable properties and functionalities.

DESIGN AND IMPLEMENT DYNAMIC PROGRAMMING BASED DISCRETE POWER LEVEL SMART HOME SCHEDULING USING FPGA

With the development and capabilities of the Smart Home system, people today are entering an era in which household appliances are no longer just controlled by people, but also operated by a Smart System. This results in a more efficient, convenient, comfortable, and environmentally friendly living environment. A critical part of the Smart Home system is Home Automation, which means that there is a Micro-Controller Unit (MCU) to control all the household appliances and schedule their operating times. This reduces electricity bills by shifting amounts of power consumption from the on-peak hour consumption to the off-peak hour consumption, in terms of different “hour price”. In this paper, we propose an algorithm for scheduling multi-user power consumption and implement it on an FPGA board, using it as the MCU. This algorithm for discrete power level tasks scheduling is based on dynamic programming, which could find a scheduling solution close to the optimal one. We chose FPGA as our system’s controller because FPGA has low complexity, parallel processing capability, a large amount of I/O interface for further development and is programmable on both software and hardware. In conclusion, it costs little time running on FPGA board and the solution obtained is good enough for the consumers.

Incorporating Latent Variables into Discrete Choice Models - A Simultaneous Estimation Approach Using SEM Software

Integrated choice and latent variable (ICLV) models represent a promising new class of models which merge classic choice models with the structural equation approach (SEM) for latent variables. Despite their conceptual appeal, applications of ICLV models in marketing remain rare. We extend previous ICLV applications by first estimating a multinomial choice model and, second, by estimating hierarchical relations between latent variables. An empirical study on travel mode choice clearly demonstrates the value of ICLV models to enhance the understanding of choice processes. In addition to the usually studied directly observable variables such as travel time, we show how abstract motivations such as power and hedonism as well as attitudes such as a desire for flexibility impact on travel mode choice. Furthermore, we show that it is possible to estimate such a complex ICLV model with the widely available structural equation modeling package Mplus. This finding is likely to encourage more widespread application of this appealing model class in the marketing field.

Dynamic merge of discrete goods flow – Impact on throughput and efficiency

Continuous conveyors with a dynamic merge were developed with adaptable control equipment to differentiate these merges from competing Stop-and-Go merges. With a dynamic merge, the partial flows are manipulated by influencing speeds so that transport units need not stop for the merge. This leads to a more uniform flow of materials, which is qualitatively observable and verifiable in long-term measurements. And although this type of merge is visually mesmerizing, does it lead to advantages from the view of material flow technology? Our study with real data indicates that a dynamic merge shows a 24% increase in performance, but only for symmetric or nearly symmetric flows. This performance advantage decreases as the flows become less symmetric, approaching the throughput of traditional Stop-and-Go merges. And with a cost premium for a continuous merge of approximately 10% due to the additional technical components (belt conveyor, adjustable drive engines, software, etc.), this restricts their economical use.

Light curing through glass ceramics with a second- and a third-generation LED curing unit: effect of curing mode on the degree of conversion of dual-curing resin cements

Objectives The aim of this study was to measure the degree of conversion (DC) of five dual-curing resin cements after different curing modes with a second- and a third-generation light-emitting diode (LED) curing unit. Additionally, irradiance of both light curing units was measured at increasing distances and through discs of two glass ceramics for computer-aided design/manufacturing (CAD/CAM). Materials and methods Irradiance and spectra of the Elipar FreeLight 2 (Standard Mode (SM)) and of the VALO light curing unit (High Power Mode (HPM) and Xtra Power Mode (XPM)) were measured with a MARC radiometer. Irradiance was measured at increasing distances (control) and through discs (1.5 to 6 mm thickness) of IPS Empress CAD and IPS e.max CAD. DC of Panavia F2.0, RelyX Unicem 2 Automix, SpeedCEM, BisCem, and BeautiCem SA was measured with an attenuated total reflectance–Fourier transform infrared spectrometer when self-cured (negative control) or light cured in SM for 40 s, HPM for 32 s, or XPM for 18 s. Light curing was performed directly (positive control) or through discs of either 1.5- or 3-mm thickness of IPS Empress CAD or IPS e.max CAD. DC was analysed with Kruskal–Wallis tests followed by pairwise Wilcoxon rank sum tests (α = 0.05). Results Maximum irradiances were 1,545 mW/cm2 (SM), 2,179 mW/cm2 (HPM), and 4,156 mW/cm2 (XPM), and all irradiances decreased by >80 % through discs of 1.5 mm, ≥95 % through 3 mm, and up to >99 % through 6 mm. Generally, self-curing resulted in the lowest DC. For some cements, direct light curing did not result in higher DC compared to when light cured through ceramic discs. For other cements, light curing through ceramic discs of 3 mm generally reduced DC. Conclusions Light curing was favourable for dual-curing cements. Some cements were more susceptible to variations in curing mode than others. Clinical relevance When light curing a given cement, the higher irradiances of the third-generation LED curing unit resulted in similar DC compared to the second-generation one, though at shorter light curing times.

Perceived malleability of self versus the world and its impact on youths’ control orientation and well-being in the US, Germany, and India

Primary control is defined as changing the world to fit the self, while secondary control is defined as changing the self to fit the world. To understand why different individuals prefer different kinds of control processes, we proposed a research project looking at US, German and Indian young adults. We hypothesize that theories of self and the world (fixed vs. malleable; Dweck, 1999) affect the prevailing mode of control used. Furthermore, adolescents’ cultural background is assumed to affect their self-world theories as well as the adaptiveness of specific modes of control. For example, in the US, where the self is tended to be seen as fixed and the world as malleable, primary control prevails and is more adaptive than secondary control while the reverse is expected for India. We present the theoretical outline and methodology of the study as well as first results.

Small quantity but large effect — How minor phases control strain localization in upper mantle shear zones

Low viscosity domains such as localized shear zones exert an important control on the geodynamics of the uppermost mantle. Grain size reduction and subsequent strain localization related to a switch from dislocation to diffusion creep is one mechanism to form low viscosity domains. To sustain strain localization, the grain size of mantle minerals needs to be kept small over geological timescales. One way to keep olivine grain sizes small is by pinning of mobile grain boundaries during grain growth by other minerals (second phases). Detailed microstructural studies based on natural samples from three shear zones formed at different geodynamic settings, allowed the derivation of the olivine grain-size dependence on the second-phase content. The polymineralic olivine grain-size evolution with increasing strain is similar in the three shear zones. If the second phases are to pin the mobile olivine grain boundary the phases need to be well mixed before grain growth. We suggest that melt-rock and metamorphic reactions are crucial for the initial phase mixing in mantle rocks. With ongoing deformation and increasing strain, grain boundary sliding combined with mass transfer processes and nucleation of grains promotes phase mixing resulting in fine-grained polymineralic mixtures that deform by diffusion creep. Strain localization due to the presence of volumetrically minor minerals in polymineralic mantle rocks is only important at high strain deformation (ultramylonites) at low temperatures (<~800°C). At smaller strain and stress conditions and/or higher temperatures other parameters like overall energy available to deform a given rock volume, the inheritance of mechanical anisotropies or the presence of water or melts needs to be considered to explain strain localization in the upper mantle.

{\it cis\/} -acting determinants in the control of MuSVts110 RNA splicing

Like other simple retroviruses the murine sarcoma virus ts110 (MuSVts110) displays an inefficient mode of genome splicing. But, unlike the splicing phenotypic of other retroviruses, the splicing event effected upon the transcript of MuSVts110 is temperature sensitive. Previous work in this laboratory has established that the conditionally defective nature of MuSVts110 RNA splicing is mediated in cis by features in the viral transcript. Here we show that the 5$\sp\prime$ splice site of the MuSVts110 transcript acts as a point of control of the overall splicing efficiency at both permissive and nonpermissive temperatures for splicing. We strengthened and simultaneously weakened the nucleotide structure of the 5$\sp\prime$ splice site in an attempt to elucidate the differential effects each of the two known critical splicing components which interact with the 5$\sp\prime$ splice site have on the overall efficiency of intron excision. We found that a transversion of the sixth nucleotide, resulting in the formation of a near-consensus 5$\sp\prime$ splice site, dramatically increased the overall efficiency of MuSVts110 RNA splicing and abrogated the thermosensitive nature of this splicing event. Various secondary mutations within this original transversion mutant, designed to selectively decrease specific splicing component interactions, lead to recovery of inefficient and thermosensitive splicing. We have further shown that a sequence of 415 nucleotides lying in the downstream exon of the viral RNA and hypothesized to act as an element in the temperature-dependent inhibition of splicing displays a functional redundancy throughout its length; loss and/or replacement of any one sequence of 100 nucleotides within this sequence does not, with one exception detailed below, diminish the degree to which MuSVts110 RNA is inhibited to splice at the restrictive temperature. One specific deletion, though, fortuitously juxtaposed and activated cryptic consensus splicing signals for the excision of a cryptic intron within the downstream exon and markedly potentiated--across a newly defined cryptic exon--the splicing event effected upon the upstream, native intron. We have exploited this mutant of MuSVts110 to further an understanding of the process of exon definition and intron definition and show that the polypyrimidine tract and consensus 3$\sp\prime$ splice site, as well as the 5$\sp\prime$ splice site, within the intron at the 3$\sp\prime$ flank of the defined exon are required for the exon's definition; implying that definition of the downstream intron is required for the in vivo definition of the proximal, upstream exon. Finally; we have shown, through the construction of heterologous mutants of MuSVts110 employing a foreign 3$\sp\prime$ end-forming sequence, that efficiency of transcript splicing can be increased--to a degree which abrogates its thermosensitive nature--in direct proportion to increasing proximity of the 3$\sp\prime$ end-forming signal to the terminal 3$\sp\prime$ splice site. ^

A numerical discrete element study on the influence of an embedded viscoelastic-plastic layer at different viscosity values

The major aim of this study was to examine the influence of an embedded viscoelastic-plastic layer at different viscosity values on accretionary wedges at subduction zones. To quantify the effects of the layer viscosity, we analysed the wedge geometry, accretion mode, thrust systems and mass transport pattern. Therefore, we developed a numerical 2D 'sandbox' model utilising the Discrete Element Method. Starting with a simple pure Mohr Coulomb sequence, we added an embedded viscoelastic-plastic layer within the brittle, undeformed 'sediment' package. This layer followed Burger's rheology, which simulates the creep behaviour of natural rocks, such as evaporites. This layer got thrusted and folded during the subduction process. The testing of different bulk viscosity values, from 1 × 10**13 to 1 × 10**14 (Pa s), revealed a certain range where an active detachment evolved within the viscoelastic-plastic layer that decoupled the over- and the underlying brittle strata. This mid-level detachment caused the evolution of a frontally accreted wedge above it and a long underthrusted and subsequently basally accreted sequence beneath it. Both sequences were characterised by specific mass transport patterns depending on the used viscosity value. With decreasing bulk viscosities, thrust systems above this weak mid-level detachment became increasingly symmetrical and the particle uplift was reduced, as would be expected for a salt controlled forearc in nature. Simultaneously, antiformal stacking was favoured over hinterland dipping in the lower brittle layer and overturning of the uplifted material increased. Hence, we validated that the viscosity of an embedded detachment strongly influences the whole wedge mechanics, both the respective lower slope and the upper slope duplex, shown by e.g. the mass transport pattern.