A Comparative Analysis of the Interactions of the E6 Proteins from Cutaneous and Genital Papillomaviruses with p53 and E6AP in Correlation to Their Transforming Potential

AbstractA common necessity for all papillomaviruses is to induce DNA synthesis in quiescent cells. This is commonly achieved by the E7 gene product, which interferes with the function of members of the retinoblastoma family controlling transition from the G1-phase to the S-phase of the cell cycle. Uncontrolled entry into S-phase activates, however, negative growth control signals which have to be bypassed to achieve production of progeny viruses. In addition to inherent activities of the E7 protein, high risk genital types encode an E6 protein that overcomes p53-mediated G1-arrest and apoptosis in concert with the cellular factor E6AP by targeting p53 for the enhanced ubiquitin-dependent degradation. The key question, which of these functions of genital E6 and E7 proteins is responsible for the carcinogenic phenotype, is still not completely answered. In contrast to high risk genital types no immortalizing or transforming activities have been found for the E7 proteins of the high risk cutaneous HPV8 and 47. On the other hand the ability of the E6 protein to transform established rodent fibroblasts seems to be a property shared by high risk genital and cutaneous types. To examine the existence of a common E6-mediated transforming pathway for both virus groups we compared the properties of the cutaneous E6 proteins with already known functions of E6 proteins of genital viruses. For this we analyzed the E6 proteins of low risk and high risk cutaneous and genital papillomaviruses with respect to cell transformation, to their abilities to bind, degradate, and influence the activity of human p53, and to bind E6AP. The results of our study demonstrate a clear lack of interaction between the transforming E6 proteins of HPV1 and HPV8 and both cellular proteins p53 and E6AP. In contrast, we found E6AP-independent binding of HPV16 E6 and HPV6 E6 to p53, although both proteins were different in their transforming potential. Of all four proteins investigated, only HPV16 E6 was able to bind to p53 and E6AP and to induce degradation of the p53 protein in the reticulocyte system. When we investigated in frame deletion mutants of the E6 protein of HPV16 for their abilities to bind to p53 or E6AP, degradate, and inhibit the transactivation function of p53 and to transform rodent fibroblasts, no correlation between the different activities could be found. Mutants still able to bind p53 and E6AP lacked transforming ability and other mutants that were transformation-competent were deficient in p53 and E6AP binding

Compatibility of Filler and Base Metals in Heat Exchanger Manufacturing Process

Aluminum is one of the most commonly used metals for manufacturing heat exchanger. Mass production of compact aluminum heat exchangers can be achieved by furnace or flame brazing with the assistance of fluxes. It is well known that a brazing process relies on the capillary flow of liquid filler metal on the base surfaces of various heat exchanger components. Proper selection of heater exchanger materials is essential for the success of a brazing process. For example, the 6xxx series aluminum alloys are a popular selection in production processes due to their excellent mechanical strength and good machinability. However, the high percentage of Mg content in this alloy category makes it difficult to braze these alloys by CAB furnace processes. On the other hand, the 3xxx series aluminum alloys with Mn as major alloying element are suitable candidates for CAB brazed aluminum heat exchangers because of the excellent wettability of Al based filler metal when assisted by fluxes. In this study, selected commercially available aluminum alloys are used for wettability tests by Al based filler metals under CAB brazing condition. During the manufacturing or installation processes of the aluminum heat exchangers, there is often the need to join components that are made of dissimilar metals, such as Al/Cu joints and Al/stainless steel joints. Therefore, wetting behaviors of selected filler metals on commonly used Cu and/or SS surfaces are investigated as well. The phenomena closely related to liquid filler metal wetting behaviors on base metal with different material compositions are studied using sophisticated visualization tools and facilities such as heating stage and transparent furnace. Metallurgical cross section samples are prepared and examined using optical microscope to study the interactions between filler and base metals

Design and Investigation of a Transcritical R744 Refrigerated Container for Military Applications

This paper describes the design and performance evaluation of a transcritical R744 (CO2) multi-temperature, mobile refrigerated container system. The efficient and widespread use of R744 in both large-scale supermarket refrigeration systems and small-scale glass-door merchandisers has been shown through numerous studies and field demonstrations in recent years, indicating the suitability of this refrigerant to almost any refrigeration application. However, the extreme operating conditions of this refrigeration application intended for use in ambient temperatures up to 57°C while still maintaining a frozen temperature of -20°C make using R744 as a refrigerant a unique challenge here. The targeted use of the refrigerated container is for military applications, but a successfully developed system will show that R744 is a suitable refrigerant for a range of container applications. In order to achieve reasonable efficiency at the extreme conditions of this application, several improvements have been implemented: Improved gas cooler performance with a microchannel heat exchanger, internal heat exchange, and expansion work recovery with an ejector. The benefits of each of these improvements are discussed, and preliminary results are presented to show the realistic performance enhancement that can be achieved with each of these improvements. The results presented in this paper show that while the very high ambient temperature of this system presents a unique challenge, it also allows for very significant COP improvement using each of the above improvements methods

Influence of Surface Morphology on Wetting Behaviors of Liquid Metal during Aluminum Heat Exchanger Fabrication

The market demand for aluminum brazed exchangers in air conditioning and refrigeration industry is continually growing owing mostly to the cost and weight savings of aluminum materials, with undisputed compactness and low charge. Manufacturing of aluminum heat exchangers requires reliable metal bonding technology to join together various components, such as tubes, fins and header manifolds. Controlled atmosphere brazing (CAB) of aluminum is the state-of-the-art technology for mass production of compact aluminum heat exchangers. Traditionally, the development of a brazing process relies on trial and error in practice. However, modern manufacturing process requires good understanding of scientific principles involved in the brazing operations. It is well known that a brazing process is assisted by the capillary flow of liquid filler metal on the base surfaces of various heat exchanger components. Therefore a good understanding of the molten flow behavior on aluminum surfaces is critical in quality assurance of the brazed heat exchangers. Capillary flow occurring at high temperature level during brazing is usually much more complicated than the wetting in an inert system with a smooth solid surface. For example, the flow of liquid is not only controlled by surface tension force, but also influenced by interactions between liquid and base metal materials. In addition, the metal surface of a heat exchanger component to be brazed is usually not smooth due to the fabrication process such as extrusion or hot/cold rolling. In this paper, the phenomena closely related to liquid filler metal wetting behaviors on base metal with different surface morphologies are presented. Experimental facilities such as heating stage microscopy system and transparent furnace are used to visualize the capillary flow of molten filler metal under typical CAB brazing conditions. The influence of the base metal surface morphology on wetting behavior as well as brazed joint quality are examined, assisted by metallographic analysis of re-solidified brazing joints. The physical and chemical phenomena in the interaction between liquid (molten flux and filler metal) and solid (base metal) are described. The results from this study provide useful insights on how material selection and surface treatment can affect the brazing process and brazed heat exchanger quality

Extremely Low Refrigerant Charge Beverage Display Cooler Technology Using Propane

The majority of beverage manufacturers prefer natural refrigerants over synthetic refrigerant options as the working fluid for their beverage display cooling equipment. The two major refrigerants considered for these light commercial applications are CO2 (carbon dioxide) and R290 (propane). CO2, used in a transcritical cycle, offers advantages in terms of flammability, however, reduced performance at high ambient temperatures and safety issues related to the high working pressures need to be addressed in order to design efficient and cost-competitive systems. The challenges encountered with CO2 are typically no concern for R290; however, the major risk associated with propane is the flammability of the refrigerant. One way to mitigate the risk is rigorous reduction of refrigerant charge to levels that are substantially below legal limits. This task has been accomplished by employing experimentally validated simulation models that can be used to reliably predict the refrigerant charge in each component at different ambient conditions. Design and optimization efforts have to be focused on the compressor oil type and charge amount which dissolves large quantities of propane that does not contribute to generating the desired cooling effect. The other component that bears significant potential to reduce refrigerant charge is the condenser; low internal volumes are desired that can provide an optimal balance between required refrigerant charge, heat transfer, and pressure drop. A serpentine style microchannel heat exchanger design featuring low fin density on the air side was developed and implemented. The reduced number of fins on the air side reduces maintenance requirements and allows the system to be used in dusty environments. The improvements along with further optimizations were implemented into a beverage cooler holding 700 cans with a volume of 355mL per can. The achieved cooling capacity was on the order of 1 kW featuring a propane refrigerant charge of less than 50 g. The performance of the redesigned beverage display cooler was experimentally validated at an ambient temperature of 40oC and it was found that all of the manufacturers’ pull-down and energy consumption test requirements were successfully achieved

Improvements in Refrigerant Flow Distribution Using an Expansion Valve with Integrated Distributor

Many factors, such as loading, flow circuiting, phase separation, and distributor effectiveness determine how uniformly refrigerant is distributed within a multicircuited heat exchanger. This work describes the development of a test procedure for evaluation of refrigerant flow distribution in a multicircuited round tube evaporator as well as a comparison between a typical valve/distributor combination and a novel expansion device that integrates the distributor into the valve body. The results of this study show that refrigerant flow distribution can be made more uniform through implementation of this device

Accelerated Thermal Cycling test for Heat Exchangers Used in Reversible Heat Pump

With increasing efficiency standards and higher energy costs, the demand for reversible air-conditioning/heat pump systems is increasing throughout the stationary market. The heat exchangers in such reversible systems must perform reliably as both evaporator and condenser. The outdoor coil, specifically, is subject to very large changes in both operational pressures and temperatures. With this increase in demand and the gradual shift of the industry to aluminum microchannel coil design, comes a need to better understand and quantify the reliability of the heat exchangers. This paper presents the development of an accelerated thermal cycling test method using refrigerant at typical pressures and temperatures to demonstrate the reliability of said heat exchangers. This method employs a technique of switching the heat exchanger between condensing and evaporation modes rapidly while monitoring strain at various locations of concern to quantify any shift in strain caused by fatigue

Successful Design, Implementation, And Validation Of Transcritical R744 Technology For Beverage Display Coolers

Glass door merchandisers are used in grocery and convenience stores to display chilled beverages or refrigerated foods. Among other possible choices for this application, carbon dioxide (R744, CO2) is seen as a promising low-GWP refrigerant alternative that is non-flammable and non-toxic. While R744 itself is less costly than synthetic alternatives, successful implementation of high-performance, low-cost transcritical R744 technology is challenging. This paper summarizes important R744-specific design issues and differences in comparison to conventional R134a bottle coolers. Due to cost reasons, it is highly desired to use relatively conventional components, including round-tube-plate-fin heat exchanger designs, fixed geometry capillary tubes (instead of variable geometry expansion valves), and single-speed compressors. While a conventional round-tube-plate fin evaporator designs deliver acceptable results, transcritical R744 systems require substantially different heat exchanger designs in order to deliver suitable performance when used as gas cooler. Internal heat exchange, which in conventional R134a systems is often achieved by wrapping the capillary tube around the compressor suction line, plays a much more important role in transcritical R744 systems, and shows large optimization potential. Experiments also show that proper capillary tube sizing and refrigerant charge optimization have much bigger impact on transcritical R744 systems in terms of cooling performance and energy efficiency in comparison to R134a systems. Presented is an example of a successful R744 bottle cooler design that is on par with a comparable R134a system in terms of performance and cost. This low-cost, high performance design has been implemented and experimentally validated