Caloxin2A 1 is a novel peptide that inhibits the activity of Plasma Membrane Calcium ATPase (PMCA). PMCA is known to play a role in homeostasis of cytosolic calcium and cell signaling. There are 4 genes (PMCA1-4) that code for the various isoforms of the calcium pump. Based on hydropathy plots, PMCA proteins have 5 putative extracellular domains. We screened combinatorial peptide phage display library for binding to specific extracellular targets. Caloxin 2A1 was obtained as a peptide sequence that would bind to the 2nd putative extracellular domain of PMCA 1 isoform. Caloxin2A1 selectively inhibited the Ca2+-Mg2+ ATPase activity in human erythrocyte leaky ghosts that express mainly PMCA 4 isoform. It produced 50% inhibition of the pump activity at 0.4 mM. Caloxin2A1 inhibited the formation of the acid stable 140 kDa acyl phosphate in the reaction cycle of the calcium pump in the human erythrocyte leaky ghosts. It also produced endothelium dependent relaxation in the pig coronary artery. The random peptide phage display library was screened again with higher stringency to obtain caloxin with higher affinity in order to be cost effective and with greater therapeutic potential. This time, the targets were the 2nd putative extracellular domain of PMCA 1 and 2nd and 3rd putative domains of PMCA 4. The peptides selected for binding to the 2nd putative extracellular domain of PMCA 4 selectively inhibited the Ca2^+-Mg^2+ ATPase activity in human erythrocyte leaky ghosts but with a similar affinity as Caloxin2A1. The peptide selected for binding to the 3rd putative extracellular domain of PMCA 4 was hydrophobic and water insoluble. Substitution of its C-terminus amino acid with lysine residue made the peptide water-soluble and it did inhibit the Ca^2 +-Mg^2 + ATPase with slightly higher affinity. However, the inhibition was due to hydrophobicity of the peptide as the randomized version of the peptide also produced inhibition. We have obtained the first selective inhibitor of PMCA and shown that perturbing extracellular targets can affect protein activity even though most of the functional groups of this protein are in the cytosol. / Thesis / Master of Science (MS)

This paper describes a novel concept for a low cost variable delivery external gear pump (VD-EGP). The proposed VD-EGP is based on the realization of a variable timing for the connections of the internal displacement chambers with the inlet and outlet ports. With respect to a standard EGP, an additional element (slider) is used along with asymmetric gears to realize the variable timing principle. Previously performed tests confirmed the validity of the concept, for a design capable of varing the flow in the 65%-100% range. Although the VD-EGP concept is suitable for various flow control system typologies (manual, electro-actuated, hydraulically flow- or pressure- compensated), this paper particularly details the design and the test results for a prototype that includes both a manual flow control system and a pressure compensator. Flow vs pressure and volumetric efficiency curves are discussed along with transient (outlet flow fluctuation) features of the VD-EGP.

Most current designs for Left Ventricular Assist Devices (LVAD) are based on rotary pumps due to their small size and lack of valves. However, the majority of FDA approved LVADs are larger, positive displacement pumps. One reason for this may be because positive displacement pumps produce pulsatile flow, similar to that of the natural heart, while rotary pumps produce continuous flow. Continuous flow has been shown to support the circulation for short periods of time during open-heart surgery, but it has seen limited success with long-term support. It is thought that pulsatile flow provides many metabolic advantages to patients with high total peripheral resistance (TPR) and lower flowrates. This study focused on modifying a continuous flow multiple disk centrifugal pump (MDCP) into a pulsatile pump, to allow for the combined benefits of the pulsatility from positive displacement pumps and the small size and valveless design of rotary pumps. An efficiency study was carried out by evaluating the hydraulic work output and the power requirements of the pump. The pump was evaluated in both pulsatile and continuous flow modes. In continuous mode, the pump was able to maintain a flow of 5.5 L/min against a pressure head of 60mmHg at 1155rpm. Other LVADs have reported rotational speeds around 2400rpm for centrifugal and 10,000rpm for axial pumps to produce flows around 5 L/min. This indicates that the MDCP is capable of producing flowrates at lower rotational speeds than other LVADs, lessening the mechanical wear of the parts, thus potentially increasing the device's lifespan. In pulsatile mode, cardiac outputs of 5 L/min were achieved against a 55/27mmHg outlet pressure. Higher pressures were unattainable with our current testing apparatus, but the results from the pulsatile tests prove that the MDCP can be operated in a pulsatile fashion and produce normal flowrates at low pressures. The pump efficiency was lower than expected, around 0.7-9% in continuous mode and 3-18% in pulsatile mode, consuming 3.5-28W and 0.5-2.3W, respectively. Utilizing a smaller motor may produce higher efficiencies, since the power requirements will be less without decreasing the flowrates, but a further study should be conducted in order to verify this.

The TurboPiston Pump was invented to make use of merits such as, high flow rates often seen in centrifugal pumps and high pressures associated with positive displacement pumps. The objective of this study is to manufacture a plastic model 12” TurboPiston Pump to demonstrate the working principle and a metal prototype for performance testing. In addition, this research includes the study of the discharge valve to estimate the valve closing time and fluid mass being recycled back into the cylinder through hand calculations. Furthermore, a transient simulation was performed in CFD using Fluent to provide a better estimate of what will happen in the actual pump while running. Additionally, an experimental rig was designed to investigate the performance of the first generation valve on the TurboPiston Pump known as the flapper valve. Means to improve the hydrodynamic performance of both valves have been identified for future study.

Due to the continuous power supply reduction, Charge Pumps, also referred to as DC-DC converters, circuits are widely used in integrated circuits (ICs) to generate high voltages for many applications, such as EEP-ROMs, Flash memories for programming and erasing of the floating gate, switched capacitor circuits, operational amplifiers, voltage regulators, LCD drivers, piezoelectricactuators, etc. A charge pump is a kind of DC to DC converter that uses capacitors as energy storage elements to create either a higher or lower voltage power source. The development of the charge pumps is motivated by ever increasing the needs for the small form factor (i.e small size and low weight), high-conversion-efficiency and low costpower management system, which is the best candidate suitable to meet the needs of continuosly shrinking portable electronic devices like MP3 players, cellular phones, PDA's. / text

This paper describes a novel concept for a low cost variable delivery external gear pump (VD-EGP). The proposed VD-EGP is based on the realization of a variable timing for the connections of the internal displacement chambers with the inlet and outlet ports. With respect to a standard EGP, an additional element (slider) is used along with asymmetric gears to realize the variable timing principle. Previously performed tests confirmed the validity of the concept, for a design capable of varing the flow in the 65%-100% range. Although the VD-EGP concept is suitable for various flow control system typologies (manual, electro-actuated, hydraulically flow- or pressure- compensated), this paper particularly details the design and the test results for a prototype that includes both a manual flow control system and a pressure compensator. Flow vs pressure and volumetric efficiency curves are discussed along with transient (outlet flow fluctuation) features of the VD-EGP.

Heating, Ventilating and Air Conditioning Systems (HVAC) are not only one of the most energy consuming components in buildings but also contribute to green house gas emissions. As a result often environmental design strategies are focused on the performance of these systems. New HVAC technologies such as Geothermal Heat Pump systems have relatively high performance efficiencies when compared to typical systems and therefore could be part of whole-building performance design strategies. In collaboration with the Virginia Tech Corporate Research Center, Inc., this research studies the energy consumption and cost benefits of the Geothermal Heat Pump System that has been integrated and operated in the KnowledgeWorks I and II buildings located on the Virginia Tech campus. The purpose of this thesis is to understand the energy and cost benefits of the Geothermal Heat Pumps System when compared to the conventional package variable air volume (VAV) with hot water coil heating and air-source heat pump systems using computer simulation and statistical models. The quantitative methods of building energy performance and life-cycle cost analyses are applied to evaluate the results of simulation models, the in-situ monitoring data, and the associated documents. This understanding can be expanded to the higher level of architectural systems integration. / Master of Science

Due to the increasing demand, nonclog type sewage pumps are designed and manufactured in large amounts all over the world. However, a methodology on the design of these special duty pumps is not encountered in the literature. Therefore, the manufacturers tend to develop their own empirical methodologies. In this thesis, a nonclog pump is designed and constructed on the basis of suitable approaches of known centrifugal pump design methods. In this frame, a nonclog type submersible pump that is capable of handling solids, up to a diameter of 80 mm is aimed to be designed. The designed pump delivers 100 l/s flow rate against a head of 24 m. The rotational speed of the pump is 1000 rpm. Design procedure and the important points that differ nonclog pump design from standard centrifugal pump designs are given. In addition, hydraulic characteristics of two nonclog pumps, one of which is the pump designed in this study, are investigated by means of computational fluid dynamics (CFD) code. The designed pump is manufactured and tested in Layne Bowler Pump Company Inc. The test result indicates that design point is reached with a deviation in the limits of the related standard. Wire to water total best efficiency obtained by the test is 60%. Close agreement between results of actual test and numerical experimentation performed by CFD code shows that CFD analysis is a quite useful tool in predicting the hydraulic characteristics of nonclog pumps. Moreover, the pump is tested at 750 rpm and the test results are found to be in good agreement with the similitude anaysis results.

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