Studying Key Amino Acids in the Function of Ras Interference 1 (Rinl) SH2 and Vps9 Domains

Receptor mediated endocytosis effectively removes the "ears" with which a cell would "hear" a signal conveyed by extracellular signaling molecules, but does not necessarily block the signaling pathway in which the endocytosed receptor participates. In the process of signal attenuation, this newly formed vesicle is fused with a phagosome and the receptor molecules are degraded. Receptor mediated endocytosis as a way to attenuate epidermal growth factor (EGF) and insulin signaling will be the focus here. Ras Interference 1 (Rin 1) is a multifunctional protein involved in intracellular membrane trafficking and receptor mediated endocytosis through its Rab5 Guanine Exchange Factor and SH2 domains. The goal of this investigation is to determine the role of key amino acids involved in the interaction of Rinl with Epidermal Growth Factor Receptor and Rab5. To elucidate this role, a number of point mutations have been created and the effects of each mutation on Rin 1 function will be investigated. Key amino acids in the SH2 and Vps9 Domain were identified and effects of mutations on rate of endocytosis were observed.

Recurrent Tibial Tunnel Cyst Formation Following Anterior Cruciate Ligament Reconstruction and Interference Screw Removal

A unique case of a collegiate athlete who suffered an anterior cruciate ligament injury leading to the formation of a synovial cyst is described. The cyst, localized over the tibial tunnel, resulted from irritation caused by the removal of interference screws.

Peak -to -average power ratio reduced parallel interference cancellation Multicarrier-Code Division Multiple Access system with anti -interference property

Orthogonal Frequency-Division Multiplexing (OFDM) has been proved to be a promising technology that enables the transmission of higher data rate. Multicarrier Code-Division Multiple Access (MC-CDMA) is a transmission technique which combines the advantages of both OFDM and Code-Division Multiplexing Access (CDMA), so as to allow high transmission rates over severe time-dispersive multi-path channels without the need of a complex receiver implementation. Also MC-CDMA exploits frequency diversity via the different subcarriers, and therefore allows the high code rates systems to achieve good Bit Error Rate (BER) performances. Furthermore, the spreading in the frequency domain makes the time synchronization requirement much lower than traditional direct sequence CDMA schemes. There are still some problems when we use MC-CDMA. One is the high Peak-to-Average Power Ratio (PAPR) of the transmit signal. High PAPR leads to nonlinear distortion of the amplifier and results in inter-carrier self-interference plus out-of-band radiation. On the other hand, suppressing the Multiple Access Interference (MAI) is another crucial problem in the MC-CDMA system. Imperfect cross-correlation characteristics of the spreading codes and the multipath fading destroy the orthogonality among the users, and then cause MAI, which produces serious BER degradation in the system. Moreover, in uplink system the received signals at a base station are always asynchronous. This also destroys the orthogonality among the users, and hence, generates MAI which degrades the system performance. Besides those two problems, the interference should always be considered seriously for any communication system. In this dissertation, we design a novel MC-CDMA system, which has low PAPR and mitigated MAI. The new Semi-blind channel estimation and multi-user data detection based on Parallel Interference Cancellation (PIC) have been applied in the system. The Low Density Parity Codes (LDPC) has also been introduced into the system to improve the performance. Different interference models are analyzed in multi-carrier communication systems and then the effective interference suppression for MC-CDMA systems is employed in this dissertation. The experimental results indicate that our system not only significantly reduces the PAPR and MAI but also effectively suppresses the outside interference with low complexity. Finally, we present a practical cognitive application of the proposed system over the software defined radio platform.

Novel insights into the mechanisms of regulation of tyrosine kinase receptors by Ras Interference 1

Receptor-tyrosine kinases (RTKs) are membrane bound receptors characterized by their intrinsic kinase activity. RTK activities play an essential role in several human diseases, including cancer, diabetes and neurodegenerative diseases. RTK activities have been regulated by the expression or silencing of several genes as well as by the utilization of small molecules. Ras Interference 1 (Rin1) is a multifunctional protein that becomes associated with activated RTKs upon ligand stimulation. Rin1 plays a key role in receptor internalization and in signal transduction via activation of Rab5 and association with active form of Ras. This study has two main objectives: (1) It determines the role of Rin1 in the regulation of several RTKs focusing on insulin receptor. This was accomplished by studying the Rin1-insulin receptor interaction using a variety of biochemical and morphological assays. This study shows a novel interaction between the insulin receptor and Rin1 through the Vps9 domain. Two more RTKs (epidermal growth factor receptor and nerve growth factor receptor) also interacted with the SH2 domain of Rin1. The effect of the Rin1-RTK interaction on the activation of both Rab5 and Ras was also studied during receptor internalization and intracellular signaling. Finally, the role of Rin1 was examined in two differentiation processes (adipogenesis and neurogenesis). Rin1 showed a strong inhibitory effect on 3T3-L1 preadipocyte differentiation but it seems to show a modest effect in PC12 neurite outgrowth. These data indicate a selective function and specific interaction of Rin1 toward RTKs. (2) It examines the role of the small molecule Dehydroleucodine (DhL) on several key signaling molecules during adipogenesis. This was accomplished by studying the differentiation of 3T3-L1 preadipocytes exposed to different concentrations of DhL in different days of the adipocyte formation process. The results indicate that DhL selectively blocked adipocyte formation, as well as the expression of PPARγ, and C/EBP&agr;. However, DhL treatment did not affect Rin1 or Rab5 expression and their activities. Taken together, the data indicate a potential molecular mechanism by which proteins or small molecules regulate selective and specific RTK intracellular membrane trafficking and signaling during cell growth and differentiation in normal and pathological conditions.

Peak-to-Average Power Ratio Reduced Parallel Interference Cancellation Multicarrier-Code Division Multiple Access System with Anti-Interference Property

Orthogonal Frequency-Division Multiplexing (OFDM) has been proved to be a promising technology that enables the transmission of higher data rate. Multicarrier Code-Division Multiple Access (MC-CDMA) is a transmission technique which combines the advantages of both OFDM and Code-Division Multiplexing Access (CDMA), so as to allow high transmission rates over severe time-dispersive multi-path channels without the need of a complex receiver implementation. Also MC-CDMA exploits frequency diversity via the different subcarriers, and therefore allows the high code rates systems to achieve good Bit Error Rate (BER) performances. Furthermore, the spreading in the frequency domain makes the time synchronization requirement much lower than traditional direct sequence CDMA schemes. There are still some problems when we use MC-CDMA. One is the high Peak-to-Average Power Ratio (PAPR) of the transmit signal. High PAPR leads to nonlinear distortion of the amplifier and results in inter-carrier self-interference plus out-of-band radiation. On the other hand, suppressing the Multiple Access Interference (MAI) is another crucial problem in the MC-CDMA system. Imperfect cross-correlation characteristics of the spreading codes and the multipath fading destroy the orthogonality among the users, and then cause MAI, which produces serious BER degradation in the system. Moreover, in uplink system the received signals at a base station are always asynchronous. This also destroys the orthogonality among the users, and hence, generates MAI which degrades the system performance. Besides those two problems, the interference should always be considered seriously for any communication system. In this dissertation, we design a novel MC-CDMA system, which has low PAPR and mitigated MAI. The new Semi-blind channel estimation and multi-user data detection based on Parallel Interference Cancellation (PIC) have been applied in the system. The Low Density Parity Codes (LDPC) has also been introduced into the system to improve the performance. Different interference models are analyzed in multi-carrier communication systems and then the effective interference suppression for MC-CDMA systems is employed in this dissertation. The experimental results indicate that our system not only significantly reduces the PAPR and MAI but also effectively suppresses the outside interference with low complexity. Finally, we present a practical cognitive application of the proposed system over the software defined radio platform.