SPARC is a collagen‐binding, matricellular glycoprotein with diverse roles in tissue remodeling and development. Previous studies have demonstrated that SPARC is required in Drosophila for larval development and maintenance of the fat body, an organ that incorporates endocrine, growth and immune functions. I have characterized effects of loss and knockdown of SPARC in the fat body. Loss‐of‐function analyses revealed remodeling of adipocytes demarcated by cell rounding and dense accumulation of extracellular matrix (ECM) beneath an abnormally thick basement membrane. Remodeling of adipocytes mediated by expression of matrix metalloproteinase 2 (MMP2) was found to cause ECM breakdown and accumulation of hemocytes, indicating endogenous fat body remodeling is mechanistically distinct from that which occurs upon silencing of SPARC. Knockdown of the lysyl hydroxylase, dPlod, in the fat body, revealed abnormal intracellular co‐localization of SPARC with Collagen IV, but not with Laminin. The data indicate SPARC is required for ECM homeostasis during development.

Empirical performance models of fan airflow, primary airflow and power consumption were developed for series and parallel variable air volume fan powered terminal units. An experimental setup and test procedure were created to test the terminal units at typical design pressures and airflows. Each terminal unit observed in this study used an 8 in (20.3 cm) primary air inlet. Two fan motor control methods were considered. The primary control of interest was the electronically commutated motor (ECM) controller. Data collected were compared with previous research regarding silicon rectified control (SCR) units. Generalized models were developed for both series and parallel terminal units. Coefficients for performance models were then compared with comparable SCR controlled units. Non-linear statistical modeling was performed using SPSS software (2008). In addition to airflow and power consumption modeling, power quality was also quantified. Relationships between real power (watts) and apparent power (VA) were presented as well as harmonic frequencies and total harmonic distortion. Power quality was recorded for each ECM controlled terminal unit tested. Additional tests were also made to SCR controlled terminal units used in previous research (Furr 2006). The airflow and power consumption performance models had an R2 equal to 0.990 or greater for every terminal unit tested. An air leakage model was employed to account for leakage in the parallel designed VAV terminal units when the internal fan was turned off. For the leakage model, both ECM and SCR controlled units achieved an R2 greater than or equal to 0.918.

Empirical models of airflow and power consumption were developed for series and parallel variable air volume fan powered terminal units (FPTUs). An experimental setup and test procedure were developed to test the terminal units over typical operating ranges. The terminal units in this study used either an 8 in. (20.32 cm) or a 12 in. (30.48 cm) primary air inlet. All terminal units utilized electronically commutated motor (ECM) controllers. Data collected were compared against previous data collected for silicon controlled rectifier (SCR) units. Generalized models were developed for both series and parallel units, and compared against models developed for SCR units. In addition to the performance modeling, power factor and power quality data were also collected for each terminal unit. The power quality analysis included recording and analyzing harmonic distortion for current, voltage, and power up to the 25th harmonic. The total harmonic distortion (THD) was also recorded and presented. For the series terminal units, models were developed for fan airflow, fan power, and primary airflow. The models for fan airflow all had R2 values above 0.987. The models for fan power all had R2 values above 0.968. The models for primary airflow all had R2 values above 0.895. For the parallel terminal units, models were developed for leakage, fan airflow, fan power, and primary airflow. All of the leakage models had R2 values above 0.826. All of the fan airflow models had R2 values above 0.955. All of the fan power models had R2 values above 0.922. All of the primary airflow models had R2 values above 0.872. The real power THD was below 1.5 percent for both series and parallel FPTUs. The current THD ranged from 84 percent to 172 percent for series FPTUs and from 83 percent to 183 percent for parallel FPTUs. The voltage THD was below 1.4 percent for both series and parallel FPTUs. The performance models developed will help improve the accuracy of building energy simulation programs for heating, ventilation, and air conditioning (HVAC) systems utilizing ECM controlled FPTUs. Increasing the accuracy of these simulations will allow HVAC system designers to better optimize their designs for specific building types in a wide variety of climates.

Semi-empirical models for series fan-powered variable air volume terminal units (FPTUs) were developed based on models of the primary, plenum, fan airflow and the fan power consumption. The experimental setups and test procedures were developed respectively for primary, plenum and fan airflow to test each component of the FPTUs at typical design pressures and airflows. Two sizes of the terminal units from three manufacturers were used in this study. All of the FPTUs were equipped with electronically commutated motors (ECM). Data provided by the models were compared against the data from previous experiments to prove the models’ validity. Regression modeling was performed by using SigmaStat. The model of primary airflow had an R2 above 0.948 for all the terminal units evaluated while the plenum airflow model had an R2 above 0.99. For all the terminal units, the R2 of the fan airflow model was ranged from 0.973 to 0.998. Except for one fan, the fan power consumption model was able to characterize the power performance and had an R2 above 0.986. By combining the airflow and power models, the model for series FPTU was developed. Verification was made to prove the FPTU model’s validity by comparing the measured and predicted data of airflow and power consumption. Correction factors were used in the primary airflow model to compensate for the difference caused by large measurement errors and the system effects. The predicted values were consistent with measurements and no offset was needed in the primary airflow model. Generally, the newly established model was able to describe the airflow performance as well as power consumption of series FPTUs without adding complexity.

In this paper, we examine the relationship between outward FDI and trades across Taiwan Strait during the period 1994Q4 to 2007Q4. We modify the export function, import function and trade function by including outward FDI variable to reflect the effect of bilateral trade between Taiwan and China. Empirical evidences indicate that the coefficient is significantly crucial to the long-run relationship. Due to the failure of a linear error-correction model (ECM) in describing the dynamics of exports and trades, we apply a nonlinear ECM to examine its dynamics and find supporting to the appropriateness of the nonlinear model empirically. Furthermore, outward FDI in percentages of Taiwan GDP was found increasing exports and decreasing imports across Taiwan Strait in percentages of Taiwan GDP. Then, the results also indicate the possibility of a positive effect of the ratio of China GDP to Taiwan GDP on the ratio of import to Taiwan GDP and a negative effect of the ratio of export to Taiwan GDP. It possibly offsets the balance of trade surplus at the same time. Finally, the bilateral trade across Taiwan Strait raises while the FDI ratio is increasing. China becomes the most important trade partner to Taiwan in recent years.

No description available.

No description available.

CLCA2 is a p53-inducible transmembrane protein that is frequently downregulated in breast cancer. CLCA2 is a 943 amino acid type I transmembrane protein that is cleaved near amino acid 700 to produce a diffusible 100kD product. The N-terminus contains a hydrolase-like domain with well-conserved HEXXH zinc binding amino acid motif that was proposed to cleave the precursor auto-proteolytically. We investigate the auto-proteolysis of CLCA2 precursor. Using membrane extracts or purified protein from CLCA2-transfected cells, we show here that CLCA2 cleavage is catalyzed by zinc and inhibited by metal chelator EDTA. Moreover, an E165Q mutation in the metal binding site abolished processing without affecting stability or trafficking. The mutant could be cleaved by co-transfected wild type CLCA2, showing that the mutation had not caused an un-cleavable conformation and suggesting that it occurs in trans. Wild type CLCA2 was able to cleave CLCA2 E165Q mutant in vitro only after denaturation and renaturation, suggesting that a conformational shift is required for cleavage. The efficiency of cleavage increased steeply with increasing concentration of precursor, consistent with trans proteolysis but not cis or cleavage by another agent. Accordingly, CLCA2 molecules bearing different epitope tags formed a stable complex that could be co-immunoprecipitated. Cleavage appears to be specific within isoforms; CLCA1 was unable to neither cleave CLCA2 nor form a stable complex with it. Furthermore, cleavage causes a conformational shift: an N-terminal antibody that immunoprecipitates the precursor fails to precipitate the N-terminal product unless it is first denatured with ionic detergent. We found that cleavage is enhanced by p53 induction due to DNA damage, implying that the cleavage has functional consequences for stress response. Moreover, we found that HEK and MCF10A cells expressing the E165Q mutant had a higher proliferation rate than cells expressing wild type CLCA2, suggesting that the metalloprotease activity contributes to the anti-proliferative effect of CLCA2. Physiologically, CLCA2 plays an essential role in epithelial differentiation. It is induced during epithelial differentiation in immortalized human mammary epithelial cells (HMEC), and its knockdown causes epithelial to mesenchymal transition (EMT). To determine how CLCA2 promotes epithelial differentiation, we searched for interactors using membrane dihybrid screening. We discovered a strong interaction with Epithelial V-like Antigen 1 (EVA1) and confirmed by co-immunoprecipitation. Like CLCA2, EVA1 is a type I transmembrane protein that is regulated by p53 family. EVA1 resembles tight junction proteins called Junctional Adhesion Molecules (JAMs) by structure but we found by confocal analysis that EVA1 is localized the lateral interface at cell-cell junctions. Analysis of transcriptional profiles revealed that EVA1 is frequently downregulated in breast tumors and breast cancer cell lines, especially those of mesenchymal phenotype, and upregulated during epithelial differentiation. Like CLCA2, knockdown of EVA1 resulted in rapid EMT in immortalized HMEC. The interacting domains were delimited by deletion analysis, revealing that both the proteins interact via their transmembrane segments (TMS). The interaction was specific, as other transmembrane proteins did not interact with CLCA2 or EVA1. We also found that CLCA2 binds to ZO-1 and beta-catenin at its c-terminus but EVA1 does not. Interestingly, we found that EVA1 does interact with ZO-1 in the presence of CLCA2, indicating that these three form a complex at the cell-cell junctions that allows stabilization of belt-like adherens junctions (AJ). On the other hand CLCA2 may also stabilize adherens junctions by sequestering beta-catenin at the cell-cell junctions. These results indicate that CLCA2 plays a key role in maintaining epithelial differentiation via multiple ways. Either by binding to beta-catenin or forming a complex with EVA1 and ZO-1, it plays a pivotal role in maintaining epithelial differentiation. This explains the downregulation of both CLCA2 and EVA1 during tumor progression.

Implantable cardiovascular biomaterials have been widely applied in multiple cardiovascular disorders such as coronary artery disease, heart failure, and abdominal aortic aneurysms. However the failure modes of cardiovascular biomaterials are not uncommon, which is mainly due to the complications on blood-contacting surfaces such as thrombosis, calcification, and inflammation. Endothelium locates the inner surface of vessel lumen and is a critical regulator of vascular homeostasis. However, a readily available functional autologous source of endothelium has been hard to achieve. Human blood outgrowth endothelial cells (BOECs), cultured from peripheral blood mononuclear cells are proliferative and express endothelial protein profiles and as such are a very promising novel cell source for cardiovascular biomaterials coating. Endothelial nitric oxide synthase (eNOS) is an important regulator of vascular homeostasis and loss of eNOS activity is a hallmark of endothelial dysfunction. My data demonstrated that BOECs express markedly lower eNOS protein, mRNA as well as activity levels when compared to mature endothelial cells (ECs). My first project was to use transient transfection methods along with minicircle DNA to enhance eNOS expression levels in BOECs. Two promoters were tested in BOECs, the CMV promoter (pMini-CMV-eNOS) and the EF1α promoter (pMini-EF1α-eNOS). Transfection with pMini-CMV-eNOS achieved 24.8 ± 5.1 times more eNOS expression when compared to null transfected cells at 24 hours, a marked improvement over that achieved with conventional PVAX plasmid (10.2 ± 4.7 fold increase) or pMini-EF1α-eNOS (8.2 ± 1.2 fold increase both compared to null transfected control). pMini-CMV-eNOS mediated overexpression improved cell migration and network formation. When cultured on Osteopontin (OPN) coated surfaces, transient transfection with plasmid eNOS in BOECs can markedly enhance cell spreading and adhesion to ECM modified surfaces. These results suggest that eNOS expression in BOECs is suboptimal and BOECs may be functionally improved by techniques to enhance expression of this critical homeostatic regulator. Extracellular matrix (ECM) proteins have been shown to negatively regulate eNOS expression and NO production in mature ECs. In addition, the deposition of Col IV and Col I in BOECs is higher compared to that in mature ECs. Thus, I have proposed that the lower eNOS expression/activity in BOECs compared to mature ECs is due to higher ECM deposition. When grown on fibronectin, type I collagen, type IV collagen and laminin, significantly decreased eNOS protein in HUVECs were found compared to cells on polystyrene. Interestingly, when cultured on polystyrene, BOECs express significantly more extracellular matrix (ECM) proteins especially type I collagen compared to mature ECs. Blocking collagen synthesis significantly enhanced eNOS expression in BOECs (1.77 ± 0.41 fold increase). My results suggest that the regulation of eNOS in BOECs and mature ECs is similar and the reduced eNOS level in BOECs may be due to their increased collagen production. ECM proteins regulate intracellular signaling transduction primarily through integrin signaling associated with focal adhesion complexes. I have proposed that ECM proteins regulation on eNOS signaling in BOECs and mature ECs is through integrin and integrin-associated proteins. Matrix mediated eNOS downregulation was blocked by β1 integrin siRNA and focal adhesion kinase siRNA transfection in both BOECs and HUVECs. In addition, inhibitors of actin polymerization (e.g. ROCK inhibitors and cytochalasin D) block the effect of ECM on eNOS signaling. Taken together, my results suggest that ECM proteins regulate eNOS expression via a β1 integrin/FAK/actin polymerization dependent mechanism.

En el presente trabajo se formula la propuesta de un Sistema de Información para la Gestión de Expedientes de Crédito en una entidad del sector microfinanzas del Perú. La propuesta se basa en un enfoque de eficiencia basado en el crecimiento del número de créditos otorgados y la cantidad de años de funcionamiento que tiene la entidad, han generado que tanto el número de expedientes de crédito a administrar y el volumen de espacio físico requerido para su almacenamiento, se conviertan en factores críticos que actualmente generan incidencias colaterales a los principales procesos de negocio como son el otorgamiento y la recuperación de créditos. Si bien el expediente de crédito no es un objetivo en sí de los procesos de negocio, su utilización esta normada por la Superintendencia de Banca Seguros y AFP por lo tanto existe también un factor normativo que la entidad debe cumplir; específicamente los documentos obligatorios a incluir en el expediente de créditos y el tiempo de conservación del expediente de crédito el cual por requerimientos normativos es de diez años. Ante este escenario el presente trabajo propone un sistema de información basado en un expediente de crédito digital, que tiene como principal factor el cambio de formato del expediente de crédito, para pasar de un expediente físico a un expediente digital, para ello se apoya en tres componentes principales; los sistemas de contenidos empresariales, la masificación de los servicios de digitalización y el entorno normativo peruano que permite el uso de tecnologías para el tratamiento de documentos digitales con valor legal. / Tesis