Evaluation of the cytotoxic and cytostatic activities of medicinal plants used by Peruvian healers against cancer-related symptoms

Twelve plants used medicinally in Callejon de Huaylas, Department of Ancash, northeastern Peru were selected and screened in vitro for cytotoxic and cytostatic activities. Traditional preparations, aqueous extracts and organic extracts (methanol:dimethyl chloride) were tested against murine leukemia P388 cells using flow cytometry. Seventy-five percent or more of the traditional and aqueous extracts were cytostatic at concentrations of 1mg/ml. For organic extracts, cytostatic activity ranged from 8.3% (at 6.25 μg/ml) to 58.3% (at 100 μg/ml). Quinchamalium procumbens, Ophryosporus chilca and Baccharis genistelloides showed strong activity. Extracts of Brachyotum rostratum, Monnina salicifolia, and Orthrosanthus chimboracensis were particularly interesting, since they were cytostatic but not cytotoxic at concentrations of 0.5 mg/ml. These Andean plants merit further analysis. The high percentage of activity found among the traditional preparations suggests that the traditional medical knowledge of Callejon de Huaylas healers deserves respect and merits further research. ^

Impact of Late Holocene climate variability and anthropogenic activities on Biscayne Bay (Florida, U.S.A.): Evidence from diatoms

Shallow marine ecosystems are experiencing significant environmental alterations as a result of changing climate and increasing human activities along coasts. Intensive urbanization of the southeast Florida coast and intensification of climate change over the last few centuries changed the character of coastal ecosystems in the semi-enclosed Biscayne Bay, Florida. In order to develop management policies for the Bay, it is vital to obtain reliable scientific evidence of past ecological conditions. The long-term records of subfossil diatoms obtained from No Name Bank and Featherbed Bank in the Central Biscayne Bay, and from the Card Sound Bank in the neighboring Card Sound, were used to study the magnitude of the environmental change caused by climate variability and water management over the last ~ 600 yr. Analyses of these records revealed that the major shifts in the diatom assemblage structures at No Name Bank occurred in 1956, at Featherbed Bank in 1966, and at Card Sound Bank in 1957. Smaller magnitude shifts were also recorded at Featherbed Bank in 1893, 1942, 1974 and 1983. Most of these changes coincided with severe drought periods that developed during the cold phases of El Niño Southern Oscillation (ENSO), Atlantic Multidecadal Oscillation (AMO) and Pacific Decadal Oscillation (PDO), or when AMO was in warm phase and PDO was in the cold phase. Only the 1983 change coincided with an unusually wet period that developed during the warm phases of ENSO and PDO. Quantitative reconstructions of salinity using the weighted averaging partial least squares (WA-PLS) diatom-based salinity model revealed a gradual increase in salinity at the three coring locations over the last ~ 600 yr, which was primarily caused by continuously rising sea level and in the last several decades also by the reduction of the amount of freshwater inflow from the mainland. Concentration of sediment total nitrogen (TN), total phosphorus (TP) and total organic carbon (TOC) increased in the second half of the 20th century, which coincided with the construction of canals, landfills, marinas and water treatment plants along the western margin of Biscayne Bay. Increased magnitude and rate of the diatom assemblage restructuring in the mid- and late-1900s, suggest that large environmental changes are occurring more rapidly now than in the past.

Interdependencies in corporate development: Relationship between strategic alliance and acquisition activities

A substantial amount of work in the field of strategic management has attempted to explain the antecedents and outcomes of organizational learning. Though multinational corporations simultaneously engage in various types of tasks, activities, and strategies on a regular basis, the transfer of organizational learning in a multi-task context has largely remained under-explored in the literature. To inform our understanding in this area, this dissertation aimed at synthesizing findings from two parallel research streams of corporate development activities: strategic alliances and acquisitions. Structured in the form of two empirical studies, this dissertation examines: 1) the strategic outcomes of alliance experience of previously allying partners in terms of subsequent acquisition attempts, and 2) the performance implications of prior alliance experience for acquisitions. The first study draws on the relational view of inter-organizational governance to explain how various deal-specific and dyadic characteristics of a partnership relate to partnering firms' post-alliance acquisition attempts. This model theorizes on a variety of relational mechanisms to build a cohesive theory of inter-organizational exchanges in a multi-task setting where strategic alliances ultimately lead to a firm's decision to commit further resources. The second study applies organizational learning theory, and specifically examines whether frequency, recency, and relatedness of different dimensions of prior alliances, beyond the dyad-level experience, relate to an acquirer's superior post-acquisition performance. The hypotheses of the studies are tested using logistic and ordinary least square regressions, respectively. Results analyzed from a sample of cross-border alliance and acquisition deals attempted (for study I) and/or completed (for study II) during the period of 1991 to 2011 generally support the theory that relational exchange determines acquiring firms' post alliance acquisition behavior and that organizational routines and learning from prior alliances influence a future acquirer's financial performance. Overall, the empirical findings support our overarching theory of interdependency, and confirm the transfer effect of learning across these alternate, yet related corporate strategies of alliance and acquisition.^

Site specific growth of metal catalyzed silica nanowires for biological and chemical sensing

In this research the integration of nanostructures and micro-scale devices was investigated using silica nanowires to develop a simple yet robust nanomanufacturing technique for improving the detection parameters of chemical and biological sensors. This has been achieved with the use of a dielectric barrier layer, to restrict nanowire growth to site-specific locations which has removed the need for post growth processing, by making it possible to place nanostructures on pre-pattern substrates. Nanowires were synthesized using the Vapor-Liquid-Solid growth method. Process parameters (temperature and time) and manufacturing aspects (structural integrity and biocompatibility) were investigated. Silica nanowires were observed experimentally to determine how their physical and chemical properties could be tuned for integration into existing sensing structures. Growth kinetic experiments performed using gold and palladium catalysts at 1050°C for 60 minutes in an open-tube furnace yielded dense and consistent silica nanowire growth. This consistent growth led to the development of growth model fitting, through use of the Maximum Likelihood Estimation (MLE) and Bayesian hierarchical modeling. Transmission electron microscopy studies revealed the nanowires to be amorphous and X-ray diffraction confirmed the composition to be SiO2 . Silica nanowires were monitored in epithelial breast cancer media using Impedance spectroscopy, to test biocompatibility, due to potential in vivo use as a diagnostic aid. It was found that palladium catalyzed silica nanowires were toxic to breast cancer cells, however, nanowires were inert at 1μg/mL concentrations. Additionally a method for direct nanowire integration was developed that allowed for silica nanowires to be grown directly into interdigitated sensing structures. This technique eliminates the need for physical nanowire transfer thus preserving nanowire structure and performance integrity and further reduces fabrication cost. Successful nanowire integration was physically verified using Scanning electron microscopy and confirmed electrically using Electrochemical Impedance Spectroscopy of immobilized Prostate Specific Antigens (PSA). The experiments performed above serve as a guideline to addressing the metallurgic challenges in nanoscale integration of materials with varying composition and to understanding the effects of nanomaterials on biological structures that come in contact with the human body.

Impact of Late Holocene Climate Variability and Anthropogenic Activities on Biscayne Bay (Florida, U.S.A.): Evidence From Diatoms

Shallow marine ecosystems are experiencing significant environmental alterations as a result of changing climate and increasing human activities along coasts. Intensive urbanization of the southeast Florida coast and intensification of climate change over the last few centuries changed the character of coastal ecosystems in the semi-enclosed Biscayne Bay, Florida. In order to develop management policies for the Bay, it is vital to obtain reliable scientific evidence of past ecological conditions. The long-term records of subfossil diatoms obtained from No Name Bank and Featherbed Bank in the Central Biscayne Bay, and from the Card Sound Bank in the neighboring Card Sound, were used to study the magnitude of the environmental change caused by climate variability and water management over the last ~ 600 yr. Analyses of these records revealed that the major shifts in the diatom assemblage structures at No Name Bank occurred in 1956, at Featherbed Bank in 1966, and at Card Sound Bank in 1957. Smaller magnitude shifts were also recorded at Featherbed Bank in 1893, 1942, 1974 and 1983. Most of these changes coincided with severe drought periods that developed during the cold phases of El Niño Southern Oscillation (ENSO), Atlantic Multidecadal Oscillation (AMO) and Pacific Decadal Oscillation (PDO), or when AMO was in warm phase and PDO was in the cold phase. Only the 1983 change coincided with an unusually wet period that developed during the warm phases of ENSO and PDO. Quantitative reconstructions of salinity using the weighted averaging partial least squares (WA-PLS) diatom-based salinity model revealed a gradual increase in salinity at the three coring locations over the last ~ 600 yr, which was primarily caused by continuously rising sea level and in the last several decades also by the reduction of the amount of freshwater inflow from the mainland. Concentration of sediment total nitrogen (TN), total phosphorus (TP) and total organic carbon (TOC) increased in the second half of the 20th century, which coincided with the construction of canals, landfills, marinas and water treatment plants along the western margin of Biscayne Bay. Increased magnitude and rate of the diatom assemblage restructuring in the mid- and late-1900s, suggest that large environmental changes are occurring more rapidly now than in the past.

Interdependencies in Corporate Development: Relationship between Strategic Alliance and Acquisition Activities

A substantial amount of work in the field of strategic management has attempted to explain the antecedents and outcomes of organizational learning. Though multinational corporations simultaneously engage in various types of tasks, activities, and strategies on a regular basis, the transfer of organizational learning in a multi-task context has largely remained under-explored in the literature. To inform our understanding in this area, this dissertation aimed at synthesizing findings from two parallel research streams of corporate development activities: strategic alliances and acquisitions. Structured in the form of two empirical studies, this dissertation examines: 1) the strategic outcomes of alliance experience of previously allying partners in terms of subsequent acquisition attempts, and 2) the performance implications of prior alliance experience for acquisitions. The first study draws on the relational view of inter-organizational governance to explain how various deal-specific and dyadic characteristics of a partnership relate to partnering firms’ post-alliance acquisition attempts. This model theorizes on a variety of relational mechanisms to build a cohesive theory of inter-organizational exchanges in a multi-task setting where strategic alliances ultimately lead to a firm’s decision to commit further resources. The second study applies organizational learning theory, and specifically examines whether frequency, recency, and relatedness of different dimensions of prior alliances, beyond the dyad-level experience, relate to an acquirer’s superior post-acquisition performance. The hypotheses of the studies are tested using logistic and ordinary least square regressions, respectively. Results analyzed from a sample of cross-border alliance and acquisition deals attempted (for study I) and/or completed (for study II) during the period of 1991 to 2011 generally support the theory that relational exchange determines acquiring firms’ post alliance acquisition behavior and that organizational routines and learning from prior alliances influence a future acquirer’s financial performance. Overall, the empirical findings support our overarching theory of interdependency, and confirm the transfer effect of learning across these alternate, yet related corporate strategies of alliance and acquisition.

Site Specifc Growth of Metal Catalyzed Silica Nanowires for Biological and Chemical Sensing

In this research the integration of nanostructures and micro-scale devices was investigated using silica nanowires to develop a simple yet robust nanomanufacturing technique for improving the detection parameters of chemical and biological sensors. This has been achieved with the use of a dielectric barrier layer, to restrict nanowire growth to site-specific locations which has removed the need for post growth processing, by making it possible to place nanostructures on pre-pattern substrates. Nanowires were synthesized using the Vapor-Liquid-Solid growth method. Process parameters (temperature and time) and manufacturing aspects (structural integrity and biocompatibility) were investigated. Silica nanowires were observed experimentally to determine how their physical and chemical properties could be tuned for integration into existing sensing structures. Growth kinetic experiments performed using gold and palladium catalysts at 1050 ˚C for 60 minutes in an open-tube furnace yielded dense and consistent silica nanowire growth. This consistent growth led to the development of growth model fitting, through use of the Maximum Likelihood Estimation (MLE) and Bayesian hierarchical modeling. Transmission electron microscopy studies revealed the nanowires to be amorphous and X-ray diffraction confirmed the composition to be SiO2 . Silica nanowires were monitored in epithelial breast cancer media using Impedance spectroscopy, to test biocompatibility, due to potential in vivo use as a diagnostic aid. It was found that palladium catalyzed silica nanowires were toxic to breast cancer cells, however, nanowires were inert at 1µg/mL concentrations. Additionally a method for direct nanowire integration was developed that allowed for silica nanowires to be grown directly into interdigitated sensing structures. This technique eliminates the need for physical nanowire transfer thus preserving nanowire structure and performance integrity and further reduces fabrication cost. Successful nanowire integration was physically verified using Scanning electron microscopy and confirmed electrically using Electrochemical Impedance Spectroscopy of immobilized Prostate Specific Antigens (PSA). The experiments performed above serve as a guideline to addressing the metallurgic challenges in nanoscale integration of materials with varying composition and to understanding the effects of nanomaterials on biological structures that come in contact with the human body.

Localized surface plasmon resonance biosensors for real-time biomolecular binding study

Surface Plasmon Resonance (SPR) and localized surface plasmon resonance (LSPR) biosensors have brought a revolutionary change to in vitro study of biological and biochemical processes due to its ability to measure extremely small changes in surface refractive index (RI), binding equilibrium and kinetics. Strategies based on LSPR have been employed to enhance the sensitivity for a variety of applications, such as diagnosis of diseases, environmental analysis, food safety, and chemical threat detection. In LSPR spectroscopy, absorption and scattering of light are greatly enhanced at frequencies that excite the LSPR, resulting in a characteristic extinction spectrum that depends on the RI of the surrounding medium. Compositional and conformational change within the surrounding medium near the sensing surface could therefore be detected as shifts in the extinction spectrum. This dissertation specifically focuses on the development and evaluation of highly sensitive LSPR biosensors for in situ study of biomolecular binding process by incorporating nanotechnology. Compared to traditional methods for biomolecular binding studies, LSPR-based biosensors offer real-time, label free detection. First, we modified the gold sensing surface of LSPR-based biosensors using nanomaterials such as gold nanoparticles (AuNPs) and polymer to enhance surface absorption and sensitivity. The performance of this type of biosensors was evaluated on the application of small heavy metal molecule binding affinity study. This biosensor exhibited ∼7 fold sensitivity enhancement and binding kinetics measurement capability comparing to traditional biosensors. Second, a miniaturized cell culture system was integrated into the LSPR-based biosensor system for the purpose of real-time biomarker signaling pathway studies and drug efficacy studies with living cells. To the best of our knowledge, this is the first LSPR-based sensing platform with the capability of living cell studies. We demonstrated the living cell measurement ability by studying the VEGF signaling pathway in living SKOV-3 cells. Results have shown that the VEGF secretion level from SKOV-3 cells is 0.0137 ± 0.0012 pg per cell. Moreover, we have demonstrated bevacizumab drug regulation to the VEGF signaling pathway using this biosensor. This sensing platform could potentially help studying biomolecular binding kinetics which elucidates the underlying mechanisms of biotransportation and drug delivery.

Localized Surface Plasmon Resonance Biosensors for Real-Time Biomolecular Binding Study

Surface Plasmon Resonance (SPR) and localized surface plasmon resonance (LSPR) biosensors have brought a revolutionary change to in vitro study of biological and biochemical processes due to its ability to measure extremely small changes in surface refractive index (RI), binding equilibrium and kinetics. Strategies based on LSPR have been employed to enhance the sensitivity for a variety of applications, such as diagnosis of diseases, environmental analysis, food safety, and chemical threat detection. In LSPR spectroscopy, absorption and scattering of light are greatly enhanced at frequencies that excite the LSPR, resulting in a characteristic extinction spectrum that depends on the RI of the surrounding medium. Compositional and conformational change within the surrounding medium near the sensing surface could therefore be detected as shifts in the extinction spectrum. This dissertation specifically focuses on the development and evaluation of highly sensitive LSPR biosensors for in situ study of biomolecular binding process by incorporating nanotechnology. Compared to traditional methods for biomolecular binding studies, LSPR-based biosensors offer real-time, label free detection. First, we modified the gold sensing surface of LSPR-based biosensors using nanomaterials such as gold nanoparticles (AuNPs) and polymer to enhance surface absorption and sensitivity. The performance of this type of biosensors was evaluated on the application of small heavy metal molecule binding affinity study. This biosensor exhibited ~7 fold sensitivity enhancement and binding kinetics measurement capability comparing to traditional biosensors. Second, a miniaturized cell culture system was integrated into the LSPR-based biosensor system for the purpose of real-time biomarker signaling pathway studies and drug efficacy studies with living cells. To the best of our knowledge, this is the first LSPR-based sensing platform with the capability of living cell studies. We demonstrated the living cell measurement ability by studying the VEGF signaling pathway in living SKOV-3 cells. Results have shown that the VEGF secretion level from SKOV-3 cells is 0.0137 ± 0.0012 pg per cell. Moreover, we have demonstrated bevacizumab drug regulation to the VEGF signaling pathway using this biosensor. This sensing platform could potentially help studying biomolecular binding kinetics which elucidates the underlying mechanisms of biotransportation and drug delivery.