Multifunctional nanoparticles in cancer: In vitro characterization, in vivo distribution, and cellular response after laser-NIR dye-induced heating

A novel biocompatible and biodegradable polymer, termed poly(Glycerol malate co-dodecanedioate) (PGMD), was prepared by thermal condensation method and used for fabrication of nanoparticles (NPs). PGMD NPs were prepared using the single oil emulsion technique and loaded with an imaging/hyperthermia agent (IR820) and a chemotherapeutic agent (doxorubicin, DOX). The size of the void PGMD NPs, IR820-PGMD NPs and DOX-IR820-PGMD NPs were approximately 90 nm, 110 nm, and 125 nm respectively. An acidic environment (pH=5.0) induced higher DOX and IR820 release compared to pH=7.4. DOX release was also enhanced by exposure to laser, which increased the temperature to 42°C. Cytotoxicity of DOX-IR820-PGMD NPs was comparable in MES-SA but was higher in Dx5 cells compared to free DOX plus IR820 (p<0.05). The combination of hyperthermia (HT) and chemotherapy improved cytotoxicity in both cell lines. We also explored the cellular response after rapid, short-term and low thermal dose (laser/Dye/NP) induced-heating, and compared it to slow, long-term and high thermal dose cell incubator heating by investigating the reactive oxygen species (ROS) level, hypoxia-inducible factor-1&agr; (HIF-1&agr;) and vascular endothelial growth factor (VEGF) expression. The cytotoxicity of IR820-PGMD NPs after laser/Dye/NP HT resulted in higher cancer cell killing compared to incubator HT. ROS level, HIF-1&agr; and VEGF expression were elevated under incubator HT, while maintained at the baseline level under the laser/Dye/NP HT. In vivo mouse studies showed that NP formulation significantly improved the plasma half-life of IR820 after tail vein injection. Significant lower IR820 content was observed in kidney in DOX-IR820-PGMD NP treatment as compared to free IR820 treatment in our biodistribution studies (p<0.05). In conclusion, both IR820-PGMD NPs and DOX-IR820-PGMD NPs were successfully developed and used for both imaging and therapeutic purposes. Rapid and short-term laser/Dye/NP HT, with a low thermal dose, did not up-regulate HIF-1&agr; and VEGF expression, whereas slow and long-term incubator HT, with a high thermal dose, can enhance expression of both HIF-1&agr; and VEGF.^

Changes in Caribbean paleoproductivity, diversity and benthic foraminiferal test size caused by the Neogene closing of the tropical Atlantic-Pacific ocean gateway

The purpose of this study was to test 3 hypotheses: (a) that late Miocene to early Pliocene constriction and complete closure of the Central American Seaway (CAS), connecting tropical Atlantic and East Equatorial Pacific (EEP) oceans, caused decreased productivity in the Caribbean, due to reduced coastal upwelling and an end to the connection with high-productivity Pacific waters, (b) reduced paleoproductivity resulted in decreased diversity in the Caribbean and, (c) this decreased availability of food (reduced paleoproductivity) was responsible for larger mean test size in the three most common benthic foraminiferal species Epistominella exigua, Oridorsalis umbonatus and Globocassidulina subglobosa. ^ These are tested by applying correlation analysis to 7 groups of paleoceanographic proxies, 3 indices of diversity measures and mean test size data from the Caribbean Ocean Drilling Project Site 999, to 47 core samples for the interval between 8.3-2.5 Ma. Results are compared with published Caribbean and Pacific deep-sea records. ^ The Caribbean, between 8.3-7.9 Ma, experienced reduced current velocity and lower ventilation of bottom waters. Thereafter, until 4.2 Ma, the seasonality of phytodetritus input increased and ventilation further reduced. From 4.2-2.5 Ma, paleoproductivity decreased, current velocity reduced, ventilation improved, and the seasonality of phytodetrital input decreased dramatically. The benthic foraminiferal diversity followed the same trend as paleoproductivity. Individual correlation analysis between mean test size of benthic foraminiferal species Epistominella exigua, Oridorsalis umbonatus and Globocassidulina subglobosa and paleoceanographic proxies yielded a positive and significant relationship with paleoproductivity. However, a combined datasets of all 3 species yielded a negative and significant relationship with species abundance. ^ Thus, the study concludes that (a) the gradual closure of the CAS led Caribbean diversity and paleoproductivity to decrease abruptly at 7.9 Ma, when the nutrient-rich Pacific deep waters were cut off, and then, again with the complete closure of the seaway at 4.2 Ma, (b) diversity and paleoproductivity are positively correlated in the Caribbean and (c) that the availability of food is an overriding factor that influences mean test size; lower availability of food and decreased abundance leads to larger test size. ^

Rio and the Reds: The Comando Vermelho, Organized Crime and Brazil’s Economic Ascent [Student’s Paper Series]

Brazil’s growing status as a potential world power cannot obscure the characteristics of its other reality: that of a country with vast inequalities and high crime rates. The Comando Vermelho, the most prominent organized crime syndicate in Rio de Janeiro, besieges the beauty and charm that attracts tourists to this city. The CV arose not only as a product of the political dictatorship of the seventies, but also of the disenfranchised urban poor crammed into Rio’s favela slums. Today, the CV presents a powerful challenge to the State’s control of parts of Rio territory. As Brazil’s soft power projection grows, it is seriously challenged by its capacity to eliminate organized crime. Economic growth is not sufficient to destroy a deeply embedded organization like the CV. In fact, Brazil’s success may yet further retrench the CV’s activities. Culpability for organized crime cannot be merely limited to the gangs, but must also be shared among the willing consumers, among whom can be found educated and elite members of society, as well as the impoverished and desperate. The Brazilian government needs a top-down response addressing the schism between rich and poor. However, Brazil’s citizens must also take responsibility and forge a bottom-up response to the drug- and corruption-riddled elements of its most respected members of society. Brazil must target reform across public health, housing, education and above all, law enforcement. Without such changes, Brazil will remain a two-track democracy. Rio’s wealthy will still be able to revel in the city’s beauty albeit from behind armored cars and fortified mansions, while the city’s poor will yield – either as victims or perpetrators – to the desperate measures of organized crime.

Selection and passage of county land preservation voter referendum: The role of government

County jurisdictions in America are increasingly exercising self-government in the provision of public community services through the context of second order federalism. In states exercising this form of contemporary governance, county governments with "reformed" policy-making structures and professional management practices, have begun to rival or surpass municipalities in the delivery of local services with regional implications such as environmental protection (Benton 2002, 2003; Marando and Reeves, 1993). ^ The voter referendum, a form of direct democracy, is an important component of county land preservation and environmental protection governmental policies. The recent growth and success of land preservation voter referendums nationwide reflects an increase in citizen participation in government and their desire to protect vacant land and its natural environment from threats of over-development, urbanization and sprawl, loss of open space and farmland, deterioration of ecosystems, and inadequate park and recreational amenities. ^ The study's design employs a sequential, mixed method. First, a quantitative approach employs the Heckman two-step model. It is fitted with variables for the non-random sample of 227 voter referendum counties and all non-voter referendum counties in the U.S. from 1988 to 2009. Second, the qualitative data collected from the in-depth investigation of three South Florida county case studies with twelve public administrator interviews is transformed for integration with the quantitative findings. The purpose of the qualitative method is to complement, explain and enrich the statistical analysis of county demographic, socio-economic, terrain, regional, governance and government, political preference, environmentalism, and referendum-specific factors. ^ The research finds that government factors are significant in terms of the success of land preservation voter referendums; more specifically, the presence of self-government authority (home rule charter), a reformed structure (county administrator/manager or elected executive), and environmental interest groups. In addition, this study concludes that successful counties are often located coastal, exhibit population and housing growth, and have older and more educated citizens who vote democratic in presidential elections. The analysis of case study documents and public administrator interviews finds that pragmatic considerations of timing, local politics and networking of regional stakeholders are also important features of success. Further research is suggested utilizing additional public participation, local government and public administration factors.^

The effects of school mobility in pre -assessment grade levels on student performance and school accountability in urban Title I schools

This study examined the effects of student mobility and educational enrollment experiences on academic achievement. The educational progress, school enrollments and transfers of inner-city elementary students were tracked over a four-year period. Student achievement was measured by criterion-referenced reading tests administered in the second semester of the third grade. It further analyzed the degree to which the switch to different basal reading textbooks interrupted the continuity of education thereby contributing to the detrimental effects of intra-district mobility. ^ Mobility histories of 2,913 third grade students were collected to evaluate the number of times each student entered or withdrew from a Miami-Dade County Public School beginning in August 2000 through March 2004, and distinguished between transfers that occurred during the academic school year and those that occurred during summer months. Data were analyzed using Pearson correlations and multiple regressions to determine if school mobility contributed to performance on the Florida Comprehensive Assessment Third Grade Reading Test (FCAT). Transferring from one school to another was found to have a significant negative impact on student test scores. Transfers within the academic school year were more detrimental than transfers that occurred during the summer months. Third grade students who transferred into schools that used the same reading textbook series were found to have significantly higher FCAT reading scores than third graders who transferred into schools that used different reading textbooks. ^ The effects of mobility rates on overall school performance were also examined. Data was collected on 124 Title I elementary schools to determine the degree to which mobility affected school accountability scores. Title I schools with high student mobility rates had significantly lower accountability scores than schools with lower student mobility rates. ^ The results of this study highlight the impact of education and housing policy and imply a need for programs and practices that promote stability in the early elementary years. ^

Developing an enhanced model for combined heat and air infiltration energy simulation

The need for efficient, sustainable, and planned utilization of resources is ever more critical. In the U.S. alone, buildings consume 34.8 Quadrillion (1015) BTU of energy annually at a cost of $1.4 Trillion. Of this energy 58% is utilized for heating and air conditioning. ^ Several building energy analysis tools have been developed to assess energy demands and lifecycle energy costs in buildings. Such analyses are also essential for an efficient HVAC design that overcomes the pitfalls of an under/over-designed system. DOE-2 is among the most widely known full building energy analysis models. It also constitutes the simulation engine of other prominent software such as eQUEST, EnergyPro, PowerDOE. Therefore, it is essential that DOE-2 energy simulations be characterized by high accuracy. ^ Infiltration is an uncontrolled process through which outside air leaks into a building. Studies have estimated infiltration to account for up to 50% of a building's energy demand. This, considered alongside the annual cost of buildings energy consumption, reveals the costs of air infiltration. It also stresses the need that prominent building energy simulation engines accurately account for its impact. ^ In this research the relative accuracy of current air infiltration calculation methods is evaluated against an intricate Multiphysics Hygrothermal CFD building envelope analysis. The full-scale CFD analysis is based on a meticulous representation of cracking in building envelopes and on real-life conditions. The research found that even the most advanced current infiltration methods, including in DOE-2, are at up to 96.13% relative error versus CFD analysis. ^ An Enhanced Model for Combined Heat and Air Infiltration Simulation was developed. The model resulted in 91.6% improvement in relative accuracy over current models. It reduces error versus CFD analysis to less than 4.5% while requiring less than 1% of the time required for such a complex hygrothermal analysis. The algorithm used in our model was demonstrated to be easy to integrate into DOE-2 and other engines as a standalone method for evaluating infiltration heat loads. This will vastly increase the accuracy of such simulation engines while maintaining their speed and ease of use characteristics that make them very widely used in building design.^

Developing an Enhanced Model for Combined Heat and Air Infiltration Energy Simulation

The need for efficient, sustainable, and planned utilization of resources is ever more critical. In the U.S. alone, buildings consume 34.8 Quadrillion (1015) BTU of energy annually at a cost of $1.4 Trillion. Of this energy 58% is utilized for heating and air conditioning. Several building energy analysis tools have been developed to assess energy demands and lifecycle energy costs in buildings. Such analyses are also essential for an efficient HVAC design that overcomes the pitfalls of an under/over-designed system. DOE-2 is among the most widely known full building energy analysis models. It also constitutes the simulation engine of other prominent software such as eQUEST, EnergyPro, PowerDOE. Therefore, it is essential that DOE-2 energy simulations be characterized by high accuracy. Infiltration is an uncontrolled process through which outside air leaks into a building. Studies have estimated infiltration to account for up to 50% of a building’s energy demand. This, considered alongside the annual cost of buildings energy consumption, reveals the costs of air infiltration. It also stresses the need that prominent building energy simulation engines accurately account for its impact. In this research the relative accuracy of current air infiltration calculation methods is evaluated against an intricate Multiphysics Hygrothermal CFD building envelope analysis. The full-scale CFD analysis is based on a meticulous representation of cracking in building envelopes and on real-life conditions. The research found that even the most advanced current infiltration methods, including in DOE-2, are at up to 96.13% relative error versus CFD analysis. An Enhanced Model for Combined Heat and Air Infiltration Simulation was developed. The model resulted in 91.6% improvement in relative accuracy over current models. It reduces error versus CFD analysis to less than 4.5% while requiring less than 1% of the time required for such a complex hygrothermal analysis. The algorithm used in our model was demonstrated to be easy to integrate into DOE-2 and other engines as a standalone method for evaluating infiltration heat loads. This will vastly increase the accuracy of such simulation engines while maintaining their speed and ease of use characteristics that make them very widely used in building design.

Selection and Passage of County Land Preservation Voter Referendum: The Role of Government

County jurisdictions in America are increasingly exercising self-government in the provision of public community services through the context of second order federalism. In states exercising this form of contemporary governance, county governments with “reformed” policy-making structures and professional management practices, have begun to rival or surpass municipalities in the delivery of local services with regional implications such as environmental protection (Benton 2002, 2003; Marando and Reeves, 1993). The voter referendum, a form of direct democracy, is an important component of county land preservation and environmental protection governmental policies. The recent growth and success of land preservation voter referendums nationwide reflects an increase in citizen participation in government and their desire to protect vacant land and its natural environment from threats of over-development, urbanization and sprawl, loss of open space and farmland, deterioration of ecosystems, and inadequate park and recreational amenities. The study’s design employs a sequential, mixed method. First, a quantitative approach employs the Heckman two-step model. It is fitted with variables for the non-random sample of 227 voter referendum counties and all non-voter referendum counties in the U.S. from 1988 to 2009. Second, the qualitative data collected from the in-depth investigation of three South Florida county case studies with twelve public administrator interviews is transformed for integration with the quantitative findings. The purpose of the qualitative method is to complement, explain and enrich the statistical analysis of county demographic, socio-economic, terrain, regional, governance and government, political preference, environmentalism, and referendum-specific factors. The research finds that government factors are significant in terms of the success of land preservation voter referendums; more specifically, the presence of self-government authority (home rule charter), a reformed structure (county administrator/manager or elected executive), and environmental interest groups. In addition, this study concludes that successful counties are often located coastal, exhibit population and housing growth, and have older and more educated citizens who vote democratic in presidential elections. The analysis of case study documents and public administrator interviews finds that pragmatic considerations of timing, local politics and networking of regional stakeholders are also important features of success. Further research is suggested utilizing additional public participation, local government and public administration factors.

A study of gas holdup properties of selected non-Newtonian simulants

The U.S. Department of Energy (DOE) needs a design basis to properly design a PJM and ventilation systems for the Waste Treatment Plant vessels. In order to meet DOE's needs for proper ventilation and PJM design technologies, Florida International University's Hemispheric Center for Environmental Technology (FIU-HCET) has studied the properties for gas holdup in selected non Newtonian fluids with physicochemical properties comparable to nuclear waste. The primary purpose of this research was to study the holdup properties of selected non - Newtonian simulants and quantify the level of gas holdup in selected simulants using continuous argon injection in five gallons vessel. Gas holdup tests involved the injection of gas bubbles in simulant waste in scaled prototypic vessels. The holdup was measured as a function of injection rate in the vessel. Tests were performed with both Laponite, Clay 12%, Clay 27% and Qard 13.5. This work showed that the percentage of holdup was about 3% for all simulants despite the significant differences in rheology.