Reactions of singlet oxygen and singlet oxygen mimics with dicyclopropylethylenes: Comparison of reactivity and mechanisms

An extensive study of the reaction pathways of 1,1-dicyclopropyl ethylene, cis- and trans- 1,2-dicyclopropylethylenes has been undertaken with different electrophiles 4-methyl-1,2,4-triazoline-3,5-dione (MTAD), tetracyanoethylene (TCNE), and singlet oxygen $\rm(\sp1O\sb2).$ Comparison of reactivity and reaction mechanisms among the electrophiles is investigated. Singlet oxygen exhibits significantly lower reactivity compared to the other electrophiles. MTAD and TCNE react with dicyclopropylethylenes to produce predominantly $\sp{\prime\prime}2+2\sp{\prime\prime}$ adducts and a small amount of the "ene" adducts. The $\sp{\prime\prime}2+2\sp{\prime\prime}$ is the major product presumably because of the high activation energy leading to the highly strained "ene" products. Solvent trapping studies provide strong evidence of a "stepwise" mechanism, involving a zwitterionic or aziridinium imide as an intermediate from the study of the reactions products of dicyclopropylethylenes and MTAD. ^

Sequence analysis of complementary DNAs encoding C3 in the nurse shark ({\it Ginglymostoma cirratum\/})

Mammalian C3 is a pivotal complement protein, encoded for by a single gene. In some vertebrate species multiple C3 isoforms are products of different C3 genes. The goal of this study was to determine whether multiple genes encode for shark C3. A protocol was developed for the isolation of mRNA from shark blood for the isolation of C3 cDNA clones. RT-PCR amplification of mRNA, using sense (GCGEQNM) and antisense (TWLTAYV) primers encoding conserved regions of human C3, yielded 21 clones. The C3-like clones isolated shared 97% similarity with each other and 40% similarity to human C3. RACE-PCR amplification of shark liver RNA, using gene specific primers, yielded products ranging from 1800bp to 3000bp. Deduced amino acid sequence, corresponding to 408bp of the 1800bp fragment, was obtained which showed 51% similarity to human C3. These results suggest that nurse shark C3 might be encoded for by more than one gene. ^

Health beliefs and health care options of disparate black communities in the United States

According to the 1999 U.S. Census, there were approximately thirty-three million African Americans and approximately 1.8 million non-Hispanic black immigrants in the United States. The 1997 U.S. Census estimated that there were as many as 554,000 foreign-born Haitians and 505,000 foreign-born Jamaicans living in the United States, mainly residing in Florida and New York. The U.S. Census claims that blacks are one of the largest emerging ethnic groups in America constituting at least twelve percent of this country's population. Because of this increase, their specific health beliefs and health care options are increasingly nationally significant. ^ In the present intra-black and inter-ethnic study, two hundred seventy African Americans, Haitian immigrants, and Jamaican immigrants residing in South Florida were quantitatively and qualitatively surveyed in order to investigate their health beliefs and health care options. According to the reviewed literature, the three black ethnic groups researched in this study have not been compared or contrasted before in relation to these beliefs and health care choices. ^ As was discovered by the present research, differing health beliefs and health care options were the cultural products of the ethnic differences of the researched communities. It was expected that differing health beliefs among the researched black groups might indicate disparate patterns of health care utilization of either western or non-western models. Additionally, it was projected that by investigating the health beliefs and the health care options of these emerging black ethnic groups, western health care providers in the United States could become better versed in medically servicing growing ethnically-disparate black populations. The study yielded results about the researched groups that supported major findings in the reviewed literature. The data were reported and examined, and theoretical generalizations from the data were discussed. The most important of these findings was that, within a race, health beliefs and health care options were determined by specific ethno-cultural variables dependent on national origins. ^

Occurrence and environmental fate of Irgarol 1051, a new antifouling agent

The purpose of this study is to characterize the degradation products of Irgarol 1051(2-methylthio-4-tertbutylamino-6-cyclopropylamino- s-triazine), a compound recently developed for use as an antifouling agent on boat hulls. The photolytic fate of this compound in different natural waters will be used in the development of a monitoring program designed to survey the occurrence of this compound and its degradation products in South Florida marinas, the Miami River and surrounding coastal areas. ^ The transformation of Irgarol 1051 and degradation rate constants were characterized in a photo-reactor under simulated natural conditions. The degradation pathway in the UVB-UVA region (300nm to 350nm) closely resembled the transformations under natural conditions in the pond, showing that both direct photolysis and the presence of natural sensitizers play an important role in the abiotic transformation of this compound. Irgarol 1051 has an average environmental half-life of 10 days in surface waters. Average concentrations from samples around Biscayne Bay and the Miami River increased from 1–5 ng/L during 1999 and increased to between 28 and 38 ng/L in 2001, respectively. Irgarol concentrations showed a strong correlation with concentrations of its major transformation product, M1, from samples collected as part of the study ([M1]/[Irgarol] = 0.247, R2 = 0.9165, n = 125). ^

Mechanistic studies on the advanced oxidation and photochemical transformation of cyanotoxins (microcystins)

The increased occurrence of cyanobacteria (blue-green algae) blooms and the production of associated cyanotoxins have presented a threat to drinking water sources. Among the most common types of cyanotoxins found in potable water are microcystins (MCs), a family of cyclic heptapeptides containing substrates. MCs are strongly hepatotoxic and known to initiate tumor promoting activity. The presence of sub-lethal doses of MCs in drinking water is implicated as one of the key risk factors for an unusually high occurrence of primary liver cancer. ^ A variety of traditional water treatment methods have been attempted for the removal of cyanotoxins, but with limited success. Advanced Oxidation Technologies (AOTs) are attractive alternatives to traditional water treatments. We have demonstrated ultrasonic irradiation and UV/H2O2 lead to the degradation of cyanotoxins in drinking water. These studies demonstrate AOTs can effectively degrade MCs and their associated toxicity is dramatically reduced. We have conducted detailed studies of different degradation pathways of MCs and conclude that the hydroxyl radical is responsible for a significant fraction of the observed degradation. Results indicate preliminary products of the sonolysis of MCs are due to the hydroxyl radical attack on the benzene ring and substitution and cleavage of the diene of the Adda peptide residue. AOTs are attractive methods for treatment of cyanotoxins in potable water supplies. ^ The photochemical transformation of MCs is important in the environmental degradation of MCs. Previous studies implicated singlet oxygen as a primary oxidant in the photochemical transformation of MCs. Our results indicate that singlet oxygen predominantly leads to degradation of the phycocyanin, pigments of blue green algae, hence reducing the degradation of MCs. The predominant process involves isomerization of the diene (6E to 6Z) in the Adda side chain via photosensitized isomerization involving the photoexcited phycocyanin. Our results indicate that photosensitized processes play a key role in the environmental fate and elimination of MCs in the natural waters. ^

The development of optimized high performance liquid chromatography systems for the analysis of improvised explosives

Existing instrumental techniques must be adaptable to the analysis of novel explosives if science is to keep up with the practices of terrorists and criminals. The focus of this work has been the development of analytical techniques for the analysis of two types of novel explosives: ascorbic acid-based propellants, and improvised mixtures of concentrated hydrogen peroxide/fuel. In recent years, the use of these explosives in improvised explosive devices (IEDs) has increased. It is therefore important to develop methods which permit the identification of the nature of the original explosive from post-blast residues. Ascorbic acid-based propellants are low explosives which employ an ascorbic acid fuel source with a nitrate/perchlorate oxidizer. A method which utilized ion chromatography with indirect photometric detection was optimized for the analysis of intact propellants. Post-burn and post-blast residues if these propellants were analyzed. It was determined that the ascorbic acid fuel and nitrate oxidizer could be detected in intact propellants, as well as in the post-burn and post-blast residues. Degradation products of the nitrate and perchlorate oxidizers were also detected. With a quadrupole time-of-flight mass spectrometer (QToFMS), exact mass measurements are possible. When an HPLC instrument is coupled to a QToFMS, the combination of retention time with accurate mass measurements, mass spectral fragmentation information, and isotopic abundance patterns allows for the unequivocal identification of a target analyte. An optimized HPLC-ESI-QToFMS method was applied to the analysis of ascorbic acid-based propellants. Exact mass measurements were collected for the fuel and oxidizer anions, and their degradation products. Ascorbic acid was detected in the intact samples and half of the propellants subjected to open burning; the intact fuel molecule was not detected in any of the post-blast residue. Two methods were optimized for the analysis of trace levels of hydrogen peroxide: HPLC with fluorescence detection (HPLC-FD), and HPLC with electrochemical detection (HPLC-ED). Both techniques were extremely selective for hydrogen peroxide. Both methods were applied to the analysis of post-blast debris from improvised mixtures of concentrated hydrogen peroxide/fuel; hydrogen peroxide was detected on variety of substrates. Hydrogen peroxide was detected in the post-blast residues of the improvised explosives TATP and HMTD.

The problematics of mestizaje in the Indigenist Peruvian novels of "Yawar Fiesta" (1941) by Jose Maria Arguedas, "El mundo es ancho y ajeno" (1941) by Ciro Algeria, and "Los rios profundos" (1958) by Jose Maria Arguedas

This study was a critical reassessment of the problematics of mestizaje in three representative texts pertaining to the Indigenist Peruvian narrative: Yawar Fiesta (1941) by José María Arguedas; El mundo es ancho y ajeno (1941) by Ciro Alegría; and Los ríos profundos (1958) by José María Arguedas. As this investigation demonstrated, Alegría's and Arguedas' writings went beyond the reach of Indianism and orthodox Indigenism, which were prevalent during the first decades of the twentieth century, to emphasize, the values of the Indian peasantry as well as those of the mestizo and mestiza: the products of Indian and white unions, who were also considered representatives of the Peruvian culture. ^ The first chapter traced the historical process of mestizaje and demonstrated how the discursive practice of this mestizaje was expressed in the Indigenist Peruvian narrative. The chronological organization of the chapters in this dissertation paralleled the evolution of this narrative.^ The relevance of my research lies on the important contribution it makes to the field of Indigenist literature, by seeing mestizaje as both a reconstruction and a reinterpretation of the idea of nation, identity and cultural interchange. In Alegría's and Arguedas' novels, the Indigenous reality was not only seen as an isolated phenomenon, but also as the dichotomy of European versus Indian values. As a result, Indigenist narrative presented a true and all encompassing world; therefore, Alegría's and Arguedas' narrative deepened our understanding of the aspects of a multicultural society.^ In order to accomplish this analysis, research was conducted in areas such as history, languages, ethnology, ethnography, anthropology, folklore, religion, and syncretism. My study was based on works such as Antonio Cornejo Polar's heterogeneous literatures, Mijail Bajtín's conception of dialogism and polyphony, Benedict Anderson's Imagined Communities, Angel Rama's notion of transculturation, Homi Bhabha's liminal space, Walter Ong's study of orality and literacy, and Julia Kristeva's theory of abjection, among others.^

Assessment of biodegradable magnesium alloys for enhanced mechanical and biocompatible properties

Biomaterials have been used for more than a century in the human body to improve body functions and replace damaged tissues. Currently approved and commonly used metallic biomaterials such as, stainless steel, titanium, cobalt chromium and other alloys have been found to have adverse effects leading in some cases, to mechanical failure and rejection of the implant. The physical or chemical nature of the degradation products of some implants initiates an adverse foreign body reaction in the tissue. Some metallic implants remain as permanent fixtures, whereas others such as plates, screws and pins used to secure serious fractures are removed by a second surgical procedure after the tissue has healed sufficiently. However, repeat surgical procedures increase the cost of health care and the possibility of patient morbidity. This study focuses on the development of magnesium based biodegradable alloys/metal matrix composites (MMCs) for orthopedic and cardiovascular applications. The Mg alloys/MMCs possessed good mechanical properties and biocompatible properties. Nine different compositions of Mg alloys/MMCs were manufactured and surface treated. Their degradation behavior, ion leaching, wettability, morphology, cytotoxicity and mechanical properties were determined. Alloying with Zn, Ca, HA and Gd and surface treatment resulted in improved mechanical properties, corrosion resistance, reduced cytotoxicity, lower pH and hydrogen evolution. Anodization resulted in the formation of a distinct oxide layer (thickness 5-10 μm) as compared with that produced on mechanically polished samples (~20-50 nm) under ambient conditions. It is envisaged that the findings of this research will introduce a new class of Mg based biodegradable alloys/MMCs and the emergence of innovative cardiovascular and orthopedic implant devices.^

A geochemical study of crustal plutonic rocks from the southern Mariana Trench forearc: Relationship to volcanic rocks erupted during subduction initiation

Two suites of intermediate-felsic plutonic rocks were recovered by dredges RD63 and RD64 (R/V KK81-06-26) from the northern wall of the Mariana trench near Guam, which is located in the southern part of the Izu-Bonin-Mariana (IBM) island arc system. The locations of the dredges are significant as the area contains volcanic rocks (forearc basalts and boninites) that have been pivotal in explaining processes that occur when one lithospheric plate initially begins to subduct beneath another. The plutonic rocks have been classified based on petrologic and geochemical analyses, which provides insight to their origin and evolution in context of the surrounding Mariana trench. Based on whole rock geochemistry, these rocks (SiO2: 49-78 wt%) have island arc trace element signatures (Ba, Sr, Rb enrichment, Nb-Ta negative anomalies, U/Th enrichment), consistent with the adjacent IBM volcanics. Depletion of rare earth elements (REEs) relative to primitive mantle and excess Zr and Hf compared to the middle REEs indicate that the source of the plutonic rocks is similar to boninites and transitional boninites. Early IBM volcanic rocks define isotopic fields (Sr, Pb, Nd and Hf-isotopes) that represent different aspects of the subduction process (e.g., sediment influence, mantle provenance). The southern Mariana plutonic rocks overlap these fields, but show a clear distinction between RD63 and RD64. Modeling of the REEs, Zr and Hf shows that the plutonic suites formed via melting of boninite crust or by crystallization from a boninite-like magma rather than other sources that are found in the IBM system. The data presented support the hypothesis that the plutonic rocks from RD63 and RD64 are products of subduction initiation and are likely pieces of middle crust in the forearc exposed at the surface by faulting and serpentine mudvolcanoes. Their existence shows that intermediate-felsic crust may form very early in the history of an intra-oceanic island arc system. Plutonic rocks with similar formation histories may exist in obducted suprasubduction zone ophiolites and would be evidence that felsic-intermediate forearc plutonics are eventually accreted to the continents.

Speciation, metabolism, toxicity, and protein-binding of different arsenic species in human cells

Despite of its known toxicity and potential to cause cancer, arsenic has been proven to be a very important tool for the treatment of various refractory neoplasms. One of the promising arsenic-containing chemotherapeutic agents in clinical trials is Darinaparsin (dimethylarsinous glutathione, DMA III(GS)). In order to understand its toxicity and therapeutic efficacy, the metabolism of Darinaparsin in human cancer cells was evaluated. With the aim of detecting all potential intermediates and final products of the biotransformation of Darinaparsin and other arsenicals, an analytical method employing high performance liquid chromatography inductively coupled mass spectrometry (HPLC-ICP-MS) was developed. This method was shown to be capable of separating and detecting fourteen human arsenic metabolites in one chromatographic run. The developed analytical technique was used to evaluate the metabolism of Darinaparsin in human cancer cells. The major metabolites of Darinaparsin were identified as dimethylarsinic acid (DMAV), DMA III(GS), and dimethylarsinothioyl glutathione (DMMTAV(GS)). Moreover, the method was employed to study the conditions and mechanisms of formation of thiol-containing arsenic metabolites from DMAIII(GS) and DMAV as the mechanisms of formation of these important As species were unknown. The arsenic sulfur compounds studied included but were not limited to the newly discovered human arsenic metabolite DMMTA V(GS) and the unusually highly toxic dimethylmonothioarsinic acid (DMMTAV). It was found that these species may form from hydrogen sulfide produced in enzymatic reactions or by utilizing the sulfur present in protein persulfides. Possible pathways of thiolated arsenical formation were proposed and supporting data for their existence provided. In addition to known mechanism of arsenic toxicity such as protein-binding and reactive oxygen formation, it was proposed that the utilization of thiols from protein persulfides during the formation of thiolated arsenicals may be an additional mechanism of toxicity. The toxicities of DMAV(GS), DMMTA V, and DMMTAV(GS) were evaluated in cancer cells, and the ability of these cells to take the compounds up were compared. When assessing the toxicity by exposing multiple myeloma cells to arsenicals externally, DMMTAV(GS) was much less toxic than DMAIII(GS) and DMMTAV, probably as a result of its very limited uptake (less than 10% and 16% of DMAIII(GS) and DMMTAV respectively).^

Reactions of singlet oxygen and singlet oxygen mimics with dicyclopropylethylenes: comparison of reactivity and mechanisms

An extensive study of the reaction pathways of 1,1- dicyclopropyl ethylene, cis- and trans- 1,2-dicyclopropylethylenes has been undertaken with different electrophiles 4-methyl-1,2,4- triazoline-3,5-dione (MTAD), tetracyanoethylene (TCNE), and singlet oxygen (102). Comparison of reactivity and reaction mechanisms among the electrophiles is investigated. Singlet oxygen exhibits significantly lower reactivity compared to the other electrophiles. MTAD and TCNE react with dicyclopropylethylenes to produce predominantly "2+2" adducts and a small amount of the "ene" adducts. The "2+2" is the major product presumably because of the high activation energy leading to the highly strained "ene" products. Solvent trapping studies provide strong evidence of a "stepwise" mechanism, involving a zwitterionic or aziridinium imide as an intermediate from the study of the reactions products of dicyclopropylethylenes and MTAD.