Urogenital leiomyosarcoma in an alpaca

A mass in the pelvic canal of a 4-year-old pregnant alpaca hembra diagnosed as leiomyosarcoma of the urogenital tract was confirmed by biopsy. Following a tube cystotomy, the alpaca was presented 33 d later, 2 d after the tube cystotomy had been dislodged. A dead cria was delivered by caesarean section.

Identification of novel rhoptry proteins in Neospora caninum by LC/MS-MS analysis of subcellular fractions

Apicomplexan parasites possess an apical complex that is composed of two secretory organelles recognized as micronemes and rhoptries. Rhoptry contents are secreted into the parasitophorous vacuole during the host cell invasion process. Several rhoptry proteins have been identified in Toxoplasma gondii and seem to be involved in host-pathogen interactions and some of them are considered to be important virulence factors. Only one rhoptry protein, NcROP2, has been identified and extensively characterized in the closely related parasite Neospora caninum, and this has showed immunoprotective properties. Thus, with the aim of increasing knowledge of the rhoptry protein repertoire in N. caninum, a subcellular fractionation of tachyzoites was performed to obtain fractions enriched for this secretory organelle. 2-D SDS-PAGE followed by MS and LC/MS-MS were applied for fraction analysis and 8 potential novel rhoptry components (NcROP1, 5, 8, 30 and NcRON2, 3, 4, 8) and several kinases, proteases and phosphatases proteins were identified with a high homology to those previously found in T. gondii. Their existence in N. caninum tachyzoites suggests their involvement in similar events or pathways that occur in T. gondii. These novel proteins may be considered as targets that could be useful in the future development of immunoprophylactic measures.

Improved protocol for chromatofocusing on the ProteomeLab PF2D

Beckman-Coulter has recently introduced the ProteomeLab PF2D for 2-D liquid separation of protein samples. The system features separation in the first dimension by chromatofocusing, followed by RP chromatography in the second dimension, allowing the analysis of complex proteomics samples. When used by the standard protocol, reproducibility and column life times are limited, making the use of the instrument very costly. We here present an improved protocol for chromatofocusing, which enhances column life by at least fivefold.

The relationship between coagulation and the extend of surgery and postoperative infection in surgical infants below 6 months of age

AIM: First to assess coagulation changes after surgery in children below 6 months of age. Second to detect differences attributable to the extent of surgery and postoperative infection. MATERIALS AND METHODS: Blood counts, haemoglobin concentration (Hb), haematocrit (Ht), prothrombine time (PT), activated partial thromboplastine time (aPTT) and thrombelastography (TEG) were studied pre- and 2+/-1/2 d postoperatively. Patients were divided in 3 groups. I: minor surgery without access to the abdomen or thorax (n=51); II: abdominal or thoracic interventions (n=24); III: abdominal surgery with postoperative sepsis (n=11). RESULTS: Preoperative values of Hb, Ht and INR were related to the age of the infant. Postoperatively clot strength and formation rate increased in gr. I (p<0.05). In gr. II, clot formation was initiated earlier (p<0.05) even though PT decreased (p<0.05). In group III, patients postoperatively developed a tendency for hypocoagulability in all TEG-parameters, but not in plasmatic coagulation. Postoperative TEG measurements were significantly inferior in gr. III when compared to gr. I and II. CONCLUSION: Our findings suggest activation of whole blood coagulation in the uncomplicated postoperative period despite of a decrease in plasmatic coagulation. In sepsis, only thrombelastography, but not plasmatic coagulation was affected.

Tumor necrosis factor-alpha: alternative role as an inhibitor of osteoclast formation in vitro

TNFalpha is known to stimulate the development and activity of osteoclasts and of bone resorption. The cytokine was found to mediate bone loss in conjunction with inflammatory diseases such as rheumatoid arthritis or chronic aseptic inflammation induced by wear particles from implants and was suggested to be a prerequisite for the loss of bone mass under estrogen deficiency. In the present study, the regulation of osteoclastogenesis by TNFalpha was investigated in co-cultures of osteoblasts and bone marrow or spleen cells and in cultures of bone marrow and spleen cells grown with CSF-1 and RANKL. Low concentrations of TNFalpha (1 ng/ml) caused a >90% decrease in the number of osteoclasts in co-cultures, but did not affect the development of osteoclasts from bone marrow cells. In cultures with p55TNFR(-/-) osteoblasts and wt BMC, the inhibitory effect was abrogated and TNFalpha induced an increase in the number of osteoclasts in a dose-dependent manner. Osteoblasts were found to release the inhibitory factor(s) into the culture supernatant after simultaneous treatment with 1,25(OH)(2)D(3) and TNFalpha, this activity, but not its release, being resistant to treatment with anti-TNFalpha antibodies. Dexamethasone blocked the secretion of the TNFalpha-dependent inhibitor by osteoblasts, while stimulating the development of osteoclasts. The data suggest that the effects of TNFalpha on the differentiation of osteoclast lineage cells and on bone metabolism may be more complex than hitherto assumed and that these effects may play a role in vivo during therapies for inflammatory diseases.

Enhancing sealing of fetal membrane defects using tissue engineered native amniotic scaffolds in the rabbit model

OBJECTIVE: The purpose of this study was to compare the efficacy of native engineered amniotic scaffolds (AS) and polyesterurethane scaffolds (DegraPol) and document wound healing response when sealing iatrogenic fetal membrane defects in the rabbit model. STUDY DESIGN: Native AS were engineered from freshly harvested membranes of 23 days' gestational age (GA; term = 31-2 d). Acellularity of AS was assessed by histology, light and scanning electron microscopy. Fetal membrane defects were created by 14 gauge-needle puncture at GA 23 days and primarily closed with AS (n = 10) or DegraPol (n = 10) or left unclosed (positive controls; n = 10). Sixty-one sacs served as negative controls. At GA 30 days a second look hysterotomy was performed to assess presence of amniotic fluid (AF) and harvest plugging sites for microscopic evaluation. RESULTS: Engineered AS had a cell-free collagenous fiber network. AF was significantly higher only in the DegraPol group (78%; P < .05) compared to the AF in positive controls (17%). Integration of plugs in the fetal membrane defect was better with AS than DegraPol, with higher reepithelialization rates (AS: 52.5% +/- 6.5%; DegraPol: 11.6% +/- 2.6%; P < .001) and proliferation indices (AS: 0.47 +/- 0.03; DegraPol: 0.28 +/- 0.04; P = .001). In both treatment groups, cell proliferation in the myometrium was increased (P < .05). CONCLUSION: Native AS seal iatrogenic fetal membrane defects better than DegraPol. Within a week, there is abundant reepithelilization and minimal local inflammation. This yields the proof of principle that engineered native, amniotic membrane scaffolds enhance fetal membrane wound healing response.

Clinical performance of a new laser fluorescence device for detection of occlusal caries lesions in permanent molars

OBJECTIVES: To determine the clinical performance of a laser fluorescence device (DIAGNOdent pen, KaVo) to discriminate between different occlusal caries depths (D(0)-D(1-4); D(0-2)-D(3,4)) in permanent molars. METHODS: In this prospective, randomized two-centre-study 120 sound/uncavitated carious sites in 120 patients were measured after visual and radiographic caries assessment. In cases of operative intervention (n=86), the lesion depths after caries removal were recorded (reference). In cases of preventive intervention (n=34), the sites were reassessed visually/radiographically after 12 months to verify the status assessed before (reference). The discrimination performance was determined statistically (Mann-Whitney test, Spearman's rho coefficient, and areas under the receiver operating characteristic curves (AUCs)). Sensitivities (SE) and specificities (SP) were plotted as a function of the measured values and cut-off values for the mentioned thresholds suggested. RESULTS: Sound sites (n=13) had significantly minor fluorescence values than carious sites (n=107) (P<0.0001) as had sites with no/enamel caries (n=63) compared to dentinal caries (n=57). The AUCs for the same discriminations were 0.92 and 0.78 (P<0.001). For the D(0)-D(1-4) threshold, a cut-off at a value of 12 (SE: 0.88, SP: 0.85) and for the D(0-2)-D(3,4) threshold at 25 (SE: 0.67, SP: 0.79) can be suggested. A moderate positive correlation between the measurements and the caries depths was calculated (rho=+0.57, P=0.01). CONCLUSION: Within this study, the device's discrimination performance for different caries depths was moderate to very good and it may be recommended as adjunct tool in the diagnosis of occlusal caries.

Development of one-dimensional and two-dimensional computational tools that simulate steady internal condensing flows in terrestrial and zero-gravity environments

This dissertation presents an effective quasi one-dimensional (1-D) computational simulation tool and a full two-dimensional (2-D) computational simulation methodology for steady annular/stratified internal condensing flows of pure vapor. These simulation tools are used to investigate internal condensing flows in both gravity as well as shear driven environments. Through accurate numerical simulations of the full two dimensional governing equations, results for laminar/laminar condensing flows inside mm-scale ducts are presented. The methodology has been developed using MATLAB/COMSOL platform and is currently capable of simulating film-wise condensation for steady (and unsteady flows). Moreover, a novel 1-D solution technique, capable of simulating condensing flows inside rectangular and circular ducts with different thermal boundary conditions is also presented. The results obtained from the 2-D scientific tool and 1-D engineering tool, are validated and synthesized with experimental results for gravity dominated flows inside vertical tube and inclined channel; and, also, for shear/pressure driven flows inside horizontal channels. Furthermore, these simulation tools are employed to demonstrate key differences of physics between gravity dominated and shear/pressure driven flows. A transition map that distinguishes shear driven, gravity driven, and “mixed” driven flow zones within the non-dimensional parameter space that govern these duct flows is presented along with the film thickness and heat transfer correlations that are valid in these zones. It has also been shown that internal condensing flows in a micro-meter scale duct experiences shear driven flow, even in different gravitational environments. The full 2-D steady computational tool has been employed to investigate the length of annularity. The result for a shear driven flow in a horizontal channel shows that in absence of any noise or pressure fluctuation at the inlet, the onset of non-annularity is partly due to insufficient shear at the liquid-vapor interface. This result is being further corroborated/investigated by R. R. Naik with the help of the unsteady simulation tool. The condensing flow results and flow physics understanding developed through these simulation tools will be instrumental in reliable design of modern micro-scale and spacebased thermal systems.

Controlling electronic and magnetic properties of ultra narrow multilayered nanowires

Interest in the study of magnetic/non-magnetic multilayered structures took a giant leap since Grünberg and his group established that the interlayer exchange coupling (IEC) is a function of the non-magnetic spacer width. This interest was further fuelled by the discovery of the phenomenal Giant Magnetoresistance (GMR) effect. In fact, in 2007 Albert Fert and Peter Grünberg were awarded the Nobel Prize in Physics for their contribution to the discovery of GMR. GMR is the key property that is being used in the read-head of the present day computer hard drive as it requires a high sensitivity in the detection of magnetic field. The recent increase in demand for device miniaturization encouraged researchers to look for GMR in nanoscale multilayered structures. In this context, one dimensional(1-D) multilayerd nanowire structure has shown tremendous promise as a viable candidate for ultra sensitive read head sensors. In fact, the phenomenal giant magnetoresistance(GMR) effect, which is the novel feature of the currently used multilayered thin film, has already been observed in multilayered nanowire systems at ambient temperature. Geometrical confinement of the supper lattice along the 2-dimensions (2-D) to construct the 1-D multilayered nanowire prohibits the minimization of magnetic interaction- offering a rich variety of magnetic properties in nanowire that can be exploited for novel functionality. In addition, introduction of non-magnetic spacer between the magnetic layers presents additional advantage in controlling magnetic properties via tuning the interlayer magnetic interaction. Despite of a large volume of theoretical works devoted towards the understanding of GMR and IEC in super lattice structures, limited theoretical calculations are reported in 1-D multilayered systems. Thus to gauge their potential application in new generation magneto-electronic devices, in this thesis, I have discussed the usage of first principles density functional theory (DFT) in predicting the equilibrium structure, stability as well as electronic and magnetic properties of one dimensional multilayered nanowires. Particularly, I have focused on the electronic and magnetic properties of Fe/Pt multilayered nanowire structures and the role of non-magnetic Pt spacer in modulating the magnetic properties of the wire. It is found that the average magnetic moment per atom in the nanowire increases monotonically with an ~1/(N(Fe)) dependance, where N(Fe) is the number of iron layers in the nanowire. A simple model based upon the interfacial structure is given to explain the 1/(N(Fe)) trend in magnetic moment obtained from the first principle calculations. A new mechanism, based upon spin flip with in the layer and multistep electron transfer between the layers, is proposed to elucidate the enhancement of magnetic moment of Iron atom at the Platinum interface. The calculated IEC in the Fe/Pt multilayered nanowire is found to switch sign as the width of the non-magnetic spacer varies. The competition among short and long range direct exchange and the super exchange has been found to play a key role for the non-monotonous sign in IEC depending upon the width of the Platinum spacer layer. The calculated magnetoresistance from Julliere's model also exhibit similar switching behavior as that of IEC. The universality of the behavior of exchange coupling has also been looked into by introducing different non-magnetic spacers like Palladium, Copper, Silver, and Gold in between magnetic Iron layers. The nature of hybridization between Fe and other non-magnetic spacer is found to dictate the inter layer magnetic interaction. For example, in Fe/Pd nanowire the d-p hybridization in two spacer layer case favors anti-ferromagnetic (AFM) configuration over ferromagnetic (FM) configuration. However, the hybridization between half-filled Fe(d) and filled Cu(p) state in Fe/Cu nanowire favors FM coupling in the 2-spacer system.

Integration of computational models and experimental characterization to study internal frost damage in cementitious materials

The objective of this doctoral research is to investigate the internal frost damage due to crystallization pore pressure in porous cement-based materials by developing computational and experimental characterization tools. As an essential component of the U.S. infrastructure system, the durability of concrete has significant impact on maintenance costs. In cold climates, freeze-thaw damage is a major issue affecting the durability of concrete. The deleterious effects of the freeze-thaw cycle depend on the microscale characteristics of concrete such as the pore sizes and the pore distribution, as well as the environmental conditions. Recent theories attribute internal frost damage of concrete is caused by crystallization pore pressure in the cold environment. The pore structures have significant impact on freeze-thaw durability of cement/concrete samples. The scanning electron microscope (SEM) and transmission X-ray microscopy (TXM) techniques were applied to characterize freeze-thaw damage within pore structure. In the microscale pore system, the crystallization pressures at sub-cooling temperatures were calculated using interface energy balance with thermodynamic analysis. The multi-phase Extended Finite Element Modeling (XFEM) and bilinear Cohesive Zone Modeling (CZM) were developed to simulate the internal frost damage of heterogeneous cement-based material samples. The fracture simulation with these two techniques were validated by comparing the predicted fracture behavior with the captured damage from compact tension (CT) and single-edge notched beam (SEB) bending tests. The study applied the developed computational tools to simulate the internal frost damage caused by ice crystallization with the two dimensional (2-D) SEM and three dimensional (3-D) reconstructed SEM and TXM digital samples. The pore pressure calculated from thermodynamic analysis was input for model simulation. The 2-D and 3-D bilinear CZM predicted the crack initiation and propagation within cement paste microstructure. The favorably predicted crack paths in concrete/cement samples indicate the developed bilinear CZM techniques have the ability to capture crack nucleation and propagation in cement-based material samples with multiphase and associated interface. By comparing the computational prediction with the actual damaged samples, it also indicates that the ice crystallization pressure is the main mechanism for the internal frost damage in cementitious materials.

EXPERIMENTAL AND COMPUTATIONAL STUDIES OF ELECTROMAGNETIC CLOAKING AT MICROWAVES

An invisibility cloak is a device that can hide the target by enclosing it from the incident radiation. This intriguing device has attracted a lot of attention since it was first implemented at a microwave frequency in 2006. However, the problems of existing cloak designs prevent them from being widely applied in practice. In this dissertation, we try to remove or alleviate the three constraints for practical applications imposed by loosy cloaking media, high implementation complexity, and small size of hidden objects compared to the incident wavelength. To facilitate cloaking design and experimental characterization, several devices and relevant techniques for measuring the complex permittivity of dielectric materials at microwave frequencies are developed. In particular, a unique parallel plate waveguide chamber has been set up to automatically map the electromagnetic (EM) field distribution for wave propagation through the resonator arrays and cloaking structures. The total scattering cross section of the cloaking structures was derived based on the measured scattering field by using this apparatus. To overcome the adverse effects of lossy cloaking media, microwave cloaks composed of identical dielectric resonators made of low loss ceramic materials are designed and implemented. The effective permeability dispersion was provided by tailoring dielectric resonator filling fractions. The cloak performances had been verified by full-wave simulation of true multi-resonator structures and experimental measurements of the fabricated prototypes. With the aim to reduce the implementation complexity caused by metamaterials employment for cloaking, we proposed to design 2-D cylindrical cloaks and 3-D spherical cloaks by using multi-layer ordinary dielectric material (εr>1) coating. Genetic algorithm was employed to optimize the dielectric profiles of the cloaking shells to provide the minimum scattering cross sections of the cloaked targets. The designed cloaks can be easily scaled to various operating frequencies. The simulation results show that the multi-layer cylindrical cloak essentially outperforms the similarly sized metamaterials-based cloak designed by using the transformation optics-based reduced parameters. For the designed spherical cloak, the simulated scattering pattern shows that the total scattering cross section is greatly reduced. In addition, the scattering in specific directions could be significantly reduced. It is shown that the cloaking efficiency for larger targets could be improved by employing lossy materials in the shell. At last, we propose to hide a target inside a waveguide structure filled with only epsilon near zero materials, which are easy to implement in practice. The cloaking efficiency of this method, which was found to increase for large targets, has been confirmed both theoretically and by simulations.

Advanced Nanostructured Electro-Catalysts for Electricity Generation and Biorenewable Alcohol Conversion

In my Ph.D research, a wet chemistry-based organic solution phase reduction method was developed, and was successfully applied in the preparation of a series of advanced electro-catalysts, including 0-dimensional (0-D) Pt, Pd, Au, and Pd-Ni nanoparticles (NPs), 1-D Pt-Fe nanowires (NWs) and 2-D Pd-Fe nanoleaves (NLs), with controlled size, shape, and morphology. These nanostructured catalysts have demonstrated unique electro-catalytic functions towards electricity production and biorenewable alcohol conversion. The molecular oxygen reduction reaction (ORR) is a long-standing scientific issue for fuel cells due to its sluggish kinetics and the poor catalyst durability. The activity and durability of an electro-catalyst is strongly related with its composition and structure. Based on this point, Pt-Fe NWs with a diameter of 2 - 3 nm were accurately prepared. They have demonstrated a high durability in sulfuric acid due to its 1-D structure, as well as a high ORR activity attributed to its tuned electronic structure. By substituting Pt with Pd using a similar synthesis route, Pd-Fe NLs were prepared and demonstrated a higher ORR activity than Pt and Pd NPs catalysts in the alkaline electrolyte. Recently, biomass-derived alcohols have attracted enormous attention as promising fuels (to replace H2) for low-temperature fuel cells. From this point of view, Pd-Ni NPs were prepared and demonstrated a high electro-catalytic activity towards ethanol oxidation. Comparing to ethanol, the biodiesel waste glycerol is more promising due to its low price and high reactivity. Glycerol (and crude glycerol) was successfully applied as the fuel in an Au-anode anion-exchange membrane fuel cell (AEMFC). By replacing Au with a more active Pt catalyst, simultaneous generation of both high power-density electricity and value-added chemicals (glycerate, tartronate, and mesoxalate) from glycerol was achieved in an AEMFC. To investigate the production of valuable chemicals from glycerol electro-oxidation, two anion-exchange membrane electro-catalytic reactors were designed. The research shows that the electro-oxidation product distribution is strongly dependent on the anode applied potential. Reaction pathways for the electro-oxidation of glycerol on Au/C catalyst have been elucidated: continuous oxidation of OH groups (to produce tartronate and mesoxalate) is predominant at lower potentials, while C-C cleavage (to produce glycolate) is the dominant reaction path at higher potentials.

TERPENE AND TERPENOID EMISSIONS AND SECONDARY ORGANIC AEROSOL PRODUCTION

Approximately 90% of fine aerosol in the Midwestern United States has a regional component with a sizable fraction attributed to secondary production of organic aerosol (SOA). The Ozark Forest is an important source of biogenic SOA precursors like isoprene (> 150 mg m-2 d-1), monoterpenes (10-40 mg m-2 d-1), and sesquiterpenes (10-40 mg m-2d-1). Anthropogenic sources include secondary sulfate and nitrate and biomass burning (51-60%), vehicle emissions (17-26%), and industrial emissions (16-18%). Vehicle emissions are an important source of volatile and vapor-phase, semivolatile aliphatic and aromatic hydrocarbons that are important anthropogenic sources of SOA precursors. The short lifetime of SOA precursors and the complex mixture of functionalized oxidation products make rapid sampling, quantitative processing methods, and comprehensive organic molecular analysis essential elements of a comprehensive strategy to advance understanding of SOA formation pathways. Uncertainties in forecasting SOA production on regional scales are large and related to uncertainties in biogenic emission inventories and measurement of SOA yields under ambient conditions. This work presents a bottom-up approach to develop a conifer emission inventory based on foliar and cortical oleoresin composition, development of a model to estimate terpene and terpenoid signatures of foliar and bole emissions from conifers, development of processing and analytic techniques for comprehensive organic molecular characterization of SOA precursors and oxidation products, implementation of the high-volume sampling technique to measure OA and vapor-phase organic matter, and results from a 5 day field experiment conducted to evaluate temporal and diurnal trends in SOA precursors and oxidation products. A total of 98, 115, and 87 terpene and terpenoid species were identified and quantified in commercially available essential oils of Pinus sylvestris, Picea mariana, and Thuja occidentalis, respectively, by comprehensive, two-dimensional gas chromatography with time-of-flight mass spectrometric detection (GC × GC-ToF-MS). Analysis of the literature showed that cortical oleoresin composition was similar to foliar composition of the oldest branches. Our proposed conceptual model for estimation of signatures of terpene and terpenoid emissions from foliar and cortical oleoresin showed that emission potentials of the foliar and bole release pathways are dissimilar and should be considered for conifer species that develop resin blisters or are infested with herbivores or pathogens. Average derivatization efficiencies for Methods 1 and 2 were 87.9 and 114%, respectively. Despite the lower average derivatization efficiency of Method 1, distinct advantages included a greater certainty of derivatization yield for the entire suite of multi- and poly-functional species and fewer processing steps for sequential derivatization. Detection limits for Method 1 using GC × GC- ToF-MS were 0.09-1.89 ng μL-1. A theoretical retention index diagram was developed for a hypothetical GC × 2GC analysis of the complex mixture of SOA precursors and derivatized oxidation products. In general, species eluted (relative to the alkyl diester reference compounds) from the primary column (DB-210) in bands according to n and from the secondary columns (BPX90, SolGel-WAX) according to functionality, essentially making the GC × 2GC retention diagram a Carbon number-functionality grid. The species clustered into 35 groups by functionality and species within each group exhibited good separation by n. Average recoveries of n-alkanes and polyaromatic hydrocarbons (PAHs) by Soxhlet extraction of XAD-2 resin with dichloromethane were 80.1 ± 16.1 and 76.1 ± 17.5%, respectively. Vehicle emissions were the common source for HSVOCs [i.e., resolved alkanes, the unresolved complex mixture (UCM), alkylbenzenes, and 2- and 3-ring PAHs]. An absence of monoterpenes at 0600-1000 and high concentrations of monoterpenoids during the same period was indicative of substantial losses of monoterpenes overnight and the early morning hours. Post-collection, comprehensive organic molecular characterization of SOA precursors and products by GC × GC-ToFMS in ambient air collected with ~2 hr resolution is a promising method for determining biogenic and anthropogenic SOA yields that can be used to evaluate SOA formation models.

Study of particle movement in the nearshore region of Lake Superior with radioisotope tracers

Biogeochemical processes in the coastal region, including the coastal area of the Great Lakes, are of great importance due to the complex physical, chemical and biological characteristics that differ from those on either the adjoining land or open water systems. Particle-reactive radioisotopes, both naturally occurring (210Pb, 210Po and 7Be) and man-made (137Cs), have proven to be useful tracers for these processes in many systems. However, a systematic isotope study on the northwest coast of the Keweenaw Peninsula in Lake Superior has not yet been performed. In this dissertation research, field sampling, laboratory measurements and numerical modeling were conducted to understand the biogeochemistry of the radioisotope tracers and some particulate-related coastal processes. In the first part of the dissertation, radioisotope activities of 210Po and 210Pb in a variability of samples (dissolved, suspended particle, sediment trap materials, surficial sediment) were measured. A completed picture of the distribution and disequilibrium of this pair of isotopes was drawn. The application of a simple box model utilizing these field observations reveals short isotope residence times in the water column and a significant contribution of sediment resuspension (for both particles and isotopes). The results imply a highly dynamic coastal region. In the second part of this dissertation, this conclusion is examined further. Based on intensive sediment coring, the spatial distribution of isotope inventories (mainly 210Pb, 137Cs and 7Be) in the nearshore region was determined. Isotope-based focusing factors categorized most of the sampling sites as non- or temporary depositional zones. A twodimensional steady-state box-in-series model was developed and applied to individual transects with the 210Pb inventories as model input. The modeling framework included both water column and upper sediments down to the depth of unsupported 210Pb penetration. The model was used to predict isotope residence times and cross-margin fluxes of sediments and isotopes at different locations along each transect. The time scale for sediment focusing from the nearshore to offshore regions of the transect was on the order of 10 years. The possibility of sediment longshore movement was indicated by high inventory ratios of 137Cs: 210Pb. Local deposition of fine particles, including fresh organic carbon, may explain the observed distribution of benthic organisms such as Diporeia. In the last part of this dissertation, isotope tracers, 210Pb and 210Po, were coupled into a hydrodynamic model for Lake Superior. The model was modified from an existing 2-D finite difference physical-biological model which has previously been successfully applied on Lake Superior. Using the field results from part one of this dissertation as initial conditions, the model was used to predict the isotope distribution in the water column; reasonable results were achieved. The modeling experiments demonstrated the potential for using a hydrodynamic model to study radioisotope biogeochemistry in the lake, although further refinements are necessary.

CTL induction by cross-priming is restricted to immunodominant epitopes

CTL are induced by two pathways, i.e. direct priming, where tumor cells present tumor antigens to naïve specific CTL, and cross-priming, where professional APC cross-present captured tumor antigens to CTL. Here, we examined direct priming versus cross-priming after immunizing (H-2(b) x H-2(d)) F1 mice with either H-2(b) or H-2(d) positive tumor cells transfected with the GP or nucleoprotein (NP) of lymphocytic choriomeningitis virus (LCMV). Cross-priming was observed for the immunodominant epitopes LCMV-gp33 and -np118, although direct induction resulted in higher CTL frequencies. In contrast, CTL specific for the subdominant epitopes LCMV-gp283 or -np396 were induced only if epitopes were presented directly on MHC class I molecules of the immunizing cell. The broader repertoire and the higher CTL frequencies induced after vaccination with haplotype-matched tumor cells resulted in more efficient anti-tumor and antiviral protection. Firstly, our results indicate that certain virus and tumor antigens may not be detected by CD8(+) T cells because of impaired cross-priming. Secondly, efficient cross-priming contributes to the immunodominant nature of a tumor-specific CTL epitope. Thirdly, vaccine strategies using autologous or syngenic antigen-expressing cells induce a broader repertoire of tumor-specific CTL and higher CTL frequencies.