The Effects of Radiation and Temperature Stress on an Aquatic Ecosystem

A thesis presented to the faculty of the School of Sciences and Mathematics at Morehead State University in partial fulfillment of the requirements for the Degree of Master of Science in Biology by Gene L. Samsel, Jr. on May 14, 1968

Inferences on Sicilian Mesolithic subsistence patterns from cross-sectional geometry and entheseal changes

Using cross-sectional geometry (CSG), entheseal changes (ECs), and presence of external auditory meatus exostosis (EAE), this study tests the hypothesis—based on isotopic and zooarchaeological evidence—that in the Sicilian Mesolithic terrestrial rather than marine resources were predominantly exploited, in substantial continuity with previous Epigravettian hunters. Results show similarities in the general frequency of ECs—a rough proxy for overall activity—with Late Pleistocene hunters, in contrast with Mesolithic coastal foragers or Neolithic herders/farmers. Yet, CSG suggests that this possible continuity in the type of resources exploited was accompanied by a behavioral change, and in particular the abandonment of the throwing technology, possibly in favor of new tools such as traps and the bow and arrow. In fact, the dramatic decrease in humeral bilateral asymmetry documented at a European level with the Pleistocene-Holocene transition can be found also in the Sicilian Mesolithic. Results for the lower limb appear compatible with a certain degree of terrestrial mobility in a rugged environment. The frequency of EAE suggests that activities related to water were present but not common; however, their prominence is difficult to determine given the small sample size. The pattern of information provided by the proxies for activity used here is complex and partially contrasting, but has the potential to integrate and enrich archeological methods and biochemical approaches. This study corroborates a varied scenario of continuity and discontinuity in subsistence at the Pleistocene-Holocene transition, and highlights the importance of a regional bioarchaeological approach of human biological and behavioral adaptations

Kinetic Anomalies in Addition-Aggregation Processes

We investigate irreversible aggregation in which monomer-monomer, monomer-cluster, and cluster-cluster reactions occur with constant but distinct rates K_{MM}, K_{MC}, and K_{CC}, respectively. The dynamics crucially depends on the ratio gamma=K_{CC}/K_{MC} and secondarily on epsilon=K_{MM}/K_{MC}. For epsilon=0 and gamma<2, there is conventional scaling in the long-time limit, with a single mass scale that grows linearly in time. For gamma >= 2, there is unusual behavior in which the concentration of clusters of mass k, c_k decays as a stretched exponential in time within a boundary layer k<k* propto t^{1-2/gamma} (k* propto ln t for gamma=2), while c_k propto t^{-2} in the bulk region k>k*. When epsilon>0, analogous behaviors emerge for gamma<2 and gamma >= 2.Comment: 6 pages, 2 column revtex4 format, for submission to J. Phys.

Renormalisation-theoretic analysis of non-equilibrium phase transitions I: The Becker-Doring equations with power law rate coefficients

We study in detail the application of renormalisation theory to models of cluster aggregation and fragmentation of relevance to nucleation and growth processes. We investigate the Becker-Dorging equations, originally formulated to describe and analyse non-equilibrium phase transitions, and more recently generalised to describe a wide range of physicochemical problems. In the present paper we analyse how the systematic coarse-graining renormalisation of the \BD system of equations affects the aggregation and fragmentation rate coefficients. We consider the case of power-law size-dependent cluster rate coefficients which we show lead to only three classes of system that require analysis: coagulation-dominated systems, fragmentation-dominated systems and those where coagulation and fragmentation are exactly balanced. We analyse the late-time asymptotics associated with each class.Comment: 18 pages, to appear in J Phys A Math Ge

Assessment of response of kidney tumours to rapamycin and atorvastatin in Tsc1+/- mice

Atorvastatin is widely used to lower blood cholesterol and to reduce risk of cardiovascular disease–associated complications. Epidemiological investigations and preclinical studies suggest that statins such as atorvastatin have antitumor activity for various types of cancer. Tuberous sclerosis (TSC) is a tumor syndrome caused by TSC1 or TSC2 mutations that lead to aberrant activation of mTOR and tumor formation in multiple organs. Previous studies have demonstrated that atorvastatin selectively suppressed growth and proliferation ofmouse Tsc2 null embryonic fibroblasts through inhibition ofmTOR. However, atorvastatin alone did not reduce tumor burden in the liver and kidneys of Tsc2+/− mice as assessed by histological analysis, and no combination therapy of rapamycin and atorvastatin has been tried. In this study, we used T2-weightedmagnetic resonance imaging to track changes in tumor number and size in the kidneys of a Tsc1+/− mousemodel and to assess the efficacy of rapamycin and atorvastatin alone and as a combination therapy. We found that rapamycin alone or rapamycin combined with atorvastatin significantly reduced tumor burden, while atorvastatin alone did not. Combined therapy with rapamycin and atorvastatin appeared to be more effective for treating renal tumors than rapamycin alone, but the difference was not statistically significant. We conclude that combined therapy with rapamycin and atorvastatin is unlikely to provide additional benefit over rapamycin as a single agent in the treatment of Tsc-associated renal tumors

First Observation of Quantum Oscillations in the Ferromagnetic Superconductor UCoGe

We succeeded in growing high quality single crystals of the ferromagnetic superconductor UCoGe and measured the magnetoresistance at fields up to 34T. The Shubnikov-de Haas signal was observed for the first time in a U-111 system (UTGe, UTSi, T: transition metal). A small pocket Fermi surface (F~1kT) with large cyclotron effective mass 25m0 was detected at high fields above 22T, implying that UCoGe is a low carrier system accompanyed with heavy quasi-particles. The observed frequency decreases with increasing fields, indicating that the volume of detected Fermi surface changes nonlinearly with field. The cyclotron mass also decreases, which is consistent with the decrease of the A coefficient of resistivity.Comment: 5 pages, 5 figures, accepted for publication in J. Phys. Soc. Jp

Ferromagnetism and Superconductivity in Uranium Compounds

Recent advances on ferromagnetic superconductors, UGe2, URhGe and UCoGe are presented. The superconductivity (SC) peacefully coexists with the ferromagnetism (FM), forming the spin-triplet state of Cooper pairs. The striking new phenomena, such as SC reinforced by the magnetic field, are associated with Ising-type ferromagnetic fluctuations. A variety of ferromagnetic ordered moments between UGe2, URhGe and UCoGe affords to understand the relation between FM, tricriticality and SC.Comment: 11 pages, 16 figures, accepted for publication in J. Phys. Soc. Jpn. as a review article of Special Topics of "Recent developments in superconductivity

Mitochondrially targeted ceramide LCL-30 inhibits colorectal cancer in mice

The sphingolipid ceramide is intimately involved in the growth, differentiation, senescence, and death of normal and cancerous cells. Mitochondria are increasingly appreciated to play a key role in ceramide-induced cell death. Recent work showed the C16-pyridinium ceramide analogue LCL-30 to induce cell death in vitro by mitochondrial targeting. The aim of the current study was to translate these results to an in vivo model. We found that LCL-30 accumulated in mitochondria in the murine colorectal cancer cell line CT-26 and reduced cellular ATP content, leading to dose- and time-dependent cytotoxicity. Although the mitochondrial levels of sphingosine-1-phosphate (S1P) became elevated, transcription levels of ceramide-metabolising enzymes were not affected. In mice, LCL-30 was rapidly absorbed from the peritoneal cavity and cleared from the circulation within 24 h, but local peritoneal toxicity was dose-limiting. In a model of subcutaneous tumour inoculation, LCL-30 significantly reduced the proliferative activity and the growth rate of established tumours. Sphingolipid profiles in tumour tissue also showed increased levels of S1P. In summary, we present the first in vivo application of a long-chain pyridinium ceramide for the treatment of experimental metastatic colorectal cancer, together with its pharmacokinetic parameters. LCL-30 was an efficacious and safe agent. Future studies should identify an improved application route and effective partners for combination treatment

Application of B cell immortalization for the isolation of antibodies and B cell clones from vaccine and infection settings

The isolation and characterization of neutralizing antibodies from infection and vaccine settings informs future vaccine design, and methodologies that streamline the isolation of antibodies and the generation of B cell clones are of great interest. Retroviral transduction to express Bcl-6 and Bcl-xL and transform primary B cells has been shown to promote long-term B cell survival and antibody secretion in vitro, and can be used to isolate antibodies from memory B cells. However, application of this methodology to B cell subsets from different tissues and B cells from chronically infected individuals has not been well characterized. Here, we characterize Bcl-6/Bcl-xL B cell immortalization across multiple tissue types and B cell subsets in healthy and HIV-1 infected individuals, as well as individuals recovering from malaria. In healthy individuals, naïve and memory B cell subsets from PBMCs and tonsil tissue transformed with similar efficiencies, and displayed similar characteristics with respect to their longevity and immunoglobulin secretion. In HIV-1-viremic individuals or in individuals with recent malaria infections, the exhausted CD27-CD21- memory B cells transformed with lower efficiency, but the transformed B cells expanded and secreted IgG with similar efficiency. Importantly, we show that this methodology can be used to isolate broadly neutralizing antibodies from HIV-infected individuals. Overall, we demonstrate that Bcl-6/Bcl-xL B cell immortalization can be used to isolate antibodies and generate B cell clones from different B cell populations, albeit with varying efficiencies

Serum IL-6: a candidate biomarker for intracranial pressure elevation following isolated traumatic brain injury

<p>Abstract</p> <p>Background</p> <p>Increased intracranial pressure (ICP) is a serious, life-threatening, secondary event following traumatic brain injury (TBI). In many cases, ICP rises in a delayed fashion, reaching a maximal level 48-96 hours after the initial insult. While pressure catheters can be implanted to monitor ICP, there is no clinically proven method for determining a patient's risk for developing this pathology.</p> <p>Methods</p> <p>In the present study, we employed antibody array and Luminex-based screening methods to interrogate the levels of inflammatory cytokines in the serum of healthy volunteers and in severe TBI patients (GCS≤8) with or without incidence of elevated intracranial pressure (ICP). De-identified samples and ELISAs were used to confirm the sensitivity and specificity of IL-6 as a prognostic marker of elevated ICP in both isolated TBI patients, and polytrauma patients with TBI.</p> <p>Results</p> <p>Consistent with previous reports, we observed sustained increases in IL-6 levels in TBI patients irrespective of their ICP status. However, the group of patients who subsequently experienced ICP ≥ 25 mm Hg had significantly higher IL-6 levels within the first 17 hours of injury as compared to the patients whose ICP remained ≤20 mm Hg. When blinded samples (n = 22) were assessed, a serum IL-6 cut-off of <5 pg/ml correctly identified 100% of all the healthy volunteers, a cut-off of >128 pg/ml correctly identified 85% of isolated TBI patients who subsequently developed elevated ICP, and values between these cut-off values correctly identified 75% of all patients whose ICP remained ≤20 mm Hg throughout the study period. In contrast, the marker had no prognostic value in predicting elevated ICP in polytrauma patients with TBI. When the levels of serum IL-6 were assessed in patients with orthopedic injury (n = 7) in the absence of TBI, a significant increase was found in these patients compared to healthy volunteers, albeit lower than that observed in TBI patients.</p> <p>Conclusions</p> <p>Our results suggest that serum IL-6 can be used for the differential diagnosis of elevated ICP in isolated TBI.</p