Pathobiologic Markers of the Ewing Sarcoma Family of Tumors: State of the Art and Prediction of Behaviour

Over the past three decades, the outcome of Ewing sarcoma family tumor (ESFT) patients who are nonmetastatic at presentation has improved considerably. The prognosis of patients with metastatic disease at the time of diagnosis and recurrence after therapy remains dismal. Drug-resistant disease at diagnosis or at relapse remains a major cause of mortality among patients diagnosed with ESFT. In order to improve the outcome for patients with potential relapse, there is an urgent need to find reliable markers that either predict tumor behaviour at diagnosis or identify therapeutic molecular targets at the time of recurrence. An improved understanding of the cell of origin and the molecular pathways that regulate tumorigenicity in ESFT should aid us in the search for novel therapies for ESFT. The purpose of this paper is thus to outline current concepts of sarcomagenesis in ESFT and to discuss ESFT patterns of differentiation and molecular markers that might affect prognosis or direct future therapeutic development

SKITTER foot design

A mechanical design team was formed to design a foot for the lunar utility vehicle SKITTER. The primary design was constrained to be a ski pole design compatible with the existing femur-tibia design legs. The lunar environment had several important effects on the foot design. Three materials were investigated for the SKITTER foot: aluminum alloys, cold worked stainless steel alloys, and titanium alloys. Thin film coatings were investigated as a method of wear reduction for the foot. The performance of the foot is dependent on the action of the legs. The range of motion for the legs was determined to be vertical to 15 degrees above horizontal. An impact analysis was performed for the foot movement, but the results were determined to be inconclusive due to unknown soil parameters. The initial foot design configuration consisted of an annulus attached to the pointed pole. The annulus was designed to prevent excess sinkage. Later designs call for a conical shaped foot with a disk at the point of the tibia attachment. The conical design was analyzed for strength and deflection by two different approaches. A deformable body analysis was performed for the foot under crane load in crane position, and also under actuator load in the vertical position. In both cases, the deflection of the foot was insignificant and the stresses well below the strength of the titanium alloy

Activity of opioid ligands in cells expressing cloned mu opioid receptors

BACKGROUND: The aim of the present study was to describe the activity of a set of opioid drugs, including partial agonists, in a cell system expressing only mu opioid receptors. Receptor activation was assessed by measuring the inhibition of forskolin-stimulated cyclic adenosine mono phosphate (cAMP) production. Efficacies and potencies of these ligands were determined relative to the endogenous ligand β-endorphin and the common mu agonist, morphine. RESULTS: Among the ligands studied naltrexone, WIN 44,441 and SKF 10047, were classified as antagonists, while the remaining ligands were agonists. Agonist efficacy was assessed by determining the extent of inhibition of forskolin-stimulated cAMP production. The rank order of efficacy of the agonists was fentanyl = hydromorphone = β-endorphin > etorphine = lofentanil = butorphanol = morphine = nalbuphine = nalorphine > cyclazocine = dezocine = metazocine ≥ xorphanol. The rank order of potency of these ligands was different from that of their efficacies; etorphine > hydromorphone > dezocine > xorphanol = nalorphine = butorphanol = lofentanil > metazocine > nalbuphine > cyclazocine > fentanyl > morphine >>>> β-endorphin. CONCLUSION: These results elucidate the relative activities of a set of opioid ligands at mu opioid receptor and can serve as the initial step in a systematic study leading to understanding of the mode of action of opioid ligands at this receptor. Furthermore, these results can assist in understanding the physiological effect of many opioid ligands acting through mu opioid receptors

Activation profiles of opioid ligands in HEK cells expressing δ opioid receptors

BACKGROUND: The aim of the present study was to characterize the activation profiles of 15 opioid ligands in transfected human embryonic kidney cells expressing only δ opioid receptors. Activation profiles of most of these ligands at δ opioid receptors had not been previously characterized in vitro. Receptor activation was assessed by measuring the inhibition of forskolin-stimulated cAMP production. RESULTS: Naltrexone and nalorphine were classified as antagonists at δ opioid receptor. The other ligands studied were agonists at δ opioid receptors and demonstrated IC(50 )values of 0.1 nM to 2 μM, maximal inhibition of 39–77% and receptor binding affinities of 0.5 to 243 nM. The rank order of efficacy of the ligands tested was metazocine = xorphanol ≥ fentanyl = SKF 10047 = etorphine = hydromorphone = butorphanol = lofentanil > WIN 44,441 = Nalbuphine = cyclazocine ≥ met-enkephalin >> morphine = dezocine. For the first time these data describe and compare the function and relative efficacy of several ligands at δ opioid receptors. CONCLUSIONS: The data produced from this study can lead to elucidation of the complete activation profiles of several opioid ligands, leading to clarification of the mechanisms involved in physiological effects of these ligands at δ opioid receptors. Furthermore, these data can be used as a basis for novel use of existing opioid ligands based on their pharmacology at δ opioid receptors

Pharmacological profiles of opioid ligands at Kappa opioid receptors

BACKGROUND: The aim of the present study was to describe the activity of a set of opioid drugs, including partial agonists, in a human embryonic kidney cell system stably expressing only the mouse κ-opioid receptors. Receptor activation was assessed by measuring the inhibition of cyclic adenosine mono phosphate (cAMP) production stimulated by 5 μM forskolin. Intrinsic activities and potencies of these ligands were determined relative to the endogenous ligand dynorphin and the κ agonist with the highest intrinsic activity that was identified in this study, fentanyl. RESULTS: Among the ligands studied naltrexone, WIN 44,441 and dezocine, were classified as antagonists, while the remaining ligands were agonists. Intrinsic activity of agonists was assessed by determining the extent of inhibition of forskolin-stimulated cAMP production. The absolute levels of inhibition of cAMP production by each ligand was used to describe the rank order of intrinsic activity of the agonists; fentanyl = lofentanil ≥ hydromorphone = morphine = nalorphine ≥ etorphine ≥ xorphanol ≥ metazocine ≥ SKF 10047 = cyclazocine ≥ butorphanol > nalbuphine. The rank order of affinity of these ligands was; cyclazocine > naltrexone ≥ SKF 10047 ≥ xorphanol ≥ WIN 44,441 > nalorphine > butorphanol > nalbuphine ≥ lofentanil > dezocine ≥ metazocine ≥ morphine > hydromorphone > fentanyl. CONCLUSION: These results elucidate the relative activities of a set of opioid ligands at κ-opioid receptor and can serve as the initial step in a systematic study leading to understanding of the mode of action of these opioid ligands at this receptor

Historical Analysis of Submerged Aquatic Vegetation (SAV) in the Potomac River and Analysis of Bay-wide SAV Data to Establish a New Acreage Goal : Final Report

Throughout most regions of the Chesapeake Bay and its tributaries both direct and anecdotal evidence has indicated that large-scale declines of submerged aquatic vegetation (SAV) occurred in the late 1960s and early 1970s (Orth and Moore 1983). These declines have been related to increasing amounts of non-point inputs of nutrients and sediments in the bay system resulting from development of the bay’s shorelines and watershed (Twilley et al. 1985). Currently there are approximately 89,659 acres of SAV in Chesapeake Bay (Orth et al. 2003). Although it has been estimated that this is approximately 15% of the bay’s historical SAV distribution, most comprehensive analyses have been based on 1971 or later aerial photography and the distributions of SAV prior to this time in many regions are not well known. SAV is a highly valuable resource and its presence serves as an important indicator of local water quality conditions (Dennison et al. 1993). SAV growth and survival can be decreased by high levels of turbidity and nutrient enrichment. Because SAV beds are non-motile, their presence serves as an integrating measure of variable water quality conditions in local areas (Moore et al. 1996). Because of the direct relationships between SAV and water quality, trends in the distribution and abundance of SAV over time are also very useful in understanding trends in water quality. Review of photographic evidence from a number of sites dating back to 1937 suggests that SAV, once abundant throughout the Chesapeake Bay system, have declined from historical levels and therefore water quality conditions may have similarly deteriorated (Orth and Moore 1983)

The Maritime Archaeology of Duplex Drive Tanks in the United Kingdom.

The catastrophe at Dieppe in 1942, where unsupported infantry attempted to capture a fortified beachhead, showed the allied forces how difficult such a venture was. As part of the invasion plan for what became Operation NEPTUNE or the Normandy landings, the allied staff saw the need for armoured support for the first waves of troops ashore. This need evolved into the concept of ‘swimming tanks’ that would land a few minutes ahead of the first infantry waves. The development of such a weapon was undertaken in conditions of absolute secrecy in the UK from late 1942 onwards. This secrecy led to the destruction of much of the historical records that relate to these armoured vehicles, leaving a confused and largely unknown record of what was an important aspect of WWII. This project sets out to record the known examples of such vehicles on the coast of the UK including a group lost as part of ‘Exercise SMASH’, the largest live ammunition exercise of the war, a full scale beach assault training exercise with all supporting arms including amphibious tanks. Though six tanks were lost during the exercise in conditions, which are not fully understood, the loss led to the changing of the operational plans for D-Day. Using archaeological and historic data, this project offers an alternative interpretation for these loses and provides a better understanding of their subsequent impact on Operation NEPTUNE

Geriatric Interdisciplinary Team Training

Educational Objectives 1. To demonstrate the importance of training health care professionals in inter-disciplinary teamwork and geriatric health issues. 2. To increase one’s knowledge of the roles and responsibilities of the various disciplines involved in interdisciplinary teamwork