Atypical scrapie in a Swiss goat and implications for transmissible spongiform encephalopathy surveillance

Different types of transmissible spongiform encephalopathies (TSEs) affect sheep and goats. In addition to the classical form of scrapie, both species are susceptible to experimental infections with the bovine spongiform encephalopathy (BSE) agent, and in recent years atypical scrapie cases have been reported in sheep from different European countries. Atypical scrapie in sheep is characterized by distinct histopathologic lesions and molecular characteristics of the abnormal scrapie prion protein (PrP(sc)). Characteristics of atypical scrapie have not yet been described in detail in goats. A goat presenting features of atypical scrapie was identified in Switzerland. Although there was no difference between the molecular characteristics of PrP(sc) in this animal and those of atypical scrapie in sheep, differences in the distribution of histopathologic lesions and PrP(sc) deposition were observed. In particular the cerebellar cortex, a major site of PrP(sc) deposition in atypical scrapie in sheep, was found to be virtually unaffected in this goat. In contrast, severe lesions and PrP(sc) deposition were detected in more rostral brain structures, such as thalamus and midbrain. Two TSE screening tests and PrP(sc) immunohistochemistry were either negative or barely positive when applied to cerebellum and obex tissues, the target samples for TSE surveillance in sheep and goats. These findings suggest that such cases may have been missed in the past and could be overlooked in the future if sampling and testing procedures are not adapted. The epidemiological and veterinary public health implications of these atypical cases, however, are not yet known.

Cytokine activation and disease progression in patients with stable moderate chronic heart failure

BACKGROUND: Activation of the cytokine and the complement system is associated with disease progression in severe congestive heart failure (CHF). Magnitude and prognostic relevance of cytokine and complement activation remain uncertain in patients with moderate CHF. OBJECTIVES: Measurement of cytokine and complement activation in patients with moderate CHF and testing whether C-reactive protein (CRP) can serve as a surrogate marker of their activation, adding independent prognostic information when co-measured with B-type natriuretic peptide (BNP). METHODS: The 118 study participants were separated into three groups based on pre-determined CRP and BNP levels: Group I (n = 27; CRP > 5 mg/liter, BNP > or = 200 pg/ml); Group II (n = 46; CRP < or = 5 mg/liter, BNP > or = 200 pg/ml); and Group III (n = 45; CRP < or = 5 mg/liter, BNP < 200 pg/ml). RESULTS: Mortality was high in Group I (30%; log-rank p < 0.001) but low in Groups II and III (2% and 4%, respectively; log rank, p = 0.7). No differences were observed for left ventricular ejection fraction (LVEF) and left ventricular end-diastolic diameter (LVEDD) between Groups I and II (31 +/- 16 vs 32 +/- 14% and 66 +/- 16 vs 65 +/- 11 mm, respectively), whereas in Group III LVEF was higher (42 +/- 17%, p = 0.002) with smaller LVEDD (57 +/- 13 mm, p = 0.012). Cytokine sCD14 and tumor necrosis factor (TNF)-alpha levels were not different between the three groups. However, interleukin-6 levels (9.75 +/- 8.17 pg/ml, p = 0.001) and the terminal complement complex C5b-9 (109.9 +/- 68 ng/ml; p = 0.04) were elevated in Group I, both correlating with CRP (interleukin-6: r = 0.5, p < 0.001; C5b-9: r = 0.41, p = 0.001). CONCLUSIONS: CRP may be used as a surrogate parameter for interleukin-6 and complement activation in moderate CHF. CRP in combination with BNP identifies a high-risk group with a tendency for poor outcome not discriminated by cardiac function.

Price risk management in the copper market using commodity derivatives and options strategies

Metals price risk management is a key issue related to financial risk in metal markets because of uncertainty of commodity price fluctuation, exchange rate, interest rate changes and huge price risk either to metals’ producers or consumers. Thus, it has been taken into account by all participants in metal markets including metals’ producers, consumers, merchants, banks, investment funds, speculators, traders and so on. Managing price risk provides stable income for both metals’ producers and consumers, so it increases the chance that a firm will invest in attractive projects. The purpose of this research is to evaluate risk management strategies in the copper market. The main tools and strategies of price risk management are hedging and other derivatives such as futures contracts, swaps and options contracts. Hedging is a transaction designed to reduce or eliminate price risk. Derivatives are financial instruments, whose returns are derived from other financial instruments and they are commonly used for managing financial risks. Although derivatives have been around in some form for centuries, their growth has accelerated rapidly during the last 20 years. Nowadays, they are widely used by financial institutions, corporations, professional investors, and individuals. This project is focused on the over-the-counter (OTC) market and its products such as exotic options, particularly Asian options. The first part of the project is a description of basic derivatives and risk management strategies. In addition, this part discusses basic concepts of spot and futures (forward) markets, benefits and costs of risk management and risks and rewards of positions in the derivative markets. The second part considers valuations of commodity derivatives. In this part, the options pricing model DerivaGem is applied to Asian call and put options on London Metal Exchange (LME) copper because it is important to understand how Asian options are valued and to compare theoretical values of the options with their market observed values. Predicting future trends of copper prices is important and would be essential to manage market price risk successfully. Therefore, the third part is a discussion about econometric commodity models. Based on this literature review, the fourth part of the project reports the construction and testing of an econometric model designed to forecast the monthly average price of copper on the LME. More specifically, this part aims at showing how LME copper prices can be explained by means of a simultaneous equation structural model (two-stage least squares regression) connecting supply and demand variables. A simultaneous econometric model for the copper industry is built: {█(Q_t^D=e^((-5.0485))∙P_((t-1))^((-0.1868) )∙〖GDP〗_t^((1.7151) )∙e^((0.0158)∙〖IP〗_t ) @Q_t^S=e^((-3.0785))∙P_((t-1))^((0.5960))∙T_t^((0.1408))∙P_(OIL(t))^((-0.1559))∙〖USDI〗_t^((1.2432))∙〖LIBOR〗_((t-6))^((-0.0561))@Q_t^D=Q_t^S )┤ P_((t-1))^CU=e^((-2.5165))∙〖GDP〗_t^((2.1910))∙e^((0.0202)∙〖IP〗_t )∙T_t^((-0.1799))∙P_(OIL(t))^((0.1991))∙〖USDI〗_t^((-1.5881))∙〖LIBOR〗_((t-6))^((0.0717) Where, Q_t^D and Q_t^Sare world demand for and supply of copper at time t respectively. P(t-1) is the lagged price of copper, which is the focus of the analysis in this part. GDPt is world gross domestic product at time t, which represents aggregate economic activity. In addition, industrial production should be considered here, so the global industrial production growth that is noted as IPt is included in the model. Tt is the time variable, which is a useful proxy for technological change. A proxy variable for the cost of energy in producing copper is the price of oil at time t, which is noted as POIL(t ) . USDIt is the U.S. dollar index variable at time t, which is an important variable for explaining the copper supply and copper prices. At last, LIBOR(t-6) is the 6-month lagged 1-year London Inter bank offering rate of interest. Although, the model can be applicable for different base metals' industries, the omitted exogenous variables such as the price of substitute or a combined variable related to the price of substitutes have not been considered in this study. Based on this econometric model and using a Monte-Carlo simulation analysis, the probabilities that the monthly average copper prices in 2006 and 2007 will be greater than specific strike price of an option are defined. The final part evaluates risk management strategies including options strategies, metal swaps and simple options in relation to the simulation results. The basic options strategies such as bull spreads, bear spreads and butterfly spreads, which are created by using both call and put options in 2006 and 2007 are evaluated. Consequently, each risk management strategy in 2006 and 2007 is analyzed based on the day of data and the price prediction model. As a result, applications stemming from this project include valuing Asian options, developing a copper price prediction model, forecasting and planning, and decision making for price risk management in the copper market.

Simulating dioxane transport in a heterogeneous glacial aquifer system (Washtenaw County, Michigan) using publicly available models and data

The primary challenge in groundwater and contaminant transport modeling is obtaining the data needed for constructing, calibrating and testing the models. Large amounts of data are necessary for describing the hydrostratigraphy in areas with complex geology. Increasingly states are making spatial data available that can be used for input to groundwater flow models. The appropriateness of this data for large-scale flow systems has not been tested. This study focuses on modeling a plume of 1,4-dioxane in a heterogeneous aquifer system in Scio Township, Washtenaw County, Michigan. The analysis consisted of: (1) characterization of hydrogeology of the area and construction of a conceptual model based on publicly available spatial data, (2) development and calibration of a regional flow model for the site, (3) conversion of the regional model to a more highly resolved local model, (4) simulation of the dioxane plume, and (5) evaluation of the model's ability to simulate field data and estimation of the possible dioxane sources and subsequent migration until maximum concentrations are at or below the Michigan Department of Environmental Quality's residential cleanup standard for groundwater (85 ppb). MODFLOW-2000 and MT3D programs were utilized to simulate the groundwater flow and the development and movement of the 1, 4-dioxane plume, respectively. MODFLOW simulates transient groundwater flow in a quasi-3-dimensional sense, subject to a variety of boundary conditions that can simulate recharge, pumping, and surface-/groundwater interactions. MT3D simulates solute advection with groundwater flow (using the flow solution from MODFLOW), dispersion, source/sink mixing, and chemical reaction of contaminants. This modeling approach was successful at simulating the groundwater flows by calibrating recharge and hydraulic conductivities. The plume transport was adequately simulated using literature dispersivity and sorption coefficients, although the plume geometries were not well constrained.

AN EXPERIMENTAL STUDY OF PARTIAL LOW RISK DEPLOYMENT IN A FIXED VEHICLE ENVIRONMENT

This study will look at the passenger air bag (PAB) performance in a fix vehicle environment using Partial Low Risk Deployment (PLRD) as a strategy. This development will follow test methods against actual baseline vehicle data and Federal Motor Vehicle Safety Standards 208 (FMVSS 208). FMVSS 208 states that PAB compliance in vehicle crash testing can be met using one of three deployment methods. The primary method suppresses PAB deployment, with the use of a seat weight sensor or occupant classification sensor (OCS), for three-year old and six-year old occupants including the presence of a child seat. A second method, PLRD allows deployment on all size occupants suppressing only for the presents of a child seat. A third method is Low Risk Deployment (LRD) which allows PAB deployment in all conditions, all statures including any/all child seats. This study outlines a PLRD development solution for achieving FMVSS 208 performance. The results of this study should provide an option for system implementation including opportunities for system efficiency and other considerations. The objective is to achieve performance levels similar too or incrementally better than the baseline vehicles National Crash Assessment Program (NCAP) Star rating. In addition, to define systemic flexibility where restraint features can be added or removed while improving occupant performance consistency to the baseline. A certified vehicles’ air bag system will typically remain in production until the vehicle platform is redesigned. The strategy to enable the PLRD hypothesis will be to first match the baseline out of position occupant performance (OOP) for the three and six-year old requirements. Second, improve the 35mph belted 5th percentile female NCAP star rating over the baseline vehicle. Third establish an equivalent FMVSS 208 certification for the 25mph unbelted 50th percentile male. FMVSS 208 high-speed requirement defines the federal minimum crash performance required for meeting frontal vehicle crash-test compliance. The intent of NCAP 5-Star rating is to provide the consumer with information about crash protection, beyond what is required by federal law. In this study, two vehicles segments were used for testing to compare and contrast to their baseline vehicles performance. Case Study 1 (CS1) used a cross over vehicle platform and Case Study 2 (CS2) used a small vehicle segment platform as their baselines. In each case study, the restraints systems were from different restraint supplier manufactures and each case contained that suppliers approach to PLRD. CS1 incorporated a downsized twins shaped bag, a carryover inflator, standard vents, and a strategic positioned bag diffuser to help disperse the flow of gas to improve OOP. The twin shaped bag with two segregated sections (lobes) to enabled high-speed baseline performance correlation on the HYGE Sled. CS2 used an A-Symmetric (square shape) PAB with standard size vents, including a passive vent, to obtain OOP similar to the baseline. The A-Symmetric shape bag also helped to enabled high-speed baseline performance improvements in HYGE Sled testing in CS2. The anticipated CS1 baseline vehicle-pulse-index (VPI) target was in the range of 65-67. However, actual dynamic vehicle (barrier) testing was overshadowed with the highest crash pulse from the previous tested vehicles with a VPI of 71. The result from the 35mph NCAP Barrier test was a solid 4-Star (4.7 Star) respectfully. In CS2, the vehicle HYGE Sled development VPI range, from the baseline was 61-62 respectively. Actual NCAP test produced a chest deflection result of 26mm versus the anticipated baseline target of 12mm. The initial assessment of this condition was thought to be due to the vehicles significant VPI increase to 67. A subsequent root cause investigation confirmed a data integrity issue due to the instrumentation. In an effort to establish a true vehicle test data point a second NCAP test was performed but faced similar instrumentation issues. As a result, the chest deflect hit the target of 12.1mm; however a femur load spike, similar to the baseline, now skewed the results. With noted level of performance improvement in chest deflection, the NCAP star was assessed as directional for 5-Star capable performance. With an actual rating of 3-Star due to instrumentation, using data extrapolation raised the ratings to 5-Star. In both cases, no structural changes were made to the surrogate vehicle and the results in each case matched their perspective baseline vehicle platforms. These results proved the PLRD is viable for further development and production implementation.

Epigenetic diversity increases the productivity and stability of plant populations

Biological diversity within species can be an important driver of population and ecosystem functioning. Until now, such within-species diversity effects have been attributed to underlying variation in DNA sequence. However, within-species differences, and thus potentially functional biodiversity, can also be created by epigenetic variation. Here, we show that epigenetic diversity increases the productivity and stability of plant populations. Epigenetically diverse populations of Arabidopsis thaliana produce up to 40% more biomass than epigenetically uniform populations. The positive epigenetic diversity effects are strongest when populations are grown together with competitors and infected with pathogens, and they seem to be partly driven by complementarity among epigenotypes. Our study has two implications: first, we may need to re-evaluate previous within-species diversity studies where some effects could reflect epigenetic diversity; second, we need to incorporate epigenetics into basic ecological research, by quantifying natural epigenetic diversity and testing for its ecological consequences across many different species.

Radiographic and safety details of vertebral body stenting: results from a multicenter chart review

BACKGROUND Up to one third of BKP treated cases shows no appreciable height restoration due to loss of both restored height and kyphotic realignment after balloon deflation. This shortcoming has called for an improved method that maintains the height and realignment reached by the fully inflated balloon until stabilization of the vertebral body by PMMA-based cementation. Restoration of the physiological vertebral body height for pain relief and for preventing further fractures of adjacent and distant vertebral bodies must be the main aim for such a method. A new vertebral body stenting system (VBS) stabilizes the vertebral body after balloon deflation until cementation. The radiographic and safety results of the first 100 cases where VBS was applied are presented. METHODS During the planning phase of an ongoing international multicenter RCT, radiographic, procedural and followup details were retrospectively transcribed from charts and xrays for developing and testing the case report forms. Radiographs were centrally assessed at the institution of the first/senior author. RESULTS 100 patients (62 with osteoporosis) with a total of 103 fractured vertebral bodies were treated with the VBS system. 49 were females with a mean age of 73.2 years; males were 66.7 years old. The mean preoperative anterior-middle-posterior heights were 20.3-17.6-28.0 mm, respectively. The mean local kyphotic angle was 13.1[degree sign]. The mean preoperative Beck Index (anterior edge height/posterior edge height) was 0.73, the mean alternative Beck Index (middle height/posterior edge height) was 0.63. The mean postoperative heights were restored to 24.5-24.6-30.4 mm, respectively. The mean local kyphotic angle was reduced to 8.9[degree sign]. The mean postoperative Beck Index was 0.81, the mean alternative one was 0.82. The overall extrusion rate was 29.1%, the symptomatic one was 1%. In the osteoporosis subgroup there were 23.8% extrusions. Within the three months followup interval there were 9% of adjacent and 4% of remote new fractures, all in the osteoporotic group. CONCLUSIONS VBS showed its strengths especially in realignment of crush and biconcave fractures. Given that fracture mobility is present, the realignment potential is sound and increases with the severity of preoperative vertebral body deformation.

CHARACTERIZING AND TREATING THE NEUROPATHOLOGY OF TUBEROUS SCLEROSIS COMPLEX IN THE MOUSE

Tuberous sclerosis complex (TSC) is a multisystem, autosomal dominant disorder affecting approximately 1 in 6000 births. Developmental brain abnormalities cause substantial morbidity and mortality and often lead to neurological disease including epilepsy, cognitive disabilities, and autism. TSC is caused by inactivating mutations in either TSC1 or TSC2, whose protein products are known inhibitors of mTORC1, an important kinase regulating translation and cell growth. Nonetheless, neither the pathophysiology of the neurological manifestations of TSC nor the extent of mTORC1 involvement in the development of these lesions is known. Murine models would greatly advance the study of this debilitating disorder. This thesis will describe the generation and characterization of a novel brain-specific mouse model of TSC, Tsc2flox/ko;hGFAP-Cre. In this model, the Tsc2 gene has been removed from most neurons and glia of the cortex and hippocampus by targeted Cre-mediated deletion in radial glial neuroprogenitor cells. The Tsc2flox/ko;hGFAP-Cre mice fail to thrive beginning postnatal day 8 and die from seizures around 23 days. Further characterization of these mice demonstrated megalencephaly, enlarged neurons, abnormal neuronal migration, altered progenitor pools, hypomyelination, and an astrogliosis. The similarity of these defects to those of TSC patients establishes this mouse as an excellent model for the study of the neuropathology of TSC and testing novel therapies. We further describe the use of this mouse model to assess the therapeutic potential of the macrolide rapamycin, an inhibitor of mTORC1. We demonstrate that rapamycin administered from postnatal day 10 can extend the life of the mutant animals 5 fold. Since TSC is a neurodevelopmental disorder, we also assessed in utero and/or immediate postnatal treatment of the animals with rapamycin. Amazingly, combined in utero and postnatal rapamycin effected a histologic rescue that was almost indistinguishable from control animals, indicating that dysregulation of mTORC1 plays a large role in TSC neuropathology. In spite of the almost complete histologic rescue, behavioral studies demonstrated that combined treatment resulted in poorer learning and memory than postnatal treatment alone. Postnatally-treated animals behaved similarly to treated controls, suggesting that immediate human treatment in the newborn period might provide the most opportune developmental timepoint for rapamycin administration.

Probing the Allende meteorite with a miniature laser-ablation mass analyser for space application

We measured the elemental composition on a sample of Allende meteorite with a miniature laser ablation mass spectrometer. This Laser Mass Spectrometer (LMS) has been designed and built at the University of Bern in the Department of Space Research and Planetary Sciences with the objective of using such an instrument on a space mission. Utilising the meteorite Allende as the test sample in this study, it is demonstrated that the instrument allows the in situ determination of the elemental composition and thus mineralogy and petrology of untreated rocky samples, particularly on planetary surfaces. In total, 138 measurements of elemental compositions have been carried out on an Allende sample. The mass spectrometric data are evaluated and correlated with an optical image. It is demonstrated that by illustrating the measured elements in the form of mineralogical maps, LMS can serve as an element imaging instrument with a very high spatial resolution of µm scale. The detailed analysis also includes a mineralogical evaluation and an investigation of the volatile element content of Allende. All findings are in good agreement with published data and underline the high sensitivity, accuracy and capability of LMS as a mass analyser for space exploration.

The Nature of Scientific Proof in the Age of Simulations. Is numerical mimicry a third way of establishing truth?

Is numerical mimicry a third way of establishing truth? Kevin Heng received his M.S. and Ph.D. in astrophysics from the Joint Institute for Laboratory Astrophysics (JILA) and the University of Colorado at Boulder. He joined the Institute for Advanced Study in Princeton from 2007 to 2010, first as a Member and later as the Frank & Peggy Taplin Member. From 2010 to 2012 he was a Zwicky Prize Fellow at ETH Z¨urich (the Swiss Federal Institute of Technology). In 2013, he joined the Center for Space and Habitability (CSH) at the University of Bern, Switzerland, as a tenure-track assistant professor, where he leads the Exoplanets and Exoclimes Group. He has worked on, and maintains, a broad range of interests in astrophysics: shocks, extrasolar asteroid belts, planet formation, fluid dynamics, brown dwarfs and exoplanets. He coordinates the Exoclimes Simulation Platform (ESP), an open-source set of theoretical tools designed for studying the basic physics and chemistry of exoplanetary atmospheres and climates (www.exoclime.org). He is involved in the CHEOPS (Characterizing Exoplanet Satellite) space telescope, a mission approved by the European Space Agency (ESA) and led by Switzerland. He spends a fair amount of time humbly learning the lessons gleaned from studying the Earth and Solar System planets, as related to him by atmospheric, climate and planetary scientists. He received a Sigma Xi Grant-in-Aid of Research in 2006

Shaping the PSF to nearly top-hat profile: CHEOPS laboratory results

Spreading the PSF over a quite large amount of pixels is an increasingly used observing technique in order to reach extremely precise photometry, such as in the case of exoplanets searching and characterization via transits observations. A PSF top-hat profile helps to minimize the errors contribution due to the uncertainty on the knowledge of the detector flat field. This work has been carried out during the recent design study in the framework of the ESA small mission CHEOPS. Because of lack of perfect flat-fielding information, in the CHEOPS optics it is required to spread the light of a source into a well defined angular area, in a manner as uniform as possible. Furthermore this should be accomplished still retaining the features of a true focal plane onto the detector. In this way, for instance, the angular displacement on the focal plane is fully retained and in case of several stars in a field these look as separated as their distance is larger than the spreading size. An obvious way is to apply a defocus, while the presence of an intermediate pupil plane in the Back End Optics makes attractive to introduce here an optical device that is able to spread the light in a well defined manner, still retaining the direction of the chief ray hitting it. This can be accomplished through an holographic diffuser or through a lenslet array. Both techniques implement the concept of segmenting the pupil into several sub-zones where light is spread to a well defined angle. We present experimental results on how to deliver such PSF profile by mean of holographic diffuser and lenslet array. Both the devices are located in an intermediate pupil plane of a properly scaled laboratory setup mimicking the CHEOPS optical design configuration. © (2014) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.

Optical Light Curve Observations to Determine Attitude States of Space Debris

The currently proposed space debris remediation measures include the active removal of large objects and “just in time” collision avoidance by deviating the objects using, e.g., ground-based lasers. Both techniques require precise knowledge of the attitude state and state changes of the target objects. In the former case, to devise methods to grapple the target by a tug spacecraft, in the latter, to precisely propagate the orbits of potential collision partners as disturbing forces like air drag and solar radiation pressure depend on the attitude of the objects. Non-resolving optical observations of the magnitude variations, so-called light curves, are a promising technique to determine rotation or tumbling rates and the orientations of the actual rotation axis of objects, as well as their temporal changes. The 1-meter telescope ZIMLAT of the Astronomical Institute of the University of Bern has been used to collect light curves of MEO and GEO objects for a considerable period of time. Recently, light curves of Low Earth Orbit (LEO) targets were acquired as well. We present different observation methods, including active tracking using a CCD subframe readout technique, and the use of a high-speed scientific CMOS camera. Technical challenges when tracking objects with poor orbit redictions, as well as different data reduction methods are addressed. Results from a survey of abandoned rocket upper stages in LEO, examples of abandoned payloads and observations of high area-to-mass ratio debris will be resented. Eventually, first results of the analysis of these light curves are provided.