Modeling nigrostriatal degeneration in organotypic cultures, a new ex vivo model of Parkinson’s disease

Parkinson’s disease (PD) is the second most frequent neurodegenerative disorder afflicting 2% of the population older than 65 years worldwide. Recently, brain organotypic slices have been used to model neurodegenerative disorders, including PD. They conserve brain three-dimensional architecture, synaptic connectivity and its microenvironment. This model has allowed researchers a simple and rapid method to observe cellular interactions and mechanisms. In the present study, we developed an organotypic PD model from rat brains that includes all the areas involved in the nigrostriatal pathway in a single slice preparation, without using neurotoxins to induce the dopaminergic lesion. The mechanical transection of the nigrostriatal pathway obtained during slice preparation induced PD-like histopathology. Progressive nigrostriatal degeneration was monitored combining innovative approaches, such as diffusion tensor magnetic resonance imaging (DT-RMI) to follow fiber degeneration and mass spectrometry to quantify striatal dopamine content, together with bright-field and fluorescence microscopy imaging. A substantia nigra dopaminergic cell number decrease was observed by immunohistochemistry against rat tyrosine hydroxylase (TH) reaching 80% after 2 days in culture associated with a 30% decrease of striatal TH-positive fiber density, a 15% loss of striatal dopamine content quantified by mass spectrometry and a 70% reduction of nigrostriatal fiber fractional anisotropy quantified by DT-RMI. In addition, a significant decline of medium spiny neuron density was observed from days 7 to 16. These sagittal organotypic slices could be used to study the early stage of PD, namely dopaminergic degeneration, and the late stage of the pathology with dopaminergic and GABAergic neuron loss. This novel model might improve the understanding of PD and may represent a promising tool to refine the evaluation of new therapeutic approaches

A Demand-Side Management Experience in Existing Building Commissioning

As part of a suite of demand-side management (DSM) program offerings, Xcel Energy provides a recommissioning program to its Colorado commercial customers. The program has a summer peak-demand savings goal of 7.8 MW to be achieved by 2005. Commenced in 2002 as a pilot, the program offers no-cost recommissioning services and incentives to participants to buy-down implementation costs to achieve a one-year simple payback. To date, four projects are complete and twenty-three more are underway. It is anticipated that approximately 65 projects will be completed through the program by 2005. This paper describes the basic program design and implementation process. The choices made in response to market barriers and program constraints are highlighted. In addition, the paper details the marketing efforts, the competitive bidding process, the standardized program elements, measurement and verification activities, and project savings to date. For each program aspect, program successes, uncertainties, and lessons learned are presented

Frequency offset corrected inversion (FOCI) pulses for use in localized spectroscopy

Gradient localized spectroscopy techniques suffer from a well documented spatial localization error caused by the difference in chemical shifts between resonances. This results in the acquisition of spectra from partially overlapping spatial regions of the sample, with each resonance representing a different region. The image-selected in vivo spectroscopy technique uses hyperbolic secant inversion pulses, where the main limitation in reducing this error is in the RF power available for application of the selective RF pulse. This spatial localization error may be dramatically reduced by increasing, and temporally shaping, the gradient pulse during slice-selective spin inversion. The performance of these RF pulses have been experimentally verified

Age of HIV Acquisition Affects the Risk of Multi-Morbidity after 25 Years of Infection Exposure

Introduction: Understanding the intersection of HIV, aging and health is crucial due to the increasing number of people aging with HIV. Objective: The objective of the study was to assess the prevalence of, and risk factors for individual comorbidities and multi-morbidity in people living with HIV with similar duration of HIV infection, notwithstanding a 25-year difference at the time of HIV acquisition. Methods: In a cross-sectional multicentre retrospective study, we compared three match-control age groups. The "Young" were selected from Romania and included HIV-positive patients prenatally infected and assessed at the age of 25-30 years. The "Old" and the "Geriatric" were selected from Italy. These respectively included subjects infected with HIV at the age of 25 years and assessed at the age of 50-55 years, and those infected at the age of 50 years and assessed at the age of 75-80 years. Each group was sex and age matched in a 1: 5 ratio with controls selected from the CINECA ARNO database from Italy. We described non-infectious comorbidities (NICM), including cardiovascular disease, hypertension, dyslipidaemia, diabetes, chronic kidney disease, and multi-morbidity (MM >= 3 NICM). Results: MM prevalence in the "Young" group compared to controls was 6.2% vs 0%, while in the "Geriatric" was "68.2% vs 3.6%. Using "Young" as a reference, in multivariate analyses, predictors for MM were as follows: HIV serostatus (OR=47.75, IQR 14.78-154.25, p<0.01) and "Geriatric" vs "Young" (OR=30.32, IQR 5.89-155.98, p<0.01). Conclusion: These data suggest that age at acquisition of HIV should be considered as a risk factor for NICM and MM

Construction and Performance of Large-Area Triple-GEM Prototypes for Future Upgrades of the CMS Forward Muon System

At present, part of the forward RPC muon system of the CMS detector at the CERN LHC remains uninstrumented in the high-\eta region. An international collaboration is investigating the possibility of covering the 1.6 < |\eta| < 2.4 region of the muon endcaps with large-area triple-GEM detectors. Given their good spatial resolution, high rate capability, and radiation hardness, these micro-pattern gas detectors are an appealing option for simultaneously enhancing muon tracking and triggering capabilities in a future upgrade of the CMS detector. A general overview of this feasibility study will be presented. The design and construction of small (10\times10 cm2) and full-size trapezoidal (1\times0.5 m2) triple-GEM prototypes will be described. During detector assembly, different techniques for stretching the GEM foils were tested. Results from measurements with x-rays and from test beam campaigns at the CERN SPS will be shown for the small and large prototypes. Preliminary simulation studies on the expected muon reconstruction and trigger performances of this proposed upgraded muon system will be reported.Comment: 7 pages, 25 figures, submitted for publication in conference record of the 2011 IEEE Nuclear Science Symposium, Valencia, Spai

An overview of the design, construction and performance of large area triple-GEM prototypes for future upgrades of the CMS forward muon system

GEM detectors are used in high energy physics experiments given their good spatial resolution, high rate capability and radiation hardness. An international collaboration is investigating the possibility of covering the 1.6 < vertical bar eta vertical bar < 2.4 region of the CMS muon endcaps with large-area triple-GEM detectors. The CMS high-eta area is actually not fully instrumented, only Cathode Strip Chamber (CSC) are installed. The vacant area presents an opportunity for a detector technology able to to cope with the harsh radiation environment; these micropattern gas detectors are an appealing option to simultaneously enhance muon tracking and triggering capabilities in a future upgrade of the CMS detector. A general overview of this feasibility study is presented. Design and construction of small (10cm x 10cm) and full-size trapezoidal (1m x 0.5m) triple-GEM prototypes is described. Results from measurements with x-rays and from test beam campaigns at the CERN SPS is shown for the small and large prototypes. Preliminary simulation studies on the expected muon reconstruction and trigger performances of this proposed upgraded muon system are reported

Modal Logics of Topological Relations

Logical formalisms for reasoning about relations between spatial regions play a fundamental role in geographical information systems, spatial and constraint databases, and spatial reasoning in AI. In analogy with Halpern and Shoham's modal logic of time intervals based on the Allen relations, we introduce a family of modal logics equipped with eight modal operators that are interpreted by the Egenhofer-Franzosa (or RCC8) relations between regions in topological spaces such as the real plane. We investigate the expressive power and computational complexity of logics obtained in this way. It turns out that our modal logics have the same expressive power as the two-variable fragment of first-order logic, but are exponentially less succinct. The complexity ranges from (undecidable and) recursively enumerable to highly undecidable, where the recursively enumerable logics are obtained by considering substructures of structures induced by topological spaces. As our undecidability results also capture logics based on the real line, they improve upon undecidability results for interval temporal logics by Halpern and Shoham. We also analyze modal logics based on the five RCC5 relations, with similar results regarding the expressive power, but weaker results regarding the complexity

Prime-boost therapeutic vaccination in mice with DNA/DNA or DNA/Fowlpox virus recombinants expressing the Human Papilloma Virus type 16 E6 and E7 mutated proteins fused to the coat protein of Potato virus X

The therapeutic antitumor potency of a prime-boost vaccination strategy was explored, based on the mutated, nontransforming forms of the E6 (E6F47R) and E7 (E7GGG) oncogenes of Human Papilloma Virus type 16 (HPV16), fused to the Potato virus X (PVX) coat protein (CP) sequence. Previous data showed that CP fusion improves the immunogenicity of tumor-associated antigens and may thus increase their efficacy. After verifying the correct expression of E6F47RCP and E7GGGCP inserted into DNA and Fowlpox virus recombinants by Western blotting and immunofluorescence, their combined use was evaluated for therapy in a pre-clinical mouse model of HPV16-related tumorigenicity. Immunization protocols were applied using homologous (DNA/DNA) or heterologous (DNA/Fowlpox) prime-boost vaccine regimens. The humoral immune responses were determined by ELISA, and the therapeutic efficacy evaluated by the delay in tumor appearance and reduced tumor volume after inoculation of syngeneic TC-1* tumor cells. Homologous DNA/DNA genetic vaccines were able to better delay tumor appearance and inhibit tumor growth when DNAE6F47RCP and DNAE7GGGCP were administered in combination. However, the heterologous DNA/Fowlpox vaccination strategy was able to delay tumor appearance in a higher number of animals when E6F47RCP and in particular E7GGGCP were administered alone

Immobilisation of engineered molecules on electrodes and optical surfaces,

ABSTRACT Monolayers of genetically modified proteins with an hexahistidine tag, (His)6, were obtained by using a Ni -NTA chelator synthesized on gold sputtered surfaces (via sulphide bonds), or on gold and graphite (via sililating agents) working electrodes of screen-printed devices. Two kinds of proteins were produced and purified for this study: a) a recombinant antibody, derived from the &apos;single chain Fv&apos; ( scFv) format; b) a photosystem II (PSII) core complex isolated from the mutant strain CP43-H of the thermophilic cyanobacterium Synechococcus elongatus. An scFv, previously isolated from a synthetic &apos;phage display&apos; library, was further engineered with an alkaline phosphatase activity genetically added between the carbossi-terminal of the scFvs and the (His)6 to allow direct measurement of immobilisation. Renewable specific binding of (His)6-proteins to gold and graphite surfaces and fast and sensitive electrochemical or optical detection of analytes were obtained. Additionally, &quot;on chip&quot; protein preconcentration was conveniently achieved for biosensing purposes, starting from crude unpurified extracts and avoiding protein purification steps

Ground state properties of a Tonks-Girardeau Gas in a periodic potential

In this paper, we investigate the ground-state properties of a bosonic Tonks-Girardeau gas confined in a one-dimensional periodic potential. The single-particle reduced density matrix is computed numerically for systems up to $N=265$ bosons. Scaling analysis of the occupation number of the lowest orbital shows that there are no Bose-Einstein Condensation(BEC) for the periodically trapped TG gas in both commensurate and incommensurate cases. We find that, in the commensurate case, the scaling exponents of the occupation number of the lowest orbital, the amplitude of the lowest orbital and the zero-momentum peak height with the particle numbers are 0, -0.5 and 1, respectively, while in the incommensurate case, they are 0.5, -0.5 and 1.5, respectively. These exponents are related to each other in a universal relation.Comment: 9 pages, 10 figure