3,434 research outputs found
Endogenous growth and property rights over renewable resources
We study how different regimes of access rights to renewable natural resources - namely, open access versus full property rights â affect sustainability, growth and welfare in the context of modern endogenous growth theory. Resource exhaustion may occur under both regimes but is more likely to arise under open access. Moreover, under full property rights, positive resource rents increase expenditures on manufacturing goods and temporarily accelerate productivity growth, but also yield a higher resource price at least in the short-to-medium run. We characterize analytically and quantitatively the modelâs dynamics to assess the welfare implications of differences in property rights enforcement
Efficacy assessment of a novel endolysin PlyAZ3aT for the treatment of ceftriaxone-resistant pneumococcal meningitis in an infant rat model.
BACKGROUND
Treatment failure in pneumococcal meningitis due to antibiotic resistance is an increasing clinical challenge and alternatives to antibiotics warrant investigation. Phage-derived endolysins efficiently kill gram-positive bacteria including multi-drug resistant strains, making them attractive therapeutic candidates. The current study assessed the therapeutic potential of the novel endolysin PlyAZ3aT in an infant rat model of ceftriaxone-resistant pneumococcal meningitis.
METHODS
Efficacy of PlyAZ3aT was assessed in a randomized, blinded and controlled experimental study in infant Wistar rats. Meningitis was induced by intracisternal infection with 5 x 107 CFU/ml of a ceftriaxone-resistant clinical strain of S. pneumoniae, serotype 19A. Seventeen hours post infection (hpi), animals were randomized into 3 treatment groups and received either (i) placebo (phosphate buffered saline [PBS], n = 8), (ii) 50 mg/kg vancomycin (n = 10) or (iii) 400 mg/kg PlyAZ3aT (n = 8) via intraperitoneal injection. Treatments were repeated after 12 h. Survival at 42 hpi was the primary outcome; bacterial loads in cerebrospinal fluid (CSF) and blood were secondary outcomes. Additionally, pharmacokinetics of PlyAZ3aT in serum and CSF was assessed.
RESULTS
PlyAZ3aT did not improve survival compared to PBS, while survival for vancomycin treated animals was 70% which is a significant improvement when compared to PBS or PlyAZ3aT (p<0.05 each). PlyAZ3aT was not able to control the infection, reflected by the inability to reduce bacterial loads in the CSF, whereas Vancomycin sterilized the CSF and within 25 h. Pharmacokinetic studies indicated that PlyAZ3aT did not cross the blood brain barrier (BBB). In support, PlyAZ3aT showed a peak concentration of 785 ÎŒg/ml in serum 2 h after intraperitoneal injection but could not be detected in CSF.
CONCLUSION
In experimental pneumococcal meningitis, PlyAZ3aT failed to cure the infection due to an inability to reach the CSF. Optimization of the galenic formulation e.g. using liposomes might enable crossing of the BBB and improve treatment efficacy
Plastid genomes of two brown algae, Ectocarpus siliculosus and Fucus vesiculosus: further insights on the evolution of red-algal derived plastids
<p>Abstract</p> <p>Background</p> <p>Heterokont algae, together with cryptophytes, haptophytes and some alveolates, possess red-algal derived plastids. The chromalveolate hypothesis proposes that the red-algal derived plastids of all four groups have a monophyletic origin resulting from a single secondary endosymbiotic event. However, due to incongruence between nuclear and plastid phylogenies, this controversial hypothesis remains under debate. Large-scale genomic analyses have shown to be a powerful tool for phylogenetic reconstruction but insufficient sequence data have been available for red-algal derived plastid genomes.</p> <p>Results</p> <p>The chloroplast genomes of two brown algae, <it>Ectocarpus siliculosus </it>and <it>Fucus vesiculosus</it>, have been fully sequenced. These species represent two distinct orders of the Phaeophyceae, which is a major group within the heterokont lineage. The sizes of the circular plastid genomes are 139,954 and 124,986 base pairs, respectively, the size difference being due principally to the presence of longer inverted repeat and intergenic regions in <it>E. siliculosus</it>. Gene contents of the two plastids are similar with 139-148 protein-coding genes, 28-31 tRNA genes, and 3 ribosomal RNA genes. The two genomes also exhibit very similar rearrangements compared to other sequenced plastid genomes. The tRNA-Leu gene of <it>E. siliculosus </it>lacks an intron, in contrast to the <it>F. vesiculosus </it>and other heterokont plastid homologues, suggesting its recent loss in the Ectocarpales. Most of the brown algal plastid genes are shared with other red-algal derived plastid genomes, but a few are absent from raphidophyte or diatom plastid genomes. One of these regions is most similar to an apicomplexan nuclear sequence. The phylogenetic relationship between heterokonts, cryptophytes and haptophytes (collectively referred to as chromists) plastids was investigated using several datasets of concatenated proteins from two cyanobacterial genomes and 18 plastid genomes, including most of the available red algal and chromist plastid genomes.</p> <p>Conclusion</p> <p>The phylogenetic studies using concatenated plastid proteins still do not resolve the question of the monophyly of all chromist plastids. However, these results support both the monophyly of heterokont plastids and that of cryptophyte and haptophyte plastids, in agreement with nuclear phylogenies.</p
The Air Microwave Yield (AMY) experiment - A laboratory measurement of the microwave emission from extensive air showers
The AMY experiment aims to measure the microwave bremsstrahlung radiation
(MBR) emitted by air-showers secondary electrons accelerating in collisions
with neutral molecules of the atmosphere. The measurements are performed using
a beam of 510 MeV electrons at the Beam Test Facility (BTF) of Frascati INFN
National Laboratories. The goal of the AMY experiment is to measure in
laboratory conditions the yield and the spectrum of the GHz emission in the
frequency range between 1 and 20 GHz. The final purpose is to characterise the
process to be used in a next generation detectors of ultra-high energy cosmic
rays. A description of the experimental setup and the first results are
presented.Comment: 3 pages -- EPS-HEP'13 European Physical Society Conference on High
Energy Physics (July, 18-24, 2013) at Stockholm, Swede
Parkinson's Disease and Cancer
Epidemiological evidence suggests a reduced incidence of many common types of cancers in individuals with Parkinson's disease (PD). Parkinson's disease and cancer are two diseases that result from an excessive signaling by one of two forces driving cells to opposite directions. PD results from the excessive death of dopaminergic neurons in the substantia nigra pars compacta (SNc) in the brain, while uncontrolled growth is the key property of cancer. Parkinson's disease is a complex disorder, probably due in most of the cases to the interaction of environment and genes. Many genes responsible for familial forms of PD are supposed to have a supportive role in regulating or maintaining the cell cycle, a fact that allows us to assume their interaction in tumorigenesis. Understanding the nature of these processes may help researchers find new and more efficacious therapeutic approaches for both diseases
A phase I study of dexosome immunotherapy in patients with advanced non-small cell lung cancer
BACKGROUND: There is a continued need to develop more effective cancer immunotherapy strategies. Exosomes, cell-derived lipid vesicles that express high levels of a narrow spectrum of cell proteins represent a novel platform for delivering high levels of antigen in conjunction with costimulatory molecules. We performed this study to test the safety, feasibility and efficacy of autologous dendritic cell (DC)-derived exosomes (DEX) loaded with the MAGE tumor antigens in patients with non-small cell lung cancer (NSCLC). METHODS: This Phase I study enrolled HLA A2+ patients with pre-treated Stage IIIb (N = 4) and IV (N = 9) NSCLC with tumor expression of MAGE-A3 or A4. Patients underwent leukapheresis to generate DC from which DEX were produced and loaded with MAGE-A3, -A4, -A10, and MAGE-3DPO4 peptides. Patients received 4 doses of DEX at weekly intervals. RESULTS: Thirteen patients were enrolled and 9 completed therapy. Three formulations of DEX were evaluated; all were well tolerated with only grade 1â2 adverse events related to the use of DEX (injection site reactions (N = 8), flu like illness (N = 1), and peripheral arm pain (N = 1)). The time from the first dose of DEX until disease progression was 30 to 429+ days. Three patients had disease progression before the first DEX dose. Survival of patients after the first DEX dose was 52â665+ days. DTH reactivity against MAGE peptides was detected in 3/9 patients. Immune responses were detected in patients as follows: MAGE-specific T cell responses in 1/3, increased NK lytic activity in 2/4. CONCLUSION: Production of the DEX vaccine was feasible and DEX therapy was well tolerated in patients with advanced NSCLC. Some patients experienced long term stability of disease and activation of immune effector
Effect of tetramethylammonium hydroxide on nucleation, surfacemodification and growth ofmagnetic nanoparticles.
Nanoparticles of magnetite (Fe3O4) were obtained by reacting ferric chloride with sodium sulphite, through the reductionprecipitation
method. The effects of adding tetramethylammonium hydroxide (TMAOH) during or after the precipitation of the
iron oxide were studied in an attempt to obtain well-dispersed magnetite nanoparticles. Accordingly, the following experimental
conditions were tested: (i) precipitation in absence of TMAOH (sample Mt), (ii) the same as (i) after peptizing with TMAOH
(Mt1), (iii) TMAOH added to the reaction mixture during the precipitation of magnetite (Mt2). Analyses with transmission
electron microscopy (TEM), X-ray diffraction, M?ossbauer spectroscopy, attenuated total reflectance Fourier transform infrared
spectroscopy (ATR-FTIR), zeta potential, and magnetization measurements up to 2.5 T revealed that magnetite was normally
formed also in the medium containing TMAOH. The degree of particles agglomeration was monitored with laser diffraction
and technique and inspection of TEM images. The relative contributions of N?eel and Brownian relaxations on the magnetic heat
dissipation were studied by investigating the ability of suspensions of these magnetite nanoparticles to release heat in aqueous
and in hydrogel media. Based on ATR-FTIR and zeta potential data, it is suggested that the surfaces of the synthesized magnetite
particles treated with TMAOH become coated with (CH3)4N+ cations
Merging Mouse Transcriptome Analyses with Parkinson's Disease Linkage Studies
The hallmark of Parkinson's disease (PD OMIM #168600) is the degeneration of the nigral dopaminergic system affecting approximately 1% of the human population older than 65. In pursuit of genetic factors contributing to PD, linkage and association studies identified several susceptibility genes. The majority of these genes are expressed by the dopamine-producing neurons in the substantia nigra. We, therefore, propose expression by these neurons as a selection criterion, to narrow down, in a rational manner, the number of candidate genes in orphan PD loci, where no mutation has been associated thus far. We determined the corresponding human chromosome locations of 1435 murine cDNA fragments obtained from murine expression analyses of nigral dopaminergic neurons and combined these data with human linkage studies. These fragments represent 19 genes within orphan OMIM PD loci. We used the same approach for independent association studies and determined the genes in neighborhood to the peaks with the highest LOD score value. Our approach did not make any assumptions about disease mechanisms, but it, nevertheless, revealed α-synuclein, NR4A2 (Nurr1), and the tau genes, which had previously been associated to PD. Furthermore, our transcriptome analysis identified several classes of candidate genes for PD mutations and may also provide insight into the molecular pathways active in nigral dopaminergic neurons
The ANTARES Optical Beacon System
ANTARES is a neutrino telescope being deployed in the Mediterranean Sea. It
consists of a three dimensional array of photomultiplier tubes that can detect
the Cherenkov light induced by charged particles produced in the interactions
of neutrinos with the surrounding medium. High angular resolution can be
achieved, in particular when a muon is produced, provided that the Cherenkov
photons are detected with sufficient timing precision. Considerations of the
intrinsic time uncertainties stemming from the transit time spread in the
photomultiplier tubes and the mechanism of transmission of light in sea water
lead to the conclusion that a relative time accuracy of the order of 0.5 ns is
desirable. Accordingly, different time calibration systems have been developed
for the ANTARES telescope. In this article, a system based on Optical Beacons,
a set of external and well-controlled pulsed light sources located throughout
the detector, is described. This calibration system takes into account the
optical properties of sea water, which is used as the detection volume of the
ANTARES telescope. The design, tests, construction and first results of the two
types of beacons, LED and laser-based, are presented.Comment: 21 pages, 18 figures, submitted to Nucl. Instr. and Meth. Phys. Res.
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